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Options and more Options: Psychopharmacology for Behavioral Health Concerns Peter F. Bidey, DO, MSEd, FACOFP Vice Chair and Assistant Professor, Department of Family Medicine Philadelphia College of Osteopathic Medicine

Prepared with Assistance by Deana M. Bidey, DO Child, Adolescent, and Adult Psychiatrist Faculty Disclosure

It is the policy of the Intensive Osteopathic Update (IOU) organizers that all individuals in a position to control content disclose any relationships with commercial interests upon nomination/invitation of participation. Disclosure documents are reviewed for potential conflict of interest (COI), and if identified, conflicts are resolved prior to confirmation of participation. Only those participants who had no conflict of interest or who agreed to an identified resolution process prior to their participation were involved in this CME activity.

All faculty in a position to control content for this session have indicated they have no relevant financial relationships to disclose.

The content of this material/presentation in this CME activity will not include discussion of unapproved or investigational uses of products or devices. Outline – The Usual Suspects

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• ADHD Statistics

• Primary care offices provide about half of all mental health care for common psychiatric disorders such as anxiety, ADHD, depression, behavioral problems, and substance use. • Adults with serious mental illness and substance use disorders also have higher rates of chronic physical illnesses and die earlier, often by 13-30 years, than the general population. • When a referral is made to a mental health provider, only about 50% of patients follow through with making an appointment. • About half of all mental health disorders begin by the age of 14y/o, therefore most children with mental health conditions are first treated in the primary care setting instead of a specialized mental health setting. Keys to Remember

1. What is my first line therapy?

2. Do I have other options • Preferably Non-controlled substances • What do I have to monitor

3. Do I need Psychology?

4. Do I need Psychiatry? Case #1

Amanda is a 23y/o caucasian female who recently graduated from college with a degree in early childhood education. She is to begin her first job at a local elementary school in the fall. Over the summer, Amanda admitted to feeling fatigued, slow and sluggish during the day despite having an increase in sleep over the last few weeks. She admits to having a difficult time preparing her curriculum plan for the school year due to an inability to focus/concentrate. Her appetite has been diminished as she just “doesn’t feel hungry.” In the past, Amanda always enjoyed spending time with her friends at the lake but recently she has been more withdrawn and isolative. “I just don’t enjoy being around others right now because I don’t want to bring them down with my bad attitude.” She admits to feeling easily irritated and sometimes thinks, “people would be better off without me.” She denies self-injury but admits to sometimes hoping that she doesn’t wake up in the morning. Amanda admits to feeling this way almost everyday for several weeks now. She was reluctant to ask for help as she felt this way before during her freshman year in college when she was able to just “work through it even though my friends suggested I go talk to someone.” She seeks treatment today at the request of her parents who noticed that she has not been acting like herself recently. She was seen briefly by her PCP where she completed a PHQ9 form with a score of 18. She denies substance use or any past medical problems. She denies daily medications other than a MVI. She denies the use of birth control. Home and serum tests came back negative. Case #1

What is the suggested treatment plan for Amanda? a) These symptoms are likely secondary to her adjustment from college and her transition into her first job, she is likely to be fine and will not need further treatment following her initial assessment. b) Initiate medication management c) Begin combination medication management with intensive psychotherapy d) Admit to an inpatient psychiatric unit for safety and risk assessment Case #1

What medication would be first line in treating Amanda’s symptoms? a) Selective Reuptake Inhibitors (SNRIs) b) Selective Reuptake Inhibitors (SSRIs) c) Antipsychotics d) Mood Stabilizing Agents Case #1

After being on SSRI treatment for the past 6 weeks with appropriate dose titration and overall good tolerance/no ADRs, Amanda has shown a slight improvement in her symptoms of depression. She denies feelings of passive SI and has had a better outlook about her future. Her PHQ9 score improved as well indicating a score of 13 (original 18). She is still having difficulty with an increase in sleep as well as lack in energy and motivation to complete her school work. She recently started seeing a local psychotherapist for weekly supportive therapy and initiation of CBT. The psychotherapist has Amanda on a waitlist for a recommended psychiatrist. What would be your next step? a) Switch Amanda to another SSRI b) Switch Amanda to an SNRI c) Discuss adjunctive therapy to increase the effectiveness of current SSRI and treat residual symptoms d) Give Amanda a (ie. Ritalin/) to improve her focus/motivation/energy (Could this also be undiagnosed adult ADD?) Treatment Overview

