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1 Supplementary Online Content Blumenthal SR, Castro VM, Clements CC, et al. An electronic health records study of long-term weight gain following antidepressent use. JAMA Psychiatry. Published online June 4, doi: /jamapsychiatry efigure. Mean observed percent weight change after index prescription. etable 1. Dictionary of indication diagnoses. etable 2. Sensitivity analysis: Association of sociodemographic, health status, and concomitant treatment covariates with weight change in mixed-effects model, limited to antidepressant-treated patients only. etable 3. Sensitivity analysis: Association of medication prescription with weight change, from mixed-effects model; individuals with antipsychotic exposure excluded. etable 4. Logistic regression model to predict discontinuation before 12-month observation. etable 5. Sensitivity analysis: Association of medication prescription with weight change, from mixed-effects model weighted average of 12-month completers and dropouts. etable 6. 3-month mean predicted and observed weight change by drug. etable 7. 6-month mean predicted and observed weight change by drug. etable 8. 9-month mean predicted and observed weight change by drug. etable month mean predicted and observed weight change by drug. This supplementary material has been provided by the authors to give readers additional information about their work
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3 efigure. Mean observed percent weight change after index prescription A B
4 (A) Antidepressants and Albuterol; (B) Weight loss medications. Note difference in scale between (A) and (B), reflecting weight loss versus gain.
5 etable 1. Dictionary of indication diagnoses Diagnosis Code Code Type Code Description Anxiety ICD 9 Billing Code Organic anxiety syndrome Anxiety 300 ICD 9 Billing Code Neurotic disorders Anxiety 3000 ICD 9 Billing Code Anxiety states Anxiety ICD 9 Billing Code Anxiety state, unspecified Anxiety ICD 9 Billing Code Panic disorder Anxiety ICD 9 Billing Code Generalized anxiety disorder Anxiety ICD 9 Billing Code Other anxiety states Anxiety ICD 9 Billing Code Hysteria, unspecified Anxiety ICD 9 Billing Code Phobia, unspecified Anxiety ICD 9 Billing Code Agoraphobia with panic attacks Anxiety ICD 9 Billing Code Agoraphobia without mention of panic attacks Anxiety ICD 9 Billing Code Social phobia Anxiety ICD 9 Billing Code Other isolated or simple phobias Anxiety 3003 ICD 9 Billing Code Obsessive compulsive disorders Anxiety 3005 ICD 9 Billing Code Neurasthenia Anxiety ICD 9 Billing Code Other neurotic disorders Anxiety 3009 ICD 9 Billing Code Unspecified neurotic disorder Anxiety ICD 9 Billing Code Prolonged posttraumatic stress disorder Anxiety 3130 ICD 9 Billing Code Overanxious disorder specific to childhood and adolescence Anxiety 3131 ICD 9 Billing Code Misery and unhappiness disorder specific to childhood and adolescence Anxiety ICD 9 Billing Code Shyness disorder of childhood Anxiety ICD 9 Billing Code Introverted disorder of childhood Anxiety 3133 ICD 9 Billing Code Relationship problems specific to childhood and adolescence Anxiety ICD 9 Billing Code Identity disorder of childhood or adolescence Anxiety ICD 9 Billing Code Academic underachievement disorder of childhood or adolescence Anxiety LPA310 EMR Problem List Panic attacks LMR 310 Anxiety LPA519 EMR Problem List Anxiety LMR 519 Anxiety LPA656 EMR Problem List Obsessive compulsive disorder LMR 656 Anxiety LPA835 EMR Problem List Post traumatic stress disorder LMR 835 Anxiety LPA851 EMR Problem List Panic disorder LMR 851 Anxiety LPB12959 EMR Problem List Anxiety LMR Anxiety