Lamotrigine Therapy for Bipolar Depression: Analysis of Self-Reported Patient Data

TL;DR

This study reanalyzed data from a clinical trial to evaluate the effectiveness of lamotrigine in treating bipolar depression, finding it reduces symptoms but requires at least 44 weeks for consistent results.

Contribution

It provides an unbiased classification analysis of lamotrigine efficacy and identifies the time frame for statistically significant outcomes in bipolar depression treatment.

Findings

Lamotrigine plus Quetiapine decreased depressive symptoms.

Significant effects observed after 44 weeks of treatment.

Classification accuracy of 62% for predicting treatment response.

Abstract

Background: Depression in people with bipolar disorder is a major cause of long-term disability, possibly leading to early mortality and currently, limited safe and effective therapies exist. A double-blinded randomized placebo-controlled trial (CEQUEL study) was conducted to evaluate the efficacy of Lamotrigine plus Quetiapine versus Quetiapine monotherapy in patients with bipolar type I or type II disorders. Objective: The objective of our study was to reanalyze CEQUEL data and determine an unbiased classification accuracy for active lamotrigine versus placebo. We also wanted to establish the time it took for the drug to provide statistically significant outcomes. Methods: Between October 21, 2008 and April 27, 2012, 202 participants from 27 sites in United Kingdom were randomly assigned to two treatments; 101: lamotrigine, 101: placebo. The primary variable used for estimating depressive symptoms was based on the Quick Inventory of Depressive Symptomatology-self report version 16 (QIDS-SR16). We analyze the data using feature engineering and simple classifiers. Results: From weeks 10 to 14, the mean difference in QIDS-SR16 ratings between the groups was -1.6317 (P=.09; sample size=81, 77; 95% CI -0.2403 to 3.5036). From weeks 48 to 52, the mean difference was -2.0032 (P=.09; sample size=54, 48; 95% CI -0.3433 to 4.3497). The coefficient of variation and detrended fluctuation analysis (DFA) exponent alpha had the greatest explanatory power. The out-of-sample classification accuracy for the 138 participants who reported more than 10 times after week 12 was 62%. A consistent classification accuracy higher than the no-information benchmark was obtained in week 44. Conclusions: Lamotrigine plus Quetiapine treatment decreased depressive symptoms in patients, but with substantial temporal instability. A trial of at least 44 weeks was required to achieve consistent results.