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.

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

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

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

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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.

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.

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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

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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, eszopiclone, flurazepam, halazepam, ketazolam, lorazepam, meprobamate, midazolam, nitrazepam, oxazepam, prazepam, quazepam, ramelteon, temazepam, triazolam, zaleplon, zolpidem Anticonvulsant-mood carbamazepine, divalproex, gabapentin, lamotrigine, stabilizers oxcarbazepine, topiramate, valproate, valproic acid Lithium lithium

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d. Covariates for metabolic conditions and related medical services

Covariate ICD-9-CMa diagnosis codes CPT-4b procedure codes Overweight/obese 278.0, 783.1, V77.8, V85.3, V85.4, V85.53, V85.54 Acanthosis nigricans 701.2 Weight management V65.3 97802, 97803 Hyperlipidemia 272.0-272.2, 272.4 Hypothyroidism 243, 244 Hypothyroid screening V77.0 84436, 84443 Hyperthyroidism 242 Other thyroid gland 240, 241, 245, 246 disorder Nutritional deficiency 260-269 Insulin 251.1, 277.7 83525 resistance/metabolic syndrome Other endocrine 240, 241, 245, 246, 253, 255, disorder 258, 259.0, 259.1 Symptoms related to 783.5, 788.42, 790.2 high blood glucose Other metabolic 270, 271, 272.3, 272.5-272.9, disorder 275.0-275.3, 277.2-277.6, 277.8, 277.9 Metabolic screening 80048, 80050, 80053, 80054 test Lipid test 80061, 82465, 83700, 83701, 83715, 83716, 83721, 84478, 83718 Glucose test V77.1 82947, 82948, 82950, 82951, 82952, 83036, 82962 aICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification bCPT-4: Current Procedure Terminology

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e. Covariates for cardiovascular conditions and related medical services

Covariate ICD-9-CMa diagnosis codes Hypertension (diagnosed) 401-405 Congenital anomalies of 745-747 heart and circulatory system Acute myocardial 410 infarction Ischemic heart disease 411-414, 429.7 Cardiac valve disease 394, 396, 424.0 (mitral) Other cardiac valve 395, 397, 424.1-424.3 disease Conduction disorder 426 Arrhythmia 427 Cardiomyopathy 425 Heart failure 428 Occlusion of cerebral 430-434, 436 arteries Transient cerebral 435 ischemia Other cerebrovascular 437, 438 disease Peripheral vascular 440.2, 440.3, 443, 444.2, 444.8, 445.0, 785.4 disease Renal insufficiency 582-588 Other cardiovascular 390-459 (except codes listed above) disease Cardiovascular symptoms 780.2, 785.0, 785.1, 785.2, 785.3, 785.50, 785.51, 785.9, 786.5 aICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification

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f. Covariates for cardiovascular medications

Covariate Generic name Angiotensin-converting- benazepril, captopril, enalapril, enalaprilat, fosinopril, enzyme (ACE) inhibitor lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril Angiotensin II Receptor candesartan, eprosartan, irbesartan, losartan, olmesartan, Blocker (ARB) telmisartan, valsartan Beta blocker acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, pindolol, propranolol, sotalol, timolol Antilipemic agent atorvastatin, cholestyramine, colesevelam, colestipol, ezetimibe, fenofibrate, fenofibrate, fenofibric acid, fluvastatin, gemfibrozil, lovastatin, niacin, niacin (inositol niacinate), omega-3 fatty acids, pravastatin, rosuvastatin, simvastatin Cardiotonic agent digoxin, milrinone Calcium channel blocker amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil Antithrombotic agents alteplase, anagrelide, cilostazol, clopidogrel, dalteparin, enoxaparin, eptifibatide, fondaparinux, heparin, ticlopidine, tinzaparin, warfarin Other cardiovascular adenosine, aliskiren, ambrisentan, amiodarone, amyl nitrite, disease medications bosentan, diazoxide, dipyridamole, disopyramide, dofetilide, doxazosin, eplerenone, epoprostenol, flecainide, hydralazine, iloprost, isosorbide, isoxsuprine, lidocaine, mecamylamine, mexiletine, minoxidil, nesiritide, nitroglycerin, papaverine, prazosin, procainamide, propafenone, quinidine, ranolazine, reserpine, spironolactone, terazosin, treprostinil