LPB519 EMR Problem List Anxiety LMR 519 Depression ICD 9 Billing Code Organic affective syndrome Depression 296 ICD 9 Billing Code Affective psychoses Depression 2962 ICD 9 Billing Code Major depressive disorder, single episode Depression ICD 9 Billing Code Major depressive disorder, single episode, unspecified degree Depression ICD 9 Billing Code Major depressive disorder, single episode, mild degree Depression ICD 9 Billing Code Major depressive disorder, single episode, moderate degree Depression ICD 9 Billing Code Major depressive disorder, single episode, severe degree, without mention of psychotic behavior Depression ICD 9 Billing Code Major depressive disorder, single episode, severe degree, specified as with psychotic behavior
6 Depression ICD 9 Billing Code Major depressive disorder, single episode, in partial or unspecified remission Depression ICD 9 Billing Code Major depressive disorder, single episode in full remission Depression 2963 ICD 9 Billing Code Major depressive disorder, recurrent episode Depression ICD 9 Billing Code Major depressive disorder, recurrent episode, unspecified degree Depression ICD 9 Billing Code Major depressive disorder, recurrent episode, mild degree Depression ICD 9 Billing Code Major depressive disorder, recurrent episode, moderate degree Depression ICD 9 Billing Code Major depressive disorder, recurrent episode, severe degree, without mention of psychotic behavior Depression ICD 9 Billing Code Major depressive disorder, recurrent episode, severe degree, specified as with psychotic behavior Depression ICD 9 Billing Code Major depressive disorder, recurrent episode, in partial or unspecified remission Depression ICD 9 Billing Code Major depressive disorder, recurrent episode, in full remission Depression 2969 ICD 9 Billing Code Other and unspecified affective psychoses Depression ICD 9 Billing Code Unspecified affective psychosis Depression ICD 9 Billing Code Other specified affective psychoses Depression 3004 ICD 9 Billing Code Neurotic depression Depression 309 ICD 9 Billing Code Adjustment reaction Depression 3090 ICD 9 Billing Code Adjustment reaction with brief depressive reaction Depression 3091 ICD 9 Billing Code Adjustment reaction with prolonged depressive reaction Depression 3092 ICD 9 Billing Code Adjustment reaction with predominant disturbance of other emotions Depression ICD 9 Billing Code Emancipation disorder of adolescence and early adult life Depression ICD 9 Billing Code Specific academic or work inhibition Depression ICD 9 Billing Code Adjustment reaction with anxious mood Depression ICD 9 Billing Code Adjustment reaction with mixed emotional features Depression ICD 9 Billing Code Other adjustment reactions with predominant disturbance of other emotions Depression 3093 ICD 9 Billing Code Adjustment reaction with predominant disturbance of conduct Depression 3094 ICD 9 Billing Code Adjustment reaction with mixed disturbance of emotions and conduct Depression 3098 ICD 9 Billing Code Other specified adjustment reactions Depression ICD 9 Billing Code Adjustment reaction with physical symptoms Depression ICD 9 Billing Code Adjustment reaction with withdrawal Depression ICD 9 Billing Code Other specified adjustment reactions Depression 3099 ICD 9 Billing Code Unspecified adjustment reaction Depression 311 ICD 9 Billing Code Depressive disorder, not elsewhere classified Depression 7807 ICD 9 Billing Code Malaise and fatigue Depression ICD 9 Billing Code Other malaise and fatigue Depression LPA1002 EMR Problem List Abnormal grief reaction LMR 1002 Depression LPA101 EMR Problem List Depression LMR 101 Depression LPA1304 EMR Problem List Adjustment disorder LMR 1304 Depression LPA144 EMR Problem List Fatigue LMR 144 Depression LPA1593 EMR Problem List Depression LMR 1593 Depression LPA407 EMR Problem List Suicidal tendencies LMR 407 Depression LPA684 EMR Problem List Seasonal affective disorder LMR 684 Depression LPA751 EMR Problem List Dysthymia LMR 751 Depression LPB101 EMR Problem List Depression LMR 101 Depression LPB1593 EMR Problem List Depression LMR 1593
