Pooled analysis assessing the efficacy and safety of amphetamine derivative adjunctive therapy for bipolar depression.

OBJECTIVE

The bipolar pharmacopoeia targeting depression is significantly underdeveloped. Despite high rates of attention deficit symptoms, there has been inadequate investigation of stimulants as a treatment intervention for adults with bipolar depression.

METHODS

Data were pooled from two, 8-week, randomized, placebo-controlled trials of adjunctive mixed d-amphetamine/l-amphetamine salt (MAS) and lisdexamfetamine (LDX). The primary outcome measure was baseline-to-endpoint change in the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included treatment response and remission (50%MADRS reduction, MADRS < 10), and improvement as measured by the Clinical Global Impression for Bipolar Disorder (CGI-BP). The primary safety assessment was the Young Mania Rating Scale (YMRS).

RESULTS

Fifty-seven bipolar [BD-I: n = 23 (40.4%); BD-II: n = 34 (59.6%); male: n = 17 (29.8%); female: n = 40 (70.2%); mean age = 40.1 ± 11.3 years] depressed participants were randomized. There were no significant group differences in baseline demographics (all p ≥ 0.14). In age-adjusted analysis, participants receiving adjunctive LDX/MAS (n = 26) in comparison to placebo (n = 31) showed greater improvement in MADRS (mean % reduction: 54.6% vs. 25.6%; 95% CI: 9.1, 48.9; p = 0.005), with higher response (65.7% vs. 16.7%; p < 0.001), remission (48.8 vs. 15.3%; p = 0.007) and CGI-BP improvement rates (65.0% vs. 23.5%; p = 0.001). There was no between-group difference in YMRS scores at baseline or endpoint (p ≥ 0.36).

CONCLUSIONS

In this pooled controlled analysis, 8-week adjunctive amphetamine was associated with reduction in depressive symptoms in carefully selected patients with bipolar depression, with no increased risk of treatment-emergent mania/hypomania. Further studies are encouraged to identify clinical correlates of treatment response guiding clinicians when to consider this potentially effective treatment.