1) Serotonin specific uptake inhibitors (SSRIs) - 1st line treatment - SSRIs that are FDA approved for depression include: (Prozac), (Paxil), (Zoloft), (Celexa), (Lexapro) - Escitalopram (Lexapro): FDA approved treatment for adolescent depression (ages 12-17y/o) - Fluoxetine (Prozac): FDA approved treatment depression in children and adolescents (ages 8-18y/o) - Note: a) Dose titration to most effective dose is often necessary; b) GI side effects are often breakthrough and are gone within 1-2 weeks after starting an SSRI; c) allow at least 4 weeks to see full therapeutic effect; d) black box warning issued for suicidal thoughts and behavior, not suicide itself. 2) Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) - (Effexor/Effexor XR) and (Cymbalta) - 2nd line treatment medications if two trials of SSRIs were ineffective in symptom control 3) Tricyclic (TCAs) - , Amitryptiline, , , Notriptyline, and - Less commonly used due to high risk with overdose and heart related effects. Antidepressant Treatment Overview

4) Monoamine Oxidase Inhibitors (MAOIs) - Isocarboxazid, , Selegiline, Tranylcypromine - (treatment of atypical depression or MDD with atypical features) 5) Other antidepressants: - Buproprion (Wellbutrin), (mainly bedtime dosing to aide in sleep), (Viibryd; serotonin modulator), (Trintellix; serotonin modulator) 6) Augmenting agents sometimes used with antidepressant therapy include: - (Abilify – FDA approved for multiple conditions in both children and adults), (Rexulti – FDA approved for treatment resistant/augmentation to antidepressant therapy and schizophrenia in adults), (Seroquel – FDA approved augment antidepressant therapy or for Bipolar depression), Lithium (more so Bipolar depression with high risk for suicide), T3 (liothyronine supplementation), and (Ritalin) Adjunct to Antidepressant therapy – Aripiprazole (Abilify)

Abilify • Second generation antipsychotic; partial agonist • FDA approved for: - Depression (adjunct) - Acute mania/mixed mania (ages > 10y/o) - Bipolar maintenance - Schizophrenia (ages > 13y/o) - Schizophrenia maintenance - related irritability in children ages 6-17y/o Aripiprazole (Abilify)

• Before starting aripiprazole (or any ): - Weigh all patients and track BMI during treatment - Obtain waist circumference, , fasting plasma glucose, and fasting lipid profile

• After starting aripiprazole (or any atypical antipsychotic): - BMI monthly for 3 months, then quarterly - blood pressure, fasting plasma glucose and fasting lipids within 3 months of treatment and then annually (earlier and more frequent for patients with diabetes or who have gained > 5% of initial weight; monitor for diabetic ketoacidosis, DKA) - patients with low WBC or hx of drug induced leukopenia/neutropenia should have a CBC monitored monthly during initial treatment, any sign of decline in WBC, aripiprazole should be discontinued (stop if absolute neutrophil count < 1,000/mm3 - Abnormal Involuntary Movement Scale (AIMS) re: risk for akathisia/extrapyramidal symptoms (EPS) as an ADR to aripiprazole treatment/use • Scale available free of charge at: https://ucedd.georgetown.edu/DDA/documents/tool_aims.pdf Aripiprazole (Abilify)

• Dosing and Use: - initial approved dose recommendation is 10-15mg/day; maximum approved dose 30mg/day (higher than 15mg/day likely for treatment of schizophrenia or bipolar illness) - dosing at 2-15mg/day is usual range as an adjunct to antidepressant therapy; increase by up to 5mg/day qweek, for slower dose titration increase by 2mg/week as to limit ADRs – discontinuation of medication/weaning should occur in a similar way - elderly and children, dosing should be started low and go slow with titration - no need for dose adjustment in renally or hepatically impaired - monitor BP in cardiac patients due to risk for orthostatic during initial dosing - pregnancy – category C risk; unknown if aripiprazole is secreted in breast milk, recommend either to discontinue drug or bottle feed - decrease dose by 50% in poor CYP2D6 metabolizers Aripiprazole (Abilify)

• Adverse Drug Reactions (ADRs): - dizziness (orthostatic hypotension, occasionally during initial dosing) - - activation (may be good for amotivation depression; decrease incident by lowering the dose or starting at a lower dose) - akathisia (internal restlessness/inability to sit still) - extrapyramidal symptoms (EPS) - nausea/vomiting - unlikely to have sedation; less likely to have weight gain (as compared to other atypical antipsychotics) Depression Nonpharmacological Treatment • Most effective treatment for depression: combination medication management with psychotherapy.

