pril 2014

Treatments for Attention Deficit

Hyperactivity Disorder in Adults

FINAL PHARMACOEPIDEM IOLOGY REPORT

December 2015

Study Team: Diana Martins, Wayne Khuu, Mina Tadrous, Zhan Yao, Luke William Spooner, Samantha Singh, Kimberly Fernandes, Sandra Knowles, David Juurlink, Mike Paterson, Muhammad Mamdani, Tara Gomes

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Conflict of Interest Statement

Muhammad Mamdani was a member of an advisory board for Hoffman La Roche, Pfizer, Novartis, GlaxoSmithKline and Eli Lilly Canada. Tara Gomes, Muhammad Mamdani and David Juurlink have received grant funding from the Ministry of Health and Long-term Care. No other study members report any affiliations or financial involvement (e.g., employment, consultancies, honoraria, stock options, expert testimony, grants or patents received or pending, or royalties) that may present a potential conflict of interest in the ADHD Medication Drug Class Review.

Acknowledgments

This review was supported by the Ontario Drug Policy Research Network which is funded by a grant from the Ontario Ministry of Health and Long-Term Care Health System Research Fund. This study was also supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this material are based on data and information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed herein are those of the author, and not necessarily those of CIHI. Datasets provided by ICES were linked using unique encoded identifies and analyzed at ICES. The statements, findings, conclusions, views, and opinions contained and expressed in the report are based in part on data obtained under license from IMS Health Canada Inc. concerning the following information service(s): Geographic Prescription Monitor (GPM12), data period October 1 2009 –January 31 2015. All Rights Reserved. The statements, findings, conclusions, views, and opinions expressed herein are not necessarily those of IMS Health Canada Inc. or any of its affiliated or subsidiary entities.

Study Team

Pharmacoepidemiology Team: Diana Martins, Mina Tadrous, Wayne Khuu, Luke William Spooner, Zhan Yao, Samantha Singh, Kimberly Fernandes, Sandra Knowles, David Juurlink, Mike Paterson, Muhammad Mamdani, Tara Gomes

Note

Some details are censored in this report so as not to preclude publication. Publications (when available) and/or final unpublished reports will be available on the ODPRN website (www.odprn.ca).

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Contents Executive Summary ...... 6 Introduction ...... 10 IMS Geographic Prescription Monitor (GPM12) ...... 10 Canadian Institute for Health Information NPDUIS ...... 10 Administrative Databases in Ontario ...... 11 Ontario Drug Benefit Database ...... 11 Other Health Administrative Databases ...... 11 Methods ...... 11 National and Provincial Trends in ADHD Medication Use ...... 11 Cross-Provincial Comparisons of Provincially-Funded ADHD Medication Use ...... 12 Characteristics of Provincially-Funded ADHD Medication Users in Ontario in 2013 ...... 12 Patterns of ADHD Medication Use among Adult New Users in Ontario ...... 12 Patterns of ADHD Medication Use among Youth in Ontario ...... 13 Possible Misuse of Treatments for ADHD in Public Drug Programs across Canada ...... 13 Exhibits and Findings ...... 14 National Trends in Utilization of ADHD Medications ...... 14 Exhibit 1: Total Number of Prescriptions for ADHD Medications Dispensed to All Individuals in Canada, by Payer and Quarter ...... 14 Exhibit 2: Total Number of Prescriptions for ADHD Medications Dispensed to All Individuals in Canada in Q4 2014, by Payer and Drug ...... 16 Exhibit 3: Total Number of Prescriptions and Cost for ADHD Medications Dispensed to Adults Aged 19 and Older in Canada, by Drug and Quarter ...... 17 Exhibit 4: Rate of Prescriptions for ADHD medications Dispensed to Adults Aged 19 and Older in Canada in 2013, by Drug and Age ...... 18 Exhibit 5: Rate of Prescriptions for ADHD medications Dispensed to Adults Aged 19 and Older in Canada in 2013, by Drug Class and Age ...... 18 Cross Provincial Trends in Utilization of ADHD Medications among Adults ...... 20 Exhibit 6: Population-Adjusted Rate of Prescriptions for ADHD medications Dispensed to Adults Aged 19 and Older in Canada, by Province and Quarter ...... 20 Exhibit 7: Population-Adjusted Rate of Publicly-funded ADHD medication Users Aged 18 and Older in Canada, by Province and Year ...... 22 Cross Provincial ADHD Medication Utilization among Adult Public Drug Plan Beneficiaries ...... 23 Exhibit 8: Population-Adjusted Rate of Publicly-funded ADHD Medication Users Aged 18 and Older in Canada in 2014, by Province ...... 23 Exhibit 9: Population-Adjusted Rate of Publicly-funded ADHD Stimulant Medication Users

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among Adults Aged 18 and Older in Canada in 2014, by Province and Drug Class ...... 24 Exhibit 10: Population-Adjusted Rate of Publicly-funded ADHD Medication Users among Adults Aged 18 and Older in Canada in 2014, by Province and Drug ...... 25 Exhibit 11: Population-Adjusted Rate of Publicly-funded ADHD Medication Users among Adults Aged 18 and Older in Canada in 2014, by Province and Age ...... 26 Trends in Utilization of ADHD Medications among Adults in Ontario ...... 27 Exhibit 13: Total Number of Prescriptions and Cost for ADHD Medications Dispensed to Adults Aged 19 and Older in Ontario, by Drug and Quarter ...... 27 Exhibit 14: Total Number of Provincially-Funded Prescriptions for ADHD Medications Dispensed to Adults Aged 18 and Older in Ontario, by Drug and Quarter ...... 28 Trends in Number of Brand Name vs. Generic Stimulant Medication Users in Ontario ...... 29 Exhibit 15a: Total Number of Provincially-Funded Generic ADHD Stimulant Medication Users Aged 18 and Older by Drug Type and by Year ...... 29 Exhibit 15b: Total Number of Provincially-Funded Brand Name ADHD Stimulant Medication Users Aged 18 and Older by Drug Type and by Year ...... 29 Exhibit 16: Total Number of Provincially-Funded Long-Acting Methylphenidate Users Aged 18 and Older, by Brand Name vs. Generic Formulations and Year...... 31 Exhibit 17: Publically-Funded ADHD Medication Use in the Year Prior to and After Initiating Brand Name Methylphenidate Extended Release (Concerta) in Ontario in 2013 ...... 33 Exhibit 18: Average Daily and Monthly Cost of Publically-Funded Brand Name (Concerta) and Generic Methylphenidate Extended-Release in Ontario in 2014 ...... 34 Characteristics of Provincially-Funded ADHD Medication Users in Ontario in 2013 ...... 35 Exhibit 19a: Characteristics of Provincially-Funded ADHD Medications Users Aged 18 and Older in Ontario in 2013, by Drug ...... 35 Exhibit 19b: Characteristics of Provincially-Funded ADHD Medications Users Aged 18 and Older in Ontario in 2013, by Drug ...... 36 Patterns of ADHD Medication Use among Adult New Users in Ontario ...... 38 Exhibit 20: Patterns of Provincially-Funded ADHD Medications Use among Adult Continuous Users Aged 18 and Older in Ontario between 2002 and 2012, by Drug Initiated ...... 38 Exhibit 21: Patterns of Provincially-Funded ADHD Medications Use among Adult Continuous Users Aged 18 and Older in Ontario between 2002 and 2012, by Age at Initiation ...... 39 Exhibit 22: Patterns of Provincially-Funded Stimulant ADHD Medications Use among Adult Continuous Users Aged 18 and Older in Ontario between 2002 and 2012, by Drug Class at Initiation ...... 39 Exhibit 23: Characteristics of Dual Therapy among Continuous Users of Atomoxetine in Ontario between 2002 and 2012 ...... 41 Patterns of ADHD Medication Continuation into Adulthood among Youth in Ontario ...... 42

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Exhibit 24: Description of Provincially-Funded Continuous ADHD Medication Users who Turned 18 over the Study Period in Ontario ...... 42 Possible Misuse of Treatments for ADHD in Public Drug Programs across Canada ...... 44 Exhibit 25: Percent of Potentially Inappropriate Prescriptions Dispensed for ADHD Medications, among Users Aged 18 and Older in Canada in 2013 and 2014, by Province and Age Group ...... 44 Health Equity ...... 46 Limitations ...... 46 Data Availability ...... 46 Generalizability...... 47 Adherence ...... 47 Overall Conclusion...... 47 Reference List ...... 48 Review of the Observational Literature ...... 49 Objectives ...... 49 Methods ...... 49 Search Strategy ...... 49 Inclusion criteria: ...... 49 Results ...... 49 Conclusions ...... 54 Literature Review References ...... 55 Appendix A: Public Plan Listings for ADHD Medications in Canada, by Province ...... 57 Appendix B: Medline Search Strategy ...... 58 Appendix C: Summary of Included Studies ...... 59 Appendix D: Quarterly ADHD Medication Use Data, by Drug and Age ...... 69 Appendix E: Number of ADHD Medication Users by Drug Groups ...... 136 Appendix F: Number of Users of ADHD Medications in NS and NB, 2013 ...... 143

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Executive Summary Overall National and Provincial Trends in ADHD Medication Use The number of prescriptions dispensed and the cost of medications used to treat ADHD among users age 19 years of age or older in Canada has increased by 78% and 94% between the fourth quarter (Q4) of 2009 and Q4 of 2014, respectively. In Q4 2014, there were 4,008,735 prescriptions for ADHD medications dispensed nationally costing $297.4 million. Half of all ADHD medications dispensed were privately funded (50.2%; 2,013,897 prescriptions) and a third (31%; 1,253,693 prescriptions) were paid for by provincially-funded drug coverage programs in Q4 2014. The majority of all ADHD medications dispensed in Q4 2014 (59.0%; 2,364,101 prescriptions) were for methylphenidate, which was consistent among all payers (56.6% private, 63.8% public, 55.8% cash, 72.3% Noninsured Health Benefits (NIHB)).

Among adults aged 19 years and older in Canada, the increase in prescriptions dispensed (119% increase) and cost (153% increase) of ADHD medications was even greater between Q4 2009 and Q2 2014. By Q2 2014, 1,603,896 prescriptions for ADHD medications were dispensed costing $111.1 million. In Q2 2014, over half of prescriptions dispensed to treat ADHD in adults (58.4%; 937,374 prescriptions) were for methylphenidate, followed by lisdexamfetamine (13.6%; 217,416 prescriptions), dextroamphetamine (12.9%; 273,026 prescriptions), mixed-salt amphetamine (9.6%; 153,616 prescriptions), atomoxetine (5.2%; 84,008 prescriptions), and guanfacine (0.3%; 4,753 prescriptions).

In 2013, the highest rate of ADHD medication prescribing was to those aged 19-29 years (368.2 prescriptions per 1,000 population) followed by those aged 30-64 years (275.1 prescriptions per 1,000 population), and 65 years and older (44.8 prescriptions per 1,000 population).

Cross-Provincial Comparisons of ADHD Medication Use The rate of ADHD medication prescribing to adults aged 19 years and older has been increasing since Q4 2009 across all provinces in Canada. In Q2 2014, Ontario had the third lowest rate of ADHD medications dispensed which was lower than the national average (55 and 69 prescriptions per eligible population, in Ontario and Canada respectively).

Similarly, among public drug plan beneficiaries aged 18 years and older, the rate of ADHD medication users has increased across all provinces in Canada (no data for Quebec). In 2014, Newfoundland and Labrador had the highest rate of users, which was 50% higher than the national average (11.3 and 7.5 users per 1,000 eligible population, in Newfoundland and Labrador and Canada respectively). Ontario had the highest number of ADHD medication users (N=22,309) in Canada, while the rate of users was similar to the rate in Canada (8.1 and 7.5 users per 1,000 eligible population, in Ontario and Canada, respectively). Among stimulant ADHD medication users in 2014, the rate of short-acting stimulant users was higher than the rate of long-acting stimulant users in Newfoundland and Labrador. In Ontario, the rate of long-acting stimulant medication users was 6.5 users per 1,000 eligible compared to 2.5 users per 1,000 eligible. Methylphenidate was the most commonly utilized publicly funded ADHD medication across all provinces in 2014, except in British Columbia and Alberta which

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had higher rates of dextroamphetamine use.

Patterns of ADHD Medication Use in Ontario Similar to national trends, the number of prescriptions dispensed and costs for ADHD medications among adults aged 19 years and older in Ontario have increased 82% (from 271,684 prescriptions to 493,571 prescriptions) and 112% (from $17.9 million to $39.2 million) between Q4 2009 and Q2 2014, respectively. Methylphenidate was the most commonly dispensed ADHD medication (57.4% of prescriptions) in Q2 2014.

Among publicly funded adults aged 18 and older in Ontario, the number of ADHD prescriptions dispensed increased nearly 2-fold from 67,521 prescriptions in Q4 2009 to 132,083 prescriptions in Q4 2014. In Q4 2014, total public drug program expenditure for ADHD for adults aged 18 years and older products was approximately $6.5 million. A total of 5.8 million prescriptions for these drugs were dispensed in fiscal year 2013-2014 for adults, at a cost of $394.1 million. The majority of prescriptions dispensed in Q4 2014 were for methylphenidate (67.6%; 89,265 prescriptions), followed by lisdexamfetamine (16.3%; 21,520 prescriptions), mixed-salt amphetamine (10.1%; 13,308 prescriptions), dextroamphetamine (4.6%; 6,274 prescriptions), and atomoxetine (1.3%; 1,716 prescriptions).

The number of provincially-funded stimulant ADHD medication users of all ages increased by 156.9% between 2008 and 2014, which was driven by an increase in long-acting brand name products. In 2013, the number of brand name stimulant ADHD medication users surpassed the number of generic stimulant users (12,274 and 10,219 users, respectively). Since being listed on the Ontario public drug formulary in 2009, the number of provincially-funded extended release (ER) methylphenidate users has increased 194.3% from 2,496 users in 2009 to 7,345 users by 2014. The introduction of reimbursement programs , referred to as brand-name drug reimbursement cards, has allowed brand name companies to maintain a large market share by offering to pay the cost difference between the brand and generic costs for the patients. For this reason, there were consistently more brand-name methylphenidate ER users compared to generic users (except in 2011) over the study period, which may reflect the introduction of brand-name drug reimbursement cards. This is unique given that the use of generic drugs is expected to be greater than the use of brand name drugs when generic versions are available and the primary option.

In 2013, there were 2,311 new users of brand ER methylphenidate (Concerta) in the Ontario Public Drug Program, of which approximately 40% (N= 939) did not have any ADHD medications dispensed in the year prior to initiation. In 2014, despite a higher number of prescriptions for brand name methylphenidate ER (Concerta) compared to generic ER methylphenidate, the average cost of prescriptions per 30 days was not significantly different (standardized difference < 0.1) between brand name (Concerta) (Median = $68; IQR = $50- 116) and generic methylphenidate ER (Median = $72; IQR = $53-121).

Characteristics of ADHD Medication Users in Ontario There were 19,615 adults aged 18 and older who were prescribed provincially-funded ADHD medications in Ontario in 2013.The majority of users were dispensed methylphenidate (66.5%; N=13,049), were under 65 years of age (86.3%; N=16,929), more than half were

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male (54.9%; N=10,778) and the majority lived in urban areas (88.4%; N=17,344). Among those younger than 65, the highest number of users was found among those aged 36-64. The proportion of users with an identified ADHD diagnosis in the past 10 years varied between treatment groups, from 38.8% among dextroamphetamine users to 69.9% among atomoxetine users. Although lisdexamfetamine, mixed-salt amphetamine, and atomoxetine are not indicated for new users of these drugs, lisdexamfetamine was the most commonly newly initiated treatment (36.3%; N=906), and nearly one quarter of mixed-salt amphetamine (22.7%; N=520) and atomoxetine (24.5%; N=35) users had no prior use of ADHD medications dispensed through the public drug program. Among new-users of atomoxetine (N=619) approximately a third (32.8%; N=203) received a stimulant therapy along with their atomoxetine. Atomoxetine is currently reimbursed as a monotherapy.

Patterns of ADHD Medication Use and Discontinuation among New Users in Ontario There were approximately 15,500 individuals aged 18 and older who initiated an ADHD medication in Ontario between 2002 and 2012, the majority of whom initiated methylphenidate (80-85%). Patients on lisdexamfetamine and mixed-salt amphetamine were most likely to switch to another drug within 6 months of therapy initiation (12-14%) compared to other users (<10%). The median time to discontinuing any ADHD therapy among new users was 325 to 350 days. This differed significantly by the drug initiated, ranging from 300- 325 days among methylphenidate users to 575-600 days for atomoxetine (the only non- stimulant) users. When comparing users who initiated a stimulant ADHD medication (short acting stimulants and long-acting stimulants, the median time to discontinuation for patients on short-acting stimulants (275-300 days) was significantly shorter compared to patients on long-acting stimulants (375-400 days). The median time to ADHD medication discontinuation also differed significantly across age groups, with younger (ages 18 to 25) and older (ages 65 and older) users discontinuing ADHD medication use sooner (250-275 days) compared to users aged 26 to 35 and users aged 36 to 64 (325 – 425).

Patterns of ADHD Medication Use among Youth in Ontario There were approximately 32,500 youth aged younger than 18 in Ontario who received two or more provincially-funded ADHD medication prescriptions within 180 days between 2002 and 2013, of whom approximately 16-20% continued to use these medications past their 17th birthday. Among those who continued use of an ADHD medication after their 17th birthday, close to half continued their use into adulthood (past 18th birthday). On average, the median time to ADHD medications for these individuals following their 18th birthday was greater than a year. A large number of those who stopped therapy (56-60%) were still ODB eligible meaning other factors may influence the continuation of ADHD therapy at this transition.

Possible Misuse of Treatments for ADHD across Canada A potentially inappropriate stimulant ADHD medication prescription was identified as such if it was an early refill of a prior stimulant ADHD medication (filled within 1 to 7 days of a prior prescription that had a quantity of 30 days or more) and was from both a different doctor and different pharmacy than the prior prescription. The percent of stimulant ADHD medication prescriptions that were potentially inappropriate in 2013 and 2014 was low (<0.3%) across all provinces in Canada. Ontario had the highest percent of potentially inappropriate ADHD

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medications prescribed, followed by Alberta and British Columbia, which ranged between 0.2- 0.5% in 2013 and 2014. The number of prescriptions that were potentially inappropriate was less than 100 across all provinces, except Ontario and British Columbia which largely exceeded 100 (data not shown).

Summary of Observational Literature Review A review of the observational literature on misuse, abuse, and diversion of prescription stimulants in both the general, ADHD-diagnosed, and prescription-holder population was conducted. The studies reviewed, all of which were surveys, suggest that misuse of prescription stimulants is prevalent, both in prescription and non-prescription holder populations. Only one Canadian study was included in this observational literature review highlighting the need for further research in Canada surrounding misuse and diversion of prescription stimulants. The prevalence of misuse was higher among college students compared to the general population. The few studies that examined motives for misuse found that in adults and college students misuse was primarily to improve concentration and increase alertness. Among studies that reviewed specific medication misuse, the majority suggested that dextroamphetamine, amphetamine and amphetamine mixed-salts were the most commonly misused stimulants. However, a limitation of the studies that reviewed specific medication misuse is that they do not account for availability of medications, prescription rate, or user preferences. Studies that explored how misusers access these medications suggest that prescription holders are a significant source.

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Introduction In Canada, there are currently six medications that are used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD). These medications can be divided into stimulant therapies (dextroamphetamine, lisdexamfetamine, methylphenidate, mixed-salt amphetamine), and non-stimulant therapies (atomoxetine, guanfacine). Stimulant medications can be further divided into short-acting (dextroamphetamine, methylphenidate) and long- acting (dextroamphetamine, lisdexamfetamine, methylphenidate, mixed-salt amphetamine) stimulants. These medications differ in their public plan listings on provincial formularies across Canada. Detailed information on public plan listings is provided in Appendix A.

The objectives of this report are to:

1. To present national and provincial utilization trends in use of treatments for ADHD among adults in Canada, by drug dispensed and by payer (public drug programs, private insurers, cash payment and Non-Insured Health Benefits). 2. To present cross provincial comparisons of the trends in utilization of treatments for ADHD among adults in public drug programs across Canada using population- adjusted rates of use. 3. To examine trends in use of medications used to treat ADHD among adults funded through the Ontario Public Drug Program. 4. To describe characteristics of adult patients prescribed provincially-funded treatment for ADHD in Ontario 5. To describe the course and length of ADHD medication therapy among users in Ontario. 6. To investigate possible misuse of treatments for ADHD in public drug programs across Canada 7. To summarize observational studies that investigated and evaluated misuse and abuse of ADHD treatments in adults

IMS Geographic Prescription Monitor (GPM12) IMS Geographic Prescription Monitor (GPM12) is a premium source of sales intelligence on retail prescription activity in Canada. Data is obtained from a representative sample of 65% of all Canadian pharmacies and is projected monthly by province or customized geography. Projections incorporate the number of pharmacies in a given area, the distance between IMS- captured and uncaptured pharmacies, and the size of the pharmacies. Projections are representative of provincial and national sales volumes. Data available through IMS Geographic Prescription Monitor (GPM12) includes prescription volumes and units (e.g. tablets, patches) dispensed, and are stratified by payer type (e.g. public drug plan, private drug plan, cash, Non-Insured Health Benefits). Data from IMS Geographic Prescription Monitor (GPM12) is available from the fourth quarter of 2009 to the fourth quarter of 2014.

Canadian Institute for Health Information NPDUIS The National Prescription Drug Utilization Information System (NPDUIS) was developed by the Canadian Institute for Health Information (CIHI) to provide pan-Canadian information on public drug programs. NPDUIS data can be used to obtain estimates of populations eligible for provincial drug coverage in Alberta, British Columbia (BC), Saskatchewan, Manitoba, New

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Brunswick, Nova Scotia, Newfoundland and Labrador and Labrador and Prince Edward Island (PEI). Data from NPDUIS is available from calendar year 2000 to 2014. Data is only available as of 2002 for Nova Scotia, 2005 for PEI, 2006 for BC and 2009 for Newfoundland and Labrador and Labrador.

Administrative Databases in Ontario These datasets were linked using unique, encoded identifiers and analyzed at the Institute for Clinical Evaluative Sciences (ICES).

Ontario Drug Benefit Database The Ontario Drug Benefit (ODB) database contains individual-level claims data for all prescription drugs dispensed to Ontario residents eligible for public drug funding. Eligibility criteria include unemployment, disability, high prescription drug costs relative to net household income, receipt of home care services, residence in a long-term care facility, or age 65 years or older. This database is of high quality, with an error rate of <1% and can be linked to other health administrative databases to obtain patient demographic information1. We analyzed data from the ODB between January 2000 and December 2014.

Other Health Administrative Databases We used data from the Ontario Registered Persons Database (RPDB), Canadian Institute for Health Information Discharge Abstract Database (CIHI-DAD) and National Ambulatory Care Reporting System (CIHI-NACRS), Ontario Health Insurance Plan (OHIP) and the ICES Physician Database (IPDB) to obtain patient vital statistics, describe health care utilization, and other patient comorbidities and characteristics.

Methods

All analyses were approved by the Research Ethics Board of Sunnybrook Health Sciences Centre, Toronto, Ontario.

National and Provincial Trends in ADHD Medication Use We used data from IMS Geographic Prescription Monitor (GPM12) to examine overall trends in the prescribing volumes of medications used to treat ADHD among all individuals and among adults aged 19 and older, at both national and provincial levels. We examined the number of prescriptions dispensed for ADHD medications between October 1 2009 and December 31 2014. Analyses were stratified by drug and province and by coverage (private, public, cash, Non-Insured Health Benefits) or age (19-29, 30-64, 65+). We did not have data available for individuals aged 18. Provincially funded prescriptions were those paid for through public drug programs; non-provincially-funded prescriptions were those paid for through private insurance plans, cash payments, or Non-Insured Health Benefits. All cross- provincial analyses compared population-adjusted rates.

Population Adjustment

Provincial population estimates were obtained from Statistics Canada for each year from 2009 to 2014 and used to standardize overall utilization rates (per 1,000 population) of ADHD

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medications dispensed across the provinces. Because all individuals (both those eligible for public drug programs and non-beneficiaries) might pay for ADHD medications out of pocket, measures of non-provincially funded utilization were adjusted using overall provincial population estimates from Statistics Canada.

Cross-Provincial Comparisons of Provincially-Funded ADHD Medication Use We used claims data from NPDUIS and ODB to examine trends in the number and rate of provincially funded users of ADHD medications at the provincial level between 2000 and 2014. We examined the number and rate of users in 2014. Analyses were stratified by province, drug, drug type (stimulant, non-stimulant) and age (18-25, 26-35, 36-64, 65+). Provincially funded prescriptions were those paid for through public drug programs. All cross- provincial analyses compared population-adjusted rates (per 1,000 eligible), using the number of active drug beneficiaries in each provincial drug program. Data was not available for Quebec or the territories. Data for Alberta was only available up to September 2014.

We used ODB claims data between 2007 and 2014 to examine trends in the number of users of ADHD stimulant medication (methylphenidate, dextroamphetamine, mixed salt amphetamine, lisdexamfetamine) in Ontario, stratified by brand name and generic drugs as well as by formulation (long acting, short acting). We also investigated trends in ER methylphenidate users stratified by brand and generic drugs. In order to examine potential switching between brand name ER methylphenidate (Concerta) and other ADHD medications, we created a cohort of individuals who newly brand name ER methylphenidate (Concerta) in 2013 and looked at ADHD medication use in the year prior to and after initiation. Finally, we used ODB claims data from 2014 to determine whether there were differences in the average amount paid per month between brand name and generic ER methylphenidate.

Characteristics of Provincially-Funded ADHD Medication Users in Ontario in 2013 We used claims data from ODB to perform additional analyses of utilization of ADHD medications among individuals aged 18 and older in Ontario, stratifying by drug, between January 2013 and December 2013. We excluded users who were LTC residents or who had evidence of palliative care in the past 6 months. These analyses examined demographic and clinical characteristics of adults who were prescribed an ADHD medication in Ontario.

Patterns of ADHD Medication Use among Adult New Users in Ontario We established a cohort of adults, aged 18 and older, who were new users of ADHD medications between January 1, 2002 and December 31, 2012 to examine the duration of therapy among adults in Ontario. A new user aged 66 and older was defined as having no prescription for an ADHD medication in the past year (since all of these individuals are eligible for ODB). New users aged 65 and younger was limited to those who were eligible for ODB (prescription for a drug in the past 6-12 months) and who did not have a prescription for an ADHD medication in the past 6 months. We excluded users who were LTC residents or who had evidence of palliative care in the past 6 months. We followed each individual forward from

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the time of their first prescription until they discontinued any ADHD drug therapy, died, had 2 years of follow-up, or reached the end of the study period (December 31, 2013). Patients who switched between drugs within the drug class were still considered to be persistent. Discontinuation was defined on the basis of no subsequent prescription for an ADHD medication within 180 days of the previous prescription, which is consistent with previously published studies. 2-4 Discontinuation date was defined as date of last prescription plus the day supply of the last prescription. We stratified this analysis by the ADHD drug initiated, type of stimulant initiated, and age.