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g. Covariates for reproductive, obstetric and gynecologic conditions and related medical services

Covariate ICD-9-CMa CPT-4b ICD-9-CMa diagnosis codes procedure codes procedure codes Pregnancy screening V72.4 84702, 81025 Sterilization V25.2, V26.51 58565, 58600, 66.21, 66.22, 66.29, 58605, 58611, 66.31, 66.32, 66.39 58615, 58670, 58671, S2255 Contraceptive V25.0, V25.1, management V25.4, V25.5, V25.8, V25.9 Absence of 626.0 menstruation Scanty or infrequent 626.1 menstruation Excessive or frequent 626.2 menstruation Irregular menstrual 626.4 cycle Other disorders of 626.3, 626.8, 626.9 menstruation/abnormal bleeding Cervical cancer V76.2, V72.32 88141, 88142, screening 88143, 88147, 88148, 88150, 88152, 88153, 88154, 88155, 88164, 88165, 88166, 88167, 88174, 88175 Cervical dysplasia 622.1 Ovarian cysts 620.0, 620.2 aICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification bCPT-4: Current Procedure Terminology

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h. Covariates for contraceptive medications and devices

Covariate Generic name Oral contraceptive desogestrel, drospirenone, ethinyl estradiol, estradiol, ethynodiol d-ethinyl estradiol, ethynodiol diacetate, levonorgestrel, mestranol, norethindrone, norgestimate, norgestrel Other contraceptive diaphragm (arc-spring), diaphragm (coil spring), estradiol, norethindrone, ethinyl estradiol, etonogestrel, intra-uterine device (iud), levonorgestrel, nonoxynol 9, norelgestromin, octoxynol 9 Medroxyprogesterone medroxyprogesterone

i. Covariates for respiratory/allergy conditions and related medical services

Covariate ICD-9-CMa CPT-4b diagnosis codes procedure codes Asthma 493 Bronchitis 490, 491 Other respiratory disease 492, 494-496 and allied conditions Smoking (diagnosed) 305.1, 649.0, 989.84, V15.82 99406, 99407 Sleep apnea 327.2, 780.51, 780.53, 94660 780.57 Anaphylactic 995.0, 995.27, 995.29, 995.3, reaction/allergy 995.6 Asphyxia, shortness of 786.05, 786.07, 799.0 breath, wheezing Other respiratory 786.00-786.04, 786.06, symptoms 786.09, 786.1-786.4, 786.8, 786.9 aICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification bCPT-4: Current Procedure Terminology

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j. Covariates for respiratory/allergy medications

Covariate Generic name Antihistamine acrivastine, azatadine, brompheniramine, carbinoxamine, cetirizine, chlorphenir, chlorpheniramine, clemastine, cyproheptadine, desloratadine, dexbrompheniramine, dexchlorpheniramine, diphenhydramine, doxylamine, fexofenadine, levocetirizine, loratadine, pheniramine, phenindamine, phenyltoloxamine, pyrilamine, phenyltoloxamine, triprolidine Hydroxyzine hydroxyzine Inhaled corticosteroid beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, mometasone, triamcinolone Other corticosteroid hydrocortisone, methylprednisolone, prednisolone, prednisone Bronchodilator albuterol, arformoterol, formoterol, levalbuterol, metaproterenol, pirbuterol, salmeterol, terbutaline Other asthma medications ipratropium, tiotropium, omalizumab, cromolyn, montelukast, nedocromil, zafirlukast, zileuton

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k. Covariates for other conditions and related medical services

Covariate ICD-9-CMa CPT-4b ICD-9-CMa diagnosis codes procedure codes procedure codes Intentional injury E950-E959, E980- E989 Maltreatment 994.2, 994.3, 995.5, (abuse, neglect, V15.4, V61.21, V71.5, assault) V71.81, E904.0- E904.2, E960.1, E961- E968 Psychotherapy 90810, 90811, 90812, 90813, 90814, 90815, 90823, 90824, 90825, 90826, 90827, 90828, 90829, 90832, 90834, 90833, 90836, 90837, 90838, 90839, 90840, 90845, 90846, 90847, 90849, 90853, 90857 Crohn's disease 555.0-555.2, 555.9 Ulcerative colitis 556.0-556.6, 556.8, 556.9 Other upper 530-538, 578 43200,43202, 43216, 45.11-45.14, gastrointestinal 43217,43220,43227, 45.16 disorders 43234,43239,43241, 43246,43247,43250, 43251,43255 Chronic liver 571, 572.8 disease Other liver disorders 570, 572.0-572.4, 573 Congenital 750.3, 751 anomalies of digestive system Epilepsy/seizures 345, 780.32, 780.33, 780.39 Rheumatologic 710, 712, 714, 716, disorders 719.2, 719.3, 720-722, 723.0, 723.2, 723.3, 723.6-723.9, 725-729 Other 710-739 (except codes musculoskeletal listed above) disorders/symptoms Gallbladder/biliary 574-576

Downloaded From: https://jamanetwork.com/ on 09/25/2021 tract disorder Nephrotic syndrome 581 Urinary tract 599.0 infection Hepatitis B or C 070.2, 070.3, 070.41, 070.44, 070.51, 070.54, 070.7 Tuberculosis 010-018 Other infections 001-009, 020-066, 070.0, 070.1, 070.42, 070.43, 070.49, 070.52, 070.53, 070.59, 070.6, 070.9, 080-139, 480- 488, 507, 510, 513 Malaise/fatigue 780.7 Hypersomnia 327.1, 780.54 Other organic sleep 327.0, 327.3, 327.4, disorders 327.5, 327.8, 780.50, 780.52, 780.55, 780.56, 780.58, 780.59 aICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification bCPT-4: Current Procedure Terminology

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l. Covariates for other medications

Covariate Generic name Other anticonvulsant ethosuximide, ethotoin, fosphenytoin, felbamate, medications lacosamide, levetiracetam, mephobarbital, methsuximide, phenytoin, pregabalin, primidone, rufinamide, tiagabine, vigabatrin, zonisamide Opiate analgesic codeine, dihydrocodeine, fentanyl, hydrocodone, medications hydromorphone, levorphanol, meperidine, methadone, morphine, oxycodone, oxymorphone, pentazocine, propoxyphene, tapentadol, tramadol Migraine medications almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan Muscle relaxant baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, medications dantrolene, metaxalone, methocarbamol, orphenadrine, tizanidine Antibiotics amikacin, amoxicillin, amoxicillin/potassium clavulanate, ampicillin, ampicillin/sulbactam sodium, azithromycin, aztreonam, bacitracin, carbenicillin, cefaclor, cefadroxil, cefazolin, cefdinir, cefditoren, cefepime, cefixime, cefotaxime, cefotetan, cefoxitin, cefpodoxime, cefprozil, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime, cephalexin, cephradine, chloramphenicol, ciprofloxacin, clarithromycin, clindamycin, colistin, daptomycin, demeclocycline, dicloxacillin, dirithromycin, doripenem, doxycycline, ertapenem, erythromycin, gatifloxacin, gentamicin, grepafloxacin, imipenem, kanamycin, levofloxacin, lincomycin, linezolid, loracarbef, meropenem, metronidazole, minocycline, moxifloxacin, nafcillin, nalidixic acid, neomycin, norfloxacin, ofloxacin, oxacillin, penicillin, piperacillin, polymyxin b, quinupristin/dalfopristin, rifaximin, spectinomycin, sulfadiazine, sulfamethoxazole, sulfanilamide, sulfasalazine, sulfathiazole/sulfacetamide/sulfabenzamide, sulfisoxazole, telithromycin, tetracycline, ticarcillin /potassium clavulanate, tigecycline, tobramycin, trimethoprim, vancomycin Antimycobacterial agents aminosalicylic acid, capreomycin, clofazimine, cycloserine, dapsone, ethambutol, ethionamide, isoniazid, pyrazinamide, rifabutin, rifampin

