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1 Supplementary Online Content Weitz ES, Hollon SD, Twisk J, et al. Baseline depression severity as moderator of depression outcomes between cognitive behavioral therapy vs pharmacotherapy: an individual patient data meta-analysis. Published online September 23, JAMA Psychiatry. doi: /jamapsychiatry emethods. Supplemental Methods eresults. Supplemental Results etable. Study Characteristics efigure. Interaction Between Baseline Severity and Treatment Group on Posttreatment HAM-D Scores This supplementary material has been provided by the authors to give readers additional information about their work. 1

2 emethods. Supplemental Methods Data received were checked with published papers for completeness; where small discrepancies were noted in older studies, authors were contacted for clarification and datasets were excluded in sensitivity analyses. In addition, the integrated dataset of all studies included was checked with the individual datasets provided. 2

3 eresults. Supplemental Results Sensitivity analyses: Sensitivity analyses performed with the HAM-D to examine the robustness of the finding when removing studies with special populations found little evidence of moderation as a function of severity (interaction: b=.02, p=.79). We also test whether the six studies scoring low on the quality assessment had an impact on the outcome. Comparable results were observed when studies with a quality scores less than two were removed from the analysis (interaction: b=-.02, p=.79). In order to examine the effects of being blinded to treatment (medication or placebo) on the overall results, we also ran the multi-level regression with the interaction between severity and treatment after removing studies that included a placebo control group. We also checked the robustness of the findings using the 6-item core symptom subscale of the HAM-D These sensitivity analyses, again, found no evidence of moderation when removing studies with a placebo control condition (interaction without placebo trials: b=.02,p=.81) or using the HAM-D-6 as the outcome measure (HAM-D-6 interaction: b=-.03, p=.74). Post-treatment data were more frequent in ADM than in CBT (18% vs 12%) on the HAMD and on the (13% vs 6%), but this was not related to baseline severity on the HAM-D (b=.00, p=.12) or (b=.01, p=.46). Baseline severity did not moderate the relationship between treatment and missing data on the HAM-D (b=.00, p =.36) or (b=.01, p=.78). 3

4 etable. Study Characteristics Study Recr Target Depression Psycho N ses Time N medication N Primary Qual a) Country Population therapy (wks) outcome 1. David (2008) 1 Comm MDD MDD on SCID + CT & fluoxetine 57 HAM-D + + ROM 20 & REBT 2. DeRubeis (2005) 2 Comm MDD MDD on SCID + CBT paroxetine 120 HAM-DD + + US HAM-D Dimidijian (2006) 3 Comm MDD MDD on SCID + CBT paroxetine 100 HAM-D US 20 & 4. Dunlop(2012) 4 Comm MDD MDD on SCID + CBT escitalopra 39 HAM-D, US HAM-D 15 m 5. Dunner (1996) 5 Other MDD &/ dysthymia MDD on SCID CBT fluoxetine 13 + US 6. Elkin (1989) 6 Clin MDD MDD on SADS + 7. Faramarzi (2008) 7 Other MDD + MDD on SCID + infertility Hegerl (2010) 8 Clin Mild Dep Minor dep dis, dysthymia, MDD on CIDI + 8 HAM-D Hollon (1992) 9 Clin MDD MDD on SCID + 20 & 10. Jarrett (1999) 10 Clin MDD MDD on SCID + HAM-D Kennedy (2007) 11 Clin MDD MDD on SCID Miranda (2003) 12 Other MDD MDD on CIDI (pregnant or post-partum) 13. Mohr (2001) 13 Other MDD MDD on SCID + (multiple 16 & sclerosis) HAM-D 16 CBT imipramine 57 HAM-D US CBT fluoxetine 30 + Iran CBT (grp) sertraline 83 HAM-D GER CBT imipramine 57 HAM-D + + CBT phenelzine 36 HAM-D US CBT venlafaxine 14 HAM-D CAN CBT (grp or ind) paroxetine 88 HAM-D US CBT sertraline 23 + US HAM-D US 4