Patterns of ADHD Medication Use among Youth in Ontario We established a cohort of individuals aged younger than 18 who were dispensed a treatment for ADHD between January 1, 2002 and December 31, 2012 to examine the extent to which youth continue ADHD treatment into adulthood in Ontario. We followed each individual forward from the time of their first prescription until they discontinued ADHD drug therapy, died or reached the end of the study period (December 31, 2013). Discontinuation was defined on the basis of no subsequent prescription for an ADHD medication within 180 days of the previous prescription, which is consistent with previously published studies.2-4 Discontinuation date was defined as date of last prescription. Among the youth who turned 18 by the end of the study period, we reported the number of users who were still on therapy past their 17th birthday. Of users that were still on therapy past their 17th birthday we reported how many continued therapy past their 18th birthday and the median duration of therapy after turning 18 years old.

Possible Misuse of Treatments for ADHD in Public Drug Programs across Canada We used claims data from NPDUIS and ODB to investigate potentially inappropriate prescribing of ADHD stimulants (dextroamphetamine, lisdexamfetamine, methylphenidate, mixed-salt amphetamine) among adults aged 18 and older in Canada. Possible misuse of ADHD treatments was defined by first identifying prescriptions for stimulant ADHD treatments where at least 30 units were dispensed. We then identified inappropriate prescriptions for stimulant ADHD treatments as those that were dispensed within 1-7 days of the initial prescription, were issued by a different physician and dispensed at a different pharmacy. We also performed a sensitivity analysis where we relaxed the definition of inappropriate prescriptions to include only those that were dispensed within 1-7 days of the initial prescription and where at least 30 units were dispensed. We report the number and percent of all prescriptions that are potentially inappropriate for each province by age group (18-25, 26-35, 36-64 65+). Data was not available for Quebec or the territories. Data for Alberta was only available up to September 2014.

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National Trends in Utilization of ADHD Medications Methodological Note: National trends in utilization of ADHD medications using IMS GPM12 data is presented among all individuals and among adults aged 19 and older. • The data among all individuals presents the number of prescriptions dispensed by the type of payer (public, private, cash, NIHB) and drug. • The data among adults (aged 19 and older) presents the number of prescriptions dispensed by age and drug. Data was not available for adults aged 18 years old, which is included later among drugs dispensed in public drug programs.

Exhibit 1: Total Number of Prescriptions for ADHD Medications Dispensed to All Individuals in Canada, by Payer and Quarter

Use of medications to treat ADHD has increased by 78% over the study period in Canada. By the fourth quarter of 2014, 31% of ADHD medications dispensed in Canada were paid for by provincially-funded drug coverage programs.

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Summary of Findings for Exhibit 1

1. The number of ADHD medications dispensed in Canada has increased by 77.8% over the past 5 years, from 2,253,804 prescriptions (Q4 2009) to 4,008,735 prescriptions (Q4 2014). 2. By the end of the study period, a total of $297.4 million was spent on ADHD medications nationally, an increase of approximately 94% from Q4 2009 ($153.6 million). 3. ADHD medications dispensed in Canada that were paid for by public drug coverage programs has increased by 83.1%, from 684,530 prescriptions dispensed in Q4 2009 to 1,253,693 prescriptions dispensed in Q4 2014. 4. The distribution of payers for ADHD medications dispensed in Canada in Q4 2014 was 50.2% private (2,013,897 prescriptions), 31.3% public (1,253,693 prescriptions), 17.0% cash (682,050 prescriptions), 1.5% NIHB (58,971

prescriptions), and 0.03% unknown (123 prescriptions).

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Exhibit 2: Total Number of Prescriptions for ADHD Medications Dispensed to All Individuals in Canada in Q4 2014, by Payer and Drug

Currently, methylphenidate is the most commonly dispensed ADHD medication across all payers in Canada.

Summary of Findings for Exhibit 2

1. Among all ADHD medications dispensed in Q4 2014 (4,008,735 prescriptions), over half (59.0%; 2,364,101 prescriptions) were for methylphenidate, followed by

lisdexamfetamine (16.9%; 678,893 prescriptions), mixed-salt amphetamine (7.7%; 309,684 prescriptions), atomoxetine (6.9%; 274,813 prescriptions), dextroamphetamine (6.8%; 273,026 prescriptions), and guanfacine (2.7%; 108,218 prescriptions). 2. Among all ADHD medications dispensed in Q4 2014 by private payers, over half were for methylphenidate (56.6%; 1,140,522 prescriptions) followed by lisdexamfetamine (19.7%; 396,524 prescriptions), mixed-salt amphetamine (8.1%; 162,927 prescriptions), atomoxetine (7.6%; 154,575 prescriptions), dextroamphetamine (4.4%; 88,118 prescriptions), and guanfacine (3.5%; 71,231 prescriptions). 3. Among all ADHD medications dispensed in Q4 2014 by public payers almost two- thirds were for methylphenidate (63.8%; 800,475 prescriptions) followed by lisdexamfetamine (13.5%; 168,940 prescriptions), dextroamphetamine (9.9%; 124,678 prescriptions), mixed-salt amphetamine (6.4%; 80,196 prescriptions), atomoxetine (5.4%; 67,436 prescriptions), and guanfacine (1.0%; 11,968 prescriptions).

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Exhibit 3: Total Number of Prescriptions and Cost for ADHD Medications Dispensed to Adults Aged 19 and Older in Canada, by Drug and Quarter

Utilization and costs of ADHD medications dispensed among adults (aged 19+) in Canada have increased by 119% and 153% over the study period, respectively.

Summary of Findings for Exhibit 3

1. The number of prescriptions dispensed for ADHD medications to adults (aged 19 and older) in Canada has increased by 119% over the past 5 years, from 731,349 prescriptions dispensed in Q4 2009 to 1,603,896 prescriptions dispensed in Q2 2014. 2. By the end of the study period, a total of $111.1 million was spent on ADHD medications for adults nationally, an increase of approximately 153% from Q4 2009 ($43.9 million). A total of 5.8 million prescriptions for these drugs were dispensed in the fiscal year 2013-2014 for adults, at a cost of $394.1 million.

3. Methylphenidate was the most commonly dispensed ADHD medication in adults from Q4 2009 (65%; 471,662 prescriptions) until the end of our study period in Q2 2014 (58%; 937,374 prescriptions). 4. Among all ADHD medications dispensed in Q2 2014 to adults (1,603,896 prescriptions), over half (58.4%; 937,374 prescriptions) were for methylphenidate, followed by lisdexamfetamine (13.6%; 217,416 prescriptions), dextroamphetamine (12.9%; 273,026 prescriptions), mixed-salt amphetamine (9.6%; 153,616

prescriptions), atomoxetine (5.2%; 84,008 prescriptions), and guanfacine (0.3%; 4,753 prescriptions). 5. The vast majority of ADHD medications dispensed to adults were for stimulants between Q4 2009 (93.6%; 6,824,295 prescriptions) to Q2 2014 (94.5%; 1,515,135 prescriptions) (Data not shown). This has not changed even with the large increase in total number of ADHD prescriptions in the same time period

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Exhibit 4: Rate of Prescriptions for ADHD medications Dispensed to Adults Aged 19 and Older in Canada in 2013, by Drug and Age

Exhibit 5: Rate of Prescriptions for ADHD medications Dispensed to Adults Aged 19 and Older in Canada in 2013, by Drug Class and Age

In 2013, adults aged 19-29 had the highest rate of ADHD medication use for each ADHD drug and drug class (stimulant and non-stimulant) in Canada. This rate decreased with increasing age groups.

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Summary of Findings for Exhibit 4 and Exhibit 5

1. Adults aged 30-64 were found to have the most ADHD mediations dispensed (60.5%; 3,366,868 prescriptions), followed by those aged 19-29 (35.2%; 1,960,729 prescriptions) and those aged 65 and older (4.3%; 241,043 prescriptions). Yet, the highest rate of ADHD medication use was found among those aged 19-29 years

(368.2 prescriptions per 1,000 population) followed by those aged 30-64 years (275.1 prescriptions per 1,000 population), and 65 years and older (44.8 prescriptions per 1,000 populations). 2. In adults aged 19-29 in 2013, the most commonly dispensed stimulant medication was methylphenidate (56.5%; 1,107,493 prescriptions) followed by mixed-salt amphetamine (12.9%; 252,564 prescriptions), dextroamphetamine (12.1%; 237,226 prescriptions), lisdexamfetamine (12.0%, 234,619 prescriptions), atomoxetine (6.5%; 128,040 prescriptions), and guanfacine (0.04%; 787 prescriptions)

3. Similarly, in adults aged 30-64 years in 2013, the most commonly dispensed stimulant medication was methylphenidate (61.2%; 2,062,191 prescriptions) followed by dextroamphetamine (14.3%; 479,948 prescriptions), lisdexamfetamine (11.3%, 383,067 prescriptions), mixed-salt amphetamine (8.1%; 273,050 prescriptions), atomoxetine (5.0%; 167,786 prescriptions), and guanfacine (0.02%; 826 prescriptions) 4. In 2013, among adults aged 65 years and older, the majority of dispensed

stimulant medications was for methylphenidate (76.9%; 185,368 prescriptions) followed by dextroamphetamine (15.5%; 37,242 prescriptions), mixed-salt

amphetamine (3.3%; 7,980 prescriptions), lisdexamfetamine (2.7%, 6,623 prescriptions), atomoxetine (1.6%; 3,803 prescriptions), and guanfacine (0.003%; 9 prescriptions) 5. The highest prescription rate for stimulants was found among those aged 19-29 years (344.0 per 1,000 population) followed by those aged 30-64 years (261.3 per 1,000 population), and 65 years and older (44.1 per 1,000 populations). 6. The highest prescription rate for non-stimulants was also in those aged 19-29

years (24.2 per 1,000 population) followed by those aged 30-64 years (13.8 per 1,000 population), and 65 years and over (0.71 per 1,000 population)

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Cross Provincial Trends in Utilization of ADHD Medications among Adults Methodological Note: The analysis among adults in Canada is conducted using data from IMS GPM12. Due to data availability this analysis is limited to adults aged 19 and older (data not available for adults aged 18 years old).

The analyses among adult public drug plan beneficiaries are conducted using public drug data collected by CIHI NPDUIS and ICES for adults aged 18 and older. No data was available for Quebec. Data for Alberta was only available up to September 2014. Public plan listings for ADHD medications vary across the provinces. Detailed information on public plan listings is provided in Appendix A.

Exhibit 6: Population-Adjusted Rate of Prescriptions for ADHD medications Dispensed to Adults Aged 19 and Older in Canada, by Province and Quarter

The rate of ADHD medications dispensed to adults (aged 19 years and older) has increased over the study period across all provinces. In 2014, Ontario had the third lowest rate of ADHD medications dispensed to adults.

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Summary of Findings for Exhibit 6

1. The overall rate of ADHD medications dispensed among adults (aged 19 years and older) varied between provinces in Canada (range in Q2 2014: 38.4 [Manitoba] to 105.5 [Quebec] prescriptions dispensed per 1,000 eligible

population). 2. In Q2 2014, Ontario had the third lowest rate of ADHD medications dispensed (55 prescriptions compared to the national average of 69 prescriptions per eligible population). 3. The number of ADHD prescriptions dispensed in Ontario over the study period has increased nearly two-fold from 271,682 prescriptions in Q4 2009 to 493,571 prescriptions in Q2 2014.

4. Among all ADHD medications dispensed in Ontario over the study period (7.4 million prescriptions), 96% (7.1 million prescriptions) were for stimulants (methylphenidate, lisdexamfetamine, mixed-salt amphetamine and dextroamphetamine) and only 4% (302,466 prescriptions) were for non- stimulants (atomoxetine) (data not shown). 5. Manitoba consistently exhibited the lowest rate of ADHD medication use over the study period.

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Exhibit 7: Population-Adjusted Rate of Publicly-funded ADHD medication Users Aged 18 and Older in Canada, by Province and Year

In 2014, the rate of publicly funded ADHD medication users aged 18 years and older in Ontario was similar to the national average.

Summary of Findings for Exhibit 7

1. Among public drug plan beneficiaries aged 18 years and older, the use of ADHD medications has increased across all provinces. In 2014, the highest rate of use was in Newfoundland and Labrador (98.2% increase from 5.7 to 11.3 users per 1,000 eligible population between 2009 and 2014). 2. Cross-provincial variations were noted in the number of provincially funded ADHD medication users between provinces in Canada (range in 2014: 3.5 users [Alberta] to 11.3 users [Newfoundland and Labrador] per 1,000 eligible population). 3. In 2014, the rate of users among public plan beneficiaries in Ontario was similar to the national average (8.1 users per 1,000 eligible population compared to the national average of 7.5 users per 1,000 eligible population). 4. The observed increase in rate of users in 2008/2009 is possibly related to the increase in availability of long acting stimulant medications during that time.

NOTE: Data unavailable prior to 2009 in Newfoundland and Labrador

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Cross Provincial ADHD Medication Utilization among Adult Public Drug Plan Beneficiaries

Exhibit 8: Population-Adjusted Rate of Publicly-funded ADHD Medication Users Aged 18 and Older in Canada in 2014, by Province

Province Total Total Cost Total Rate of Rate of Rate of Number Cost per Usersⱡ Stimulant Non- of User Usersⱡ Stimulant Users Usersⱡ AB 1,801 $743,368 $412.8 3.50 3.50 0.00 BC 19,068 $9,071,251 $475.7 7.65 7.57 0.11 MB 4,679 $2,577,271 $550.8 6.82 6.82 * NB 815 $388,907 $477.2 7.42 7.39 * NL 1,051 $496,456 $472.4 11.31 11.30 * NS 557 $297,673 $534.4 4.00 3.96 0.04 PE 187 $91,143 $487.4 5.75 5.75 0.00 SK 4,684 $3,318,394 $708.5 8.08 7.95 0.22 ON 22,309 $14,417,164 $646.2 8.13 8.07 0.07 ⱡper 1,000 eligible *In accordance with the CIHI privacy policy, cases where the number of active beneficiaries (*) is less than 5 (but greater than 0) have been suppressed to ensure confidentiality.

Ontario had the highest number of publicly-funded ADHD medication users and second highest rate of users when compared to other provinces in Canada in 2014. The rate of publicly-funded ADHD medication users was highest in Newfoundland and Labrador.

Summary of Findings for Exhibit 8

1. The number of publicly-funded ADHD medication users was highest in Ontario (N=22,309) and British Columbia (N=19,068), yet the rate of users was highest in Newfoundland and Labrador (11.3 users per 1,000 eligible) in 2014.

2. Stimulants were the most common ADHD medication used across all provinces in Canada, with the highest rate of use observed in Newfoundland and Labrador (11.3 users per 1,000 eligible).

3. The rate of non-stimulant use was low across all provinces, with the highest rate observed in Saskatchewan (less than 1 user per 1,000 eligible).

4. Saskatchewan and Ontario exhibited the highest cost per user ($708.5 and $646.3, respectively) for ADHD medications in 2014. 5. The rate of non-stimulant users is zero in Alberta and Prince Edward Island as they

are not covered on the public drug programs.

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Exhibit 9: Population-Adjusted Rate of Publicly-funded ADHD Stimulant Medication Users among Adults Aged 18 and Older in Canada in 2014, by Province and Drug Class

In 2014, among ADHD medication stimulant users across Canada, the rate of long- acting medication users was higher than the rate of short-acting stimulant users across all provinces, except in Newfoundland and Labrador where the rate of short- acting stimulant medication use was higher than the rate of long-acting ADHD stimulant medication use.

Summary of Findings for Exhibit 9

1. Among all stimulant ADHD medication users, the rate of long-acting stimulant users was higher than the rate of short-acting stimulant users among all provinces in

Canada in 2014, except Newfoundland and Labrador. 2. Newfoundland and Labrador had the highest rate of short-acting stimulant medication users across Canada, with 10.5 users per 1,000 eligible which was more than double the rate observed in the other provinces (<5 users per 1,000 eligible). 3. Saskatchewan had the highest rate of long-acting stimulant users (6.7 users per 1,000 eligible).

4. In Ontario, the rate of long-acting stimulant medication users was 6.5 per 1,000 eligible and exceeded the rate of short-acting stimulant users (2.5 users per 1,000 eligible).

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Exhibit 10: Population-Adjusted Rate of Publicly-funded ADHD Medication Users among Adults Aged 18 and Older in Canada in 2014, by Province and Drug

Methylphenidate had the highest rate of use across all provinces in Canada, except for British Columbia and Alberta where dextroamphetamine had the highest rate of users.

Summary of Findings for Exhibit 10 1. Methylphenidate was the most commonly used ADHD medication across the

majority of provinces and had the highest rate of users in Newfoundland and Labrador (10.7 users per 1,000 eligible) in 2014. 2. Dextroamphetamine was the most common ADHD medication used in British Columbia and Alberta (4.1 and 2.2 users per 1,000 eligible, respectively) in 2014. 3. Lisdexamfetamine, mixed-salt amphetamine, and atomoxetine had low rates of users across all provinces in Canada. 4. Ontario had the highest rate of lisdexamfetamine use (1.4 users per 1,000 eligible)

and mixed-salt amphetamine use (1.2 users per 1,000 eligible), while the rate of atomoxetine use was highest in Saskatchewan (0.2 users per 1,000 eligible).

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Exhibit 11: Population-Adjusted Rate of Publicly-funded ADHD Medication Users among Adults Aged 18 and Older in Canada in 2014, by Province and Age

The rate of ADHD medication users was highest among those aged 18-35 across all provinces in Canada in 2014.

Summary of Findings for Exhibit 11

1. The rate of ADHD medication users was highest among those aged 18-25, and declined with increasing age in all provinces in Canada in 2014, except in Newfoundland and Labrador which had higher rates among those aged 26-35. 2. In Ontario, the rate of use was highest among those aged 18-25 (61.0 users per

1,000 eligible) and declined with increasing age (aged 26-35: 41.8 users per 1,000 eligible; aged 36-64: 16.5 users per 1,000 eligible).

3. The rate of users was low among those aged 65 and older across all provinces (<3 users per 1,000 eligible).

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Trends in Utilization of ADHD Medications among Adults in Ontario

Exhibit 13: Total Number of Prescriptions and Cost for ADHD Medications Dispensed to Adults Aged 19 and Older in Ontario, by Drug and Quarter

Prescriptions for ADHD medications among all adults 19 years and older in Ontario has increased 82% over the last 5 years. Methylphenidate was consistently the most commonly prescribed ADHD product (57.4% of prescriptions in Q2 2014).

Summary of Findings for Exhibit 13 1. Utilization and costs for ADHD medications among adults aged 19 years and older have increased 82% (from 271,684 prescriptions [Q4 2009] to 493,571 prescriptions [Q2 2014]) and 112% (from $17.9 million [Q4 2009] to $39.2 million [Q2 2014]), respectively. 2. The prescription market share in the second quarter of 2014 was 57.4% methylphenidate (283,173 prescriptions), 17.3% lisdexamfetamine (85,488 prescriptions), 13.5% mixed-salt amphetamine (66,829 prescriptions), 7.7% dextroamphetamine (37,824 prescriptions), 3.6% atomoxetine (17,725 prescriptions) and 0.5% guanfacine (2,532 prescriptions). This distribution is similar to that observed nationally, except dextroamphetamine being prescribed over mixed-salt amphetamine nationally. 3. A 24-fold increase in the number of prescriptions dispensed for lisdexamfetamine was seen over the study period, with a 75.7% increase noted between Q2 2011 (23,460 prescriptions) and Q4 2011(41,218 prescriptions). This increase may be due to the addition of lisdexamfetamine to the Ontario public drug formulary in June 2011.

4. Since its introduction to the Canadian market in late 2013, the number of prescriptions for guanfacine in Ontario has increased 2-fold (from 1,102 in Q4 2013 to 2,532 prescriptions in Q2 2014), however it

was still the least commonly prescribed ADHD medication in Q2 2014 Ontario. This is likely due to guanfacine not currently being listed on the Ontario public drug plan. As well, guanfacine is not indicated in adults.

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Exhibit 14: Total Number of Provincially-Funded Prescriptions for ADHD Medications Dispensed to Adults Aged 18 and Older in Ontario, by Drug and Quarter

Similar to overall trends, methylphenidate is the most commonly prescribed ADHD product in Ontario among public drug plan beneficiaries aged 18 years and older.

Summary of Findings for Exhibit 14

1. Overall, the number of ADHD prescriptions dispensed among public plan beneficiaries has increased nearly 2-fold from 67,521 prescriptions in Q4 2009 to 132,083 prescriptions in Q4 2014. Methylphenidate was consistently the most commonly dispensed ADHD product. 2. The prescription market share in the fourth quarter of 2014 was 67.6% methylphenidate (89,265 prescriptions), 16.3% lisdexamfetamine (21,520 prescriptions), 10.1% mixed-salt amphetamine (13,308 prescriptions), 4.6% dextroamphetamine (6,274 prescriptions), and 1.3% atomoxetine (1,716 prescriptions). The low utilization of atomoxetine could be due to its restricted

access through the Ontario public drug program. This distribution is similar to overall prescribing in Ontario (provincially and non-provincially funded), with the exception of guanfacine not covered in Ontario’s public drug program. 3. Use of lisdexamfetamine increased considerably following its listing on the Ontario public drug formulary in 2011, rising from 835 prescriptions (Q2 2011) to 21,520 prescriptions (Q4 2014), making it the second most commonly prescribed ADHD product during the last quarter of 2014.

4. In Q4 2014, total expenditure for ADHD products was over $6.5 million. Of that, $2.8 million was spent on methylphenidate, $1.8 on lisdexamfetamine, $1.3 million on amphetamine mixed salts, $387,382 on dextroamphetamine and $166,255 on atomoxetine (data not shown).

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Trends in Number of Brand Name vs. Generic Stimulant Medication Users in Ontario

Exhibit 15a: Total Number of Provincially-Funded Generic ADHD Stimulant Medication Users Aged 18 and Older by Drug Type and by Year

Exhibit 15b: Total Number of Provincially-Funded Brand Name ADHD Stimulant Medication Users Aged 18 and Older by Drug Type and by Year

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The number of provincially-funded stimulant ADHD medication users has increased 156.9% between 2008 and 2014 in Ontario, which has largely been driven by an increase in long acting brand products.

Summary of Findings for Exhibit 15a and 15b

1. The number of provincially-funded stimulant ADHD medication users has increased sharply over the study period, from 8,624 users in 2008 to 22,154 users in 2014. In 2014, more stimulant ADHD medication users were using brand name drugs (69.3%; N=15,356) compared to generic drugs (45.7%; N=10,124). The large increase in the number of long-acting brand name ADHD medications is likely due to the majority of long-acting ADHD medications available in the public drug program as brand-name (73.9%, N=34 DINs) compared to generic formulations (26.1%, N=12 DINs).

2. From 2008 to 2010, the number of generic ADHD medication users increased by 40.9% (from 6,771 to 9,543 users), driven by an increase in long-acting generic users (in particular methylphenidate extended-release; data not shown), before plateauing in 2011. By 2014, more generic ADHD drug users, were prescribed long acting generic drugs (59.4%; N=6,016) compared to short acting generic drugs (51.7%; N=5,235).

3. The number of brand name ADHD medication users surpassed the number of generic users in 2013.

4. The number of ADHD brand name medication users increased by 540.9% from 2,396 users in 2008 to 15,356 users in 2014. This was largely driven by the increase in long acting brand name ADHD medication users, which comprised 88.6% (N=13,611) of brand medication users in 2014. The number of short acting brand name ADHD medication users has remained relatively low over the study period, with 2,738 users in 2014.

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Exhibit 16: Total Number of Provincially-Funded Long-Acting Methylphenidate Users Aged 18 and Older, by Brand Name vs. Generic Formulations and Year

With the listing of generic extended release methylphenidate in 2010 in Ontario, the number of brand extended release methylphenidate (Concerta) users decreased in 2011, but subsequently rose again and surpassed the number of generic users.

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Summary of Findings for Exhibit 16

1. The number of publicly-funded extended release methylphenidate users has increased since being listed in 2009, with 7,345 users by 2014. There were consistently more brand users compared to generic users (except in 2011) over the study period, which may reflect the availability of reimbursement cards.

2. Of the 7,345 extended release methylphenidate users in 2014, 62.2% (N=4,570) were using a brand name agent (Concerta) compared to 48.3% (N=3,550) using a generic formulation.

3. With the listing of generic extended release methylphenidate in 2010, the number of Concerta users decreased slightly in 2010 and 2011 along with a concurrent increase in the number of generic extended release users. However, the number of users of Concerta increased again in 2012, surpassing the number of generic drug users from 2012 to 2014.

4. The crossover in number of users in 2011 and subsequent increase in number of brand name methylphenidate (Concerta) users over generic extended release methylphenidate users could reflect a preference for brand name methylphenidate (Concerta), ongoing marketing of this brand name agent to prescribers and/or the availability of drug reimbursement cards. 5. In contrast to the trends observed for brand name and generic extended release methylphenidate, the number of users of brand name sustained release methylphenidate increased by 104.1% from 969 users in 2000 to 1,978 users in 2006 and then decreased by 64.9% to 694 users in 2014 alongside an increase in the number of users of generic sustained release methylphenidate from 0 users in 2005 to 2,584 users in 2009.

6. The number of Biphentin users has been increasing since 2007. In 2012, the number of Biphentin users (N=703) surpassed the number of brand name sustained release methylphenidate (Ritalin SR, N=600). As of 2014 there were fewer Biphentin users (N=1,342) compared to generic sustained release methylphenidate (N=2,584) and generic and brand name extended release methylphenidate (N=7,345).

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Exhibit 17: Publically-Funded ADHD Medication Use in the Year Prior to and After Initiating Brand Name Methylphenidate Extended Release (Concerta) in Ontario in 2013

Number of Users

New Brand Name Methylphenidate ER (Concerta) Users N=2,311 ADHD Medication Use in Year Prior to Index (N, %) Any ADHD (excluding Concerta) 1,372 (59.4%) Generic Methylphenidate ER* 621 (26.9%) ADHD Medication Use in Year After Index** (N, %) Any ADHD (excluding Concerta) 824 (35.7%) Generic Methylphenidate ER 342 (14.8%) Concerta 1,896 (82.0%) *ER = Extended-Release **Index defined as date of first brand name methylphenidate ER (Concerta) prescription in 2013

There were 2,311 new users of brand name methylphenidate ER (Concerta) in calendar year 2013, of which over two-thirds (40.6%; N=939) had not received any other ADHD medication in the year prior to brand name methylphenidate ER (Concerta) initiation.

