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Association of Antidepressant Medications with Incident Type 2 Diabetes Among Medicaid-Insured Youth

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Association of Antidepressant Medications with Incident Type 2 Diabetes Among Medicaid-Insured Youth Supplementary Online Content Burcu M, Zito JM, Safer DJ, et al. Association of antidepressant medications with incident type 2 diabetes among Medicaid-insured youth. JAMA Pediatrics. Published online October 16, 2017. doi:10.1001/jamapediatrics.2017.2896 eTable 1. Antidepressant Subclasses eTable 2. Operational Definitions of Life-Threatening or Serious Somatic Conditions Used to Exclude Youth eTable 3. Antidepressant Dose Equivalence Conversion Factors eTable 4. Operational Definition of Study Covariates That Included a Range of Sociodemographic, Administrative, Clinical, and Other Health Care Utilization Characteristics eTable 5. Exposure to Antidepressant Subclasses During Follow-up Among Medicaid- Insured Youth (5-20 Years Old) Who Initiated Treatment With Antidepressant Medications, 2005-2009 eTable 6. Subgroup and Sensitivity Analyses Assessing the Risk of Incident Type 2 Diabetes According to Exposure to Antidepressant Subclasses Among Medicaid-Insured Youth (5-20 Years Old) Who Initiated Treatment With Antidepressant Medications, 2005-2009 eFigure. Incidence of Type 2 Diabetes Per 10,000 Person-Months According to Disease Risk Score, Expressed as Percentile Ranks eReferences This supplementary material has been provided by the authors to give readers additional information about their work. © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 eTable 1. Antidepressant Subclasses Covariate Generic name Selective serotonin reuptake citalopram, escitalopram, paroxetine, fluoxetine, inhibitor/serotonin– fluvoxamine, sertraline, desvenlafaxine, duloxetine, norepinephrine reuptake venlafaxine inhibitors (SSRI/SNRIs) Tricyclic and other related amitriptyline, amoxapine, clomipramine, desipramine, cyclic antidepressants doxepin, imipramine, maprotiline, nortriptyline, (TCAs) protriptyline, trimipramine Other antidepressants bupropion, mirtazapine, nefazodone, trazodone © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 eTable 2. Operational Definitions of Life-Threatening or Serious Somatic Conditions Used to Exclude Youth Covariate ICD-9-CMa CPT-4b procedure ICD-9-CMa diagnosis codes codes procedure codes Sickle cell disease 282.6 Cystic fibrosis 277.0 Cerebral palsy 343 Cancer 140-165, 170-172, 36640, 51720, 61517, 174-209, 230-232, 96450, 36823, 99601, 233.0, 233.2-233.7, 99602, 96420, 96421, 233.9, 234-236, 96422, 96423, 96424, 237.0-237.6, 237.9, 96425, 96405, 96406, 238, 239 96400, 96408, 96409, 96410, 96411, 96412, 96413, 96414, 50391, 96445, 96440, 96530, 95990, 95991, 96520, 96542, 96400, 96545, 96549, 50391 Human 042-044, 079.53, V08 immunodeficiency virus (HIV) infection Organ transplant 996.8, V42.0, V42.1, 32851, 32852, 32853, 33.5, 33.6, V42.6, V42.7, 32854, 33935, 33940, 37.5, 50.5, V428.1, V428.3 33945, 38240, 38241, 52.8, 55.6 47135, 47136, 48554, 48556, 50320, 50360, 50365, 50370, 50380 Dialysis/end stage 285.21, 585.5, 585.6, 36832, 36833, 36831, 39.95, 54.98 renal disease (ESRD) 996.1, 996.73, V45.1, 90918, 90919, 90920, V56.0 90921, 90922, 90923, 90924, 90925, 90989, 90993, 90937, 90999, 90935, 90937, 90945, 90947, 90980 Respiratory failure 415.0, 416, 427.50, 31500, 94656, 94657, 96.70, 96.71, 518.5, 518.81-518.84, 94005 96.72 519.0, 799.10, V44.0, V55.0 Aplastic anemia 284 Congenital immune 279.04, 279.06, 279.2 deficiencies Down syndrome 758.0 Other lethal 758.1-758.3 © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 chromosomal anomalies Fetal metabolic 270, 271.0-271.2, diseases 271.4, 271.8, 271.9 Serious 333.4, 335.20, neuromuscular 335.21, 340, 344.0, disease 344.1, 344.89, 344.9 Hospice care V66.7 99377, 99378, G0182, G0065 aICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification bCPT-4: Current Procedure Terminology © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 eTable 3. Antidepressant Dose Equivalence Conversion Factors SSRI/SNRIs Conversion Other antidepressants Conversion factor factor Fluoxetine 1 (Reference) Bupropion 0.115 Citalopram 1.111 Mirtazapine 0.786 Escitalopram 2.222 Nefazodone 0.075 Desvenlafaxine 0.400 Trazodone 0.100 Duloxetine 0.333 Fluvoxamine 0.279 Paroxetine 1.176 Sertraline 0.406 Venlafaxine 0.268 The cumulative dose was calculated in fluoxetine dosage equivalents for selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) and other antidepressants. The dose conversion factors were adapted from previously published clinical research.1,2 Note: The