7 Depression V111 ICD 9 Billing Code Personal history of affective disorders Depression V6284 ICD 9 Billing Code Suicidal ideation Pain ICD 9 Billing Code Tension headache Pain 338 ICD 9 Billing Code Pain, not elsewhere classified Pain 3381 ICD 9 Billing Code Acute pain Pain ICD 9 Billing Code Acute pain due to trauma Pain ICD 9 Billing Code Acute post thoracotomy pain Pain ICD 9 Billing Code Other acute postoperative pain Pain ICD 9 Billing Code Other acute pain Pain 3382 ICD 9 Billing Code Chronic pain Pain ICD 9 Billing Code Chronic pain due to trauma Pain ICD 9 Billing Code Chronic post thoracotomy pain Pain ICD 9 Billing Code Other chronic postoperative pain Pain ICD 9 Billing Code Other chronic pain Pain 7194 ICD 9 Billing Code Pain in joint Pain ICD 9 Billing Code Pain in joint, site unspecified Pain ICD 9 Billing Code Pain in joint involving shoulder region Pain ICD 9 Billing Code Pain in joint involving upper arm Pain ICD 9 Billing Code Pain in joint involving forearm Pain ICD 9 Billing Code Pain in joint involving hand Pain ICD 9 Billing Code Pain in joint involving pelvic region and thigh Pain ICD 9 Billing Code Pain in joint involving lower leg Pain ICD 9 Billing Code Pain in joint involving ankle and foot Pain ICD 9 Billing Code Pain in joint involving other specified sites Pain ICD 9 Billing Code Pain in joint involving multiple sites Pain 7231 ICD 9 Billing Code Cervicalgia Pain 7241 ICD 9 Billing Code Pain in thoracic spine Pain 7242 ICD 9 Billing Code Lumbago Pain 7245 ICD 9 Billing Code Backache, unspecified Pain 7295 ICD 9 Billing Code Pain in limb Pain ICD 9 Billing Code Precordial pain Pain 7890 ICD 9 Billing Code Abdominal pain Pain ICD 9 Billing Code Abdominal pain, unspecified site Pain ICD 9 Billing Code Abdominal pain, right upper quadrant Pain ICD 9 Billing Code Abdominal pain, left upper quadrant Pain ICD 9 Billing Code Abdominal pain, right lower quadrant Pain ICD 9 Billing Code Abdominal pain, left lower quadrant Pain ICD 9 Billing Code Abdominal pain, periumbilic Pain ICD 9 Billing Code Abdominal pain, epigastric Pain ICD 9 Billing Code Abdominal pain, generalized Pain ICD 9 Billing Code Abdominal pain, other specified site; multiple sites Pain LPA1307 EMR Problem List Abdominal pain LMR 1307 Pain LPA1365 EMR Problem List Chronic pain LMR 1365 Pain LPA150 EMR Problem List Flank pain LMR 150
8 Pain LPA1520 EMR Problem List Thoracic back pain LMR 1520 Pain LPA160 EMR Problem List GI discomfort LMR 160 Pain LPA1922 EMR Problem List Ear pain LMR 1922 Pain LPA2211 EMR Problem List Back pain LMR 2211 Pain LPA2212 EMR Problem List Low Back Pain LMR 2212 Pain LPA2213 EMR Problem List Neck pain LMR 2213 Pain LPA2218 EMR Problem List Shoulder pain LMR 2218 Pain LPA2221 EMR Problem List Knee pain LMR 2221 Pain LPA2222 EMR Problem List Leg pain LMR 2222 Pain LPA2223 EMR Problem List Foot pain LMR 2223 Pain LPA226 EMR Problem List Low back pain LMR 226 Pain LPA233 EMR Problem List Lower extremity pain LMR 233 Pain LPA2354 EMR Problem List Hip pain LMR 2354 Pain LPA26 EMR Problem List Arthralgias LMR 26 Pain LPA279 EMR Problem List Neck pain LMR 279 Pain LPA3 EMR Problem List Abdominal pain LMR 3 Pain LPA3012 EMR Problem List Pain LMR 3012 Pain LPA3018 EMR Problem List Arm pain LMR 3018 Pain LPA315 