Summary of Findings for Exhibit 17

1. Over half of new brand name methylphenidate ER (Concerta) users (59%; N=1,372) in 2013 had a previous prescription for a non-Concerta ADHD drug in the year prior to initiating brand name methylphenidate ER (Concerta).

2. Only 27% (N=621) of new brand name methylphenidate ER (Concerta) users had received a prescription for generic ER in the year prior to brand name methylphenidate ER (Concerta) initiation.

3. The majority (82%; N=1,896) of individuals initiating brand name methylphenidate ER (Concerta) were dispensed at least one more Concerta prescription in the year after initiation.

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Exhibit 18: Average Daily and Monthly Cost of Publically-Funded Brand Name (Concerta) and Generic Methylphenidate Extended-Release in Ontario in 2014

Brand Name Generic Standardized Methylphenidate Methylphenidate Difference Extended Release Extended Release (Concerta) Number of Prescriptions N=118,176 N=56,575 Median (IQR) Cost Per Day ($) $2 ($2-$4) $2 ($2-$4) 0.06 Median (IQR) Cost Per 30 Days ($) $68 ($50-$116) $72 ($53-$121) 0.06

Although more brand name methylphenidate ER (Concerta) prescriptions were dispensed compared to generic methylphenidate extended release, there was no significant difference in cost between the two drugs.

Summary of Findings for Exhibit 18

1. In 2014, 118,176 prescriptions were dispensed for brand name methylphenidate ER (Concerta) and 56,575 prescriptions were dispensed for generic methylphenidate ER in Ontario. The median cost per day was $2 (IQR=$2-$4) for both of these drugs.

2. There was no significant difference in the median cost per day for dispensed generic and brand methylphenidate ER.

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Characteristics of Provincially-Funded ADHD Medication Users in Ontario in 2013

Exhibit 19a: Characteristics of Provincially-Funded ADHD Medications Users Aged 18 and Older in Ontario in 2013, by Drug

Characteristics Drug Overall Methylphenidate Dextroamphetamine Lisdexamfetamine Mixed-Salt Atomoxetine Dual Therapyⱡ Amphetamine Number of users N=19,615 N=13,049 N=1,509 N=2,496 N=2,293 N=143 N=125 Number of new users 5,245 (26.7%) 3,331 (25.5%) 442 (29.3%) 906* (36.3%) 520 (22.7%) 35 (24.5%) 11* (8.8%) Age 18-25 5,151 (26.3%) 3,309 (25.4%) 233* (15.4%) 757* (30.3%) 743* (32.4%) 63* (44.1%) 46* (36.8%) 26-35 4,400 (22.4%) 2,802 (21.5%) 304 (20.1%) 660* (26.4%) 579 (25.3%) 26-30 26-30 36-64 7,378 (37.6%) 4,964 (38.0%) 622 (41.2%) 921 (36.9%) 779 (34.0%) 46* (32.2%) 46 (36.8%) 65+ 2,686 (13.7%) 1,974 (15.1%) 350* (23.2%) 158* (6.3%) 192* (8.4%) ≤5* 6-10* Number of Males 10,778 (54.9%) 7,317 (56.1%) 717* (47.5%) 1,347 (54.0%) 1,227 (53.5%) 98* (68.5%) 72 (57.6%) Urban Residence 17,344 (88.4%) 11,437 (87.6%) 1,322 (87.6%) 2,259 (90.5%) 2,082 (90.8%) 129 (90.2%) 115* (92.0%) Income Quintile 1 6,628 (33.8%) 4,490 (34.4%) 432* (28.6%) 892 (35.7%) 732 (31.9%) 38* (26.6%) 44 (35.2%) 2 4,376 (22.3%) 2,925 (22.4%) 336 (22.3%) 558 (22.4%) 504 (22.0%) 29 (20.3%) 24 (19.2%) 3 3,210 (16.4%) 2,130 (16.3%) 253 (16.8%) 405 (16.2%) 370 (16.1%) 28 (19.6%) 24 (19.2%) 4 2,754 (14.0%) 1,802 (13.8%) 234 (15.5%) 339 (13.6%) 343 (15.0%) 18 (12.6%) 18 (14.4%) 5 2,533 (12.9%) 1,625 (12.5%) 246* (16.3%) 285 (11.4%) 333 (14.5%) 29* (20.3%) 15 (12.0%) Number with ADHD diagnosis in past 10 years 9,043 (46.1%) 6,026 (46.2%) 586* (38.8%) 1,047 (43.0%) 1,175 (51.2%) 100* (69.9%) 82* (65.6%)

Charlson Morbidity Index No hospitalization 15,481 (78.9%) 10,163 (77.9%) 1,212 (80.3%) 1,991 (79.8%) 1,873 (81.7%) 127* (88.8%) 115* (92.0%) 0 2,874 (14.7%) 1,919 (14.7%) 204 (13.5%) 414 (16.6%) 317 (13.8%) 11-15* 6-10* 1 619 (3.2%) 448 (3.4%) 51 (3.4%) 56 (2.2%) 59 (2.6%) ≤5 ≤5* 2+ 641 (3.3%) 519 (4.0%) 42 (2.8%) 31-35* 44* (1.9%) ≤5* 0* ⱡdual therapy defined as two different ADHD drugs prescribed on the same day *Indicates standardized difference > .1 between Methylphenidate and comparison group **In accordance with the ICES privacy policy, in cases where the number of total users is less than 6, this number has been suppressed to ensure confidentiality. In cases where there is only one record being suppressed, another record has been suppressed (by providing a range in values) as well in order to avoid residual disclosure issues.

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Exhibit 19b: Characteristics of Provincially-Funded ADHD Medications Users Aged 18 and Older in Ontario in 2013, by Drug

Characteristics Drug Overall Methylphenidate Dextroamphetamine Lisdexamfetamine Mixed-Salt Atomoxetine Dual Therapyⱡ Amphetamine Number of different medications used in the past year (Median (IQR)) 6 (3-11) 6 (3-11) 7 (4-12) 6* (2-10) 6 (2-10) 5* (3-9) 6* (2-10) Psychotropic use within 120 days of cohort entry (%) Antidepressants 10,594 (54.0%) 6,993 (53.6%) 797 (52.8%) 1,458 (58.4%) 1,207 (52.6%) 75 (52.4%) 64 (51.2%) Benzodiazepine 5,446 (27.8%) 3,594 (27.5%) 430 (28.5%) 666 (26.7%) 702 (30.6%) 28* (19.6%) 26* (20.8%) Mood Stabilizer 3,382 (17.2%) 2,161 (16.6%) 243 (16.1%) 557* (22.3%) 372 (16.2%) 28 (19.6%) 21 (16.8%) Antipsychotics 6,377 (32.5%) 4,174 (32.0%) 389* (25.8%) 975* (39.1%) 733 (32.0%) 69* (48.3%) 37 (29.6%)

Prescriber of Initial prescriptions General Practitioner 10,789 (55.0%) 7,624 (58.4%) 902 (59.8%) 881* (35.3%) 1,266 (55.2%) 64* (44.8%) 52* (41.6%) Psychiatrists 6,540 (33.3%) 3,872 (29.7%) 461 (30.6%) 1,323* (53.0%) 770 (33.6%) 62* (43.4%) 52* (41.6%) Other 2286 (11.7%) 1553 (11.9%) 146 (9.7%) 292 (11.7%) 257 (11.2%) 17 (11.9%) 21* (16.8%) 1 or more psychiatrists visit within 3 months 7,027 (35.8%) 4,261 (32.7%) 473 (31.3%) 1,363* (54.6%) 825 (36.0%) 52 (36.4%) 53* (42.4%) 1 or more hospitalizations in the 1,837 (9.4%) 1,293 (9.9%) 146 (9.7%) 206 (8.3%) 178 (7.8%) 9* (6.3%) 5* (4.0%) last year

Emergency visits within the last year 0 10,473 (53.4%) 6,839 (52.4%) 886* (58.7%) 1,310 (52.5%) 1,275 (55.6%) 88* (61.5%) 75* (60.0%) 1 3,929 (20.0%) 2,653 (20.3%) 304 (20.1%) 489 (19.6%) 432 (18.8%) 25 (17.5%) 26 (20.8%) 2-4 3,664 (18.7%) 2,495 (19.1%) 240 (15.9%) 471 (18.9%) 422 (18.4%) 19* (13.3%) 17* (13.6%) 5+ 1,549 (7.9%) 1,062 (8.1%) 79* (5.2%) 226 (9.1%) 164 (7.2%) 11 (7.7%) 7 (5.6%) Physician office visits within the last 10 (5-19) 10 (4-20) 9* (4-17) 12* (6-22) 9* (5-18) 8* (4-16) 9 (5-16) year (Median (IQR)) ⱡdual therapy defined as two different ADHD drugs (based on drug name) prescribed on the same day *Indicates standardized difference > .1 between Methylphenidate and comparison group **In accordance with the ICES privacy policy, in cases where the number of total users is less than 6, this number has been suppressed to ensure confidentiality. In cases where there is only one record being suppressed, another record has been suppressed (by providing a range in values) as well in order to avoid residual disclosure issues.

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There were 19,615 individuals aged 18 and older who were treated with provincially-funded ADHD medications in Ontario in 2013. Methylphenidate was the most commonly used treatment, used by 66.5% of users (N=13,049).

Summary of Findings for Exhibit 19a and Exhibit 19b

1. Among the 19,615 provincially-funded ADHD medication users in Ontario in 2013, methylphenidate was the most common treatment used (66.5%; N =13,049). The majority of users were under 65 years of age (86.3%; N=16,929), more than half were male (54.9%; N=10,778) and the majority lived in urban areas (88.4%; N=17,344). 2. Among all ADHD medication users, 5,245 (26.7%) were new users. Although lisdexamfetamine, mixed-salt amphetamine, and atomoxetine are not indicated for new users, lisdexamfetamine was the most commonly newly initiated treatment (36.3%; N=906), and nearly one quarter of mixed-salt amphetamine (22.7%; N=520) and atomoxetine (24.5%; N=35) users newly initiated treatment. These users might have received a prior prescription that was not publically funded, which may explain this access. 3. The proportion of users with an identified ADHD diagnosis in the past 10 years varied between treatment groups, from 38.8% among dextroamphetamine users to 69.9% among atomoxetine users. 4. Atomoxetine users had significantly lower rates of hospitalizations (6.3%) and emergency visits (38.5%) in the past year compared to other ADHD medication users (overall rates 9.4% and 46.6% respectively). 5. Comorbidities were similar between treatment groups. 6. Over half (54.0%; N=10,594) of ADHD medication users had used antidepressants within the past four months of their initial ADHD medication prescription during the study period. Almost one third of ADHD medication users had used benzodiazepines (27.8%; N=5,446) or antipsychotics (32.5%; N=6,377) within the past four months, and almost one fifth of ADHD medication users had used a mood stabilizer within the past four months (17.2%; N=3,382). 7. About one third (35.8%; N=7,027) of ADHD medication users had visited a psychiatrist within the three months prior to their initial ADHD medication prescription during the study period. Lisdexamfetamine users were more likely than other treatment groups to have visited a psychiatrist (54.6%; N=1,363). 8. The number of physician office visits within the last year was high among ADHD medication users (median 10; IQR 5-19).

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Patterns of ADHD Medication Use among Adult New Users in Ontario Methodological Note: This analysis is limited to new users who had more than one prescription. We have excluded new users who were dispensed both a short –acting and long-acting form of a drug at treatment initiation (N=166). We also excluded users prescribed two different drugs at treatment initiation (N=25).

Exhibit 20: Patterns of Provincially-Funded ADHD Medications Use among Adult Continuous Users Aged 18 and Older in Ontario between 2002 and 2012, by Drug Initiated

Outcomes Overall Dextroamphetamine Lisdexamfetamin Methylphenidate Mixed-Salt Atomoxetine e Amphetamine

Number of new users* N=15,250-15,500 N=1,250-1,500 N=500-750 N=12,250-12,500 N=750-1,000 N=50-100 Number of different ADHD medications over follow-up* 1 90-95% 80-85% 80-85% 90-95% 80-85% 85-90% 2 5-10% 10-15% 15-20% 5-10% 15-20% 10-15% 3+ <1% 1-5% <1% <1 1-5% <1% Change of ADHD drug from initiation within 6 months (N, %)* 5-7% 8-10% 12-14% 3-5% 12-14% 5-7% Change of ADHD drug from initiation within 1 year (N, %)* 5-7% 12-14% 14-16% 5-7% 14-16% 8-10% Kaplan Meier Analysis* Median time to discontinuation (days)* 325-350 325-350 350-375 300-325 400-425 575-600 ⱡ* Adherence to therapy at 1 year (%) 47-49% 48-50% 48-50% 45-47% 52-54% 66-68% ⱡBased on Kaplan Meier Estimates *Censored information

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Exhibit 21: Patterns of Provincially-Funded ADHD Medications Use among Adult Continuous Users Aged 18 and Older in Ontario between 2002 and 2012, by Age at Initiation

Outcomes Overall Age 18-25 Age 26-35 Age 36-64 Age 65+ Number of users* N=15,000-15,500* N=2,000-2,250* N=3,250-3,500* N=6,250-6,500* N=3,250-3,500* Kaplan Meier Analysis* Median time to discontinuation (days)* 325-350 250-275 325-350 400-425 250-275 Adherence to therapy at 1 year (%) ⱡ* 47-49% 40-42% 48-50% 50-52% 42-44% ⱡBased on Kaplan Meier Estimates *Censored information

Exhibit 22: Patterns of Provincially-Funded Stimulant ADHD Medications Use among Adult Continuous Users Aged 18 and Older in Ontario between 2002 and 2012, by Drug Class at Initiation

Outcomes Overall Long-acting stimulants Short-acting stimulants Number of users* N=15,25-15,500 N=6,750-7,000 N=8,250-8,500 Kaplan Meier Analysis* Median time to discontinuation (days)* 325-350 375-400 275-300 Adherence to therapy at 1 year (%) ⱡ* 47-49% 50-52% 44-46% ⱡBased on Kaplan Meier Estimates*Censored information

There were approximately 15,000 continuous ADHD medication users aged 18 and older in Ontario between 2002 and 2012, the majority of whom initiated methylphenidate. Duration of therapy differed significantly between drug initiated, between type of stimulant initiated and also by age.

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Summary of Findings for Exhibit 20, Exhibit 21 and Exhibit 22

1. Between 2002 and 2012, there were 20,958 adults (age 18 and older) who initiated provincially funded ADHD treatment in Ontario, among which approximately15,000 continued treatment (defined as a subsequent prescription within 180 days of their initial prescription). 2. The majority of continuous users had initiated methylphenidate (80-85%), followed by dextroamphetamine (5-10%), mixed-salt amphetamine (5-10%), lisdexamfetamine (1-5%), and atomoxetine (<1%). 3. Most users (90-95%) were only prescribed one ADHD medication over their treatment period, approximately 5-10% were prescribed 2 different medications, and less than 1% were prescribed 3 or more different medications. 4. Few (5-7%) of continuous users were prescribed a drug that was different than the drug initiated within 6 months of initiation and 5-7% were prescribed a different drug within the first year after treatment initiation. Patients on lisdexamfetamine and mixed-salt amphetamine were most likely to change drugs within 6 and 12 months of therapy initiation (12-14% at 6 months, 14-16% at 12 months). 5. The median time to discontinuing ADHD therapy among new users was 325-350 days and differed significantly by drug initiated. The median time to discontinuation was similar for users initiating dextroamphetamine (325-250 days) methylphenidate (300-325 days), and for users initiating lisdexamfetamine (350-375 days) and mixed-salt amphetamine (400- 425 days). Users who initiated atomoxetine, the only non-stimulant, had the longest median time to discontinuation (575-600 days). 6. At one year after treatment initiation, the percent of users still on therapy ranged from 46-48% among methylphenidate users to 66-68% among atomoxetine users. 7. When comparing users who initiated a stimulant ADHD medication (short acting stimulants and long-acting stimulants) the median time to discontinuation for patients on short-acting stimulants (275-300 days) was significantly shorter compared to patients on long-acting stimulants (375-400 days). 8. The median time to ADHD medication discontinuation also differed significantly across age groups. The younger (aged 18 to 25) and older (aged 65 and older) age groups discontinued ADHD medication use sooner (250-275 days) compared to users aged 26 to 35 and users aged 36 to 64 (325-425 days).

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Exhibit 23: Characteristics of Dual Therapy among Continuous Users of Atomoxetine in Ontario between 2002 and 2012

Variable N (% of number of new users) Number of new users 665 Number of new users with > 1 Rx over period of continuous use 619 (93.1%) In new users with > 1 atomoxetine Rx over period of continuous use: N (% of number of users w. > 1 atomoxetine Rx) Number of users with > 1 non-atomoxetine ADHD Rx in period of continuous use 203 (32.8%) Number of users with > 1 Rx of non-atomoxetine drugs by drug N (% of number of Users w. > 1 non-atomoxetine Rx) Methylphenidate 143 (70.4%) Amphetamine Mixed Salts 33 (16.3%) Dextroamphetamine 33 (16.3%) Lisdexamfetamine 38 (18.7%)

Of the 619 new continuous users of atomoxetine in Ontario between 2002 and 2012, approximately one-third (32.8%; N=203) received a prescription for a stimulant. Most of the atomoxetine users prescribed stimulants were co-prescribed methylphenidate (70.4%; N=143).

Summary of Findings for Exhibit 23

1. In Ontario in 2013 there were 665 new users of atomoxetine, of which 93.1% (N=619) were continuous users.

2. Of the 619 continuous atomoxetine users, approximately one-third (32.8%; N=203) were dual therapy users.

3. Of the 203 dual therapy users in addition to atomoxetine, 70.4% (N=143) were also prescribed methylphenidate, 16.3% (N=33) were also prescribed amphetamine mixed salts, 16.3% (N=33) were also prescribed dextroamphetamine, and 18.7% (N=38) were also prescribed methylphenidate.

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Patterns of ADHD Medication Continuation into Adulthood among Youth in Ontario

Exhibit 24: Description of Provincially-Funded Continuous ADHD Medication Users who Turned 18 over the Study Period in Ontario

Users that Turned 18 Users that Continued Use Users that Continued Use past 17th Users that Continued Use past over Study Period past 17th Birthday Birthday and Discontinued prior to 17th Birthday and Continued Use 18th Birthday past 18th Birthday

Number of Users (N, %*) 13,000-13,250 2,200-2,300 (16-20%) 1,000-1,100 (6-10%) 1,200-1,300 (6-10%) Number of Users that Discontinued Treatment (N, %**) -- 1,700-1,750 (76-80%) 900-950 (81-85%) 800-850 (66-70%) Number of Users with any ODB Rx in 60-365 Days after Discontinuation of ADHD Rx (N, %***)

-- 1,000-1,100 (56-60%) 500-550 (56-60%) 450-500 (56-60%) Days between Discontinuation Date and 18th Birthday (Median) ⱡ

-- -- 200-250 450-500 * Percent out of number of users that turned 18 over study period ** Percent out of number of users with continued use ***Percent out of number of users that discontinued treatment ⱡBased on Kaplan Meier Estimates

Among individuals less than 18 years old who were active users of ADHD medications after their 17th birthday, approximately half (50-55%) continued ADHD therapy for a median of 450-500 days after their 18th birthday.

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Summary of Findings for Exhibit 24

1. There were 32,500-32,600 individuals younger than 18 in Ontario who received two or more provincially-funded ADHD medication prescriptions within 180 days between 2002 and 2013. Of these continuous users, 36-40% turned 18 by the end of the study period (December 2013).

2. Among the users who were active ADHD medication users past the age of 17, approximately half (51-55%) continued their medications past their 18th birthday.

3. Of the users who received ADHD medication past the age of 18, the median time these patients spent on therapy as an adult (i.e., after their 18th birthday) was 450-500 days.

4. 66-70% of users who continued ADHD treatment into adulthood discontinued treatment prior to the follow-up period. The majority of those who stopped were still ODB eligible (56-60%). Therefore, discontinuation does not seem to be largely driven by loss of ODB eligibility.

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Possible Misuse of Treatments for ADHD in Public Drug Programs across Canada Methodological Note: Potentially inappropriate prescriptions were defined as such if the prescription met the following criteria: 1. A prescription for the same drug class (stimulant ADHD) is filled within the 1 to 7 days prior 2. The previous prescription has a quantity for 30 days or more 3. The previous prescription is written by a different physician 4. The previous prescription is filled at a different pharmacy We also performed a sensitivity analysis using criteria 1 and 2 (defined above) to define potentially inappropriate prescriptions.

Exhibit 25: Percent of Potentially Inappropriate Prescriptions Dispensed for ADHD Medications, among Users Aged 18 and Older in Canada in 2013 and 2014, by Province and Age Group

Province Overall Age 18-25 Age 26-35 Age 36-64 Age 65+ Primary Analysis (all 4 criteria): AB 0.2-0.5% * 0.2-0.5% 0.2-0.5% * BC 0.2-0.5% 0.2-0.5% 0.2-0.5% 0.2-0.5% 0.0-0.1% MB 0.0-0.1% 0.0-0.1% 0.0-0.1% ** * NB 0.0-0.1% * 0.0-0.1% * 0.0-0.1% NF 0.0-0.1% 0.2-0.5% 0.0-0.1% 0.0-0.1% 0.0-0.1% NS * 0.0-0.1% 0.0-0.1% * 0.0-0.1% PE * 0.0-0.1% 0.0-0.1% * 0.0-0.1% SK 0.0-0.1% 0.0-0.1% 0.0-0.1% 0.0-0.1% 0.0-0.1% ON 0.2-0.5% 0.2-0.5% 0.2-0.5% 0.2-0.5% 0.0-0.1% *In accordance with the CIHI privacy policy, cases where the number of active beneficiaries (*) is less than 5 (but greater than 0) have been suppressed to ensure confidentiality. In cases where only one record has been suppressed for a given province, the record with the next lowest value has also been suppressed (**) in order to avoid residual disclosure issues.

The percent of ADHD medication prescriptions that were potentially inappropriate in 2013 and 2014 was low (<0.5%) across all provinces in Canada.

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Summary of Findings for Exhibit 25

1. Ontario had the highest percent of potentially inappropriate ADHD medications prescribed, followed by Alberta and British Columbia, which ranged between 0.2- 0.5% in 2013 and 2014. 2. The number of prescriptions that were potentially inappropriate was less than 100

across all provinces, except Ontario and British Columbia (over 500 and 1500, respectively) (data not shown). 3. The percent of potentially inappropriate ADHD medication prescriptions was generally highest among individuals aged 26-35 years old (up to 0.5%). The percent of potentially inappropriate ADHD medication prescriptions was highest in Ontario among individuals aged 18-25 (0.2-0.5%) and 26-35 (0.2-0.5%) and highest in Alberta among individuals aged 36-64 (0.2-0.5%). Potentially inappropriate prescriptions dispensed to individuals aged 65 and older was low (<0.1%) across all provinces.

4. The percent of potentially inappropriate short acting stimulant ADHD medication prescriptions in Ontario was similar to the rate of potentially inappropriate

prescriptions for all stimulant ADHD medications (data not shown).

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46 FINAL REPORT Health Equity

Analyses in Ontario suggest that there is not a major equity issue in access to these medications by age or sex. The majority of these drugs in Ontario are being used by individuals younger than 65 and just over half of all users were male. Methylphenidate and dextroamphetamine are the most commonly used medications, likely due to access as a general benefit on public drug formularies across Canada. Access to atomoxetine, guanfacine, and mixed salt amphetamine use may be limited in Canada, due to the restricted listing or unavailability of these drugs in public drugs programs. However, methylphenidate is still the most commonly accessed drug across all payers (private, cash, public, NIHB) in Canada, suggesting it might be the more preferred drug. Given the cost of these medications, affordability may be a barrier to some patients without private or public drug coverage. Limitations

Data Availability Several limitations to availability of data warrant discussion:

1. No data is available for the Territories, and therefore all analyses are restricted to inter-provincial comparisons. 2. IMS Geographic Prescription Monitor (GPM12) does not collect patient-level data, and therefore information on privately funded prescriptions is only available at the prescription and unit (e.g. tablet) level. 3. There is no data available for publicly paid prescriptions in Quebec from NPDUIS. Therefore, we will be unable to make comparisons between Ontario rates and rates of use in Quebec. 4. Data on the number of individuals eligible for public drug coverage was based on active beneficiaries annually. Therefore, these may slightly underestimate the true size of the public beneficiary population; however, this does reflect the number of active beneficiaries (e.g. those filling at least one prescription over a given year) each year. 5. Among users younger than 66 in the patterns of use analysis, if a patient appears to discontinue treatment, we do not know if they truly discontinued treatment or if they lost eligibility for public drug coverage. 6. We limited new users younger than 66 to those who were eligible for ODB in the 6-12 months prior to their initial prescription. It is possible that individuals had prior use of medications that were not captured in the ODB database (paid through cash or private insurance). 7. All data presented are based on prescriptions filled. We are unable to confirm whether a patient actually took the medication.

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Generalizability 1. Some analyses using IMS Geographic Prescription Monitor (GPM12) data reflect medications dispensed among those aged 18 or 19 and older, and therefore are only generalizable to this population. 2. All analyses among public drug beneficiaries using NPDUIS and ODB data were restricted to those aged 18 and older, and therefore are only generalizable to this population.

Adherence All data used in these analyses are based on dispensing patterns, and therefore we do not know whether subjects actually took the medications. This is particularly questionable among the population of individuals who were dispensed only one prescription for an ADHD medication. It is possible that they never tried the medication, or tried it and did not finish their initial course of therapy. For this reason, we restricted our adherence measures to users who were dispensed more than one prescription.

Overall Conclusion

The use of ADHD medication in adults is growing rapidly in Canada across all provinces, with the majority of prescriptions being covered through private or public payers. The rate of ADHD medication users was highest among younger individuals (ages 18-35) across all provinces in Canada in 2014. Non-stimulant ADHD medication use represents a minor proportion of ADHD medication use, likely due to the restricted listing and availability of these drugs, and the fact that they may be used as a second- or third-line treatment option.

The differences observed for use of ADHD medications based on formulations across provinces may be related to listing, prescribing habits, and abuse. The rate of publicly- funded ADHD medication use is highest in Newfoundland and Labrador, which was almost double the national average. The use of short-acting stimulants in Newfoundland and Labrador is more than double the rate of long-acting stimulants and likely driving the high rate of use in this province. Despite Ontario having the highest number of publicly- funded ADHD medication users, the rate of use is similar to the national average. Methylphenidate had the highest rate of users across all provinces in Canada, except British Columbia and Alberta where dextroamphetamine had the highest rate of users.