• 4 most effective and commonly used psychotherapies: 1) Cognitive Behavioral Therapy (CBT) 2) Interpersonal psychotherapy (IPT) 3) Problem-solving therapy (PST) 4) Psychodynamic Psychotherapy

• Behavioral therapy and Family therapy are also helpful in treating children and adolescents.

• Psychoeducation – clients, caregivers, and family

• Relaxation Techniques – deep breathing, mindfulness, yoga, acupuncture

• Promote awareness of stressors and regular patterns of activity and sleep (especially in individuals diagnosed with Bipolar illness) Case #2

Shelly is a 30y/o female with no prior mental health history. At 2am, she presented to the local emergency department for complaints of chest pain and shortness of breath. After 20 minutes of difficulty with breathing and the feeling of numbness/tingling in her extremities, she called her mother who drove her to the ER as she felt like she was “losing control.” She claims that these symptoms had awoken her from sleep. Medical workup, which included vitals, an EKG, bloodwork, and pulse oximetry were unremarkable. On medical history, Shelly admitted that several months ago, she and her boyfriend of 5 years had suffered a 1st trimester miscarriage. After the loss of the pregnancy, their relationship began to struggle ultimately resulting in their separation. Shelly admits that the loss of her boyfriend and baby has been difficult. She has been seeking comfort in friends and family. She admits to occasional use of but recent use has increased in the past few months. She admits to drinking a glass or two of wine at night to aide in sleep. Her only medication is an OTC MVI. She admits to always being a “worry wart” but that the “worry” has increased recently. She worries about everything, even if it’s something that she can’t control. She admits to believing that her inability to relax may have played a roll in her miscarriage. Her sleep habits have recently suffered, feeling restless, especially at night has caused her some difficulty in falling asleep. She admits to feeling sad when thinking about her losses but has been keeping busy at work and spending more time with her parents. Case #2

FDA antidepressants used to treat this disorder include: a) Zoloft, Celexa, Effexor b) Lexapro, Paxil, Effexor c) Wellbutrin, Trazodone, Paxil d) Prozac, Lexapro, Effexor Case #2

A SSRI/SNRI may take several weeks to begin to work in reducing anxiety and panic symptoms. In Shelly’s case, what could be done to aide in breakthrough anxiety until antidepressant therapy begins to take effect? a) Referral to a psychotherapist specializing in women’s health b) Begin a standing or as needed dose of a ie. Ativan/Xanax/Klonopin; continue to encourage a follow-up with a psychotherapist c) Trial low dose during the day to aide in daytime anxiety symptoms and as needed Vistaril at bedtime to reduce anxiety and promote sleep initiation; continue to encourage follow-up with a psychotherapist d) Referral to a dual diagnosis (mental health/D&A) program, as her continued anxiety could be symptoms of alcohol withdrawal Medication Treatment Overview for Anxiety Disorders Panic Disorder Phobias PTSD OCD Generalized Anxiety Disorder SSRIs SSRIs (first line) SSRIs (Zoloft, Paxil) – first SSRIs (Luvox, Paxil, SSRIs (FDA approved SNRIs Benzos (Xanax, Klonopin) line treatment Zoloft, Celexa) – Lexapro & Paxil) SNRI (Effexor) Buspar Clomipramine (most SNRI (FDA approved (Treatment Buspar (non- Tricyclic Antidepressants selective out of all tri & – Effexor) resistant) benzodiazepine ) (Tofranil, Elavil) tetracyclic drugs for Buspar TCAs (Treatment MAOIs (Nardil 40mg to MAOIs (Nardil) serotonin reuptake vs. Benzodiazepines resistant) 90mg/day) Trazodone NE reuptake) Hydroxyzine/Vistaril RIMAOIs (Aurorix) Anticonvulsants Augmentation of SSRIs Others: MAOIs, Beta receptor (, with Depakote, Lithium TCAs, antagonist ( or Depakote) or Tegretol ) or short acting Reversible monoamine Other drugs: Effexor, benzos (Ativan) for oxidase inhibitors Visken, & MAOIs (Nardil) performance anxiety (RIMAs) Buspar or Klonopin (aka Catapres) (unresponsive pts) Propranolol (aka Inderal) Adding Risperdal has helped in some cases Alternative

