Lamotrigine adjunctive therapy to lithium and divalproex in depressed patients with rapid cycling bipolar disorder and a recent substance use disorder: A 12-week, double-blind, placebo-controlled pilot study

Objective: To pilot the efficacy and safety data of lamotrigine adjunctive therapy to lithium and divalproex in patients with rapid-cycling bipolar disorder (RCBD) and a recent substance use disorder (SUD). Method: Structured Clinical Interviews were used to ascertain DSM-IV diagnosis of RCBD, SUDs, and other Axis I disorders. Patients who did not meet the criteria for a bimodal response after up to 16-weeks of open-label treatment with lithium plus divalproex, as measured by MADRS (Montgomery-Asberg Depression Rating Scale) ≤19, YMRS (Young Mania Rating Scale) ≤12 and GAF (Global Assessment of Functioning) ≥51 for 4 weeks, were randomized to a 12- week, double-blind addition of lamotrigine or placebo to lithium plus divalproex. Primary and secondary outcomes were analyzed with ANCOVA, t-test, or chi-square/Fisher's exact. Results: Of 98 patients enrolled into the study, 36 were randomized to receive lamotrigine (n =18) or placebo (n = 18), and 8 patients per arm completed the study. No patient discontinued due to adverse events. The change in MADRS total score from baseline to endpoint was -9.1 ± 11.2 in lamotrigine-treated patients versus -4.5 ± 13.1 in placebo-treated patients (p = 0.27). There were no significant differences in changes in YMRS total scores and rates of response or remission. Conclusions: Lamotrigine adjunctive therapy was well tolerated in patients previously non-responsive to initial treatment of lithium plus divalproex. A larger study is warranted to determine the efficacy and safety of adjunctive lamotrigine versus placebo in RCBD with a recent SUD.