Long-acting stimulant ADHD medications, of which most are brand name products, play a major role in observed growth of use. While generic versions of extended release methylphenidate are currently listed in Ontario, there are more users of brand name methylphenidate ER (Concerta), which may indicate the availability of reimbursement cards in the public drug program.

Almost half of patients newly initiating ADHD medications stay on therapy for more than one year, but the duration differed significantly depending on drug initiated. Individuals remain on atomoxetine the longest, which may be related to disease severity, past

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treatment, and other factors. Dextroamphetamine and methylphenidate users discontinued therapy sooner compared to other drug groups, despite these being the two most commonly initiated drugs. Adherence to short-acting stimulants was also significantly worse than long-acting stimulants. Among youth who were continuous users of ADHD medications in Ontario and who were followed until adulthood, about one in ten continued ADHD therapy as an adult.

According to the literature review, abuse of ADHD medications may be high, but it is hard to measure. Generalizability of the current literature is limited because a majority of the studies focused on college students and all studies were based on self-reported surveys. Only one Canadian study was included in our review. Reference List

(1) Levy A, O'Brien B, Sellors C, Grootendorst P, Willison D. Coding accuracy of administrative drug claims in the Ontario Drug Benefit database. Canadian Journal of Clinical Pharmacology 2003; 10:67-71.

(2) Ho JM, Gomes T, Straus SE, Austin PC, Mamdani M, Juurlink DN. Adverse cardiac events in older patients receiving venlafaxine: a population-based study. The Journal of clinical psychiatry 2014; 75(6):e552-e558.

(3) Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. Bmj 2013; 346:f2610.

(4) Gomes T, Juurlink DN, Mamdani MM. Comparative adherence to oxybutynin or tolterodine among older patients. European journal of clinical pharmacology 2012; 68(1):97-99.

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49 FINAL REPORT Review of the Observational Literature

Objectives

The potential for misuse, abuse, and diversion of prescription stimulants established in randomized controlled trials is summarized in the report by the Systematic Review Team. However, these trials typically have strict inclusion criteria, and do not generally conduct research in non-Attention Deficit Hyperactivity Disorder (ADHD) diagnosed individuals. A review of the observational literature will help provide insight into misuse, abuse, and diversion of prescription stimulants in both the general, ADHD-diagnosed, and prescription-holder population.

Methods

Search Strategy We conducted a rapid review of the observational literature to investigate and understand the misuse, abuse, and diversion of prescription stimulants. The exact search strategy performed can be found in Appendix B. The inclusion criteria for text screening are below:

Inclusion criteria: • English language • Adult population • Observational studies • Stimulant misuse or diversion rate reported • Published between January 2000-May 2015

Results

Overall, 272 abstracts were reviewed and 16 potentially relevant articles were obtained in full text and their citations reviewed. Eight additional articles were identified from the article’s citations and were obtained in full text. In total, twenty-four studies were identified that met our inclusion criteria. Sixteen of these studies examined misuse in the college student population, six reviewed misuse in the adult population with and without ADHD aged 19 years and older, one reviewed misuse in adult prescription holders, and one reviewed misuse in college students who were prescription holders. Seven of these twenty-four studies also examined stimulant diversion. Conclusions from this review are limited, as all of the studies included were surveys with primary and secondary reporting rates between 10-94% and 81-96%, respectively. A summary of the studies included and their findings can be found in Appendix C.

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Misuse

Key Findings

All 24 of the studies identified examined misuse of prescription stimulants, with the majority (n=21) of these studies being conducted in the United States1-4,6-16,18-24 and the remaining conducted in Canada5, Puerto Rico4, and Switzerland.17 In the studies reviewed, the definition of misuse varied depending on whether the participant had a stimulant prescription or ADHD diagnosis. In those without an ADHD diagnosis or prescription for any stimulant, misuse was consistently defined as use of any prescription stimulant without a prescription. In contrast, among those with an ADHD diagnosis or who received prescriptions for any stimulant, misuse was defined as self-reported use of medication in a way that was not prescribed, including more frequent doses, higher doses, mixing with other drugs or using alternative routes of administrations.

A large proportion of the studies (n=22) explored the prevalence of non-prescription stimulant use in the adult population through surveys. Misuse was measured in the majority (n=22) of studies by asking if the participant had ever used a prescription stimulant that was not prescribed to them. The rate of non-prescription stimulant misuse in the general adult population ranged across studies with prevalence between 1.8%— 4.7%,9,12,14,17,18,20. However in college students, prevalence of misuse was found to be higher, with reported prevalence of misuse ranging largely between 4.6% — 48%1-8, 10, 11, 13-16, 21-24. The difference in reported misuse between college students compared to the adult population could be due to the perceived cognitive enhancing ability of these medications which is thought to lead to a higher prevalence of misuse, especially among college students.12 The large variation in rates of reported misuse could possibly be explained by vast differences in survey methods, response rates and sampling methods. For example in college students, Martins et al. (n=36,781,USA) reported the lowest prevalence of misuse (4.6%) among respondents with a 74.8% response rate using computer assisted self-interviewing, while Judson et al. (n=333, USA) reported the highest misuse (48%) among respondents with a 10% response rate using web-based survey methods.

Ten studies reported prescription stimulant misuse among a general adult population by defining misuse as “taking ADHD medication without a prescription or if prescribed, use for a reason other than doctor’s recommendation”.3,4,9,12,14,17,18,20,23,24 In total, there were only five studies that differentiated between those who misused ADHD medications without a prescription and those who had ADHD or a stimulant prescription who misused their medication.5,8,10,16,19 In the studies exploring misuse specifically in the adult population with a diagnosis of ADHD or who had a stimulant prescription, the range of lifetime misuse was found to be between 15-47.6%.5,8,10,16,19 Two articles reviewed misuse in the past year. One study (n=155, USA) found misuse in the past 6 months among prescription holders to be 23%.19 The only Canadian study identified was a small study conducted in Montreal (n=66) that reviewed misuse in the past month and found

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that 29% of prescription methylphenidate users reported misuse.5

Conclusions

Research on misuse of prescription stimulants has been primarily focused on college students and further research on misuse is needed among the general adult population. Furthermore, previous research has defined misuse in a way that includes non- prescription use of stimulants and overuse or inappropriate use of stimulants if prescribed. This definition combines both the prescription and non-prescription holders together when they are two different populations that should be explored separately. Dividing misuse into two categories in future studies, based on whether the individual has a prescription or not, will provide a better portrayal of misuse compared to the previous approaches. Limitations of the studies include small sample sizes and under reporting of misuse due to self-reporting. Further, the focus on college students limits the generalizability to the general adult population. Nevertheless, it is important to recognize the potential for abuse of prescription stimulants in the prescription holder population, among both adults and college students. Further research should focus on the prevalence and frequency of misuse in the general, prescription holder, and ADHD- diagnosed population separately in order to better understand misuse trends.

Motives for Misuse

Key Findings

Three studies explored the motives for prescription stimulant misuse. Of these three studies, two explored motives for misuse in the college population and one in the general adult population. Among college students, Judson et al. (n=333, USA) found that improving concentration (28.8%) and increasing alertness (23.4%) were the two most commonly reported motives for misuse.10 Other motives that were reported less frequently by students were to get high (6.3%), control appetite (4.2%), lose weight (3.6%), and enhance exercise (2.6%).10 In another study that explored motives for misuse in college students, Moore et al. (n=676, USA) found that in periods of high stress, such as during college midterms and final exams, a four-fold increase occurred in the misuse of prescription stimulants compared to during the first week of classes. This provides further evidence that misuse in this population is often intended to improve concentration and increase alertness to improve academic performance.16 Only one study explored motives for misuse in adults 19 years and older, here Novak et al. (n=4297, USA) found that increasing productivity (39.8%) and staying awake (23.1%) were the two most common motivations reported in this population.18

Conclusion

Overall, college students and adults were found to have similar motives for misuse. These motives are most commonly to improve concentration and increase alertness. It is important to note that few studies have been undertaken in this area and findings may not be generalizable outside of the specific populations studied. One area that had a lack

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of evidence was motives for misuse in the prescription holder population. In addition, expansion upon current research in adult and college student populations, especially in Canada where currently no studies have been performed, would be valuable for understanding the underlying reasons for misuse.

Comparisons between Medications for Misuse

Key Findings Four studies explored differences in specific stimulant medications that were being misused. 1, 13, 22, 24 No studies were found that reviewed specific stimulant misuse in the general adult population. In college students, two studies found that short-acting mixed amphetamine salt (i.e., Adderall) was misused more than methylphenidate.1,22 Another study conducted among college students in the United States (n=407) reported a similar finding, where dextroamphetamine, amphetamine and amphetamine salts were misused more compared to methylphenidate.24 Only one study among college students contradicted these findings (United States, n=150) and found that methylphenidate was misused more than amphetamines.13 Compared to the other studies in college students, this study was conducted four years earlier which may be a reason for this difference. Additionally, potential changes in accessibility and stimulant preferences could account for these differences in later studies.

Conclusion

Overall, the few research studies identified suggest dextroamphetamine is misused more that methylphenidate. A limitation of all these studies is that specific stimulant misuse was self-reported which could lead to underreporting of specific stimulant misuse. Another important limitation was that specific medication misuse did not account for availability and prescription rates of these medications making it difficult to discern if medication misuse is due to user preferences or prevalence of stimulant medications. Lastly, the majority of studies focused on medication misuse in the college student population; further research should be directed towards comparing misuse of specific stimulants in the general population.

Diversion

Key Findings

Understanding how non-prescription users access stimulants can provide insight on how to reduce misuse. Diversion of stimulant medications from prescription holders is a significant mode of access for misusers. Seven of the identified studies explored diversion of prescription stimulant medications.1,5,6,8,15,19,23 Three of these studies reviewed how non-prescription users gain access to stimulants6,8,23, three looked at diversion in those who were prescribed stimulants1,5,19, and one looked at both.15 The three survey studies that explored sources of stimulants for non-prescription users reported that most misusers obtained stimulants from friends (70%-92%).6,8,23 Other

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sources of access reported were buying 8, obtained from strangers 6, and stealing 8. One finding that is concerning is the ease of which these stimulants can be accessed. Desantis et al. (N=1811, USA) found that nearly 85% of non-prescription user respondents reported it was very or somewhat easy to obtain prescription stimulants.6 The proportion of these stimulants that come from prescription users was also explored in this study. It was found that prescription users were estimated to be the direct source of stimulant medication for almost 34% of non-prescription misusers.6

Among those with a stimulant prescription, four studies reported the occurrence of being asked to divert through selling, trading, or giving away their medications.1,4,6,19Two of these four further looked at those who actually followed through with these requests.5,19 Avodkat et al. (n=1550, USA) found that approximately 84% of prescription holders reported being asked to give their medications away at least once and 54% reported being asked to sell their medications in their lifetime.1 Another study (n=9161, USA) found that within the past year, 54% of prescription holders had been approached to sell, trade, or give away their medications.15 Rabiner et al. (n=115, USA) reported that 56% of prescription holders had been asked to give away or sell their medications in the past six months, and 13% reported that they had been approached at least six times in the last 6 months.19

Only two identified studies documented prescription holders that had actually diverted their medication.5,19 These studies measured diversion by asking directly if the prescription holders had given away or sold their medication.5,19 One of these studies (n=115, USA) found that in the past six months, 26% of prescription holders reported either giving away or selling their medication to their peers.19 Of those who gave away or sold their prescription medication in the past six months, 66% reported doing this 1-2 times, 17% 3-5 times, 10% 6-9 times, and 7% 10-19 times.19 Interestingly, comparing those who misused their prescription medication (i.e. use in higher doses than prescribed, more often than prescribed, or using someone else’s ADHD medication) to those that did not, the misuse group was significantly more likely (59%) to divert their medication compared to the non-misuse group (22%).19 This study also found that a small fraction of prescription holders (4%) reported having their medications stolen, supporting the finding by Hatung et al. that stolen medications provide a very low percentage of misusers’ supply.19 In a study conducted in Montreal, Canada, Darredeau et al. (n=66) found that 44% of prescription methylphenidate users reported diverting their medications. Of this population, 97% reported giving away their medication, 17% selling it, and 14% doing both.5 Darredeau et al. also found that those who diverted were more likely to misuse their medication compared to the non-diverter group (51.7% vs. 10.8%, respectively) supporting Rabiner et al.’s finding that misusers are more likely to divert their medications.5 A further finding was that those who were diverters were younger (22.1 vs. 29.5 years) and had received their first prescription earlier (16.2 vs. 25.8 years) than the non-diversion group.5

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Conclusion

In the general adult population aged 19 years and older, it is difficult to estimate the percentage of stimulant prescriptions holders that divert their medication since only two studies focused on diversion. However, from the seven diversion-related studies, it is evident that non-prescription holders seek out prescription holders to obtain these stimulants and out of those approached a significant proportion of the prescription holders divert their medication. It is apparent that prescription holders who divert their medications are a significant source of supply for the general misuser population. Therefore, strategies that target this group of individuals that divert their medication may be effective in reducing misuse and access to prescription stimulants in the general population.

Conclusions

The studies reviewed suggest that misuse of prescription stimulants is prevalent, both in prescription and non-prescription holder populations. Only one Canadian study was included in this observational literature review highlighting the need for further research in Canada surrounding misuse and diversion of prescription stimulants. Conclusions have limited generalizability as a majority of the studies focused on college students. The prevalence of misuse was higher among college students compared to the general population. All studies included were surveys where misuse was self-reported, limiting the validity of results due to potential non-response and social desirability bias in respondents. The few studies that examined motives for misuse found that in adults and college students misuse was primarily to improve concentration and increase alertness. Among the studies that reviewed specific medication misuse, the majority suggested that dextroamphetamine, amphetamine and amphetamine mixed salts were the most misused stimulants. However, a limitation of the studies that reviewed specific medication misuse is that they do not account for availability of medications, prescription rate, or user preferences.

Studies that explored how misusers access these medications suggest that prescription holders are a significant source. Further research should be conducted among the general adult population stratified by prescription and non-prescription holders to provide a better understanding of misuse. Accounting for prescription rates and availability of these medications in future studies would provide valuable insight on misuse rates of specific stimulants. None of the studies identified explored how to reduce misuse and abuse of these medications. Developing strategies and programs to prevent diversion in the prescription holder population could potentially limit access and reduce overall misuse of these medications in the general population.

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Literature Review References

1. Advokat CD, Guidry D, Martino L. Licit and illicit use of medications for Attention- Deficit Hyperactivity Disorder in undergraduate college students. Journal of American college health : J of ACH. 2008;56:601-6. 2. Arria AM, Wilcox HC, Caldeira KM, Vincent KB, Garnier-Dykstra LM, O'Grady KE. Dispelling the myth of "smart drugs": cannabis and alcohol use problems predict nonmedical use of prescription stimulants for studying. Addictive behaviors. 2013;38:1643-50. 3. Bavarian N, Flay BR, Ketcham PL, Smit E. Illicit use of prescription stimulants in a college student sample: a theory-guided analysis. Drug and alcohol dependence. 2013;132:665-73. 4. Betancourt J, Rios JL, Pagan I, Fabian C, Gonzalez AM, Cruz SY, et al. Non-medical use of prescription drugs and its association with socio-demographic characteristics, dietary pattern, and perceived academic load and stress in college students in Puerto Rico. Puerto Rico health sciences journal. 2013;32:89-94. 5. Darredeau C, Barrett SP, Jardin B, Pihl RO. Patterns and predictors of medication compliance, diversion, and misuse in adult prescribed methylphenidate users. Hum Psychopharmacol. 2007;22:529-36. 6. DeSantis AD, Webb EM, Noar SM. Illicit use of prescription ADHD medications on a college campus: a multimethodological approach. Journal of American college health : J of ACH. 2008;57:315-24. 7. Hall KM, Irwin MM, Bowman KA, Frankenberger W, Jewett DC. Illicit use of prescribed stimulant medication among college students. Journal of American college health : J of ACH. 2005;53:167-74. 8. Hartung CM, Canu WH, Cleveland CS, Lefler EK, Mignogna MJ, Fedele DA, et al. Stimulant medication use in college students: comparison of appropriate users, misusers, and nonusers. Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors. 2013;27:832-40. 9. Huang B, Dawson DA, Stinson FS, Hasin DS, Ruan WJ, Saha TD, et al. Prevalence, correlates, and comorbidity of nonmedical prescription drug use and drug use disorders in the United States: Results of the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 2006;67:1062-73. 10. Judson R, Langdon SW. Illicit use of prescription stimulants among college students: prescription status, motives, theory of planned behaviour, knowledge and self- diagnostic tendencies. Psychology, health & medicine. 2009;14:97-104. 11. Kaloyanides KB, McCabe SE, Cranford JA, Teter CJ. Prevalence of illicit use and abuse of prescription stimulants, alcohol, and other drugs among college students: relationship with age at initiation of prescription stimulants. Pharmacotherapy. 2007;27:666-74. 12. Kroutil LA, Van Brunt DL, Herman-Stahl MA, Heller DC, Bray RM, Penne MA. Nonmedical use of prescription stimulants in the United States. Drug Alcohol Depend. 2006;84:135-43. 13. Low KG, Gendaszek AE. Illicit use of psychostimulants among college students: A preliminary study. Psychology, Health & Medicine. 2002;7:283-7.

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14. Martins SS, Kim JH, Chen LY, Levin D, Keyes KM, Cerd M, et al. Nonmedical prescription drug use among US young adults by educational attainment. Soc Psychiatry Psychiatr Epidemiol. 2015;50:713-24. 15. McCabe SE, Teter CJ, Boyd CJ. Medical use, illicit use and diversion of prescription stimulant medication. Journal of psychoactive drugs. 2006;38:43-56. 16. Moore DR, Burgard DA, Larson RG, Ferm M. Psychostimulant use among college students during periods of high and low stress: an interdisciplinary approach utilizing both self-report and unobtrusive chemical sample data. Addictive behaviors. 2014;39:987-93. 17. N'Goran AA, Deline S, Henchoz Y, Baggio S, Studer J, Mohler-Kuo M, et al. Association between nonmedical prescription drug use and health status among young Swiss men. J Adolesc Health. 2014;55:549-55. 18. Novak SP, Kroutil LA, Williams RL, Van Brunt DL. The nonmedical use of prescription ADHD medications: results from a national Internet panel. Subst Abuse Treat Prev Policy. 2007;2:32. 19. Rabiner DL, Anastopoulos AD, Costello EJ, Hoyle RH, McCabe SE, Swartzwelder HS. The misuse and diversion of prescribed ADHD medications by college students. J Atten Disord. 2009;13:144-53. 20. Sweeney CT, Sembower MA, Ertischek MD, Shiffman S, Schnoll SH. Nonmedical use of prescription ADHD stimulants and preexisting patterns of drug abuse. J Addict Dis. 2013;32:1-10. 21. Teter CJ, McCabe SE, Cranford JA, Boyd CJ, Guthrie SK. Prevalence and motives for illicit use of prescription stimulants in an undergraduate student sample. J Am Coll Health. 2005;53:253-62. 22. Teter CJ, McCabe SE, LaGrange K, Cranford JA, Boyd CJ. Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration. Pharmacotherapy. 2006;26:1501-10. 23. Tuttle JP, Scheurich NE, Ranseen J. Prevalence of ADHD diagnosis and nonmedical prescription stimulant use in medical students. Acad Psychiatry. 2010;34:220-3. 24. Volger EJ, McLendon AN, Fuller SH, Herring CT. Prevalence of self-reported nonmedical use of prescription stimulants in North Carolina Doctor of Pharmacy students. J Pharm Pract. 2014;27:158-68.

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Appendix A: Public Plan Listings for ADHD Medications in Canada, by Province

Drug Brand BC AB SK MB ON QC NB NS PEI NL name

Amphetamine Adderall XR No No No No FB* Res No No No No mixture (Mixed amphetamine salts) Atomoxetine Strattera No No Res No Res Res No No No No Generic No No No No Res Res No No No No Dextro- Dexedrine FB FB FB FB FB* FB FB FB FB FB amphetamine Dexedrine FB FB FB FB FB* FB FB FB FB FB Spansule Lis-dexamfetamine Vyvanse No Res Res FB FB* Res No No No No dimesylate Methylphenidate Generic ER No No No FB FB* Res Res Res Res Res Concerta Res No FB FB FB* Res Res Res Res Res Generic FB FB FB FB FB* FB FB FB FB FB (Ritalin) Generic FB FB FB FB FB* FB FB FB FB FB (Ritalin SR) Biphentin No Res Res FB FB* Res Res Res Res Res Guanfacine Intuniv No No No No No Res No No No No *Therapeutic note: Stimulant medication should only be used when diagnostic criteria for narcolepsy or attention deficit disorder have been met and when stimulant medication has been demonstrated to produce clinical benefits. The use of conventional-release medication should almost always precede the use of extended-release preparations. NO=not listed RES=restricted listing BEN=unrestricted listing

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Appendix B: Medline Search Strategy

1. Prescription Drug Misuse (8385) 2. Prescription Drug Diversion (71) 3. Central Nervous System Stimulants (84322) 4. Amphetamine (17818) 5. Methylphenidate (6002) 6. Dextroamphetamine (6660) 7. 3 or 4 or 5 or 6 (84322) 8. illicit use.mp (309) 9. Metadate.mp 10. Concerta.mp 12. Focalin.mp 13. Dexmethylphenidate.mp 14. Adderall.mp 15. Desoxyn.mp 16. Lisdexamfetamine.mp 17. Vyanase.mp 18. mixed salt amphetamine.mp 19. amphetamine mixed salt.mp 20. 1 or 2 or 9 (8733) 21. 7 or 8 or 9 or 10 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 (84379) 22. 20 and 21 (272)

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Appendix C: Summary of Included Studies

Author Study Study Sample Response Drugs Country Population Age Outcomes Key Findings Comments and Design period Size Rate Included Year Advokat Survey 2004- ADHD N/A USA College 21 Prescription Misuse- Use of 43% of the Non-ADHD group reported Convenience et al. 2005 Group: Students Stimulants prescription NPSU sample (2008) 163 stimulants without Non a prescription The majority of NPSU occurred a couple of Medication given ADHD times a year (61%), it was also reported away by ADHD- Group: Diversion- monthly (30%), weekly (5.6%) and 2% once diagnosed 1,387 Diagnosed with or twice ever. students was not ADHD and being recorded asked by student to 90% of NPSU reported obtaining give or sell medications for free , 21% also reported medication or buying them instruct in faking ADHD symptoms 89% of NPS users reported taking short acting Adderall

Other stimulant medications reported for NPSU were Adderall XR (30%), Ritalin (25%), Dexedrine (18%), Concerta (17.7%), and Strattera (6.5%)

84% of the ADHD group reported being asked to give away and 54% to sell their medications

Arria et Longitudi 2004- 984 87%* USA College Not Prescription Misuse – Use of 38% of individuals reported NPSU for Longitudinal study al. (2013) nal 2008 Students Reported Stimulants any prescription studying at least once over the 4 year prospecti who were stimulant without a period Data is from single ve study enrolled in prescription or for institution within a interview at least one the experience or 40.4% and 25.4% of non-prescription geographic region semester feeling they caused stimulant users met DSM-IV criteria for may not be during all alcohol or cannabis use disorder compared generalizable

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Author Study Study Sample Response Drugs Country Population Age Outcomes Key Findings Comments and Design period Size Rate Included Year four years to 18.5% and 7.1% of non-users

92% of NPS users were also cannabis users

NPSU was associated with cannabis use, skipping class, and decreased GPA

Family income was higher for NPSU group than non-users ($78,600 vs. $71,400) Bavarian Survey 2012 520 96.3%* USA College 92.3% Prescription Misuse-Use of Prevalence of NPSU and during college Non-medical users et al. Students under 25 Stimulants prescription was 25.6% and ADHD users (2013) years old stimulants without were not a prescription or 70.0% of NPSU was initiated in college differentiated with prescription in between for NPSU excess or for Frequency of use per academic term was nonmedical 1-2 (52.9%), 3-5 (24.4%), 6-9 (9.2%), 10-19 Stimulants not purposes (5%), 20-39 (5%), and 40 (3.4%) differentiated between Oral ingestion was most popular route of administration (93.7%) with intranasal 55.2% of the (20.8%) being second participants were . female Betancou Survey Not 275 Not Puerto College 21-30 Prescription Misuse – Use of 21.5% of students had used stimulants in Convenience rt et al. reported reported Rico Students years: Stimulants prescription the previous 5 months (7.3% Monthly, 8.7% Sample (2013) 88% stimulants between Weekly, 5.5% Daily) 31-53 January-May 2011 Survey question years: Females reported misusing more than failed to 12% males (63.2% vs.36.8%) distinguish between illicit and non-illicit use of prescription drugs

67.6% of the participants were female

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Author Study Study Sample Response Drugs Country Population Age Outcomes Key Findings Comments and Design period Size Rate Included Year

Darredea In-person 2004- 66 N/A Canada Adults with 27.0± 9.4 Methylphenida Misuse – Use of in 29% reported misuse of medication at least u et al. interview 2005 a te way other than once (2007) prescription prescribed for 44% reported diverting their medication of Methylpheni Diversion – Sold these 97% reported giving it away, 17% date or gave away reported selling it, and 14% reported doing medication both.