• Non-benzodiazepine anxiolytics: - Hydroxyzine (Atarax, Marax, Vistaril) - (Buspar)

• Attempt to avoid benzodiazepine use due to high risk for tolerance and dependency. • If patient comes to you on a benzodiazepine, discuss alternative options to treat anxiety and begin slow taper. Hydroxyzine

• Blocks histamine 1 receptors • FDA approved: - anxiety and tension associated with psychoneurosis - adjunct in organic disease states in which anxiety is manifested - pruritus due to allergic conditions - sedation following general anesthesia - anxiety withdrawal symptoms in alcoholics or patients with delirium tremens (injectable) - adjunct in pre/postoperative and pre/postpartum patients to allay anxiety, control emesis, and reduce narcotic dose (injectable) - nausea and vomiting (injectable) Hydroxyzine

• Dosing and Use: - can be used as an adjunct to SSRIs or SNRIs in treating anxiety disorders - usual dosing for anxiety: 50-100mg 4 times a day (standing or prn); lower daytime dosing to manage anxiety throughout the day; higher evening dosing to aide in sedation/sleep onset/nighttime anxiety - tablet forms (10mg, 25mg, 50mg, and 100mg); capsule forms (25mg, 50mg, 100mg) - oral dosing does not require titration; taper not necessary - elderly and children, start low and go slow with dosing (age > 6y/o = 50-100mg/day in divided doses; age < 6y/o = 50mg/day in divided doses); should not be used in elderly dementia patients; monitor for paradoxical hyperactivity in children - dose adjustment is not necessary for renally, hepatically, or cardiac impaired patients - not recommended/contraindicated in early pregnancy; may be transferred through breast milk/recommend bottle feed if on this medication - advantage: no abuse liability, dependence or withdrawal Hydroxyzine

• Adverse Drug Reactions - dry mouth - sedation (early in treatment, usually breakthrough side effect which resolves/improves with time) - tremor; rare convulsions (usually at high doses) Buspar (Buspirone)

• Anxiolytic; Binds to serotonin type 1A receptors • FDA approved - Management of anxiety disorders - Short-term treatment of symptoms of anxiety Buspar (Buspirone)

• Dosing and Use: - 20–30 mg/day - Initial 15 mg twice a day; increase in 5 mg/day increments every 2– 3 days until desired efficacy is reached; maximum dose generally 60 mg/day - Generally takes within 2–4 weeks to achieve efficacy - If it is not working within 6–8 weeks, it may require a dosage increase or it may not work at all - Buspirone is often given as an augmenting agent to SSRIs or SNRIs Buspar (Buspirone)

• Use (cont): - Use with caution in renal impairment; Not recommended for patients with severe renal impairment - Use with caution in hepatic impairment; Not recommended for patients with severe hepatic impairment - Buspirone has been used to treat hostility in patients with cardiac impairment - Elderly, start with lower doses - Safety profile in children encourages its use - Not generally recommended in pregnancy, but may be safer than some other options - Buspirone does not appear to cause dependence and shows virtually no withdrawal symptoms - less severe side effects than benzodiazepines - Buspirone generally lacks sexual dysfunction - Main Disadvantage: takes 4 weeks for results, whereas benzodiazepines have immediate effects Buspar (Buspirone)

ADRs: • Dizziness, headache, nervousness, sedation, excitement • Nausea • Restlessness Case #3