5 14. Murphy (1984) 14 Clin MDD MDD on DIS + 20 & 15. Rush (1977) 15 Com MDD MDD by Feighner s + 20 & 16. Segal (2006) 16 Clin MDD MDD on SCID + HAM-D 12 CBT nortriptyline 16 HAM-D CBT imipramine 22 HAM-D CBT sertraline/ paroxetine/ venlafaxine US + US 152 HAM-D CAN a) In this column a positive or negative sign is given for four quality criteria, respectively: allocation sequence; concealment of allocation to conditions; blinding of assessors; and intention-to-treat analyses. Abbreviations: Recr, Recruitment population; Comm, Community sample; Clin, Clinical Sample; Depression, confirmation of depression; SCID, Structured clinical interview for DSM; SADS, Schedule for affective disorders and schizophrenia; DIS, diagnostic interview schedule ; CIDI, composite international diagnostic interview; CT, Cognitive therapy; REBT, rational emotive behavioural therapy; Dosage range or highest dosage week reported with average dose in parantheses; US, United States; ROM, Romania; GER, Germany; CAN, Canada References 1. David D, Szentagotai A, Lupu V, Cosman D. Rational emotive behavior therapy, cognitive therapy, and medication in the treatment of major depressive disorder: a randomized clinical trial, posttreatment outcomes, and six-month follow-up. J Clin Psychol. 2008;64(6): Medline: DeRubeis RJ, Hollon SD, Amsterdam JD, et al. Cognitive therapy vs medications in the treatment of moderate to severe depression. Arch Gen Psychiatry. 2005;62(4): Medline: Dimidjian S, Hollon SD, Dobson KS, et al. Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression. J Consult Clin Psychol. 2006;74(4): Medline: Dunlop BW, Kelley ME, Mletzko TC, Velasquez CM, Craighead WE, Mayberg HS. Depression beliefs, treatment preference, and outcomes in a randomized trial for major depressive disorder. J Psychiatr Res. 2012;46(3): Medline: Dunner DL, Schmaling KB, Hendrickson H, Becker J, Lehman A, Bea C. Cognitive therapy versus fluoxetine in the treatment of dysthymic disorder. Depression. 1996;4(1): Medline: Elkin I, Shea MT, Watkins JT, et al. National Institute of Mental Health Treatment of Depression Collaborative Research Program: general effectiveness of treatments. Arch Gen Psychiatry. 1989;46(11): Medline: Faramarzi M, Alipor A, Esmaelzadeh S, Kheirkhah F, Poladi K, Pash H. Treatment of depression and anxiety in infertile women: cognitive behavioral therapy versus fluoxetine. J Affect Disord. 2008;108(1-2): Medline:

6 8. Hegerl U, Hautzinger M, Mergl R, et al. Effects of pharmacotherapy and psychotherapy in depressed primary-care patients: a randomized, controlled trial including a patients choice arm. Int J Neuropsychopharmacol. 2010;13(1): Medline: Hollon SD, DeRubeis RJ, Evans MD, et al. Cognitive therapy and pharmacotherapy for depression: singly and in combination. Arch Gen Psychiatry. 1992;49(10): Medline: Jarrett RB, Schaffer M, McIntire D, Witt-Browder A, Kraft D, Risser RC. Treatment of atypical depression with cognitive therapy or phenelzine: a double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1999;56(5): Medline: Kennedy SH, Konarski JZ, Segal ZV, et al. Differences in brain glucose metabolism between responders to CBT and venlafaxine in a 16-week randomized controlled trial. Am J Psychiatry. 2007;164(5): Medline: Miranda J, Chung JY, Green BL, et al. Treating depression in predominantly low-income young minority women: a randomized controlled trial. JAMA. 2003;290(1): Medline: Mohr DC, Boudewyn AC, Goodkin DE, Bostrom A, Epstein L. Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis. J Consult Clin Psychol. 2001;69(6): Medline: Murphy GE, Simons AD, Wetzel RD, Lustman PJ. Cognitive therapy and pharmacotherapy: singly and together in the treatment of depression. Arch Gen Psychiatry. 1984;41(1): Medline: Rush AJ, Beck AT, Kovacs M, Hollon S. Comparative efficacy of cognitive therapy and pharmacotherapy in the treatment of depressed outpatients. Cognit Ther Res. 1977;1(1): Segal ZV, Kennedy S, Gemar M, Hood K, Pedersen R, Buis T. Cognitive reactivity to sad mood provocation and the prediction of depressive relapse. Arch Gen Psychiatry. 2006;63(7): Medline:

7 efigure. Interaction Between Baseline Severity and Treatment Group on Posttreatment HAM-D Scores HAMD post-treatment scores Baseline HAMD score (centered) CBT PHT 7