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Melancholic depression and response to lamotrigine for the treatment of acute bipolar depression: a pooled analysis of five randomized controlled trials








Melancholic depression and response to lamotrigine for the treatment of acute bipolar depression: a pooled analysis of five randomized controlled trials


Dr. Evyn Peters


Department of Psychiatry, College of Medicine, University of Saskatchewan






23 Apr 2019


In a recent study (1) we reanalyzed data from a previous trial of lamotrigine for bipolar II depression in which lamotrigine failed to separate from placebo (SCA100223). We found that lamotrigine was associated with higher odds of treatment response compared to placebo in patients with melancholic depression (a type of depression characterized by blunted emotions, loss of appetite, decreased sleep, slowed thinking, and excessive guilt) but not in patients with nonmelancholic depression.The purpose of the proposed research is to replicate this finding using data from four additional clinical trials, which would also allow us to extend it to patients with bipolar I depression. We would also be able to answer some additional questions that we were unable to in the original study:1. Compared to patients with nonmelancholic depression, is lamotrigine for melancholic depression more effective, and/or is placebo less effective?2. Is lamotrigine more effective for melancholic depression because it tends to be more severe than nonmelancholic depression? A previous study (2) suggested that the difference between lamotrigine and placebo is more pronounced in patients with more severe baseline depression, and melancholic depression tends to be more severe.Some have argued that psychomotor retardation (i.e., slowing of thoughts and actions) is the core feature of melancholic depression, with other symptoms in the DSM being mostly superfluous. Consistently, a pooled analysis of two trials (unipolar and bipolar depression) found that lamotrigine exerted its effect mostly on psychomotor retardation and depressed thinking patterns, rather than sleep, appetite, energy, or mood, although they did not test to see if patients with higher psychomotor retardation at baseline had a greater overall response to lamotrigine compared to placebo. Therefore, an additional question we would like to explore is:3. Is the DSM definition of melancholic depression a more useful predictor of response to lamotrigine than the single question regarding psychomotor retardation?



[{ "PostingID": 1806, "Title": "GSK-SCA100223", "Description": "A Multicenter, Double-Blind, Placebo-Controlled, Fixed-Dose, 8-Week Evaluation of the Efficacy and Safety of Lamotrigine in the Treatment of Depression in Patients with Type II Bipolar Disorder" },{ "PostingID": 1807, "Title": "GSK-SCA30924", "Description": "Double blind placebo controlled study of lamictal in acute bipolar depression" },{ "PostingID": 1826, "Title": "GSK-SCA40910", "Description": "A Multicenter, Double-Blind, Placebo-Controlled, Fixed-Dose Evaluation of the Safety, Efficacy, and Tolerability of LAMICTAL (Lamotrigine) in the Treatment of a Major Depressive Episode in Patients with Type I Bipolar Disorder" },{ "PostingID": 16074, "Title": "GSK-SCAA2010", "Description": "A Multicenter, Double-Blind, Placebo-Controlled, Flexible Dose (100-400mg) 10 Week Evaluation Of the Safety and Efficacy of LAMICTAL (Lamotrigine) in the Treatment of a Major Depressive Episode in Patients with Bipolar Disorder" },{ "PostingID": 16075, "Title": "GSK-SCAB2001", "Description": "A Multicenter, Double-Blind, Placebo-Controlled, Fixed Dose (50 or 200mg per day) 7 Week Evaluation of the Safety and Efficacy of LAMICTAL (Lamotrigine) in the Treatment of a Major Depressive Episode in Patients Suffering From Bipolar Disorder" }]

Statistical Analysis Plan