Hunter is an 11y/o male who presents to clinic with biological mother for initial assessment. Hunter has been struggling with his grades at school as he claims that he is unable to concentrate due to having a hard time paying attention. Hunter enjoys learning, especially math, but struggles with reading/written comprehension for which he gets extra supports. He currently has an individual education plan (IEP) and accommodations with extra time on reading assignments and testing which has been somewhat helpful. Despite these accommodations, Hunter continues to express difficulty with his focus as he is easily distracted by small noises or talking in the classroom. Hunter spends hours completing homework assignments that should normally take most 30 minutes to complete. Hunter admits to completing homework on time but gets points taken away due to forgetting to hand it in. He often fidgets and squirms in his seat and on occasion gets up out of his seat to “take a break” from the classroom which results in him getting into trouble. At home, his parents constantly yell about the clutter & mess in his room. He is often redirected several times as to encourage completion of his weekly chores. He often struggles with friendships as he can sometimes be overly intrusive and talkative ultimately “pushing” others away. This social rejection and continued academic struggles have caused Hunter to talk negatively about himself. Mother notes that Hunter has been like this “his whole life” as she had seen similar behaviors starting in daycare when the staff noted difficulty putting him down for naps during the day. ADHD – Medication Treatment

• Pharmacotherapy: - Stimulant Medications - Non-stimulant Medications • Psychosocial Interventions - Psychoeducation - Behavior Therapy - Behavioral parent training - Social Skills Groups - Evaluation and Treatment of Coexisting Learning Disorder - Group therapy ADHD Treatment – (FDA Approved)

• The American Academy of Pediatrics (AAP) & the Texas Children’s Medication Project recommend stimulants as the first line treatment for ADHD, particularly when no comorbidity is present. • Methylphenidate derived stimulants: blocks reuptake of dopamine (DA) & norepinephrine (NE) • derived stimulants: blocks reuptake + release of dopamine (DA) & norepinephrine (NE) ADHD Treatment – Stimulants (FDA Approved)

• At baseline, AACAP practice parameters recommend the following prior to starting stimulant medication: - Physical examination (annually) - Blood pressure (quarterly) - Pulse (quarterly) - Weight (quarterly) - Height (quarterly)

• Stimulants activate CNS with increased HR and risk for sudden cardiac death. FDA recommendation: 1) for all patients: obtain cardiac hx; perform physical exam 2) for patients with concerning cardiac hx: obtain EKG or echocardiogram before stimulant medication initiation

• Dosing – start low and go slow especially in young/preschool age children or medication naive ADHD Treatment – Non-Stimulants (use if stimulants contraindicated or not tolerated)

Selective NE Reuptake Alpha 2 Adrenergic Inhibitor Agonists (FDA approved) (FDA approved) Strattera () Clonidine ER (Kapvay) Guanfacine ER (Intuniv) Non-stimulants/Adjuncts to ADHD treatment Alpha 2 Agonists

ADHD Medication Effect Size Stimulant medications 1.0 Alpha 2 medications 0.7 Atomoxetine 0.7 Data for reference: 0.2 = small effect size, 0.5 = moderate effect size, 0.8 = large effect size.

Southammakosane, C., & Schmitz, K. (2015). Pediatric psychopharmacology for treatment of ADHD, depression, and anxiety. Pediatrics, 136(2), 351-359. Non-stimulants/ADHD treatment Atomoxetine

Atomoxetine (Strattera): • Selective norepinephrine reuptake inhibitor (NRI) • Boosts neurotransmitter norepinephrine/noradrenaline and may also increase dopamine in prefrontal cortex

FDA approved: • Attention deficit hyperactivity disorder (in adults and children ages 6 and older) Non-stimulants/ADHD treatment Atomoxetine

Dosing • Forms: Capsule 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg, 100 mg • 0.5–1.2 mg/kg per day in children up to 70 kg; 40–100 mg/day in children over 70 kg and adults • For children 70 kg or less: initial dose 0.5 mg/kg per day; after 7 days can increase to 1.2 mg/kg per day either once in the morning or divided; maximum dose 1.4 mg/kg per day or 100 mg/day, whichever is less • For children over 70 kg and adults: initial dose 40 mg/day; after 7 days can increase to 80 mg/day once in the morning or divided; after 2–4 weeks can increase to 100 mg/day if necessary; maximum daily dose 100 mg • Can be given once a day in the morning • Efficacy with once-daily dosing despite a half-life of 5 hours suggests therapeutic effects persist beyond direct pharmacologic effects, unlike stimulants whose effects are generally closely correlated with plasma drug levels Non-stimulants/ADHD treatment Atomoxetine Non-stimulants/ADHD treatment Atomoxetine

