title: Efficacy of Cognitive-Behavioral Therapy for Insomnia Combined With Antidepressant Pharmacotherapy in Patients With Comorbid Depression and Insomnia: A Randomized Controlled Trial.
abstract: OBJECTIVE
  The Treatment of Insomnia and Depression (TRIAD) study evaluated the efficacy of combining depression pharmacotherapy (using MED, an ecologically valid and generalizable antidepressant medication algorithm) with cognitive-behavioral therapy for insomnia (CBT-I) among individuals with comorbid insomnia and major depressive disorder (MDD) to determine if change in insomnia severity mediates antidepressant outcome.
  
  
  METHODS
  This 16-week, 3-site, randomized controlled trial (RCT) randomly assigned 150 participants (recruited between March 2009 and August 2013), who met DSM-IV-TR criteria for insomnia and MDD and were not receiving treatment for either, to receive depression pharmacotherapy plus 7 sessions of either CBT-I or a credible control therapy for insomnia (CTRL). Depression pharmacotherapy followed a standardized 2-step algorithm, which included escitalopram, sertraline, and desvenlafaxine in a prescribed sequence. Primary measures were the Hamilton Depression Rating Scale and the depression module of the Structured Clinical Interview for DSM-IV Axis I Disorders, Research Version, Nonpatient Edition, administered by raters masked to treatment assignment, and the self-administered Insomnia Severity Index (ISI).
  
  
  RESULTS
  CBT-I was superior to CTRL in reducing insomnia severity (P = .028). The overall difference in depression remission between the treatments was not statistically significant (44% in CBT-I and 36% in CTRL; number needed to treat = 15). However, planned secondary analysis revealed that improvements in insomnia at week 6 mediated eventual remission from depression, with early change in ISI predicting depression remission in the CBT-I (P = .0002) but not in the CTRL arm (P = .26).
  
  
  CONCLUSIONS
  CBT-I is an efficacious treatment for insomnia comorbid with MDD among patients treated with antidepressant medications. Improvement in insomnia may be related to the change in depression. Future studies should identify which patients are most likely to benefit from the addition of an insomnia-focused therapy to standard antidepressant treatments.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00767624.
authors: Department of Psychiatry and Behavioral Sciences, Stanford University, 401 Quarry Rd, Stanford, CA 94305. rmanber@stanford.edu.|Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California, USA.
authors: Rachel
authors: R
authors: Manber
authors: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Daniel J
authors: DJ
authors: Buysse
authors: Department of Medicine, National Jewish Health, Denver, Colorado, USA.|Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA.
authors: Jack
authors: J
authors: Edinger
authors: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA.
authors: Andrew
authors: A
authors: Krystal
authors: Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: James F
authors: JF
authors: Luther
authors: Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Stephen R
authors: SR
authors: Wisniewski
authors: Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California, USA.
authors: Mickey
authors: M
authors: Trockel
authors: Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California, USA.|Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Helena C
authors: HC
authors: Kraemer
authors: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, and the Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
authors: Michael E
authors: ME
authors: Thase
mesh_terms: D000328:Adult; D000465:Algorithms; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000523:psychology; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents