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Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials.

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Goss, Alexander J 
Costafreda, Sergi G 
Sahakian, Barbara J 
Fu, Cynthia HY 


OBJECTIVE: Current pharmacologic treatments for a depressive episode in unipolar major depressive disorder (MDD) and bipolar depression are limited by low rates of remission. Residual symptoms include a persistent low mood and neurovegetative symptoms such as fatigue. The objective of this study was to examine the efficacy and tolerability of augmentation of first-line therapies with the novel stimulant-like agent modafinil in MDD and bipolar depression. DATA SOURCES: MEDLINE/PubMed, PsycINFO, 1980-April 2013 were searched using the following terms: (modafinil or armodafinil) and (depressi* or depressed or major depressive disorder or major depression or unipolar or bipolar or dysthymi*). Inclusion criteria were as follows: randomized controlled trial (RCT) design, sample comprising adult patients (18-65 years) with unipolar or bipolar depression, diagnosis according to DSM-IV, ICD-10, or other well-recognized criteria, modafinil or armodafinil given as augmentation therapy in at least 1 arm of the trial, and publication in English in a peer-reviewed journal. STUDY SELECTION: Double-blind, randomized, placebo-controlled clinical trials of adjunctive treatment with modafinil or armodafinil of standard treatment for depressive episodes in MDD and bipolar depression were selected. DATA EXTRACTION: Two independent appraisers assessed the eligibility of the trials. A random-effects meta-analysis with DerSimonian-Laird method was used. Moderator effects were evaluated by meta-regression. RESULTS: Data from 6 RCTs, with a total of 910 patients with MDD or bipolar depression, consisting of 4 MDD RCTs (n = 568) and 2 bipolar depression RCTs (n = 342) were analyzed. The meta-analysis revealed significant effects of modafinil on improvements in overall depression scores (point estimate = -0.35; 95% CI, -0.61 to -0.10) and remission rates (odds ratio = 1.61; 95% CI, 1.04 to 2.49). The treatment effects were evident in both MDD and bipolar depression, with no difference between disorders. Modafinil showed a significant positive effect on fatigue symptoms (95% CI, -0.42 to -0.05). The adverse events were no different from placebo. CONCLUSIONS: Modafinil is an effective augmentation strategy for acute depressive episodes, including for symptoms of fatigue, in both unipolar and bipolar disorders.



Antidepressive Agents, Antimanic Agents, Benzhydryl Compounds, Bipolar Disorder, Depressive Disorder, Major, Drug Therapy, Combination, Humans, Modafinil, Personality Inventory, Psychometrics, Randomized Controlled Trials as Topic, Wakefulness-Promoting Agents

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J Clin Psychiatry

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Physicians Postgraduate Press, Inc
Wellcome Trust (089589/Z/09/Z)
Wellcome Trust (093875/Z/10/Z)
Medical Research Council (G0001354)
Medical Research Council (G1000183)