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m. Covariates for medical care utilization (Intensity/No. of visits)

Covariate ICD-9-CMa CPT-4b procedure codes ICD-9-CMa diagnosis procedure codes codes Psychiatric 290-319, outpatient visit V40, V66.3, Psychiatric ED visit V67.3 Psychiatric hospitalization Injury-related 800-999, Fracture-related codes 79.0, 79.1, outpatient visit E800-E999 23500, 23505, 23515, 23520, 79.2, 79.3, Injury-related ED 23570, 23615, 23665, 23670, 78.1 visit 23675, 24500, 24505, 24515, Injury-related 24516, 24530, 24535, 24538, hospitalization 24545, 24546, 24560, 24565, 24566, 24575, 24576, 24577, 24579, 24582, 24586, 24620, 24635, 24650, 24655, 24665, 24666, 24670, 24675, 24685, 25500, 25505, 25515, 25520, 25525, 25526, 25530, 25535, 25545, 25560, 25565, 25574, 25575, 25600, 25605, 25606, 25607, 25608, 25609, 25622, 25624, 25628, 25630, 25635, 25645, 25650, 25651, 25652, 25680, 25685, 26600, 26605, 26607, 26608, 26615, 26645, 26650, 26665, 26720, 26725, 26727, 26735, 26740, 26742, 26746, 26755, 26756, 26765, 27230, 27232, 27235, 27236, 27238, 27240, 27244, 27245, 27246, 27248, 27254, 27500, 27501, 27502, 27503, 27506, 27507, 27508, 27509, 27510, 27511, 27513, 27514, 27520, 27524, 27530, 27532, 27535, 27536, 27538, 27540, 27750, 27752, 27756, 27758, 27759, 27760, 27762, 27766, 27780, 27784, 27786, 27788, 27792, 27808, 27810, 27814, 27816, 27818, 27822, 27823, 27824, 27825, 27826, 27827, 27828,

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Dislocation-related codes 23525, 23530, 23532, 23540, 23545, 23550, 23552, 23650, 23655, 23660, 23665, 23700, 24600, 24605, 24615, 25660, 25670, 25671, 25675, 25676, 25690, 25695, 26641, 26670, 26675, 26676, 26685, 26686, 26700, 26705, 26706, 26715, 26770, 26775, 26776, 26785, 27250, 27252, 27253, 27256, 27257, 27258, 27259, 27265, 27266, 27550, 27552, 27556, 27557, 27558, 27560, 27562, 27566, 27830, 27831, 27832, 27840, 27842, 27846, 27848, 28540, 28545, 28546, 28555, 28570, 28575, 28576, 28585, 28600, 28605, 28606, 28615, 28630, 28635, 28636, 28645, 28660, 28665, 28666, 28675 Other outpatient All outpatient visits except psychiatric or injury-related outpatient visit visits Other ED visits All ED visits except psychiatric or injury-related ED visits Other All hospitalizations except psychiatric or injury-related hospitalization hospitalizations aICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification bCPT-4: Current Procedure Terminology

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Cumulative duration of use (days) N % Mean Median IQR (Q1-Q3)b Antidepressants SSRI/SNRIc 79,285 66.3 179.7 90.0 30.0-213.0 TCAd 22,143 18.5 101.7 44.0 30.0-100.0 Other 37,609 31.4 171.3 88.0 30.0-204.0 antidepressants Note: The cumulative percentage for antidepressant subclass use adds up to >100% because study youth may use antidepressants from different subclasses during follow-up aMean follow-up: 22.8 months; Median follow-up: 19.0 months (interquartile range: 9.0- 35.0 months) bIQR: Interquartile range; Q1: First quartile; Q3: Third quartile cSSRI/SNRI: Selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor dTCA: Tricyclic and other related cyclic antidepressant

Downloaded From: https://jamanetwork.com/ on 09/25/2021 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 a. Among Medicaid-insured 10-20 year olds