ADRs: • Fatigue, sleepiness, headache, irritability • Decreased appetite, nausea, vomiting, abdominal pain • Increased heart rate (6–9 beats/min) • Increased blood pressure (2–4 mmHg) • Priapism (rare) • Severe liver damage (rare) - Rare reports of hepatotoxicity; although causality has not been established, atomoxetine should be discontinued in patients who develop jaundice or other evidence of significant liver dysfunction – Monitor LFTs regularly (q3-6 months) with use • Hypomania and rare induction of mania • Rare activation of suicidal ideation and behavior (suicidality) • Cardiovascular adverse effects, sudden death in patients with pre-existing cardiac structural abnormalities often associated with a family history of cardiac disease Non-stimulants/ADHD treatment Atomoxetine

Special Populations • Renally impaired: dose adjustment not generally necessary • For patients with moderate liver impairment, dose should be reduced to 50% of normal dose • For patients with severe liver impairment, dose should be reduced to 25% of normal dose • In cardiac impaired, use with caution because atomoxetine can increase heart rate and blood pressure • Do not use in patients with structural cardiac abnormalities • Not recommended in pregnancy or in Non-stimulants/Adjuncts to ADHD treatment Alpha 2 Agonists

• Clonidine ER (Kapvay) • Guanfacine ER (Intuniv) Clonidine ER (Kapvay)

• Antihypertensive; centrally acting alpha 2 agonist hypotensive agent, nonstimulant for ADHD; adjunct to ADHD treatment (tics/insomnia/anxiety) • FDA Approval: - Attention deficit hyperactivity disorder (ADHD) Clonidine ER (Kapvay) • Dosing and Use - Extended-release for ADHD: 0.1–0.4 mg/day

• ADRs - Dry mouth - Dizziness, constipation, sedation - Weakness, impotence, loss of libido, insomnia, headache - Major depression - Dermatologic reactions (especially with transdermal clonidine) - Hypotension, occasional syncope - Tachycardia - Nervousness, agitation - Nausea, vomiting Guanfacine ER (Intuniv)

• Centrally acting alpha 2A agonist; antihypertensive; nonstimulant for ADHD; adjunct to ADHD treatment (tics/insomnia/anxiety/severe ) • FDA Approval: - Attention deficit hyperactivity disorder (ADHD) in children ages 6–17 (Intuniv, adjunct and monotherapy) Guanfacine ER (Intuniv) • Dosing and Use - Extended-release: initial 1 mg/day; can increase by 1 mg/week; maximum dose 4 mg/day - Doses greater than 2 mg/day are associated with increased side effects - If guanfacine is terminated abruptly, rebound may occur within 2–4 days - For extended-release formulation, do not administer with high-fat meals because this increases exposure - long term use - studies of up to 2 years in ADHD - Blood pressure should be checked regularly during treatment Guanfacine ER (Intuniv)

• Use (contd.) - Use with caution in patients with recent myocardial infarction, severe coronary insufficiency, cerebrovascular disease - Use with caution in patients at risk for hypotension, bradycardia, heart block, or syncope Guanfacine ER (Intuniv)

• ADRs - Adverse effects are dose-related and usually transient - Sedation (may improve with prolonged use), dizziness - Dry mouth, constipation, abdominal pain - Fatigue, weakness - Hypotension - Sinus bradycardia, hypotension (dose-related) - Some reports of mania and aggressive behavior in ADHD patients taking guanfacine Collaboration of Care • Addressing the whole person and his/her physical and behavioral health is essential for positive health outcomes, to reduce cost, increase quality of care, and to ultimately, save lives. • When does a patient need more emergent psychiatric care: - Suicidality - Psychotic symptoms - Diagnostic questions - Developmental problems (children/adolescents) - Management review - Psychopharmacology assessment/advice - Abnormal bereavement - Family dysfunction - Substance abuse/addiction - Signs of dementia - Sleep problems - Sexual dysfunction - Physician frustration/anger/impotence References