EMR Problem List Pelvic pain LMR 315 Pain LPA37 EMR Problem List Back pain LMR 37 Pain LPA439 EMR Problem List Upper extremity pain LMR 439 Pain LPA514 EMR Problem List Shoulder pain LMR 514 Pain LPA515 EMR Problem List Knee pain LMR 515 Pain LPA516 EMR Problem List Ankle pain LMR 516 Pain LPA722 EMR Problem List Foot pain LMR 722 Pain LPA724 EMR Problem List Hip pain LMR 724 Pain LPA726 EMR Problem List Leg pain LMR 726 Pain LPA743 EMR Problem List Arm pain LMR 743 Pain LPA746 EMR Problem List Elbow pain LMR 746 Pain LPA759 EMR Problem List Epigastric discomfort LMR 759 Pain LPA827 EMR Problem List Wrist pain LMR 827 Pain LPA949 EMR Problem List Pain in joint LMR 949 Pain LPA950 EMR Problem List Limb pain LMR 950 Pain LPB12599 EMR Problem List Ankle pain LMR Pain LPB12605 EMR Problem List Hand pain LMR Pain LPB1365 EMR Problem List Psychiatric problem, nos LMR 1365 Pain LPB160 EMR Problem List Gi discomfort LMR 160 Pain LPB1922 EMR Problem List Ear pain LMR 1922 Pain LPB2211 EMR Problem List Back pain LMR 2211 Pain LPB2212 EMR Problem List Low back pain LMR 2212 Pain LPB2213 EMR Problem List Neck pain LMR 2213 Pain LPB2218 EMR Problem List Shoulder pain LMR 2218 Pain LPB2219 EMR Problem List Limb pain LMR 2219 Pain LPB2220 EMR Problem List Wrist pain LMR 2220
9 Pain LPB2221 EMR Problem List Knee pain LMR 2221 Pain LPB2222 EMR Problem List Leg pain LMR 2222 Pain LPB2223 EMR Problem List Foot pain LMR 2223 Pain LPB2354 EMR Problem List Hip pain LMR 2354 Pain LPB26 EMR Problem List Joint pains LMR 26 Pain LPB279 EMR Problem List Neck pain LMR 279 Pain LPB3012 EMR Problem List Pain LMR 3012 Pain LPB3018 EMR Problem List Arm pain LMR 3018 Pain LPB37 EMR Problem List Back pain LMR 37 Pain LPB514 EMR Problem List Shoulder pain LMR 514 Pain LPB515 EMR Problem List Knee pain LMR 515 Pain LPB516 EMR Problem List Ankle pain LMR 516 Pain LPB722 EMR Problem List Foot pain LMR 722 Pain LPB724 EMR Problem List Hip pain LMR 724 Pain LPB726 EMR Problem List Leg pain LMR 726 Pain LPB827 EMR Problem List Wrist pain LMR 827 Smoking 3051 ICD 9 Billing Code Tobacco use disorder Smoking ICD 9 Billing Code Tobacco use disorder Smoking ICD 9 Billing Code Tobacco use disorder, continuous use Smoking ICD 9 Billing Code Tobacco use disorder, episodic use Smoking ICD 9 Billing Code Tobacco use disorder, in remission Smoking LPA395 EMR Problem List Smoking LMR 395 Smoking LPA677 EMR Problem List Past smoking LMR 677 Smoking LPB395 EMR Problem List Smoking LMR 395 Smoking V1582 ICD 9 Billing Code History of tobacco use
10 etable 2. Sensitivity analysis: Association of sociodemographic, health status, and concomitant treatment covariates with weight change in mixed effects model, limited to antidepressant treated patients only Feature Beta (SE) pval Sociodemographic Age (0.001) Gender, female (0.015) Race, caucasian (0.016) Insurance, public (0.016) Health history Baseline BMI (0.001) Pre baseline weight trend (0.847) Year of index prescription (0.003) Comorbidity Index (ACCI) (0.008) Depression diagnosis (0.015) Anxiety diagnosis (0.017) Pain diagnosis (0.015) Recent smoker (0.024) Concomittant psychotherapy (0.024) Comcomittant antipsychotic (0.034) Treatment SSRI Antidepressants Citalopram REF Escitalopram (0.040) Fluoxetine (0.023) Paroxetine (0.027) Sertraline (0.027) non SSRI Antidepressants Amitriptyline (0.025) Bupropion (0.028) Duloxetine (0.051) Mirtazapine (0.058) Nortriptyline (0.034) Venlafaxine (0.034) Values are estimates (and standard error) of interaction of feature and time in mixed effect models. Model is fitted using patients with index prescription of antidepressants only (excluding control drugs); compare to Table 2.