Absolute risk per 10,000 Adjusted 95% Exposure status person-months relative riska Confidence Interval SSRI/SNRIsb Former use 0.69 1 Reference Current use 1.42 1.85 1.32-2.60 Other antidepressants Former use 1.23 1 Reference Current use 1.31 0.95 0.63-1.44 aAdjusted for disease risk score (expressed as percentile ranks), time from cohort entry (i.e., follow-up month), and exposure to tricyclic and other related cyclic antidepressants bSSRI/SNRI: Selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor

b. Not allowing for the 90-day time window to account for carry-over effects

Absolute risk per 10,000 Adjusted 95% Exposure status person-months relative riska Confidence Interval SSRI/SNRIsb Former use 0.72 1 Reference Current use 1.39 1.78 1.30-2.43 Other antidepressants Former use 1.09 1 Reference Current use 1.22 1.06 0.70-1.62 aAdjusted for disease risk score (expressed as percentile ranks), time from cohort entry (i.e., follow-up month), and exposure to tricyclic and other related cyclic antidepressants bSSRI/SNRI: Selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor

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c. Excluding Medicaid-insured youth who had usage of any psychotropic medication in the year prior to treatment initiation with antidepressants (index date)

Absolute risk per 10,000 Adjusted 95% Exposure status person-months relative riska Confidence Interval SSRI/SNRIsb Former use 0.53 1 Reference Current use 1.19 1.88 1.18-2.99 Other antidepressants Former use 0.90 1 Reference Current use 1.32 1.22 0.66-2.26 aAdjusted for disease risk score (expressed as percentile ranks), time from cohort entry (i.e., follow-up month), and exposure to tricyclic and other related cyclic antidepressants bSSRI/SNRI: Selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor

d. Among Medicaid-insured youth diagnosed with depressive disorders

Absolute risk per 10,000 Adjusted 95% Exposure status person-months relative riska Confidence Interval SSRI/SNRIsb Former use 0.56 1 Reference Current use 1.62 2.73 1.64-4.56 Other antidepressants Former use 1.26 1 Reference Current use 2.04 1.43 0.80-2.54 aAdjusted for disease risk score (expressed as percentile ranks), time from cohort entry (i.e., follow-up month), and exposure to tricyclic and other related cyclic antidepressants bSSRI/SNRI: Selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor

Downloaded From: https://jamanetwork.com/ on 09/25/2021 eFigure. Incidence of Type 2 Diabetes per 10,000 Person-Months According to Disease Risk Score, Expressed as Percentile Ranks

Note: The disease risk score was estimated in a time-dependent manner for each person in each month of follow-up. We grouped the person-months into discrete groups, expressed as percentile ranks of the estimated disease risk score distribution. To check for the validity of the disease risk score estimation, we assessed the incidence of type 2 diabetes in these groups (from the lowest to the highest risk group). The figure below shows that the risk of incident type 2 diabetes increased with increasing disease risk score.

Downloaded From: https://jamanetwork.com/ on 09/25/2021 eReferences

1. Hayasaka Y, Purgato M, Magni LR, et al. Dose equivalents of antidepressants: evidence-based recommendations from randomized controlled trials. J Affect Disord. 2015;180:179-184. 2. Safer DJ. Raising the minimum effective dose of serotonin reuptake inhibitor antidepressants: adverse drug events. J Clin Psychopharmacol. 2016;36(5):483- 491. 3. Bobo WV, Cooper WO, Stein CM, et al. Antipsychotics and the risk of type 2 diabetes mellitus in children and youth. JAMA Psychiatry. 2013;70(10):1067- 1075. 4. Rubin DM, Kreider AR, Matone M, et al. Risk for incident diabetes mellitus following initiation of second-generation antipsychotics among Medicaid-enrolled youths. JAMA Pediatr. 2015;169(4):e150285. 5. Burcu M, Zito JM, Safer DJ, Magder LS, dosReis S, Shaya FT, Rosenthal GL. Concomitant use of atypical antipsychotics with other psychotropic medication classes and the risk of type 2 diabetes mellitus. J Am Acad Child Adolesc Psychiatry. 2017;56(8):642-651.

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