Desantis Survey 2005- 1,811 N/A USA College N/A Prescription Misuse – Use of 34.5% of participants had reported NPSU Convenience et al. and 2006 Students Stimulants prescription Sample (2008) Interview stimulants without 63% reported first NPSU in college a prescription Differentiated 89% reported obtaining NPS from friends, between 8% from strangers prescription holders and non- prescription holders Hall et al. Survey N/A 381 38.1% USA College 19.4 ± Prescription Misuse- Use of 13.7% of participants had reported NPSU Study did not (2005) Students 1.66 Stimulants prescription (17% males and 11% females) measure stimulants for Frequency of use nonmedical purposes Combined prescription holders and non- prescription holders

NPSU is measured in lifetime and may not necessarily have occurred in college Hartung Survey Not 1,153 Not USA College 19.72±1. Prescription Nonmedical 26% of respondents reported stimulant 65% of et al. Reported Reported Students 45 Stimulants misuse- Use of misuse, of these 24%were non-medical respondents were

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Author Study Study Sample Response Drugs Country Population Age Outcomes Key Findings Comments and Design period Size Rate Included Year (2013) prescription misusers and 2% were medical misusers female stimulants without a prescription 15% of those with a stimulant prescription Differentiated reported misuse between Medical misuse- prescription Taking higher 81% of non-medical prescription users holders and non- doses or more received stimulants from a friend, 45% prescription frequently than bought them and 4% stole them holders prescribed

Huang et In-person 2001- 43,093 81%* USA Individuals Not Prescription Misuse – Use of 4.7% reported nonprescription use of al. (2006) interview 2002 18 years Reported Amphetamine prescription amphetamines in their lifetime and older s amphetamines without a Prevalence of lifetime misuse of prescription or if amphetamines by age was 4.4% between prescribed, in 18-29, 6.8% between 30-44, 4.9 % between greater amounts, 45-64%, and 0.4% above 65. more often, or reason other than doctor’s recommendation Judson et Web- 2007 333 1. 10% 2. USA College 19.78 ± Prescription Misuse – Use of 20% of all participants reported illicit use of Potential al. based Students 1.34 Stimulants any prescription prescription stimulants at least once in their nonresponse bias (2008) survey stimulant without a lifetime from large prescription or Use percentage of of stimulant 47.6% of prescription holders and 18.3% of those who did not medication with non-prescription holders reported misuse at respond prescription in least once in their lifetime excess or reason Differentiated other than treating Motives for illicit use included to improve between ADHD/ADD concentration prescription (28.8%), increase alertness or stay awake holders and non- Motivations (23.4%), prescription behind misuse become high (6.3%), control appetite holders (4.2%), lose weight (3.6%), enhance

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Author Study Study Sample Response Drugs Country Population Age Outcomes Key Findings Comments and Design period Size Rate Included Year exercise (2.6%), counteract the effects of other drugs (2.1%), and ‘‘other’’ (1.2%)

Kaloyanid Survey 2005 4,580 3. 85% 4. USA College 20 ± 2.0 Prescription Misuse - Use of NPSU in non-ADHD population in the past es et al. Students Stimulants any prescription month was 1.8% 2007 stimulant without a prescription Misuse in those prescribed stimulants was greater in those who initiated in college (22.7%) compared to grades 9-12 (62%), grades 5-8(5.6%), and grades K-4 (3.6%)

Kroutil et Phone 2000- Total: 2002: 79%* USA Population Stratified Stimulants Misuse – Use of Related to Adults: Nationally al. (2006) Based 2003 182,367 2001, 2000: aged 12 or by: prescribed for any prescription 5.9% of those aged 18-25 years reported Representative Interview 2002: 73-74%* older 12-17, ADHD stimulant without a misuse of ADHD stimulants at least once in Data 68,126 18-25, treatment prescription or for their lifetime with 3.5% misusing ADHD 2001: 26 and the experience or stimulants exclusively 58,680 older feeling they caused 2000: Young adults aged 18–25 55,561 years had a higher prevalence of misuse in the past year (1.3%) compared to those aged 26 or older (0.1%)

Of those who were past year stimulant users in 2000, 5.6% of 18-25 year olds and 0.1% of 26 years and older met criteria for DSM-IV stimulant abuse or dependence

Dexedrine and methylphenidate were the most frequently reported misused

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Author Study Study Sample Response Drugs Country Population Age Outcomes Key Findings Comments and Design period Size Rate Included Year medications. Low et al. Survey Not 150 93.8% USA College 20.1 Prescription Misuse – Use of Past year NPSU was reported by 35.3% of (2002) Reported Students Stimulants any prescription respondents stimulant without a prescription in the Motives behind misuse were to improve past year academic performance (23.3%), improve efficiency on academic assignments (22.0%) and combine with alcohol (19.3%)

24% of respondents reported using both Adderall and Methylphenidate while 4.0% and 7.3% used Adderall and Methylphenidate separately Martins et Survey 2008- 36,781 74.8% USA Young 18-22 Prescription Misuse – Use of NPSU in the increased from 3.6% in 2008 al. (2014) 2010 adults years old Stimulants prescription to 4.1% in 2010 stimulants without a prescription in College students in this age group had past year or for the higher prevalence of NPSU compared to experience or those with a high school diploma or less feelings they than high school education (4.6% vs. 3.1% caused vs. 3.0%)

McCabe Survey 2003 9,161 47% USA College Prescription Misuse – Use of 8.1% of undergraduate students reported et al. Students Stimulants prescription NPSU in their lifetime (2006) stimulants without a prescription 5.4% reported NPSU within the past year with 48% using 1-2 times, 34% using 3-9 Diversion- If times, and 18% using 10 or more times prescribed, approached to sell, 67% of past year NPS users reported trade or give away obtaining medication from friends and peers medication Undergraduates with medically prescribed stimulants (2%), 54% reported being approached to sell, trade, or give away their medication

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Author Study Study Sample Response Drugs Country Population Age Outcomes Key Findings Comments and Design period Size Rate Included Year

Moore et Survey Not First Not USA College 20.14 ± Prescription Misuse – Use of 11.7% and 8.5% of respondents reported 65.2% of sample al. Reported week: Reported Students 2.04 Stimulants prescription NPSU of Adderall or Ritalin at least once in was female (2014) 600 stimulants without their lifetime Midterms a prescription or if : 468 prescribed, used Misuse of Adderall and Ritalin among non- Final greater than prescription users in the first week of exams: prescribed dose classes was 0.8% and 0.3% respectively 400 In prescription users, misuse in the first week for both Adderall and Ritalin was 0%

During midterms and final exams, overall misuse of Adderall and Ritalin increased both in prescription and non-prescription holders N’Goran Survey 2010- 4,858 79%, Switzerlan Young adult At Prescription Misuse - Use of 1.88% of respondents reported NPSU in Only males et al. 2013 87.2%* d males Baseline: Stimulants prescription the past year (2014) 19.96 ± stimulants without 1.19 a prescription or if At follow- prescribed, in ways up: 21.25 not recommended ± 1.21 by a doctor Novak et Survey 2005 4,297 94.6%* USA Population 18- Prescription Misuse - Use of 7.1% of adults aged 19 to 49 reported using al. (2007) aged 18 to 25:77% Stimulants prescription non-medically ADHD medication at least 49 26-49: stimulants without once in their life 23% a prescription or for the feeling or Abuse was more prevalent in shorter acting experience medications compared to long acting ones for both lifetime (5.4% vs. 2.1%) and past year (1.6% vs. 1.0%)

4.34% of 18-25 year olds reported misuse in the past year compared to 1.27% of 26- 49 year olds

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Author Study Study Sample Response Drugs Country Population Age Outcomes Key Findings Comments and Design period Size Rate Included Year 5.

Rabiner Survey 2007 115 Not USA College Not ADHD Misuse – Use of 31% of respondents reported misuse once 69% of et al. Reported Students Reported Medication medication in in their lifetime respondents were (2009) with a higher doses than female prescription prescribed, more Medication misuse in the past 6 months for ADHD often than was reported by 23% of those taking medication prescribed, or medications using someone else’s ADHD 56% of those with prescriptions were medication during approached by peers to give or sell University medication within the past 6 months, of which 26% of them gave or sold their Diversion – How medication often were prescription holders ask to give or sell medications and the frequency that they gave away or sold medications

Sweeney Survey 2002- 443,041 Not USA Population Prescription Misuse - Use of 3.4% of the population reported engaging in Large population et al. 2009 Reported aged 12 Stimulants any prescription NPSU use No differentiation (2013) years or stimulant without a between those older prescription or for 19.45 years was the average age of first who were the experience or NPSU compared to 15.69 years for other prescribed feeling it caused drug use medicine vs. non prescribed 95.3% of those who had NPSU reported use of another illicit drug or non-medical prescription Teter et Survey 2005 4580 85% USA College 20 ± 2.0 Prescription Misuse – Use of 8.3% of respondents reported illicit use of al. (2006) Students Stimulants prescription stimulants in their lifetime, of these 65.2% Modafiinal? stimulants without reported first use in college a prescription

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Author Study Study Sample Response Drugs Country Population Age Outcomes Key Findings Comments and Design period Size Rate Included Year 5.9% reported illicit prescription stimulant use in the past year

75% of illicit prescription stimulant users reported taking amphetamine- dextroamphetamine while 25% reported using methylphenidate

Less than 3% reported using modafinal, amphetamine, methamphetamine or pemoline Teter et Survey 2003 9,161 48% USA College Not Prescription Misuse – Use of 8.1% of the sample reported illicit use of al. (2005) Students Reported stimulants prescription prescription stimulants at least once in their stimulants without lifetime a prescription 5.4% reported illicit use in the past year Tuttle et Survey Not 336 84% USA Medical Not Prescription Misuse – Use of 10% of students reported non- medical al. Reported Students Reported Stimulants prescription prescription stimulant misuse at least once (2010) stimulants without in their lifetime a prescription Of those who reported NPSU 39% used 5 or more times, 45% used between 2 and 5 times.

48% reported use during medical school

70% had obtained prescription stimulants from their peers

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Author Study Study Sample Response Drugs Country Population Age Outcomes Key Findings Comments and Design period Size Rate Included Year Volger et Survey 2012 407 39% USA Pharmacy 20-30 Prescription Misuse – Use of 8.75% of participants had NPSU during 72% of al. (2014) Students (88%) Stimulants prescription pharmacy school participants were stimulants without male a prescription Of these students 83% of had used OR legal dextroamphetamine, amphetamine and prescription of amphetamine salts while only as 14% used stimulant but use in methylphenidate a way other than prescribed 3.23% reported NPSU in the past 5 months

Note: NPSU- Non-Prescription Stimulant Use, NPS- Non-Prescription Stimulants *Secondary Response Rate

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Appendix D: Quarterly ADHD Medication Use Data, by Drug and Age

In accordance with the ICES privacy policy, in cases where the number of total users is less than 6, this number has been suppressed to ensure confidentiality. In cases where there is only one record being suppressed, another record has been suppressed (*) in order to avoid residual disclosure issues.

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Appendix D-1a. Long Acting Stimulants: Amphetamine Mixed Salts, Overall Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2008 4 * * * * 2009 1 2844 75 9585.18 39 2009 2 145093 5020 438553.42 1845 2009 3 196791 6034 591861.98 2266 2009 4 238485 7131 723097.14 2685 2010 1 269091 7906 812370.68 2950 2010 2 286582 8668 870552.98 3090 2010 3 284685 8650 872260.15 3087 2010 4 317592 9552 979553.41 3303 2011 1 327888 9960 1015562.70 3484 2011 2 354141 10826 1100975.32 3622 2011 3 332274 10250 1038852.24 3414 2011 4 344352 10846 1088006.34 3445 2012 1 334566 10734 1072855.24 3428 2012 2 348164 11257 1124896.44 3436 2012 3 331140 10580 1062804.87 3324 2012 4 349602.7 11315 1136651.31 3404 2013 1 351355 11313 1156058.33 3492 2013 2 368495 11806 1224106.22 3524 2013 3 361992 11665 1189044.52 3433 2013 4 376485 12413 1246500.20 3514 2014 1 369677 12506 1242982.47 3562 2014 2 386705 13060 1307151.42 3670 2014 3 380795 12879 1270322.40 3597 2014 4 398962 13308 1341135.73 3698

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Appendix D-1b. Long Acting Stimulants: Amphetamine Mixed Salts, Age < 18 Year Quarter Total number units Total number prescriptions Total cost ($) Total number users

2008 4 510 12 1597.92 7 2009 1 2213 61 7275.98 33 2009 2 101406 3161 306142.21 1357 2009 3 130410 3755 392780.24 1622 2009 4 156296 4456 470218.83 1910 2010 1 172873 4936 519433.83 2064 2010 2 177642 5104 536449.55 2088 2010 3 167342 4783 512573.79 2033 2010 4 189125 5391 577542.43 2194 2011 1 192007 5485 587890.41 2270 2011 2 200827 5787 620750.33 2288 2011 3 177147 5119 554252.44 2080 2011 4 181947 5315 573742.58 2056 2012 1 170333 4979 545431.48 1961 2012 2 171257 5083 551094.52 1941 2012 3 154992 4545 500663.90 1816 2012 4 163339 4877 530661.58 1834 2013 1 162375 4722 532239.71 1834 2013 2 162606 4911 538747.09 1782 2013 3 147872 4519 487569.82 1632 2013 4 154418 4712 508528.82 1661 2014 1 147159 4518 492231.44 1637 2014 2 144912 4515 487829.20 1601 2014 3 132240 4156 443307.92 1494 2014 4 139049 4378 467167.47 1532

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Appendix D-1c. Long Acting Stimulants: Amphetamine Mixed Salts, Age 18-25 Year Quarter Total number units Total number prescriptions Total cost ($) Total number users

2008 4 * ≤5 * ≤5 2009 1 * * * ≤5 2009 2 11457 510 35941.39 145 2009 3 16353 637 49754.66 183 2009 4 21447 759 67196.40 221 2010 1 24688 929 77456.59 254 2010 2 27997 1128 89250.03 287 2010 3 29014 1257 93134.36 301 2010 4 31803 1219 102477.09 320 2011 1 33945 1363 109441.27 350 2011 2 39199 1450 125110.99 397 2011 3 38499 1472 123951.44 391 2011 4 41040 1640 132806.69 413 2012 1 41541 1570 134649.78 448 2012 2 44062 1711 144433.23 446 2012 3 43680 1609 142173.08 431 2012 4 44825 1787 149278.38 457 2013 1 48022 1741 160509.28 472 2013 2 54937 1914 185287.67 542 2013 3 56182 1931 188178.60 539 2013 4 56742 2067 192381.56 528 2014 1 58619 2149 200942.65 562 2014 2 60076 2244 208154.05 584 2014 3 61457 2300 209087.97 598 2014 4 64655 2428 219466.34 650

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Appendix D-1d. Long Acting Stimulants: Amphetamine Mixed Salts, Age 26-35 Year Quarter Total number units Total number prescriptions Total cost ($) Total number users

2008 4 . 0 . 0 2009 1 * ≤5 * ≤5 2009 2 10435 608 32541.61 114 2009 3 17406 697 54135.77 170 2009 4 19180 695 59532.48 181 2010 1 22344 676 68021.37 210 2010 2 24810 812 76327.66 241 2010 3 27444 998 85624.15 259 2010 4 33051 1160 105502.63 293 2011 1 32903 1149 104901.92 303 2011 2 37496 1297 117395.22 320 2011 3 38200 1215 120294.98 323 2011 4 38433 1373 121571.17 326 2012 1 41585 1403 133316.46 355 2012 2 44529 1574 143680.71 361 2012 3 43827 1498 141233.85 391 2012 4 46561 1668 150752.23 400 2013 1 46982 1723 155247.79 433 2013 2 52333 1985 175183.16 433 2013 3 54655 2143 182401.75 467 2013 4 57595 2339 192690.62 487 2014 1 58057 2293 196411.54 509 2014 2 65587 2510 220543.07 545 2014 3 67275 2344 223068.53 555 2014 4 68393 2401 228663.00 564

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Appendix D-1e. Long Acting Stimulants: Amphetamine Mixed Salts, Age < 36-64 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2008 4 . 0 . 0 2009 1 . 0 . 0 2009 2 18134 666 53826.97 192 2009 3 28360 849 84161.13 246 2009 4 35366 1085 108549.98 318 2010 1 42233 1204 127641.18 360 2010 2 47921 1436 145208.48 392 2010 3 50799 1402 153607.72 410 2010 4 53655 1577 165623.02 415 2011 1 57982 1727 181204.78 465 2011 2 64072 2013 201163.13 510 2011 3 65503 2154 205353.67 512 2011 4 69929 2229 221457.63 540 2012 1 70489 2537 227948.06 571 2012 2 75820 2602 248036.02 579 2012 3 75057 2617 240474.97 576 2012 4 80647.7 2669 263206.10 586 2013 1 79178 2791 262166.23 623 2013 2 83197 2629 276443.18 636 2013 3 87246 2704 284387.16 656 2013 4 89765 2893 296350.00 687 2014 1 87886 3106 295510.65 698 2014 2 97639 3329 331184.59 775 2014 3 100242 3617 336368.38 777 2014 4 107615 3669 363738.83 796

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Appendix D-1f. Long Acting Stimulants: Amphetamine Mixed Salts, Age 65+ Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2008 4 . 0 . 0 2009 1 . 0 . 0 2009 2 3661 75 10101.24 37 2009 3 4262 96 11030.18 45 2009 4 6196 136 17599.45 55 2010 1 6953 161 19817.71 62 2010 2 8212 188 23317.26 82 2010 3 10086 210 27320.13 84 2010 4 9958 205 28408.24 81 2011 1 11051 236 32124.32 96 2011 2 12547 279 36555.65 107 2011 3 12925 290 34999.71 108 2011 4 13003 289 38428.27 110 2012 1 10618 245 31509.46 93 2012 2 12496 287 37651.96 109 2012 3 13584 311 38259.07 110 2012 4 14230 314 42753.02 127 2013 1 14798 336 45895.32 130 2013 2 15422 367 48445.12 131 2013 3 16037 368 46507.19 139 2013 4 17965 402 56549.20 151 2014 1 17956 440 57886.19 156 2014 2 18491 462 59440.51 165 2014 3 19581 462 58489.60 173 2014 4 19250 432 62100.09 156

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Appendix D-2a. Long Acting Stimulants: Dextroamphetamine, Overall Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2000 1 14911 233 8158.50 99 2000 2 * * * * 2000 3 * * * * 2000 4 19304 299 10432.20 116 2001 1 * * * * 2001 2 * * * * 2001 3 * * * * 2001 4 * * * * 2002 1 22390 342 12082.95 152 2002 2 23655 361 12856.97 160 2002 3 * * * * 2002 4 24347 359 12728.09 146 2003 1 * * * * 2003 2 * * * * 2003 3 * * * * 2003 4 27121 451 15081.89 164 2004 1 30716 485 16745.27 195 2004 2 30397 509 16664.82 193 2004 3 * * * * 2004 4 * * * * 2005 1 * * * * 2005 2 * * * * 2005 3 * * * * 2005 4 * * * * 2006 1 42706 741 40229.81 279 2006 2 * * * * 2006 3 41452 750 40287.98 266 2006 4 41780 739 41548.35 250 2007 1 44741 798 44822.39 259 2007 2 46779 853 45967.88 269 2007 3 45282 791 44717.30 264 2007 4 46486 912 46184.28 264 2008 1 46178 885 45955.82 258 2008 2 46907 898 47287.81 268 2008 3 47645 832 47233.13 266 2008 4 49388 840 48813.11 276 2009 1 46665 790 46197.59 270

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Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2009 2 43336 738 42780.36 241 2009 3 36050 586 35040.32 197 2009 4 33679 567 33251.21 176 2010 1 34785 609 34592.24 174 2010 2 30365 528 29789.65 163 2010 3 * * * * 2010 4 27052 450 30607.39 126 2011 1 * * * * 2011 2 * * * * 2011 3 25580 431 29297.74 112 2011 4 24903 418 28542.85 106 2012 1 * * * * 2012 2 * * * * 2012 3 * * * * 2012 4 * * * * 2013 1 * * * * 2013 2 24726 326 27764.85 124 2013 3 75305 1278 81267.87 476 2013 4 82538 1448 94033.72 518 2014 1 88744 1558 101132.05 557 2014 2 134964 2616 160357.26 841 2014 3 138175 2810 157321.09 792 2014 4 138140 2860 165174.77 783

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Appendix D-2b. Long Acting Stimulants: Dextroamphetamine, Age < 18 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2000 1 7611 178 4316.23 71 2000 2 8800 203 5082.94 76 2000 3 8926 185 5186.23 79 2000 4 9978 188 5460.10 82 2001 1 12068 208 6619.17 97 2001 2 12178 209 6673.31 99 2001 3 10454 210 5792.39 95 2001 4 13259 262 7332.29 108 2002 1 13596 257 7613.37 116 2002 2 14984 264 8264.21 122 2002 3 11908 220 6547.18 102 2002 4 13825 240 7510.33 106 2003 1 12715 228 6799.06 101 2003 2 13985 246 7785.41 109 2003 3 14411 257 7959.85 109 2003 4 13988 257 7740.79 108 2004 1 17042 288 9269.63 135 2004 2 16403 291 8968.63 131 2004 3 17679 312 12381.52 138 2004 4 19304 316 15284.89 128 2005 1 21059 364 16934.35 159 2005 2 21612 393 17463.29 171 2005 3 22013 378 17802.32 167 2005 4 26459 478 23372.46 205 2006 1 27150 489 25062.83 207 2006 2 27627 513 25648.42 206 2006 3 25851 474 24834.21 193 2006 4 25084 466 24695.99 179 2007 1 25282 500 25192.18 174 2007 2 26415 530 25688.38 179 2007 3 24686 469 24043.54 175 2007 4 24486 476 24105.84 169 2008 1 23969 452 23698.49 162 2008 2 25638 466 25121.21 169 2008 3 23803 414 23394.22 163 2008 4 25185 421 24395.90 168 2009 1 24014 402 23823.42 161

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Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2009 2 17676 297 17439.83 130 2009 3 12215 209 12038.37 90 2009 4 10964 168 10721.45 71 2010 1 10818 175 10588.16 70 2010 2 9074 165 9063.20 62 2010 3 7206 135 8146.33 47 2010 4 5606 98 6470.23 38 2011 1 3304 52 3777.33 25 2011 2 4177 66 4814.97 28 2011 3 3348 41 3795.62 20 2011 4 3194 38 3488.19 18 2012 1 3344 38 3720.07 20 2012 2 3418 37 3845.69 17 2012 3 2490 26 2850.70 14 2012 4 2320 27 2687.75 16 2013 1 2207 23 2603.54 12 2013 2 1390 19 1643.61 10 2013 3 6756 128 7897.59 55 2013 4 9449 175 11044.90 86 2014 1 8300 162 9561.81 87 2014 2 12443 246 14717.37 113 2014 3 11530 251 12501.02 97 2014 4 10708 265 12675.85 100

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Appendix D-2c. Long Acting Stimulants: Dextroamphetamine, Age 18-25 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2000 1 * * * ≤5 2000 2 1538 17 902.04 6 2000 3 1649 21 977.62 6 2000 4 * * * ≤5 2001 1 1304 19 782.63 6 2001 2 1493 20 874.32 7 2001 3 1622 25 928.63 7 2001 4 2026 27 1109.80 7 2002 1 * * * ≤5 2002 2 * * * ≤5 2002 3 1371 13 685.31 6 2002 4 * * * ≤5 2003 1 2090 20 1179.77 8 2003 2 2587 32 1452.61 10 2003 3 2277 33 1226.61 10 2003 4 2991 41 1718.32 15 2004 1 2635 41 1506.96 16 2004 2 3793 61 2162.55 19 2004 3 3645 69 2846.42 17 2004 4 3416 65 2942.22 19 2005 1 2209 37 1994.29 12 2005 2 2955 50 2497.67 16 2005 3 4551 75 3895.45 20 2005 4 4312 67 4038.29 25 2006 1 3107 59 2959.28 20 2006 2 3054 59 3096.21 18 2006 3 3103 64 3085.87 19 2006 4 3564 68 3527.15 20 2007 1 5542 80 5528.74 28 2007 2 4583 80 4587.09 27 2007 3 5429 91 5552.48 30 2007 4 6567 142 6395.84 31 2008 1 7220 151 7049.00 34 2008 2 7158 139 7254.03 35 2008 3 8099 123 7933.46 37 2008 4 7715 121 7603.48 38 2009 1 7641 99 7242.60 42

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Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2009 2 7596 125 7385.06 41 2009 3 6218 89 6008.20 34 2009 4 6788 98 6323.54 35 2010 1 7516 109 7245.14 37 2010 2 7163 100 6775.16 35 2010 3 6542 92 6726.46 31 2010 4 6766 91 7117.89 31 2011 1 6420 123 7007.22 28 2011 2 6925 135 7823.90 30 2011 3 5914 119 6826.61 29 2011 4 6546 129 7568.10 29 2012 1 6098 101 6997.03 25 2012 2 5348 86 6060.62 27 2012 3 5405 90 6114.90 26 2012 4 5343 92 5920.55 26 2013 1 4853 82 5661.94 23 2013 2 5220 68 5861.92 26 2013 3 11465 205 12962.39 78 2013 4 10934 232 12972.90 80 2014 1 12181 243 13910.46 80 2014 2 16087 315 19320.76 103 2014 3 16396 321 19242.47 107 2014 4 14929 380 18259.10 102

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Appendix D-2d. Long Acting Stimulants: Dextroamphetamine, Age 26-35 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2000 1 1721 13 946.71 7 2000 2 923 11 500.28 6 2000 3 1732 18 954.99 8 2000 4 2246 19 1230.81 8 2001 1 2040 25 1145.31 10 2001 2 1606 16 941.81 7 2001 3 1921 17 1116.32 7 2001 4 1172 15 692.57 6 2002 1 1674 17 934.46 8 2002 2 1740 22 989.43 10 2002 3 1482 20 839.96 8 2002 4 1402 21 807.61 8 2003 1 1016 20 615.41 7 2003 2 1815 55 1131.94 10 2003 3 2093 57 1227.17 9 2003 4 2233 55 1316.03 11 2004 1 2411 58 1342.82 11 2004 2 1929 44 1105.25 10 2004 3 1622 44 1321.51 8 2004 4 2556 59 2118.80 11 2005 1 2377 46 1931.07 9 2005 2 1996 51 1709.68 9 2005 3 2064 47 1787.70 10 2005 4 2345 63 2137.18 10 2006 1 2437 65 2471.31 10 2006 2 2171 64 2244.12 12 2006 3 2254 75 2497.66 12 2006 4 2606 77 2876.23 11 2007 1 3513 76 3672.02 14 2007 2 2806 75 3013.57 13 2007 3 3061 77 3329.74 14 2007 4 3657 81 3771.33 16 2008 1 3704 79 3658.46 16 2008 2 3427 78 3602.16 17 2008 3 3384 75 3584.63 18 2008 4 3093 65 3308.38 16 2009 1 2148 58 2296.33 14

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Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2009 2 4020 69 3956.58 16 2009 3 4167 58 3987.42 16 2009 4 3164 61 3316.61 15 2010 1 3142 66 3135.44 15 2010 2 3306 59 3237.91 15 2010 3 3487 61 3620.28 16 2010 4 3489 77 4051.09 15 2011 1 3594 78 4293.12 17 2011 2 4547 83 5046.11 19 2011 3 4549 74 4868.06 17 2011 4 4364 72 4688.30 16 2012 1 3809 63 4212.39 17 2012 2 4759 71 5292.98 19 2012 3 5477 62 5595.50 24 2012 4 5766 60 6104.28 19 2013 1 3465 38 3692.35 15 2013 2 5205 64 4994.94 27 2013 3 13805 292 14528.66 87 2013 4 15781 331 17523.50 93 2014 1 18261 397 20615.10 114 2014 2 28393 646 33936.65 167 2014 3 32156 813 39173.11 173 2014 4 31951 781 39078.74 169