• Lipsitt, Don R. M.D. Tipsheet: Psychiatric Referrals and Primary Care; Psychiatric Times, October, 2013. https://www.psychiatrictimes.com/tipsheets/tipsheet-psychiatric-referrals-and-primary-care • Stahl, S. M. (2008). Essential Psychopharmacology Online. https://stahlonline.cambridge.org/prescribers_guide.jsf • American Academy of Child and Adolescent Psychiatry (2016). Practice Parameters for the Assessment and Treatment of Children and Adolescents with Depressive Disorders, Volume 46, 2007. http://www.aacap.org • National Institute of Mental Health (2016). Depression. http://www.nimh.nih.gov • National Institute of Mental Health (2016). Depression and Older Adults. http://www.nimh.nih.gov (NIHSeniorHealth.gov) • Han C, Wang SM, Lee SJ, Jun TY, Pae CU. Optimizing the Use of Aripiprazole Augmentation in the Treatment of Major Depressive Disorder: From Clinical Trials to Clinical Practice. Chonnam Med J. 2015;51(2):66–80. doi:10.4068/cmj.2015.51.2.66. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543152/ • Marcus RN, McQuade RD, Carson WH, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 2008;28(2):156–65. • Citrome L. Adjunctive aripiprazole, , or quetiapine for major depressive disorder: an analysis of number needed to treat, number needed to harm, and likelihood to be helped or harmed. Postgrad Med 2010;122(4):39–48. • Malhi GS, Tanious M. Optimal frequency of lithium administration in the treatment of bipolar disorder: clinical and dosing considerations. CNS Drugs 2011;25(4):289–98. • Bawa R, Scarff JR. : a new treatment option for bipolar depression-a review. Innov Clin Neurosci. 2015;12(1-2):21–23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382136/ • Calabrese, JR et al. Lurasidone in combination with lithium or valproate for the maintenance treatment of bipolar I disorder. Eur Neuropsychopharmacol. 2017 Sep;27(9):865-876. https://www.ncbi.nlm.nih.gov/pubmed/28689688/ • Dolder, CR et al. The effects of on sleep in patients with major depressive disorder. Ann Clin Psychiatry. 2012 Aug;24(3):215-24. https://www.ncbi.nlm.nih.gov/pubmed/22860241/ • Allison Bernknopf, PharmD, BCPS, Ferris State University, Kalamazoo, Michigan. Guanfacine (Intuniv) for Attention-Deficit/Hyperactivity Disorder. Am Fam Physician. 2011 Feb 15;83(4):468-475. https://www.aafp.org/afp/2011/0215/p468.html References

• American Academy of Child and Adolescent Psychiatry (2017). Practice Parameters for the Assessment and Treatment of Children and Adolescents with Attention Deficit/Hyperactive Disorder, Volume 46, 2007. http://www.aacap.org • Croxtall JD. Clonidine extended-release: in attention-deficit hyperactivity disorder. Paediatr Drugs 2011;13(5):329–36. • National Institute of Mental Health (NIMH). Integrated Care. https://www.nimh.nih.gov/health/topics/integrated-care/index.shtml • Raney, Lori E., M.D. Integrating Primary Care and Behavioral Health: The Role of the Psychiatrist in the Collaborative Care Model. The American Journal of Psychiatry. August 1st, 2015. https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15010017 • Brunet A, Poundja J, Tremblay J, et al. Trauma reactivation under the influence of propranolol decreases posttraumatic stress symptoms and disorders: 3 open-label trials. J Clin Psychopharmacol 2011;31(4):547–50. • Cohen’s Children’s Medical Center Northwest Health. ADHD Medication Guide. December 2017. http://www.adhdmedicationguide.com/pdf/adhd_med_guide.pdf • American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.) Arlington, VA: American Psychiatric Publishing. • Sadock, Benjamin J., Kaplan & Sadock’s Synopsis of Psychiatry Behavioral Science/Clinical Psychiatry. Philadelphia: Lippincott Williams & Wilkins, 2007. Print • Southammakosane, C., & Schmitz, K. (2015). Pediatric psychopharmacology for treatment of ADHD, depression, and anxiety. Pediatrics, 136(2), 351-359.