11 etable 3. Sensitivity analysis: Association of medication prescription with weight change, from mixed effects model; individuals with antipsychotic exposure excluded. Class Treatment All Patients Mixed Effects Model Completers Mixed Effects Model Dropouts Mixed Effects Model Beta (SE) p val Beta (SE) p val Beta (SE) p val Antidepressant SSRI Citalopram REF REF REF Escitalopram (0.039) (0.044) (0.088) Fluoxetine (0.022) (0.025) (0.050) Paroxetine (0.026) (0.030) (0.061) Sertraline (0.026) (0.030) (0.058) non SSRI Amitriptyline (0.025) (0.028) (0.054) Bupropion (0.027) (0.032) (0.057) Duloxetine (0.050) (0.056) (0.112) Mirtazapine (0.060) (0.069) (0.126) Nortriptyline (0.034) (0.038) (0.074) Venlafaxine (0.034) (0.038) (0.073) Controls Weight loss Orlistat (0.104) (0.125) (0.194) Phentermine (0.066) (0.073) (0.150) Sibutramine (0.093) (0.111) (0.182) Bronchodilator Albuterol (0.025) (0.029) (0.052) Effect of drug on weight change over time excluding patients on concomitant antipsychotic treatment. Values are covariate adjusted estimates (and standard error) of interaction of drug and time compared with citalopram over time in a mixed effect model. Completers include only patients who had a weight measured at the 12 month time point; Dropouts include patients with no weight measurement at the 12 month time point
12 etable 4. Logistic regression model to predict discontinuation before 12 month observation Estimate SE z value p (Intercept) drugescitalopram drugfluoxetine drugparoxetine drugsertraline drugamitriptyline drugbupropion drugduloxetine drugmirtazapine drugnortriptyline drugvenlafaxine drugorlistat drugphentermine drugsibutramine drugalbuterol genderm Age (years) Pretreatment BMI Year Race Asian Race Black Ethnicity Hispanic Race Other Terms of a logistic regression model predicting patients who drop out before 12 month timepoint. Reference drug is citalopram, reference race is Caucasian.
