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Melancholic symptoms in bipolar depression and response to lamotrigine








Melancholic symptoms in bipolar depression and response to lamotrigine


Dr. Evyn Peters


Department of Psychiatry, University of Saskatchewan (U of S), Saskatchewan, Canada


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01 November 2016


Clinical depression encompasses a broad range of symptoms, and different symptoms are associated with different neurological processes. Each antidepressant medication affects the brain in a unique way, which may affect some symptoms but not others. Decades of research have repeatedly demonstrated that depressed patients suffering from what has been called melancholic symptoms (e.g., the inability to feel pleasure, poor appetite, sluggish thoughts and behaviour, etc.) respond better to certain antidepressants. Melancholic symptoms also occur in bipolar depression, although they have received less research. Lamotrigine, a mood-stabilizing medication with known antidepressant properties, has been shown to reverse biological processes that are known to occur in melancholic depression.
The purpose of the proposed study will be to determine if melancholic symptoms can be used to predict which patients with bipolar depression will respond to the lamotrigine. To do this, we would like to re-analyze a previous clinical trial that evaluated lamotrigine as a treatment for bipolar depression. This method is not only more cost-effective than conducting a new trial, but is also more ethical as it avoids exposure to medications side effects for the purpose of research.
Response rates for all antidepressants remain low (roughly 30%). Given the known lag-time between antidepressant initiation and response (roughly 4-6 weeks), trial-and-error prescribing is an inevitably lengthy process. A better understanding of predictors of response to medications such as lamotrigine will lead to more timely and effective treatment of patients, as well as reduced financial burden of diseases to society as a whole (e.g., less time hospitalized or on disability). Results from this study could be of particular benefit for patients with bipolar depression.
It is also worth mentioning that bipolar depression, in contrast to unipolar depression, is often treated with a combination of antidepressant and mood-stabilizing medications in order to prevent episodes of mania after the depression has subsided. Lamotrigine has both antidepressant and mood-stabilizing properties, and patients with bipolar depression can be safety managed on lamotrigine alone. Therefore, a greater understanding of which patients respond to lamotrigine could actually reduce the number of medications some patients with bipolar depression will require, and subsequently, reduce medication costs and side effects. Furthermore, compared to most antidepressants, and almost all mood-stabilizers, lamotrigine causes less weight gain and metabolic disturbances like diabetes, and is also less toxic to organs such as the liver and kidneys. Given these advantages, it seems imperative to know which patients are most likely to respond to lamotrigine.



[{ "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" }]

Statistical Analysis Plan


Peters, E. M., Bowen, R., & Balbuena, L. (2018). Melancholic Symptoms in Bipolar II Depression and Responsiveness to Lamotrigine in an Exploratory Pilot Study. Journal of clinical psychopharmacology.
DOI: 10.1097/JCP.0000000000000947

https://journals.lww.com/psychopharmacology/Fulltext/2018/10000/Melancholic_Symptoms_in_Bipolar_II_Depression_and.18.aspx