duration-response and cumulative dose-response analyses were not conducted for tricyclic and other related cyclic antidepressants (TCAs) due to their limited use. © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 eTable 4. Operational Definition of Study Covariates That Included a Range of Sociodemographic, Administrative, Clinical, and Other Health Care Utilization Characteristics a. Covariates for sociodemographic and administrative characteristics Covariate Operationalization Age group Age was calculated at each month of follow-up using the date of birth information and categorized into the following groups: 5-9, 10-14, 15-17, and 18-20 years of age Gender Female, male Race/ethnicity White, African American, Hispanic, and other (Asian, Native Hawaiian or other Pacific Islander, more than one race, or unknown race/ethnicity) Medicaid eligibility group Foster care, SSIa (youth with disabilities), and TANFb/CHIPc (youth eligible for Medicaid based on low family income) State Medicaid program California, Florida, Illinois, New Jersey Payment system Fee-for-service, managed care County-level population % population living in rural areas in the county of characteristicsd residence of Medicaid enrollees (categorized as <15.0%, 15.0-19.9%, 20.0-24.9%, and ≥25.0%); % youth population living under federal poverty level in the county of Medicaid enrollees (categorized as <10.0%, 10.0-24.9%, and ≥25.0%) Zip-code level population % population living in rural areas in the zip-code of characteristicsd residence of Medicaid enrollees (categorized as <10.0%, 10.0-24.9%, and ≥25.0%); % youth population living under federal poverty level in the zip-code of residence of Medicaid enrollees (categorized as <15.0%, 15.0-19.9%, 20.0-24.9%, 25.0- 29.9%, and ≥30.0%) Calendar year at cohort entry 2005, 2006, 2007, 2008, 2009 aSSI: Supplemental Security Income bTANF: Temporary Assistance for Needy Families cCHIP: Children’s Health Insurance Program dCounty- and zip-code level population characteristics were assessed by linking enrollees’ zip-code of residence information available in the Medicaid enrollment files to the publicly-available U.S. Census bureau information Note: Consistent with previous studies3-5 assessing the risk of type 2 diabetes in youth in other contexts, most of the study covariates were assessed at baseline [during the 365 day time window prior to the cohort entry date (index date)] to have an understanding of the health status, clinical complexity, and medical intensity. Time-dependent covariates included follow-up time, age, and exposure status to psychotropic medications. © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 b. Covariates for clinician-reported psychiatric diagnoses Covariate ICD-9-CMa diagnosis codes Schizophrenia/other 295, 297, 298 psychoses Pervasive developmental 299, 317-319 disorder/intellectual disability Tic disorders 307.2 Bipolar disorder 296.0, 296.1, 296.4-296.7, 296.80, 296.89, 301.13 Disruptive behavior 312.0-312.4, 312.81, 312.82, 312.89, 312.9, 313.81 disorders Attention- 314 deficit/hyperactivity disorder Depressive disorders 293.83, 296.2, 296.3, 296.9, 298.0, 300.4, 311 Anxiety disorders 293.84, 300.0, 300.2, 300.3, 308.3, 309.21, 309.81, 313.0, 313.2, 313.89 Adjustment disorder 308.0-308.2, 308.4, 308.9, 309.0-309.4, 309.82, 309.83, 309.89, 309.9 Communication and 307.0, 307.9, 315.0-315.2, 315.31, 315.32, 315.39, 315.9 learning disorder Personality disorder 301 (except 301.13) Somatoform spectrum 300.1, 300.5, 300.7, 300.8, 306, 307.8 disorders Sleep disorders of 307.4 nonorganic origin Eating disorders 307.1, 307.5 Alcohol abuse 291, 303, 305.0, V1.13 Other substance abuse 292, 304, 305 (except 305.0, 305.1) Other psychiatric V40, V66.3, V67.3, 290-319 (except codes listed above) disorders aICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification © 2017 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 c. Other psychotropic medication groups expressed as time-dependent covariates (current, former, or nonuse) Covariate Generic name Atypical antipsychotics aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone Conventional antipsychotics chlorpromazine, fluphenazine, haloperidol, loxapine, molindone, perphenazine, pimozide, thioridazine, thiothixene, trifluoperazine, mesoridazine, perphenazine Stimulants methylphenidate, dexmethylphenidate, amphetamine salts, dextroamphetamine, lisdexamfetamine, pemoline Central alpha agonists clonidine, guanfacine Other ADHD medication atomoxetine Anxiolytic/hypnotics alprazolam, bromazepam, buspirone, chloral hydrate, chlordiazepoxide, clonazepam, clorazepate, cloxazalam, diazepam, estazolam,
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