13 etable 5. Sensitivity analysis: Association of medication prescription with weight change, from mixed effects model weighted average of 12 month completers and dropouts. Class Treatment Missing Residual Mixed Effects Model Beta (SE) p val Antidepressant SSRI Citalopram REF Escitalopram (0.053) Fluoxetine (0.031) Paroxetine (0.038) Sertraline (0.036) non SSRI Amitriptyline (0.034) Bupropion (0.038) Duloxetine (0.068) Mirtazapine (0.078) Nortriptyline (0.048) Venlafaxine (0.046) Controls Weight loss Orlistat (0.140) Phentermine (0.100) Sibutramine (0.129) Bronchodilator Albuterol (0.037) Values are covariate adjusted estimates (and standard errors) of interaction of drug and time, representing weighted average of values for completers and dropouts. (Compare to Table 3)
14 etable 6. 3 month mean predicted and observed weight change by drug Class Treatment Predicted 3m Weight Change (kg) mean ± sd Observed 3m Weight Change (kg) mean ± sd Proportion of patients with >7% weight gain at 3m Antidepressant SSRI Citalopram 0.1 ± ± Escitalopram 0.1 ± ± Fluoxetine 0.3 ± ± Paroxetine 0.2 ± ± Sertraline 0.1 ± ± non SSRI Amitriptyline 0.4 ± ± Bupropion 0.4 ± ± Duloxetine 0.1 ± ± Mirtazapine 0.3 ± ± Nortriptyline 0.3 ± ± Venlafaxine 0.0 ± ± Controls Weight loss Orlistat 2.7 ± ± Phentermine 5.5 ± ± Sibutramine 3.7 ± ± Bronchodilator Albuterol 0.1 ± ± Predicted weight change is best linear unbiased preditor (BLUP) from primary mixed effect model adjusted for all covariates. See text for details.
15 etable 7. 6 month mean predicted and observed weight change by drug Class Treatment Predicted 6m Weight Change (kg) mean ± sd Observed 6m Weight Change (kg) mean ± sd Proportion of patients with >7% weight gain at 6m Antidepressant SSRI Citalopram 0.4 ± ± Escitalopram 0.5 ± ± Fluoxetine 0.1 ± ± Paroxetine 0.4 ± ± Sertraline 0.6 ± ± non SSRI Amitriptyline 0.4 ± ± Bupropion 0.1 ± ± Duloxetine 0.3 ± ± Mirtazapine 0.5 ± ± Nortriptyline 0.4 ± ± Venlafaxine 0.3 ± ± Controls Weight loss Orlistat 3.6 ± ± Phentermine 7.3 ± ± Sibutramine 5.0 ± ± Bronchodilator Albuterol 0.2 ± ± Predicted weight change is best linear unbiased preditor (BLUP) from primary mixed effect model adjusted for all covariates. See text for details.
16 etable 8. 9 month mean predicted and observed weight change by drug Class Treatment Predicted 9m Weight Change (kg) mean ± sd Observed 9m Weight Change (kg) mean ± sd Proportion of patients with >7% weight gain at 9m Antidepressant SSRI Citalopram 0.8 ± ± Escitalopram 0.8 ± ± Fluoxetine 0.6 ± ± Paroxetine 1.0 ± ± Sertraline 1.0 ± ± non SSRI Amitriptyline 0.6 ± ± Bupropion 0.1 ± ± Duloxetine 0.6 ± ± Mirtazapine 1.4 ± ± Nortriptyline 0.5 ± ± Venlafaxine 0.5 ± ± Controls Weight loss Orlistat 4.2 ± ± Phentermine 9.0 ± ± Sibutramine 4.8 ± ± Bronchodilator Albuterol 0.1 ± ± Predicted weight change is best linear unbiased preditor (BLUP) from primary mixed effect model adjusted for all covariates. See text for details.
17 etable month mean predicted and observed weight change by drug Class Antidepressant Controls Treatment Predicted 12m Weight Change (kg) mean ± sd Observed 12m Weight Change (kg) mean ± sd Proportion of patients with >7% weight gain at 12m SSRI Citalopram 1.3 ± ± Escitalopram 1.1 ± ± Fluoxetine 0.8 ± ± Paroxetine 1.0 ± ± Sertraline 1.0 ± ± non SSRI Amitriptyline 0.8 ± ± Bupropion 0.2 ± ± Duloxetine 0.1 ± ± Mirtazapine 2.1 ± ± Nortriptyline 0.3 ± ± Venlafaxine 1.0 ± ± Weight loss Orlistat 6.5 ± ± Phentermine 10.9 ± ± Sibutramine 4.7 ± ± Bronchodilator Albuterol 0.0 ± ± Predicted weight change is best linear unbiased preditor (BLUP) from primary mixed effect model adjusted for all covariates. See text for deta
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