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Appendix D-2e. Long Acting Stimulants: Dextroamphetamine, Age < 36-64 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2000 1 3829 28 1918.46 13 2000 2 4911 47 2514.85 16 2000 3 5881 73 3072.61 19 2000 4 4788 65 2426.85 17 2001 1 3666 60 2033.99 17 2001 2 4231 103 2433.37 17 2001 3 4641 113 2464.42 19 2001 4 4252 50 2169.52 18 2002 1 5553 56 2668.54 20 2002 2 4811 59 2467.88 19 2002 3 6289 69 2481.50 24 2002 4 8125 87 3874.12 26 2003 1 6734 80 3180.34 24 2003 2 6502 85 3062.13 26 2003 3 6821 100 3452.58 27 2003 4 6463 87 3541.75 24 2004 1 7490 87 4033.57 27 2004 2 6780 102 3645.09 27 2004 3 6046 132 4461.42 26 2004 4 5562 74 4627.13 26 2005 1 7424 108 5954.08 28 2005 2 8431 101 6768.90 31 2005 3 9267 117 7576.72 32 2005 4 8407 122 8001.52 33 2006 1 8802 120 8733.54 36 2006 2 8445 118 7924.92 35 2006 3 8531 124 8304.95 35 2006 4 8625 115 8714.31 32 2007 1 9243 131 9337.75 37 2007 2 11050 154 10925.89 41 2007 3 9659 135 9577.44 35 2007 4 9637 195 9894.11 38 2008 1 9307 189 9625.51 39 2008 2 8683 195 9382.40 36 2008 3 9877 192 10089.59 37 2008 4 10571 200 10728.97 44 2009 1 10457 203 10534.17 43

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Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2009 2 11600 212 11621.37 42 2009 3 10628 198 10604.72 44 2009 4 10045 202 10268.86 41 2010 1 10349 211 10726.48 39 2010 2 9342 180 9229.41 42 2010 3 9119 162 10320.11 39 2010 4 9713 170 11216.64 35 2011 1 9066 170 10581.87 38 2011 2 11443 195 13817.52 41 2011 3 10439 187 12207.13 40 2011 4 9619 172 11366.96 37 2012 1 9050 142 10472.48 36 2012 2 10520 136 11983.70 41 2012 3 10299 163 12269.21 38 2012 4 10849 168 12714.85 42 2013 1 10893 150 12868.17 39 2013 2 11319 165 13379.36 52 2013 3 23697 384 26925.64 125 2013 4 25528 423 29229.94 127 2014 1 29054 464 32945.72 142 2014 2 51184 997 60711.97 289 2014 3 48534 966 56069.33 247 2014 4 49781 1025 59581.96 237

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Appendix D-2f. Long Acting Stimulants: Dextroamphetamine, Age 65+ Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2000 1 * ≤5 * ≤5 2000 2 * ≤5 * ≤5 2000 3 * * * ≤5 2000 4 * * * ≤5 2001 1 * * * ≤5 2001 2 * * * ≤5 2001 3 * ≤5 * ≤5 2001 4 * ≤5 * ≤5 2002 1 * ≤5 * ≤5 2002 2 * ≤5 * ≤5 2002 3 * ≤5 * ≤5 2002 4 * ≤5 * ≤5 2003 1 * * * ≤5 2003 2 * * * ≤5 2003 3 * ≤5 * ≤5 2003 4 1446 11 765.00 6 2004 1 1138 11 592.29 6 2004 2 1492 11 783.30 6 2004 3 * * * ≤5 2004 4 * * * ≤5 2005 1 * * * ≤5 2005 2 * ≤5 * ≤5 2005 3 * ≤5 * ≤5 2005 4 * ≤5 * ≤5 2006 1 1210 8 1002.85 6 2006 2 * * * ≤5 2006 3 1713 13 1565.29 7 2006 4 1901 13 1734.67 8 2007 1 1161 11 1091.70 6 2007 2 1925 14 1752.95 9 2007 3 2447 19 2214.10 10 2007 4 2139 18 2017.16 10 2008 1 1978 14 1924.36 7 2008 2 2001 20 1928.01 11 2008 3 2482 28 2231.23 11 2008 4 2824 33 2776.38 10 2009 1 2405 28 2301.07 10

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Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2009 2 2444 35 2377.52 12 2009 3 2822 32 2401.61 13 2009 4 2718 38 2620.75 14 2010 1 2960 48 2897.02 13 2010 2 1480 24 1483.97 9 2010 3 * * * ≤5 2010 4 1478 14 1751.54 7 2011 1 * * * ≤5 2011 2 * * * ≤5 2011 3 1330 10 1600.32 6 2011 4 1180 7 1431.30 6 2012 1 * * * ≤5 2012 2 * ≤5 * ≤5 2012 3 * ≤5 * ≤5 2012 4 * * * ≤5 2013 1 * * * ≤5 2013 2 1592 10 1885.02 9 2013 3 19582 269 18953.59 131 2013 4 20846 287 23262.48 132 2014 1 20948 292 24098.96 134 2014 2 26857 412 31670.51 169 2014 3 29559 459 30335.16 168 2014 4 30771 409 35579.12 175

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Appendix D-3a. Long Acting Stimulants: Methylphenidate, Overall Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 338404 5889 200925.48 2856 2000 2 333439 5943 197890.07 2852 2000 3 290182 5274 171518.65 2533 2000 4 325125 6114 193828.29 2726 2001 1 318864 6173 190621.44 2771 2001 2 320529 6191 192123.24 2726 2001 3 290405 5723 172080.79 2514 2001 4 317571 6469 189252.23 2721 2002 1 303260 6218 181774.43 2678 2002 2 313863 6607 189688.86 2685 2002 3 297525 5888 177641.53 2538 2002 4 332190 6848 200169.00 2830 2003 1 338749 7359 206852.38 2929 2003 2 339955 7794 208792.88 2956 2003 3 339002 8108 208539.29 2909 2003 4 368282 9264 230148.84 3113 2004 1 388229 9660 243027.74 3213 2004 2 400597 10999 256568.02 3292 2004 3 375503 11006 241544.49 3054 2004 4 420391 11978 271957.30 3332 2005 1 441031 12425 284889.17 3518 2005 2 466376 12654 304993.01 3603 2005 3 445959 11498 302637.96 3417 2005 4 487653 12608 348021.14 3693 2006 1 516240 13199 380364.19 3881 2006 2 530115 13483 394376.67 3891 2006 3 490559 12524 346291.46 3759 2006 4 526093 12511 349304.12 4015 2007 1 532593 12398 361156.19 4017 2007 2 543181 12782 363286.48 4052 2007 3 524051 12910 370482.24 3924 2007 4 563938 14475 398539.62 4153 2008 1 583101 15077 420213.17 4267 2008 2 593873.9 15833 436311.74 4308 2008 3 586737 16176 435255.57 4272 2008 4 634418 17332 464256.52 4433 2009 1 653450 19156 493012.23 4768

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 921629 29321 1353146.84 7828 2009 3 955404 33031 1605079.66 8559 2009 4 1067692 37533 1951889.99 9526 2010 1 1118438 40070 2142114.23 10192 2010 2 1181320 43826 1699228.99 10725 2010 3 1136125 42418 1473164.10 10510 2010 4 1234088 44847 1641284.26 11183 2011 1 1266938 47258 1724298.25 11729 2011 2 1325277 51728 1873902.38 12163 2011 3 1276453 47668 1804104.36 11738 2011 4 1345912 50978 1917357.97 12303 2012 1 1325681 50442 1921518.89 12538 2012 2 1412201 54278 2070848.92 12993 2012 3 1352497 51518 1963716.71 12684 2012 4 1444961 55685 2134554.41 13205 2013 1 1444479 55745 2143797.18 13559 2013 2 1533361 59366 2296998.09 14042 2013 3 1490788 57890 2212707.50 13687 2013 4 1566013 60826 2360521.03 14310 2014 1 1618797 62736 2426483.42 15288 2014 2 1678824 68017 2564420.00 15456 2014 3 1638166 68655 2494784.37 15114 2014 4 1698857 73416 2646536.64 15473

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Appendix D-3b. Long Acting Stimulants: Methylphenidate, Age < 18 Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 239264 4583 144162.33 2339 2000 2 229551 4460 138357.26 2289 2000 3 191122 3595 114773.13 1982 2000 4 217245 4126 130650.08 2166 2001 1 216953 4163 130707.05 2187 2001 2 215070 4111 129384.01 2124 2001 3 184390 3428 109777.27 1885 2001 4 210234 3987 125116.36 2083 2002 1 200623 3788 119991.08 2043 2002 2 207980 3880 124875.64 2019 2002 3 193492 3421 115039.73 1892 2002 4 220655 4059 131604.01 2132 2003 1 221957 4144 133649.99 2160 2003 2 219690 4050 131395.32 2143 2003 3 207681 3751 123260.89 2060 2003 4 229124 4263 137812.10 2237 2004 1 245123 4542 147228.77 2318 2004 2 241455 4500 146022.06 2303 2004 3 210084 3878 126402.18 2039 2004 4 242322 4551 146653.35 2305 2005 1 251911 4670 152771.07 2373 2005 2 259960 4893 162463.17 2372 2005 3 235201 4295 160266.06 2169 2005 4 263326 4870 191648.10 2368 2006 1 271559 5022 210213.80 2422 2006 2 274003 5120 216910.53 2410 2006 3 254889 4727 202222.99 2320 2006 4 282519 5386 215096.44 2537 2007 1 282943 5351 221018.69 2511 2007 2 286980 5518 224158.77 2509 2007 3 263574 4969 227158.80 2316 2007 4 286378 5483 240791.16 2478 2008 1 296337 5644 254302.91 2527 2008 2 292010.5 5613 257454.96 2488 2008 3 269705 5218 247276.89 2366 2008 4 291357 5646 259427.01 2429 2009 1 296808 5704 271841.00 2534

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 473849 11536 888505.72 4754 2009 3 483083 12174 1028941.95 5170 2009 4 565359 14829 1269046.20 5881 2010 1 601176 15718 1380788.91 6288 2010 2 625671 16835 1053339.40 6485 2010 3 572074 15358 860246.04 6170 2010 4 634729 17273 968273.42 6686 2011 1 648198 17690 1000855.01 6975 2011 2 672767 18611 1068573.92 7162 2011 3 611302 16864 997318.92 6637 2011 4 662460 18453 1075339.91 6999 2012 1 655927 18487 1076388.48 7129 2012 2 693655 19685 1146065.53 7317 2012 3 633220 17911 1046935.02 6900 2012 4 688922 19813 1147482.36 7290 2013 1 692190 19827 1151604.79 7458 2013 2 718210.2 20673 1199324.66 7570 2013 3 661352 18920 1119268.34 7108 2013 4 712859 20680 1211383.51 7630 2014 1 726394 21307 1226078.00 7918 2014 2 743992.5 21993 1268206.41 7917 2014 3 695178 20719 1185021.80 7564 2014 4 742274 22412 1265716.18 7971

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Appendix D-3c. Long Acting Stimulants: Methylphenidate, Age 18-25 Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 19240 249 10893.87 129 2000 2 22525 306 12864.60 145 2000 3 20463 312 11793.76 140 2000 4 24174 328 13724.93 144 2001 1 22323 325 12364.25 148 2001 2 23287 355 13416.84 156 2001 3 23422 388 13589.78 161 2001 4 24165 422 14204.97 164 2002 1 24398 504 14626.33 173 2002 2 24500 519 14948.72 180 2002 3 22601 400 13515.59 168 2002 4 26452 504 15940.12 182 2003 1 27868 572 17055.98 213 2003 2 29040.5 734 18411.56 218 2003 3 32271 988 21200.84 240 2003 4 35938 1183 23400.18 258 2004 1 34858 1127 22997.73 268 2004 2 43110 1425 28824.54 296 2004 3 38949 1255 25907.22 272 2004 4 41575 1070 26392.43 284 2005 1 42625 1081 26843.35 314 2005 2 47678 1163 30625.44 336 2005 3 48970 1071 32026.76 339 2005 4 54591 1319 37256.30 375 2006 1 59510 1539 41371.01 409 2006 2 62805 1431 44076.48 401 2006 3 54857 1354 36002.31 397 2006 4 56298 1412 34126.63 410 2007 1 57583 1325 35506.37 405 2007 2 60496 1309 36752.05 408 2007 3 58955 1479 36469.06 409 2007 4 63770 1739 41547.51 426 2008 1 66035 1835 44713.79 460 2008 2 65012.4 1937 48309.04 442 2008 3 68324 1853 50931.85 465 2008 4 72409 1835 52626.96 483 2009 1 72389 1999 54483.36 547

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 101442 3238 155572.73 814 2009 3 108026 3556 181983.10 926 2009 4 116360 4269 213747.76 979 2010 1 122043 4631 236715.07 1074 2010 2 132552 5086 188855.62 1197 2010 3 131699 5382 173748.21 1214 2010 4 143535.5 5609 193505.56 1262 2011 1 149791.5 6323 211338.04 1336 2011 2 164938 7215 239128.34 1439 2011 3 161907 6668 244578.59 1443 2011 4 167030 6821 249402.22 1525 2012 1 166188 6462 246025.47 1564 2012 2 177689 6918 266329.70 1623 2012 3 176890 6883 270599.17 1652 2012 4 183484 7454 282585.92 1661 2013 1 182965 7476 279061.39 1732 2013 2 199515 8364 318226.09 1827 2013 3 206080 8397 322261.38 1847 2013 4 199413.2 8261 328662.90 1814 2014 1 206398 8199 334968.87 1929 2014 2 212229.5 8812 351488.72 1999 2014 3 217504 9041 357082.14 1992 2014 4 215162 9368 364563.07 1953

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Appendix D-3d. Long Acting Stimulants: Methylphenidate, Age 26-35 Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 20803 288 11878.91 102 2000 2 22217 331 12637.06 114 2000 3 22196 397 13148.43 128 2000 4 19196 443 11701.97 120 2001 1 22120 539 13589.42 126 2001 2 23579 521 14308.75 118 2001 3 22551 607 14207.59 129 2001 4 22811 657 14026.88 122 2002 1 22107 594 13195.41 122 2002 2 21120 686 13142.39 126 2002 3 22064 650 13889.68 126 2002 4 25339 718 16232.34 137 2003 1 24724 757 15529.10 150 2003 2 24862 842 16263.93 166 2003 3 25939 880 17265.84 161 2003 4 26405 1194 19014.87 166 2004 1 29248 1331 21017.43 174 2004 2 33233 1737 25007.90 191 2004 3 33383 1901 25828.79 199 2004 4 37295 1876 27950.21 207 2005 1 41656 1982 30738.00 245 2005 2 46241 2018 33148.30 266 2005 3 48453 1926 34334.53 275 2005 4 50533 1939 36169.21 299 2006 1 51397 1979 37164.08 311 2006 2 55524 2181 39918.72 314 2006 3 48718 1805 30334.05 299 2006 4 55217 1607 30230.62 305 2007 1 56387 1639 31619.55 324 2007 2 57863 1770 31193.53 348 2007 3 59328 1843 33490.52 350 2007 4 60868 2165 34987.94 355 2008 1 61126 2500 37049.69 369 2008 2 67184 2901 41330.48 405 2008 3 71250 3099 43652.32 421 2008 4 77482 3315 47707.66 465 2009 1 86557 3884 53895.00 533

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 111236 5126 106524.60 748 2009 3 121383 6646 145518.91 847 2009 4 119695 6847 162662.38 898 2010 1 133969 7829 194673.85 996 2010 2 138303 8997 168355.72 1040 2010 3 140910 8576 161864.81 1065 2010 4 141171 8770 170180.43 1079 2011 1 150644 9505 187487.34 1177 2011 2 155494 11282 208177.55 1215 2011 3 156649 10140 203467.29 1222 2011 4 159600 10206 207263.39 1265 2012 1 160569 10004 211445.99 1299 2012 2 168457 10662 228096.21 1374 2012 3 172245 9879 227706.83 1416 2012 4 172779 10429 236977.66 1390 2013 1 177421.4 10344 240771.22 1445 2013 2 190519 11172 265799.00 1544 2013 3 190692 11297 267349.36 1569 2013 4 194677 11672 271228.19 1592 2014 1 207127 12325 288208.46 1761 2014 2 214289 14381 316254.55 1769 2014 3 210086 14864 323371.38 1758 2014 4 215816 15732 337367.09 1734

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Appendix D-3e. Long Acting Stimulants: Methylphenidate, Age < 36-64 Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 51946 670 30084.51 233 2000 2 51671 745 29958.09 246 2000 3 48879 871 28589.73 225 2000 4 55482 1091 33133.38 226 2001 1 49583 1027 29785.43 244 2001 2 49954 1086 30281.75 259 2001 3 51306 1178 30586.81 269 2001 4 48062 1251 29476.15 268 2002 1 45129 1185 27981.15 260 2002 2 48250 1355 30145.76 272 2002 3 48279 1264 30125.74 262 2002 4 46757 1415 29950.83 286 2003 1 50434 1730 33164.95 317 2003 2 53610.5 2006 35806.26 333 2003 3 59722 2301 40605.25 355 2003 4 62475 2355 42045.80 361 2004 1 64061 2401 43444.10 363 2004 2 68105 3126 48557.77 403 2004 3 77186 3799 56337.49 441 2004 4 84984 4322 63374.82 445 2005 1 90545 4511 66913.39 488 2005 2 97118 4392 70407.74 524 2005 3 96040 4014 68213.87 527 2005 4 101650 4266 73614.33 537 2006 1 114097 4431 80901.21 618 2006 2 117739 4511 82361.62 638 2006 3 112851 4401 70398.35 615 2006 4 110404 3826 61421.56 630 2007 1 115500 3813 64535.64 652 2007 2 116555 3911 62739.57 655 2007 3 119793 4307 66473.16 699 2007 4 128593 4761 72403.14 735 2008 1 135457 4769 74554.54 756 2008 2 142650 5021 78452.93 801 2008 3 151520 5671 84926.80 853 2008 4 165559 6207 94168.15 890 2009 1 171366 7232 102511.52 980

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 200528 8895 174701.05 1253 2009 3 207239 10071 220292.66 1348 2009 4 224395 10874 266590.72 1457 2010 1 224144 11217 290911.98 1535 2010 2 244659 12200 258075.97 1681 2010 3 251616 12373 253761.70 1739 2010 4 271643 12427 276692.97 1825 2011 1 274267 12969 292700.10 1884 2011 2 283709 13807 320807.51 1963 2011 3 295831 13075 323516.61 2014 2011 4 303688.8 14545 342673.01 2101 2012 1 291879 14524 342799.69 2130 2012 2 312741 15935 378228.93 2212 2012 3 311632 15762 375348.18 2233 2012 4 333484 16839 412352.62 2354 2013 1 334534 16971 420220.07 2431 2013 2 359262 17864 452627.12 2564 2013 3 364379 17845 452729.58 2577 2013 4 383375.1 18620 480844.98 2666 2014 1 403738.8 19257 505888.85 3016 2014 2 425743 20927 548278.50 3069 2014 3 429951 22083 559063.34 3080 2014 4 432018 23783 586575.28 3081

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Appendix D-3f. Long Acting Stimulants: Methylphenidate, Age 65+ Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2000 1 7151 99 3905.86 53 2000 2 7475 101 4073.06 58 2000 3 7522 99 3213.60 58 2000 4 9028 126 4617.93 70 2001 1 7885 119 4175.29 66 2001 2 8639 118 4731.89 69 2001 3 8736 122 3919.34 70 2001 4 12299 152 6427.87 84 2002 1 11003 147 5980.46 80 2002 2 12013 167 6576.35 88 2002 3 11089 153 5070.79 90 2002 4 12987 152 6441.70 93 2003 1 13766 156 7452.36 89 2003 2 12752 162 6915.81 96 2003 3 13389 188 6206.47 93 2003 4 14340 269 7875.89 91 2004 1 14939 259 8339.71 90 2004 2 14694 211 8155.75 99 2004 3 15901 173 7068.81 103 2004 4 14215 159 7586.49 91 2005 1 14294 181 7623.36 98 2005 2 15379 188 8348.36 105 2005 3 17295 192 7796.74 107 2005 4 17553 214 9333.20 114 2006 1 19677 228 10714.09 121 2006 2 20044 240 11109.32 128 2006 3 19244 237 7333.76 128 2006 4 21655 280 8428.87 133 2007 1 20180 270 8475.94 125 2007 2 21287 274 8442.56 132 2007 3 22401 312 6890.70 150 2007 4 24329 327 8809.87 159 2008 1 24146 329 9592.24 155 2008 2 27017 361 10764.33 172 2008 3 25938 335 8467.71 167 2008 4 27611 329 10326.74 166 2009 1 26330 337 10281.35 174

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Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2009 2 34574 526 27842.74 259 2009 3 35673 584 28343.04 268 2009 4 41883 714 39842.93 311 2010 1 37106 675 39024.42 299 2010 2 40135 708 30602.28 322 2010 3 39826 729 23543.34 322 2010 4 43009 768 32631.88 331 2011 1 44037 771 31917.76 357 2011 2 48369 813 37215.06 384 2011 3 50764 921 35222.95 422 2011 4 53133 953 42679.44 413 2012 1 51118 965 44859.26 416 2012 2 59659 1078 52128.55 467 2012 3 58510 1083 43127.51 483 2012 4 66292 1150 55155.85 510 2013 1 57369 1127 52139.71 493 2013 2 65855 1293 61021.22 537 2013 3 68285 1431 51098.84 586 2013 4 75689 1593 68401.45 608 2014 1 75139.4 1648 71339.24 664 2014 2 82569.8 1904 80191.82 702 2014 3 85447 1948 70245.71 720 2014 4 93587 2121 92315.02 734

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Appendix D-4a. Long Acting Stimulants: Lisdexamfetamine, Overall Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2011 2 17545 835 67539.99 534 2011 3 102072 6383 400224.42 1459 2011 4 153363 7824 600015.74 2024 2012 1 177298 7859 683901.00 2308 2012 2 216050 9622 847636.12 2650 2012 3 226893 10281 879690.17 2839 2012 4 269066 11651 1041058.72 3181 2013 1 284432 12539 1103399.61 3473 2013 2 319246 13474 1237918.04 3789 2013 3 324037 14304 1253177.71 3890 2013 4 365939 16492 1421815.69 4298 2014 1 374130 17719 1489143.29 4490 2014 2 413015 19745 1664955.45 4791 2014 3 419746.1 19588 1671364.44 4867 2014 4 463101 21520 1841299.98 5290

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Appendix D-4b. Long Acting Stimulants: Lisdexamfetamine, Age < 18 Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2011 2 12279 470 46807.76 353 2011 3 67650 2273 256757.17 937 2011 4 100515 3285 385025.92 1333 2012 1 114364 3633 438673.67 1493 2012 2 136038 4269 528756.52 1686 2012 3 132645 4132 509998.57 1712 2012 4 156922 4915 602266.28 1948 2013 1 161371 5087 619571.88 2059 2013 2 178059 5537 682244.64 2181 2013 3 170066 5412 649948.58 2175 2013 4 189563 6049 724486.20 2355 2014 1 191179 6128 743344.54 2394 2014 2 206294 6661 810276.65 2493 2014 3 195386.1 6364 766633.07 2447 2014 4 217519 7131 850160.42 2663

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Appendix D-4c. Long Acting Stimulants: Lisdexamfetamine, Age 18-25 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2011 2 1308 63 5166.12 42 2011 3 8737 841 36507.15 132 2011 4 14367 876 57252.08 194 2012 1 17041 899 65782.49 221 2012 2 21626 1229 86978.99 279 2012 3 26320 1326 106177.55 320 2012 4 30899 1494 121918.53 369 2013 1 33691 1789 132949.95 414 2013 2 36852 1879 146750.49 445 2013 3 37548 2045 151065.36 460 2013 4 41995 2134 167101.52 510 2014 1 44092 2178 179547.00 544 2014 2 49699 2461 204346.55 606 2014 3 52331 2494 210554.84 637 2014 4 58553 2925 235209.22 687

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Appendix D-4d. Long Acting Stimulants: Lisdexamfetamine, Age 26-35 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2011 2 1463 120 5878.65 51 2011 3 9681 1610 43883.22 151 2011 4 13495 1870 61389.44 183 2012 1 16929 1659 70599.71 223 2012 2 20394 1893 84414.41 258 2012 3 24086 2170 98290.19 300 2012 4 29155 2287 116203.72 315 2013 1 32282 2418 128734.65 366 2013 2 37533 2495 148027.16 426 2013 3 41381 2578 161652.69 458 2013 4 46467 3453 184369.61 510 2014 1 49810 4512 210860.70 576 2014 2 56301 5135 240499.17 626 2014 3 59805 4726 247092.00 635 2014 4 64585 5029 265932.29 697

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Appendix D-4e. Long Acting Stimulants: Lisdexamfetamine, Age < 36-64 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2011 2 2041 168 8013.63 75 2011 3 12847 1568 52613.69 202 2011 4 21091 1691 81849.86 271 2012 1 24806 1564 93661.20 324 2012 2 31895 2084 124568.29 366 2012 3 36929 2475 142615.20 433 2012 4 43780 2774 169659.96 477 2013 1 49410 3075 193046.82 550 2013 2 57743 3355 226915.02 634 2013 3 64415 4043 255004.48 683 2013 4 74934 4575 298196.72 794 2014 1 77572 4610 312344.45 848 2014 2 87646 5150 359545.50 928 2014 3 97397 5621 394798.57 1000 2014 4 105982 6035 428300.17 1090

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Appendix D-4f. Long Acting Stimulants: Lisdexamfetamine, Age 65+ Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2011 2 454 14 1673.83 13 2011 3 3157 91 10463.19 37 2011 4 3895 102 14498.44 43 2012 1 4158 104 15183.93 47 2012 2 6097 147 22917.91 61 2012 3 6913 178 22608.66 74 2012 4 8310 181 31010.23 72 2013 1 7678 170 29096.31 84 2013 2 9059 208 33980.73 103 2013 3 10627 226 35506.60 114 2013 4 12980 281 47661.64 129 2014 1 11477 291 43046.60 128 2014 2 13075 338 50287.58 138 2014 3 14827 383 52285.96 148 2014 4 16462 400 61697.88 153

