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Randomized Controlled Trial
. 2016 May 3;6(5):e799.
doi: 10.1038/tp.2016.61.

Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression

L M Williams  1   2 , C Debattista  1 , A-M Duchemin  3 , A F Schatzberg  1 , C B Nemeroff  4
Affiliations
Randomized Controlled Trial

Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression

L M Williams et al. Transl Psychiatry. .

Abstract

Few reliable predictors indicate which depressed individuals respond to antidepressants. Several studies suggest that a history of early-life trauma predicts poorer response to antidepressant therapy but results are variable and limited in adults. The major goal of the present study was to evaluate the role of early-life trauma in predicting acute response outcomes to antidepressants in a large sample of well-characterized patients with major depressive disorder (MDD). The international Study to Predict Optimized Treatment for Depression (iSPOT-D) is a randomized clinical trial with enrollment from December 2008 to January 2012 at eight academic and nine private clinical settings in five countries. Patients (n=1008) meeting DSM-IV criteria for MDD and 336 matched healthy controls comprised the study sample. Six participants withdrew due to serious adverse events. Randomization was to 8 weeks of treatment with escitalopram, sertraline or venlafaxine with dosage adjusted by the participant's treating clinician per routine clinical practice. Exposure to 18 types of traumatic events before the age of 18 was assessed using the Early-Life Stress Questionnaire. Impact of early-life stressors-overall trauma 'load' and specific type of abuse-on treatment outcomes measures: response: (⩾50% improvement on the 17-item Hamilton Rating Scale for Depression, HRSD17 or on the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated, QIDS_SR16) and remission (score ⩽7 on the HRSD17 and ⩽5 on the QIDS_SR16). Trauma prevalence in MDD was compared with controls. Depressed participants were significantly more likely to report early-life stress than controls; 62.5% of MDD participants reported more than two traumatic events compared with 28.4% of controls. The higher rate of early-life trauma was most apparent for experiences of interpersonal violation (emotional, sexual and physical abuses). Abuse and notably abuse occurring at ⩽7 years of age predicted poorer outcomes after 8 weeks of antidepressants, across the three treatment arms. In addition, the abuses occurring between ages 4 and 7 years differentially predicted the poorest outcome following the treatment with sertraline. Specific types of early-life trauma, particularly physical, emotional and sexual abuse, especially when occurring at ⩽7 years of age are important moderators of subsequent response to antidepressant therapy for MDD.

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Conflict of interest statement

The iSPOT-D sponsor central management team managed the operations of the sites and the data storage and quantification. Interpretation of the data was undertaken independently from the study sponsor and preparation and review of the manuscript was undertaken by the academic authors. LMW has received consultant fees from Brain Resource and from Humana. CD has received research funding from Brain Resource, St. Jude, Jannsen, Assurex, Roche, Takeda and has received consultant fees from Pfizer and Genentech. A-MD has received research funding from Brain Resource. AFS has served as a consultant to Bay City Capital, BrainCells, CeNeRx, Cervel, Depomed, Eli Lilly, Forum, Genentech, Gilead, Jazz, Lundbeck/Takeda, McKinsey, Merck, MSI, Neuronetics, Novadel, One-Carbon, PharmaNeuroBoost, Sunovion, Synosia and Xhale; he has received honoraria from Merck; he has equity in Amnestix, BrainCells, CeNeRx, Corcept (co-founder), Delpor, Forest, Merck, Neurocrine, Novadel, Pfizer, PharmaNeuroBoost, Somaxon, Synosis, Titan and Xhale; and he receives royalties from Stanford University for patents on mifepristone use and the pharmacogenetics of antidepressant response. In the last 3 years, CBN has received a Scientific Advisory Board/Board of Directors fee from PharmaNeuroboost, Clintara/Bracket, Xhale, Taisho, Fortress, Takeda, Janssen/Ortho-McNeil and George West Mental Health Foundation. He holds stock or stock options in Xhale, Clintara/Bracket, Seattle Genetics, Celgene, Titan and Network Life Sciences. CBN has patents for Methods and devices for the transdermal delivery of lithium (US 6 375 990 BI) and Method to estimate serotonin and norepinephrine transporter occupancy after drug treatment using patient or animal serum (provisional filing April 2001). LMW was the overall academic PI for iSPOT-D (2008–2013), CD is the PI for the Stanford iSPOT-D site, A-MD is co-I for the Ohio State iSPOT-D site, AFS is co-I for the Stanford iSPOT-D site and CBN is co-I for the Miami University iSPOT-D site. Analyses were undertaken by LMW, CD and CBN and all the authors participated in interpreting results and drafting the manuscript. CD and LMW had full access to all the data in the study and they take responsibility for the integrity of the data and the accuracy of the data analysis.

Figures

Figure 1
Figure 1
CONSORT chart. HRSD17, 17-item Hamilton Rating Scale for Depression; PTSD, posttraumatic stress disorder.
Figure 2
Figure 2
The effect of abuse at age 4–7 years on prediction for HRSD17 response and remission. HRSD17, 17-item Hamilton Rating Scale for Depression.
See this image and copyright information in PMC

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