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Appendix D-5a. Short Acting Stimulants: Dextroamphetamine, Overall Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 314624 2642 99843.09 1316 2000 2 323657 2812 103624.62 1356 2000 3 297780 2368 92538.62 1218 2000 4 339589 2782 107794.38 1379 2001 1 359278 2953 114927.78 1458 2001 2 364357 2910 116378.29 1452 2001 3 335292 2591 105502.80 1330 2001 4 372323 3065 119405.39 1478 2002 1 378783 3174 122806.34 1555 2002 2 402002 3362 130468.55 1618 2002 3 368099 3175 117659.33 1487 2002 4 401909 3452 130014.51 1591 2003 1 427812 3628 139106.84 1659 2003 2 446476 3856 145258.96 1735 2003 3 429275 3678 137209.69 1654 2003 4 463047 4083 150214.36 1732 2004 1 487765 4288 159482.09 1808 2004 2 488180 4317 160090.17 1793 2004 3 473393 4081 190731.62 1702 2004 4 507448 4297 229441.07 1801 2005 1 511557 4497 233601.21 1889 2005 2 529889.5 4663 246748.57 1954 2005 3 524259 4432 243778.22 1840 2005 4 540069 4472 283348.02 1883 2006 1 544848.5 4595 299628.36 1904 2006 2 544758.5 4661 302306.32 1870 2006 3 505869.5 4217 279568.55 1721 2006 4 541026 4606 302636.63 1869 2007 1 553804.5 4954 328964.25 1925 2007 2 568624.5 5035 331261.89 1930 2007 3 546079 4878 321343.44 1862 2007 4 576443 5277 342137.59 1875 2008 1 587473 5454 350523.82 1918 2008 2 609908 5808 373310.44 1972 2008 3 598615.5 5534 360929.83 1947 2008 4 633661.5 5831 383915.60 2007 2009 1 592836 5478 362383.45 2048

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 526048 4918 328087.61 1792 2009 3 483442.5 4447 296619.86 1545 2009 4 485254.5 4528 300658.43 1515 2010 1 465076 4373 289412.03 1459 2010 2 470167 4556 298420.72 1419 2010 3 460956 4582 293750.43 1371 2010 4 461128.5 4594 309955.97 1402 2011 1 441014 4471 304831.16 1353 2011 2 456615.5 4703 322292.52 1377 2011 3 434271 4628 306797.20 1305 2011 4 428186 4607 306175.63 1327 2012 1 408500.5 4348 293310.09 1288 2012 2 419571 4359 306988.34 1284 2012 3 412793 4240 294446.88 1282 2012 4 416060.6 4280 303204.91 1263 2013 1 400092.5 4102 290024.13 1281 2013 2 415094.5 4180 303202.74 1284 2013 3 404759.5 4153 291211.85 1247 2013 4 402463.5 4285 295930.64 1274 2014 1 382441 4171 282026.48 1275 2014 2 268222.9 3267 202183.29 1099 2014 3 274585.5 3137 203126.39 999 2014 4 292423.5 3414 222207.52 1053

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Appendix D-5b. Short Acting Stimulants: Dextroamphetamine, Age < 18 Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 185210 1824 60416.19 942 2000 2 182377 1890 60101.94 968 2000 3 158021 1510 51613.66 850 2000 4 194324 1906 63683.71 1009 2001 1 204482 1964 66834.27 1056 2001 2 208682 1946 68143.70 1047 2001 3 186611 1670 60971.21 942 2001 4 218232 2046 71829.60 1067 2002 1 232507 2181 76926.67 1151 2002 2 235396 2203 78051.38 1155 2002 3 209442 1970 68954.92 1035 2002 4 232610 2201 76984.13 1142 2003 1 245725 2298 81395.25 1182 2003 2 250231 2292 82375.44 1200 2003 3 225308 2069 74176.80 1101 2003 4 247719 2319 81730.09 1166 2004 1 261174 2407 86365.93 1214 2004 2 250618 2362 82905.02 1197 2004 3 225281 2061 92335.31 1069 2004 4 252244 2272 114981.15 1153 2005 1 258062 2338 119830.41 1228 2005 2 263162 2363 123886.63 1247 2005 3 244309 2039 115432.22 1107 2005 4 261168.5 2206 138527.14 1168 2006 1 257985.5 2149 142598.62 1143 2006 2 238543.5 2060 133197.79 1104 2006 3 215661.5 1827 120540.61 972 2006 4 240703 2098 136035.99 1082 2007 1 247782 2137 147980.78 1120 2007 2 242803 2153 142371.40 1093 2007 3 214981 1887 128198.20 998 2007 4 228412 2099 136393.95 1019 2008 1 229959 2086 137894.14 1025 2008 2 235979 2106 144697.19 1035 2008 3 215445.5 1845 130876.14 979 2008 4 230387.5 2033 140428.82 1021 2009 1 217597.5 1962 133633.47 1028

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 162992 1501 102712.78 811 2009 3 117401.5 1076 74219.12 601 2009 4 112700.5 1064 70539.08 566 2010 1 105808 1013 66641.70 522 2010 2 95840.5 919 61157.46 470 2010 3 83632.5 833 54370.05 423 2010 4 81625.5 926 55940.56 435 2011 1 77868.5 859 54447.59 417 2011 2 74160 815 53312.95 396 2011 3 56466.5 632 41575.97 336 2011 4 57952.5 740 43318.00 356 2012 1 56764 738 42525.95 340 2012 2 51273 701 39003.64 323 2012 3 46148 616 35235.73 292 2012 4 48201 703 37176.61 321 2013 1 48634 696 37279.21 328 2013 2 47759 688 36471.93 328 2013 3 41589.5 598 31601.97 289 2013 4 40505.5 659 30602.17 303 2014 1 42571.5 694 32677.84 324 2014 2 34350 575 26536.02 258 2014 3 27018 491 21277.08 219 2014 4 31340 537 24317.53 239

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Appendix D-5c. Short Acting Stimulants: Dextroamphetamine, Age 18-25 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2000 1 10265 99 3404.98 42 2000 2 14433 108 4548.96 46 2000 3 10772 91 3390.02 38 2000 4 14484 100 4579.16 40 2001 1 14370 96 4550.78 40 2001 2 11419 90 3477.20 37 2001 3 11472 98 3503.86 33 2001 4 12857 110 4070.66 50 2002 1 12252 101 3887.09 39 2002 2 17043 127 5346.62 55 2002 3 17351 145 5535.86 51 2002 4 19372 154 6122.78 60 2003 1 19334 185 6242.54 69 2003 2 23051 224 7389.43 71 2003 3 22566 242 7527.00 80 2003 4 26375 283 8813.75 92 2004 1 28314 298 9457.89 93 2004 2 28829 288 9541.74 95 2004 3 33555 315 13799.98 104 2004 4 34064 361 15773.68 116 2005 1 38785 451 18062.22 126 2005 2 35870 439 16909.26 121 2005 3 37184 378 17957.17 129 2005 4 35579 334 18499.95 121 2006 1 42224 388 23363.25 139 2006 2 44466 448 25126.34 142 2006 3 39608 423 22714.60 141 2006 4 42126 441 24268.73 148 2007 1 44705 531 27475.66 151 2007 2 49941 593 29707.26 160 2007 3 47991 586 29116.01 151 2007 4 48958 534 29639.59 153 2008 1 51788 547 31421.04 166 2008 2 52280 579 32377.68 174 2008 3 58821 572 36002.20 181 2008 4 59948 566 36467.14 187 2009 1 59821.5 630 37454.32 206

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Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2009 2 54873.5 607 35124.73 194 2009 3 54723.5 554 34753.46 172 2009 4 49280 560 31739.03 165 2010 1 45489 495 29135.41 161 2010 2 45981.5 511 30125.19 156 2010 3 46224 546 31062.84 159 2010 4 48919.5 563 34147.72 163 2011 1 46447 582 32973.09 150 2011 2 50019.5 652 35341.21 157 2011 3 48284.5 782 36249.23 158 2011 4 48081.5 816 36470.49 159 2012 1 42773 736 32329.91 147 2012 2 43708.5 557 33462.42 143 2012 3 42410 594 31170.45 138 2012 4 37546 500 28379.66 120 2013 1 35718 578 27348.73 138 2013 2 39250 594 31005.52 139 2013 3 36019 577 28199.85 126 2013 4 32521 553 25318.98 122 2014 1 28348 498 22204.77 106 2014 2 18023 382 15108.23 87 2014 3 17404 313 14311.36 84 2014 4 21078 341 17210.44 93

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Appendix D-5d. Short Acting Stimulants: Dextroamphetamine, Age 26-35 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2000 1 21260 140 6628.00 62 2000 2 25487 180 8010.71 71 2000 3 26981 180 8402.45 74 2000 4 29495 173 9049.05 70 2001 1 31324 232 9997.09 89 2001 2 26082 170 8216.18 73 2001 3 24666 156 7758.04 73 2001 4 22508 147 7224.66 66 2002 1 25064 181 8119.00 72 2002 2 29266 270 9652.88 86 2002 3 27946 301 9436.37 87 2002 4 26263 316 9029.19 89 2003 1 32177 272 10469.25 91 2003 2 35824 319 11765.38 104 2003 3 38006 331 12308.83 99 2003 4 39170 347 12535.46 102 2004 1 39190 325 12424.00 101 2004 2 35590 382 11886.85 94 2004 3 34088 374 14412.26 101 2004 4 36706 336 16853.34 108 2005 1 39180 397 18348.16 114 2005 2 39673 443 18643.68 116 2005 3 42003 439 19900.41 109 2005 4 44898.5 465 23591.25 113 2006 1 48016 460 26235.90 126 2006 2 46710 496 26372.66 125 2006 3 47821 496 26471.70 130 2006 4 48946 518 27075.67 134 2007 1 56326 615 33120.42 141 2007 2 59258 632 34368.77 151 2007 3 55325 632 33105.63 149 2007 4 60851 685 36530.85 154 2008 1 59124 714 35903.58 161 2008 2 59884 813 37582.52 163 2008 3 59280 760 36451.11 169 2008 4 65091 757 40438.55 166 2009 1 67948 750 41968.71 185

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Year Quarter Total Total number Total cost ($) Total number prescriptions number units users

2009 2 65429.5 681 40729.65 174 2009 3 60730.5 648 36971.79 164 2009 4 68392 672 41581.05 180 2010 1 71479 713 44320.68 189 2010 2 73356 766 46110.47 189 2010 3 70124.5 778 45466.56 179 2010 4 74538.5 838 50881.64 193 2011 1 75026.5 867 52057.87 204 2011 2 75963 905 54408.37 210 2011 3 68971 904 49426.58 191 2011 4 67776 849 47506.70 192 2012 1 66089.5 778 46123.75 194 2012 2 72526 903 53235.68 201 2012 3 71318 790 51555.23 205 2012 4 70408 822 51228.91 189 2013 1 68747 771 49050.70 191 2013 2 72642 767 52522.22 185 2013 3 73322.5 843 54067.48 188 2013 4 73683.5 862 55343.70 196 2014 1 69891.5 820 52267.30 205 2014 2 47838.9 563 35363.30 172 2014 3 49125 542 36855.85 161 2014 4 53661 604 41114.37 181

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Appendix D-5e. Short Acting Stimulants: Dextroamphetamine, Age < 36-64 Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 65761 424 19923.50 176 2000 2 69218 453 21392.39 167 2000 3 65792 410 20293.45 151 2000 4 68102 448 21130.40 170 2001 1 79783 500 24924.04 172 2001 2 81202 537 25608.45 189 2001 3 78718 501 24812.01 185 2001 4 82619 565 25961.37 190 2002 1 78589 553 24808.16 201 2002 2 87218 588 27546.32 217 2002 3 78933 569 25107.37 205 2002 4 89655 602 28346.63 202 2003 1 94375 696 30353.45 222 2003 2 103121 823 33432.83 245 2003 3 104847 823 33402.51 252 2003 4 113328 939 36726.73 259 2004 1 122667 1055 40329.53 284 2004 2 133844 1071 43982.23 287 2004 3 139609 1107 56828.79 298 2004 4 141546 1087 63916.61 292 2005 1 144017 1088 63888.42 295 2005 2 146812 1166 67294.35 327 2005 3 157198 1326 73352.30 353 2005 4 155698 1242 81321.49 346 2006 1 157287 1378 86753.93 365 2006 2 174746 1426 96002.93 371 2006 3 162435 1259 89621.10 360 2006 4 167399 1300 92821.49 374 2007 1 168896.5 1433 99864.51 389 2007 2 175220.5 1375 101556.08 393 2007 3 185857 1501 109570.38 428 2007 4 194687 1668 115378.68 418 2008 1 207395 1801 122748.04 429 2008 2 217292.5 1966 132455.43 451 2008 3 218231 2045 132943.30 470 2008 4 228977 2133 138244.84 479 2009 1 202305 1803 122671.19 483

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 195983 1807 121448.29 452 2009 3 201983 1844 125061.41 448 2009 4 205079 1897 127169.90 443 2010 1 195920 1814 121466.65 435 2010 2 202502 1962 128743.29 436 2010 3 208010 2035 133710.58 450 2010 4 201769 1942 133865.46 452 2011 1 192250 1839 132419.49 432 2011 2 205955 1980 144811.53 454 2011 3 207538 1932 146972.06 452 2011 4 200700 1786 141879.72 449 2012 1 193272 1718 137971.28 450 2012 2 198657 1765 143554.76 454 2012 3 193303 1769 138577.75 464 2012 4 202253 1802 146145.86 456 2013 1 193026.5 1640 137976.75 451 2013 2 199836 1684 143481.96 452 2013 3 197021 1650 140678.67 458 2013 4 196341 1686 142322.87 458 2014 1 184058.5 1596 133424.58 448 2014 2 126989.5 1286 94636.64 399 2014 3 138094 1332 101866.51 363 2014 4 139635 1419 105090.38 361

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Appendix D-5f. Short Acting Stimulants: Dextroamphetamine, Age 65+ Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 65761 424 19923.50 176 2000 2 69218 453 21392.39 167 2000 3 65792 410 20293.45 151 2000 4 68102 448 21130.40 170 2001 1 79783 500 24924.04 172 2001 2 81202 537 25608.45 189 2001 3 78718 501 24812.01 185 2001 4 82619 565 25961.37 190 2002 1 78589 553 24808.16 201 2002 2 87218 588 27546.32 217 2002 3 78933 569 25107.37 205 2002 4 89655 602 28346.63 202 2003 1 94375 696 30353.45 222 2003 2 103121 823 33432.83 245 2003 3 104847 823 33402.51 252 2003 4 113328 939 36726.73 259 2004 1 122667 1055 40329.53 284 2004 2 133844 1071 43982.23 287 2004 3 139609 1107 56828.79 298 2004 4 141546 1087 63916.61 292 2005 1 144017 1088 63888.42 295 2005 2 146812 1166 67294.35 327 2005 3 157198 1326 73352.30 353 2005 4 155698 1242 81321.49 346 2006 1 157287 1378 86753.93 365 2006 2 174746 1426 96002.93 371 2006 3 162435 1259 89621.10 360 2006 4 167399 1300 92821.49 374 2007 1 168896.5 1433 99864.51 389 2007 2 175220.5 1375 101556.08 393 2007 3 185857 1501 109570.38 428 2007 4 194687 1668 115378.68 418 2008 1 207395 1801 122748.04 429 2008 2 217292.5 1966 132455.43 451 2008 3 218231 2045 132943.30 470 2008 4 228977 2133 138244.84 479 2009 1 202305 1803 122671.19 483

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 195983 1807 121448.29 452 2009 3 201983 1844 125061.41 448 2009 4 205079 1897 127169.90 443 2010 1 195920 1814 121466.65 435 2010 2 202502 1962 128743.29 436 2010 3 208010 2035 133710.58 450 2010 4 201769 1942 133865.46 452 2011 1 192250 1839 132419.49 432 2011 2 205955 1980 144811.53 454 2011 3 207538 1932 146972.06 452 2011 4 200700 1786 141879.72 449 2012 1 193272 1718 137971.28 450 2012 2 198657 1765 143554.76 454 2012 3 193303 1769 138577.75 464 2012 4 202253 1802 146145.86 456 2013 1 193026.5 1640 137976.75 451 2013 2 199836 1684 143481.96 452 2013 3 197021 1650 140678.67 458 2013 4 196341 1686 142322.87 458 2014 1 184058.5 1596 133424.58 448 2014 2 126989.5 1286 94636.64 399 2014 3 138094 1332 101866.51 363 2014 4 139635 1419 105090.38 361

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Appendix D-6a. Short Acting Stimulants: Methylphenidate, Overall Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 1274401 15022 282241.22 7291 2000 2 1269086 14914 281018.12 7205 2000 3 1116066 12749 240393.72 6194 2000 4 1235545 14273 270430.12 6723 2001 1 1248180 14650 275670.18 6852 2001 2 1240455 14855 275839.59 6750 2001 3 1132509.5 13182 243620.21 6066 2001 4 1256144 14944 276330.09 6603 2002 1 1267947 14883 279382.35 6620 2002 2 1287258 14999 283999.91 6709 2002 3 1200487 13759 258009.72 6123 2002 4 1292116 15274 283292.43 6535 2003 1 1329948 15703 293817.55 6798 2003 2 1375199 15793 301713.91 6942 2003 3 1260281.5 14296 271281.70 6350 2003 4 1320769.5 15430 291054.76 6568 2004 1 1347336.5 15849 299078.63 6761 2004 2 1347288.5 15925 299580.41 6690 2004 3 1257793 14773 276467.20 6233 2004 4 1323930 15439 293603.77 6467 2005 1 1335505 15463 295963.96 6613 2005 2 1362434 16091 303426.43 6665 2005 3 1261899.5 14763 276100.23 6143 2005 4 1332873 16220 298352.63 6545 2006 1 1352274 16657 304760.88 6560 2006 2 1341482 16626 302045.72 6536 2006 3 1233248 15319 273128.43 6026 2006 4 1282320 16029 277529.34 6215 2007 1 1296563 16299 269128.73 6228 2007 2 1322766.7 16812 257478.76 6291 2007 3 1259514.2 16490 243253.99 5948 2007 4 1336126.6 17610 261659.61 6304 2008 1 1322662.8 17314 258585.35 6274 2008 2 1310393.5 17664 259468.54 6222 2008 3 1288824.2 17356 249548.19 6005 2008 4 1351744.5 17933 263948.50 6225 2009 1 1379130.9 18246 270080.46 6473

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 1334567 17807 261579.83 6156 2009 3 1179250.4 16531 230345.23 5375 2009 4 1181697.4 16954 235337.38 5337 2010 1 1142663.3 16645 230662.55 5245 2010 2 1168879.5 16879 234619.03 5318 2010 3 1101229.5 16060 195018.04 4935 2010 4 1115943.5 16437 190470.40 4981 2011 1 1099857.4 16775 192982.11 4974 2011 2 1142461.2 17605 205098.64 5057 2011 3 1083923.5 16604 189166.82 4789 2011 4 1095776 17076 196251.75 4783 2012 1 1041883 16364 189106.24 4681 2012 2 1093060.2 16774 198698.14 4776 2012 3 1043049.4 16121 187092.64 4550 2012 4 1069124.5 16610 194109.27 4589 2013 1 1047049.4 16265 191836.20 4578 2013 2 1058973.3 17073 202370.25 4675 2013 3 1028543 17053 199741.05 4560 2013 4 1040779.2 17154 207464.18 4545 2014 1 764241.4 14208 223904.52 4134 2014 2 856190.5 15224 178827.80 4046 2014 3 884619 15619 176971.96 4086 2014 4 911080.2 15849 183220.75 4142

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Appendix D-6b. Short Acting Stimulants: Methylphenidate, Age < 18 Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 920369 10946 206072.88 5702 2000 2 890648 10614 200056.71 5594 2000 3 735860 8176 162897.28 4538 2000 4 842458 9626 188041.27 5071 2001 1 859050 9856 191817.33 5182 2001 2 838281 9590 187340.90 5013 2001 3 713927 7782 156639.64 4335 2001 4 832256 9259 183657.13 4789 2002 1 840297 9230 185218.29 4856 2002 2 843874 9333 186838.67 4894 2002 3 757896 7909 164555.25 4330 2002 4 838275 9104 184210.75 4689 2003 1 883847 9601 194241.77 4919 2003 2 884246.5 9461 193509.37 4904 2003 3 769682.5 7975 167510.26 4370 2003 4 819917 8902 181122.75 4588 2004 1 850022 9317 188258.14 4758 2004 2 832715 9098 184630.25 4631 2004 3 733204 7742 161832.35 4096 2004 4 786037 8456 174132.72 4313 2005 1 797562.5 8604 176569.37 4406 2005 2 785732.5 8629 174968.12 4328 2005 3 677410.5 7228 149977.19 3804 2005 4 735003.5 8141 164244.01 4108 2006 1 752596 8283 167608.86 4170 2006 2 748273.5 8179 165846.51 4107 2006 3 659120 7071 145821.49 3645 2006 4 684265 7574 146114.88 3782 2007 1 695992.5 7666 141310.79 3769 2007 2 695972.2 7682 131756.53 3722 2007 3 624811.8 6752 117957.23 3339 2007 4 679070 7513 128609.41 3603 2008 1 663879.2 7324 125536.28 3522 2008 2 638907 7188 121118.67 3459 2008 3 591504.7 6436 111073.34 3132 2008 4 623629.5 7005 118009.17 3305 2009 1 637605.5 7170 120574.74 3420

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 562070 6289 105933.68 3019 2009 3 420573 4696 78867.88 2295 2009 4 399007 4610 75629.59 2196 2010 1 378528.5 4397 72275.75 2077 2010 2 365653.5 4332 69951.73 2036 2010 3 307932 3576 51229.91 1709 2010 4 319832.5 3812 50865.45 1755 2011 1 307028 3643 49005.25 1715 2011 2 310779.5 3798 50618.56 1712 2011 3 260063.5 3152 42079.83 1463 2011 4 272386 3268 43928.14 1497 2012 1 251301.5 3154 41563.10 1452 2012 2 256427 3256 42914.32 1439 2012 3 222165 2780 36927.32 1262 2012 4 221060 2835 37351.18 1284 2013 1 222828.7 2815 37487.87 1291 2013 2 211851 2810 37536.07 1275 2013 3 192971.5 2572 35292.15 1172 2013 4 195783 2697 36531.62 1176 2014 1 143727.7 2272 41990.94 1072 2014 2 158119 2433 31612.63 1026 2014 3 153509.5 2369 29734.42 993 2014 4 159123 2564 31650.56 1046

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Appendix D-6c. Short Acting Stimulants: Methylphenidate, Age 18-25 Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 38608 356 8345.77 170 2000 2 39984 381 8902.83 168 2000 3 34929 405 8018.68 162 2000 4 38419 505 8868.73 185 2001 1 40457 502 9021.23 187 2001 2 42614 516 9460.56 192 2001 3 43939 480 9670.23 183 2001 4 49938 513 10634.45 209 2002 1 48807 510 10458.52 208 2002 2 49681 528 10756.16 211 2002 3 48967 589 10939.91 203 2002 4 51807 597 11592.83 229 2003 1 59891 650 13317.20 249 2003 2 66096 669 14548.27 271 2003 3 67332 684 14795.03 279 2003 4 69897.5 742 15290.70 288 2004 1 71850 775 15972.17 303 2004 2 74874.5 878 16973.05 331 2004 3 75943 892 17295.63 321 2004 4 81902 946 18635.77 348 2005 1 82385 1016 18795.90 375 2005 2 94235 1114 21350.93 397 2005 3 89554.5 1055 20219.49 379 2005 4 92421.5 1231 21490.66 406 2006 1 94905.5 1408 22711.88 415 2006 2 93843 1254 21920.16 397 2006 3 80932.5 1201 19460.15 367 2006 4 86738 1174 19547.50 378 2007 1 88783.5 1122 18952.60 399 2007 2 88593.5 1168 18104.79 386 2007 3 89192.5 1220 17963.51 389 2007 4 92706 1243 19185.60 400 2008 1 104053.5 1333 20856.98 446 2008 2 102678 1386 21166.37 430 2008 3 101979 1600 21936.99 435 2008 4 112876 1670 23592.13 484 2009 1 114075.5 1633 23342.76 490

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 113707 1620 23282.48 479 2009 3 108428 1715 23102.32 466 2009 4 115596 1791 25153.52 486 2010 1 111263.5 1738 24066.05 484 2010 2 116984.5 1713 24678.15 507 2010 3 113191 1642 21557.53 473 2010 4 108750.5 1873 21700.33 461 2011 1 110490 2004 22481.63 492 2011 2 115519 2017 23224.91 480 2011 3 114247 1915 22394.69 490 2011 4 111366 1851 21874.82 487 2012 1 104167 1753 20662.40 468 2012 2 101940 1847 21524.02 454 2012 3 100963 1808 21500.71 456 2012 4 99562.5 1766 20648.95 446 2013 1 99713 1629 20221.08 453 2013 2 100127 1629 20627.09 438 2013 3 94189 1725 21181.10 445 2013 4 98328.5 1832 23076.42 419 2014 1 69271.5 1442 23220.32 395 2014 2 78019 1403 17263.48 366 2014 3 77374.5 1351 16924.38 358 2014 4 76930.5 1349 16873.71 340

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Appendix D-6d. Short Acting Stimulants: Methylphenidate, Age 26-35 Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 56164 747 13180.75 252 2000 2 58236 674 13122.06 242 2000 3 61160 754 13972.09 262 2000 4 61969 730 13892.82 231 2001 1 57634 703 13137.47 231 2001 2 61597 809 14200.11 245 2001 3 66541 896 15537.79 241 2001 4 62220 891 14777.77 252 2002 1 72087 1014 17004.74 254 2002 2 71480 931 16489.30 269 2002 3 66941 925 15513.36 242 2002 4 69612 1041 16662.36 251 2003 1 68767 1097 16750.63 246 2003 2 72537 1168 17668.81 270 2003 3 78346 1208 18723.32 280 2003 4 83073 1187 19471.26 277 2004 1 82126 1220 19719.98 291 2004 2 76949 1234 18768.49 275 2004 3 74280 1172 18178.75 288 2004 4 76889 1065 18085.24 283 2005 1 74224 925 16911.98 300 2005 2 77872 1032 17920.20 306 2005 3 86251 1177 20009.11 333 2005 4 90185 1259 21343.80 364 2006 1 87552.5 1174 20529.47 336 2006 2 82508 1248 20065.24 337 2006 3 86637 1218 20347.84 350 2006 4 84934.5 1224 19563.08 363 2007 1 86068.5 1228 18917.02 350 2007 2 100077 1373 20061.45 393 2007 3 99559 1440 20437.02 379 2007 4 97968.5 1635 21043.59 405 2008 1 102052 1722 22191.97 424 2008 2 107041.5 1920 24007.97 439 2008 3 114333 2120 25895.36 462 2008 4 122803 2072 26565.53 489 2009 1 132058.5 2157 28180.62 525

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 140126 2373 30450.81 561 2009 3 138291.5 2396 30347.71 556 2009 4 135810 2734 31733.54 531 2010 1 141363 2758 32755.88 574 2010 2 140963.5 2688 32362.56 571 2010 3 145076.5 2563 29371.87 578 2010 4 138195 2610 27733.08 553 2011 1 137995 2667 28059.34 553 2011 2 149218 2959 31738.73 578 2011 3 148063 2673 29848.01 568 2011 4 142829.5 2717 29735.69 543 2012 1 151571.5 2755 30767.37 559 2012 2 161222 2869 33030.26 587 2012 3 162307.5 2958 33668.47 581 2012 4 164435 2930 33840.00 595 2013 1 167995 3006 34599.19 616 2013 2 158203 3128 35331.66 608 2013 3 155773.5 3042 35309.76 598 2013 4 151265.5 2864 33997.56 590 2014 1 119069.5 2511 37263.48 566 2014 2 135865 2960 32644.95 549 2014 3 140893 2888 32264.56 582 2014 4 137786.5 2656 30961.47 582

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Appendix D-6e. Short Acting Stimulants: Methylphenidate, Age < 36-64 Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 170454 1920 37397.64 650 2000 2 183435 2182 40406.26 663 2000 3 186397 2348 41356.35 675 2000 4 188616 2343 41487.33 684 2001 1 198095 2546 44221.24 724 2001 2 195641 2799 45337.73 729 2001 3 209955 2872 47095.38 758 2001 4 211093 3001 49137.55 759 2002 1 208636 2935 48124.03 760 2002 2 221749 2997 50866.91 775 2002 3 221503 3119 50801.44 768 2002 4 222020 3258 51247.69 756 2003 1 221507 3208 51526.69 802 2003 2 241481.5 3178 54693.60 858 2003 3 237567 3075 53002.12 812 2003 4 242469 3314 55759.99 816 2004 1 240101 3294 55218.55 827 2004 2 260581.5 3493 59382.02 870 2004 3 269675 3588 61791.18 928 2004 4 270433.5 3599 62019.28 916 2005 1 278930 3603 63523.31 951 2005 2 296754.5 3921 67790.79 1014 2005 3 294699.5 3862 66695.38 998 2005 4 300855 4009 69109.70 1001 2006 1 305335 4301 71422.51 1009 2006 2 304834.5 4385 71796.90 1042 2006 3 288280.5 4192 67619.90 1013 2006 4 302787 4401 69613.96 1048 2007 1 311500 4678 69192.49 1086 2007 2 313188.5 4905 66745.24 1122 2007 3 322948.5 5312 69500.25 1158 2007 4 330144.5 5366 71200.05 1176 2008 1 328451 5238 69593.46 1203 2008 2 340531.5 5472 72662.07 1198 2008 3 351726 5524 73455.42 1265 2008 4 361423.5 5503 75452.48 1258 2009 1 367686.4 5661 77316.92 1359

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 384411 5745 79794.93 1369 2009 3 375302 5859 78914.28 1326 2009 4 384017 5902 80025.20 1363 2010 1 378498.5 5892 79719.77 1384 2010 2 400734 6166 83686.76 1427 2010 3 397586 6229 75717.86 1405 2010 4 405568 6099 71571.13 1448 2011 1 409449.4 6605 75447.87 1486 2011 2 423906 6903 79762.52 1504 2011 3 411228.5 6817 77295.54 1472 2011 4 410958.5 7045 80064.02 1445 2012 1 397094 6664 76633.87 1443 2012 2 413117.5 6516 78878.69 1452 2012 3 407434.5 6343 77074.46 1425 2012 4 414410.5 6619 79871.52 1396 2013 1 409441 6558 78778.22 1423 2013 2 423400.5 6936 84010.32 1482 2013 3 423107.9 7129 86710.99 1477 2013 4 416300.5 7118 87907.00 1482 2014 1 307143.5 5764 93747.00 1342 2014 2 332597 6013 74091.85 1279 2014 3 362843 6580 78196.38 1314 2014 4 375144.5 6716 80230.16 1334

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Appendix D-6f. Short Acting Stimulants: Methylphenidate, Age 65+ Year Quarter Total number Total number Total cost ($) Total units prescriptions number users 2000 1 88806 1053 17244.18 517 2000 2 96783 1063 18530.26 538 2000 3 97720 1066 14149.32 557 2000 4 104083 1069 18139.97 552 2001 1 92944 1043 17472.91 528 2001 2 102322 1141 19500.29 571 2001 3 98147.5 1152 14677.17 549 2001 4 100637 1280 18123.19 594 2002 1 98120 1194 18576.77 542 2002 2 100474 1210 19048.87 560 2002 3 105180 1217 16199.76 580 2002 4 110402 1274 19578.80 610 2003 1 95936 1147 17981.26 582 2003 2 110838 1317 21293.86 639 2003 3 107354 1354 17250.97 609 2003 4 105413 1285 19410.06 599 2004 1 103237.5 1243 19909.79 582 2004 2 102168.5 1222 19826.60 583 2004 3 104691 1379 17369.29 600 2004 4 108668.5 1373 20730.76 607 2005 1 102403.5 1315 20163.40 581 2005 2 107840 1395 21396.39 620 2005 3 113984 1441 19199.06 629 2005 4 114408 1580 22164.46 666 2006 1 111885 1491 22488.16 630 2006 2 112023 1560 22416.91 653 2006 3 118278 1637 19879.05 651 2006 4 123595.5 1656 22689.92 644 2007 1 114218.5 1605 20755.83 624 2007 2 124935.5 1684 20810.75 668 2007 3 123002.4 1766 17395.98 683 2007 4 136237.6 1853 21620.96 720 2008 1 124227.1 1697 20406.66 679 2008 2 121235.5 1698 20513.46 696 2008 3 129281.5 1676 17187.08 711 2008 4 131012.5 1683 20329.19 689 2009 1 127705 1625 20665.42 679

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Year Quarter Total number Total number Total cost ($) Total units prescriptions number users

2009 2 134253 1780 22117.93 728 2009 3 136655.9 1865 19113.04 732 2009 4 147267.4 1917 22795.53 761 2010 1 133009.8 1860 21845.10 726 2010 2 144544 1980 23939.83 777 2010 3 137444 2050 17140.87 770 2010 4 143597.5 2043 18600.41 764 2011 1 134895 1856 17988.02 728 2011 2 143038.7 1928 19753.92 783 2011 3 150321.5 2047 17548.75 796 2011 4 158236 2195 20649.08 811 2012 1 137749 2038 19479.50 759 2012 2 160353.7 2286 22350.85 844 2012 3 150179.4 2232 17921.68 826 2012 4 169656.5 2460 22397.62 868 2013 1 147071.7 2257 20749.84 795 2013 2 165391.8 2570 24865.11 872 2013 3 162501.1 2585 21247.05 868 2013 4 179101.7 2643 25951.58 878 2014 1 125029.2 2219 27682.78 759 2014 2 151590.5 2415 23214.89 826 2014 3 149999 2431 19852.22 839 2014 4 162095.7 2564 23504.85 840

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Appendix D-7a. Non Stimulant: Atomoxetine, Overall Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2005 4 448 13 1874.51 13 2006 1 4138 107 18012.20 46 2006 2 8545 194 36897.28 90 2006 3 11952 296 52573.50 108 2006 4 * * * * 2007 1 * * * * 2007 2 * * * * 2007 3 * * * * 2007 4 * * * * 2008 1 24100 691 107875.68 212 2008 2 * * * * 2008 3 28178 800 124748.44 244 2008 4 32459 949 144460.63 259 2009 1 * * * * 2009 2 * * * * 2009 3 * * * * 2009 4 * * * * 2010 1 * * * * 2010 2 30601 868 126242.07 248 2010 3 * * * * 2010 4 * * * * 2011 1 * * * * 2011 2 * * * * 2011 3 * * * * 2011 4 * * * * 2012 1 * * * * 2012 2 * * * * 2012 3 * * * * 2012 4 * * * * 2013 1 39586 1481 149696.15 323 2013 2 * * * * 2013 3 * * * * 2013 4 * * * * 2014 1 * * * * 2014 2 * * * * 2014 3 * * * * 2014 4 * * * *

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Appendix D-7b. Non Stimulant: Atomoxetine, Age < 18 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2005 4 448 13 1874.51 13 2006 1 3585 97 15547.98 40 2006 2 7635 169 33031.24 79 2006 3 9744 223 42841.64 92 2006 4 11600 280 52104.68 110 2007 1 12601 300 56677.78 126 2007 2 14570 313 65230.06 136 2007 3 16157 360 72399.46 152 2007 4 19981 477 88741.30 168 2008 1 19580 507 87075.60 179 2008 2 21083 564 93844.76 190 2008 3 22833 593 101005.11 203 2008 4 24885 635 110256.72 208 2009 1 24694 609 107545.37 225 2009 2 24703 622 101209.76 219 2009 3 22005 551 89205.27 192 2009 4 22152 522 89537.46 191 2010 1 21229 515 86075.72 190 2010 2 21291 537 86619.11 177 2010 3 17740 466 72689.03 153 2010 4 18090 471 75686.24 157 2011 1 18712 492 76949.85 174 2011 2 21286 577 85979.11 206 2011 3 22607 621 86623.82 204 2011 4 21910 608 83078.08 198 2012 1 20859 591 80825.48 208 2012 2 22223 621 83766.74 215 2012 3 22127 650 82685.42 212 2012 4 24553 726 92847.54 217 2013 1 23280 697 88401.32 207 2013 2 23440 698 89976.04 216 2013 3 24854 751 96426.62 231 2013 4 26026 773 99502.32 243 2014 1 26266 760 99441.86 241 2014 2 26032 739 100036.50 229 2014 3 25406 749 97502.28 222 2014 4 24848 744 95985.22 219

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Appendix D-7c. Non Stimulant: Atomoxetine, Age 18-25 Year Quarter Total number Total number Total cost ($) Total number units prescriptions users 2005 4 . 0 . 0 2006 1 * ≤5 * ≤5

2006 2 578 16 2603.10 6 2006 3 984 37 4397.42 7 2006 4 1159 52 5589.57 9

2007 1 1007 66 4973.09 8 2007 2 1774 86 8377.62 12 2007 3 1391 65 6560.90 11

2007 4 2017 78 9409.44 14 2008 1 2249 79 10170.75 16 2008 2 3378 68 15193.79 20 2008 3 3053 80 13604.77 20 2008 4 4240 97 18641.10 25 2009 1 3459 111 15134.18 31

2009 2 4952 148 21522.17 36 2009 3 4161 140 17443.08 35 2009 4 4781 138 20567.28 38

2010 1 4526 130 19370.98 37 2010 2 4762 133 19516.34 36 2010 3 4699 131 19064.20 36

2010 4 3948 131 16340.37 31 2011 1 5121 161 20966.71 41 2011 2 5808 232 22848.88 42

2011 3 5908 254 21847.07 40 2011 4 6251 265 21856.48 40 2012 1 5418 249 19641.11 40

2012 2 7546 273 26852.69 52 2012 3 6936 317 26517.87 53 2012 4 7688 350 28695.98 55

2013 1 7163 316 25521.90 49 2013 2 8108 359 30652.76 58 2013 3 8042 357 30376.76 60

2013 4 8092 388 32157.60 63 2014 1 7613 380 29869.61 61 2014 2 7792 401 29682.32 58 2014 3 8662 376 32326.94 62 2014 4 7200 329 28081.60 58

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Appendix D-7d. Non Stimulant: Atomoxetine, Age 26-35 Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2005 4 . 0 . 0 2006 1 * ≤5 * ≤5 2006 2 * ≤5 * ≤5 2006 3 * * * ≤5 2006 4 * * * ≤5 2007 1 712 20 2804.73 6 2007 2 1112 25 4522.25 7 2007 3 1326 58 6085.11 8 2007 4 1414 78 6718.15 8 2008 1 1262 74 6008.79 9 2008 2 1630 104 7813.82 10 2008 3 1387 99 6420.11 12 2008 4 2090 179 9891.95 16 2009 1 1446 171 7194.19 14 2009 2 1194 78 5412.96 11 2009 3 1317 76 5442.32 14 2009 4 1390 68 6246.99 14 2010 1 2105 107 9184.19 17 2010 2 1975 114 8745.73 18 2010 3 2074 111 9284.27 17 2010 4 2154 120 9752.60 17 2011 1 2486 131 11068.84 20 2011 2 2238 117 10110.01 17 2011 3 2109 127 9338.34 17 2011 4 2136 103 8122.71 17 2012 1 2286 98 8753.22 20 2012 2 2263 90 9421.55 17 2012 3 2369 85 8230.74 20 2012 4 2304 104 8036.62 20 2013 1 3393 134 13035.37 25 2013 2 2829 134 11267.29 24 2013 3 3304 133 12282.15 28 2013 4 3858 193 14542.45 32 2014 1 4484 259 17365.56 40 2014 2 4555 198 18478.29 36 2014 3 4341 166 16863.86 41 2014 4 3983 159 15493.77 37

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Appendix D-7e. Non Stimulant: Atomoxetine, Age < 36-64 Year Quarter Total number Total number Total cost ($) Total number units prescriptions users 2005 4 . 0 . 0 2006 1 * ≤5 * ≤5 2006 2 * * * ≤5 2006 3 * * * ≤5 2006 4 473 12 2050.87 6 2007 1 769 21 3608.14 7 2007 2 950 20 4375.14 7 2007 3 700 19 3226.12 7 2007 4 807 25 3767.03 6 2008 1 1009 31 4620.54 8 2008 2 1155 32 5106.02 8 2008 3 905 28 3718.45 9 2008 4 1244 38 5670.86 10 2009 1 1661 106 7687.55 14 2009 2 1996 151 9356.40 14 2009 3 1864 70 8057.44 16 2009 4 2381 79 10528.37 16 2010 1 2404 77 10552.30 17 2010 2 2573 84 11360.89 17 2010 3 3070 108 13362.90 21 2010 4 3477 126 15051.55 23 2011 1 2844 97 12118.35 24 2011 2 3244 128 13757.47 28 2011 3 4167 155 17159.65 32 2011 4 3384 153 14139.11 25 2012 1 3833 161 15684.57 29

2012 2 4573 190 17201.62 29 2012 3 4592 193 17083.07 32 2012 4 4632 273 18161.50 32

2013 1 4730 324 18446.17 36 2013 2 5700 357 23360.70 41 2013 3 5275 354 21607.87 38

2013 4 5368 342 21924.38 45 2014 1 5324 329 20977.66 46 2014 2 5280 383 21216.77 42

2014 3 5672 399 22036.89 47 2014 4 5708 471 22846.02 47

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Appendix D-7f. Non Stimulant: Atomoxetine, Age 65+ Year Quarter Total Total number Total cost ($) Total number prescriptions number units users 2005 4 . 0 . 0 2006 1 . 0 . 0 2006 2 . 0 . 0 2006 3 . 0 . 0 2006 4 . 0 . 0 2007 1 * * * ≤5 2007 2 * ≤5 * ≤5 2007 3 * ≤5 * ≤5 2007 4 * ≤5 * ≤5 2008 1 . 0 . 0 2008 2 * ≤5 * ≤5 2008 3 . 0 . 0 2008 4 . 0 . 0 2009 1 * ≤5 * ≤5 2009 2 * ≤5 * ≤5 2009 3 * ≤5 * ≤5 2009 4 * ≤5 * ≤5 2010 1 * ≤5 * ≤5 2010 2 . 0 . 0 2010 3 * ≤5 * ≤5 2010 4 * ≤5 * ≤5 2011 1 * ≤5 * ≤5 2011 2 * ≤5 * ≤5 2011 3 * ≤5 * ≤5 2011 4 * ≤5 * ≤5 2012 1 * ≤5 * ≤5 2012 2 * * * ≤5 2012 3 * * * ≤5 2012 4 * * * ≤5 2013 1 1020 10 4291.39 6 2013 2 * * * ≤5 2013 3 * * * ≤5 2013 4 * * * ≤5 2014 1 * * * ≤5 2014 2 * * * ≤5 2014 3 * * * ≤5 2014 4 * * * ≤5

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Appendix E: Number of ADHD Medication Users by Drug Groups

Appendix E-1: Number of New Users by Drug Group, Calendar Year 2013 Drug Group Number of New Users N=5245 LONG ACTING STIMULANT AMPHETAMINE MIXED SALTS BRAND 520 LONG ACTING STIMULANT AMPHETAMINE MIXED SALTS 0 GENERIC SHORT ACTING STIMULANT DEMETHYLPHENIDATE HCL BRAND 0 LONG ACTING STIMULANT DEXTROAMPHETAMINE BRAND 207 SHORT ACTING STIMULANT DEXTROAMPHETAMINE BRAND 231 LONG ACTING STIMULANT LISDEXAMFETAMINE BRAND 906 LONG ACTING STIMULANT METHYLPHENIDATE BRAND 995 LONG ACTING STIMULANT METHYLPHENIDATE GENERIC 1135 SHORT ACTING STIMULANT METHYLPHENIDATE GENERIC 1130 SHORT ACTING STIMULANT METHYLPHENIDATE BRAND 31 NON STIMULANT ATOMOXETINE BRAND 13 NON STIMULANT ATOMOXETINE GENERIC 22

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Appendix E-2: Number of New Dual Therapy Users by Drug Group Combination, Calendar Year 2013

Drug Group 1 Drug Group 2 Number of New Users N=55 LONG ACTING STIMULANT AMPHETAMINE MIXED SALTS BRAND LONG ACTING STIMULANT DEXTROAMPHETAMINE BRAND ≤5 LONG ACTING STIMULANT AMPHETAMINE MIXED SALTS BRAND SHORT ACTING STIMULANT DEXTROAMPHETAMINE BRAND ≤5 LONG ACTING STIMULANT AMPHETAMINE MIXED SALTS BRAND LONG ACTING STIMULANT METHYLPHENIDATE GENERIC ≤5 LONG ACTING STIMULANT AMPHETAMINE MIXED SALTS BRAND SHORT ACTING STIMULANT METHYLPHENIDATE GENERIC ≤5 LONG ACTING STIMULANT DEXTROAMPHETAMINE BRAND SHORT ACTING STIMULANT DEXTROAMPHETAMINE BRAND ≤5 LONG ACTING STIMULANT DEXTROAMPHETAMINE BRAND SHORT ACTING STIMULANT METHYLPHENIDATE GENERIC ≤5 SHORT ACTING STIMULANT DEXTROAMPHETAMINE BRAND LONG ACTING STIMULANT LISDEXAMFETAMINE BRAND ≤5 SHORT ACTING STIMULANT DEXTROAMPHETAMINE BRAND LONG ACTING STIMULANT METHYLPHENIDATE BRAND ≤5 SHORT ACTING STIMULANT DEXTROAMPHETAMINE BRAND SHORT ACTING STIMULANT METHYLPHENIDATE GENERIC ≤5 LONG ACTING STIMULANT METHYLPHENIDATE BRAND LONG ACTING STIMULANT METHYLPHENIDATE GENERIC ≤5 LONG ACTING STIMULANT METHYLPHENIDATE BRAND SHORT ACTING STIMULANT METHYLPHENIDATE GENERIC ≤5 LONG ACTING STIMULANT METHYLPHENIDATE BRAND SHORT ACTING STIMULANT METHYLPHENIDATE BRAND ≤5 LONG ACTING STIMULANT METHYLPHENIDATE GENERIC SHORT ACTING STIMULANT METHYLPHENIDATE GENERIC 28

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Appendix E-3: Number of Users by Drug Group, Calendar Year 2013

Drug Group Number of Users N=19615 LONG ACTING STIMULANT AMPHETAMINE MIXED SALTS BRAND 2293 LONG ACTING STIMULANT AMPHETAMINE MIXED SALTS GENERIC 0 SHORT ACTING STIMULANT DEMETHYLPHENIDATE HCL BRAND 0 LONG ACTING STIMULANT DEXTROAMPHETAMINE BRAND 353 SHORT ACTING STIMULANT DEXTROAMPHETAMINE BRAND 1138 LONG ACTING STIMULANT LISDEXAMFETAMINE BRAND 2496 LONG ACTING STIMULANT METHYLPHENIDATE BRAND 4224 LONG ACTING STIMULANT METHYLPHENIDATE GENERIC 4212 SHORT ACTING STIMULANT METHYLPHENIDATE GENERIC 4023 SHORT ACTING STIMULANT METHYLPHENIDATE BRAND 130 NON STIMULANT ATOMOXETINE BRAND 71 NON STIMULANT ATOMOXETINE GENERIC 71

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Appendix E-4: Number of Dual Therapy Users by Drug Group Combination, Calendar Year 2013

Drug Group 1 Drug Group 2 Drug Group 3 Number of dual therapy users N=604 LONG ACTING STIMULANT LONG ACTING STIMULANT . ≤5 AMPHETAMINE MIXED SALTS DEXTROAMPHETAMINE BRAND BRAND LONG ACTING STIMULANT SHORT ACTING STIMULANT . 43 AMPHETAMINE MIXED SALTS DEXTROAMPHETAMINE BRAND BRAND LONG ACTING STIMULANT LONG ACTING STIMULANT . ≤5 AMPHETAMINE MIXED SALTS LISDEXAMFETAMINE BRAND BRAND LONG ACTING STIMULANT LONG ACTING STIMULANT . ≤5 AMPHETAMINE MIXED SALTS METHYLPHENIDATE BRAND BRAND LONG ACTING STIMULANT LONG ACTING STIMULANT . ≤5 AMPHETAMINE MIXED SALTS METHYLPHENIDATE GENERIC BRAND LONG ACTING STIMULANT SHORT ACTING STIMULANT . 10 AMPHETAMINE MIXED SALTS METHYLPHENIDATE GENERIC BRAND LONG ACTING STIMULANT SHORT ACTING STIMULANT . 18 DEXTROAMPHETAMINE BRAND DEXTROAMPHETAMINE BRAND LONG ACTING STIMULANT LONG ACTING STIMULANT . ≤5 DEXTROAMPHETAMINE BRAND LISDEXAMFETAMINE BRAND LONG ACTING STIMULANT SHORT ACTING STIMULANT . ≤5

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Drug Group 1 Drug Group 2 Drug Group 3 Number of dual therapy users DEXTROAMPHETAMINE BRAND METHYLPHENIDATE GENERIC SHORT ACTING STIMULANT LONG ACTING STIMULANT . 12 DEXTROAMPHETAMINE BRAND LISDEXAMFETAMINE BRAND SHORT ACTING STIMULANT LONG ACTING STIMULANT . ≤5 DEXTROAMPHETAMINE BRAND METHYLPHENIDATE BRAND

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Drug Group 1 Drug Group 2 Drug Group 3 Number of dual therapy users SHORT ACTING STIMULANT LONG ACTING STIMULANT . ≤5 DEXTROAMPHETAMINE BRAND METHYLPHENIDATE GENERIC SHORT ACTING STIMULANT LONG ACTING STIMULANT SHORT ACTING STIMULANT ≤5 DEXTROAMPHETAMINE BRAND METHYLPHENIDATE GENERIC METHYLPHENIDATE GENERIC SHORT ACTING STIMULANT SHORT ACTING STIMULANT . 8 DEXTROAMPHETAMINE BRAND METHYLPHENIDATE GENERIC LONG ACTING STIMULANT LONG ACTING STIMULANT . ≤5 LISDEXAMFETAMINE BRAND METHYLPHENIDATE BRAND LONG ACTING STIMULANT LONG ACTING STIMULANT . ≤5 LISDEXAMFETAMINE BRAND METHYLPHENIDATE GENERIC LONG ACTING STIMULANT LONG ACTING STIMULANT SHORT ACTING STIMULANT ≤5 LISDEXAMFETAMINE BRAND METHYLPHENIDATE GENERIC METHYLPHENIDATE GENERIC LONG ACTING STIMULANT SHORT ACTING STIMULANT . 6 LISDEXAMFETAMINE BRAND METHYLPHENIDATE GENERIC LONG ACTING STIMULANT NON STIMULANT ATOMOXETINE . ≤5 LISDEXAMFETAMINE BRAND BRAND LONG ACTING STIMULANT NON STIMULANT ATOMOXETINE . ≤5 LISDEXAMFETAMINE BRAND GENERIC LONG ACTING STIMULANT LONG ACTING STIMULANT . 27 METHYLPHENIDATE BRAND METHYLPHENIDATE GENERIC LONG ACTING STIMULANT LONG ACTING STIMULANT SHORT ACTING STIMULANT ≤5 METHYLPHENIDATE BRAND METHYLPHENIDATE GENERIC METHYLPHENIDATE GENERIC LONG ACTING STIMULANT SHORT ACTING STIMULANT . 99 METHYLPHENIDATE BRAND METHYLPHENIDATE GENERIC LONG ACTING STIMULANT SHORT ACTING STIMULANT . 30 METHYLPHENIDATE BRAND METHYLPHENIDATE BRAND

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Drug Group 1 Drug Group 2 Drug Group 3 Number of dual therapy users LONG ACTING STIMULANT NON STIMULANT ATOMOXETINE . ≤5 METHYLPHENIDATE BRAND BRAND LONG ACTING STIMULANT NON STIMULANT ATOMOXETINE . ≤5 METHYLPHENIDATE BRAND GENERIC

Drug Group 1 Drug Group 2 Drug Group 3 Number of dual therapy users LONG ACTING STIMULANT SHORT ACTING STIMULANT . 300 METHYLPHENIDATE GENERIC METHYLPHENIDATE GENERIC LONG ACTING STIMULANT SHORT ACTING STIMULANT . ≤5 METHYLPHENIDATE GENERIC METHYLPHENIDATE BRAND LONG ACTING STIMULANT NON STIMULANT ATOMOXETINE . ≤5 METHYLPHENIDATE GENERIC BRAND LONG ACTING STIMULANT NON STIMULANT ATOMOXETINE . ≤5 METHYLPHENIDATE GENERIC GENERIC SHORT ACTING STIMULANT NON STIMULANT ATOMOXETINE . ≤5 METHYLPHENIDATE GENERIC BRAND NON STIMULANT ATOMOXETINE NON STIMULANT ATOMOXETINE . ≤5 BRAND GENERIC

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Appendix F: Number of Users of ADHD Medications in NS and NB, 2013

Province # of Users Long-acting stimulants AMPHETAMINE MIXED SALTS DEXTROAMPHETAMINE METHYLPHENIDATE BRAND METHYLPHENIDATE LISDEXAMFETAMINE BRAND BRAND GENERIC BRAND

Nova Scotia and New 8 246 156 457 * Brunswick

Province # of Users

Short-acting stimulants

DEMETHYLPHENIDATE HCL DEXTROAMPHETAMINE METHYLPHENIDATE METHYLPHENIDATE BRAND BRAND GENERIC BRAND

Nova Scotia and New 0 56 548 15 Brunswick

Province # of Users

Non-stimulants

ATOMOXETINE BRAND ATOMOXETINE GENERIC

Nova Scotia and New 0 8 Brunswick Note: Data sourced from CIHI

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