Efficacy and safety of two treatment algorithms in bipolar depression consisting of a combination of lithium, lamotrigine or placebo and paroxetine

van der Loos MLM, Mulder P, Hartong EGThM, Blom MBJ, Vergouwen AC, van Noorden MS, Timmermans MA, Vieta E, Nolen WA, for the LamLit Study Group. Efficacy and safety of two treatment algorithms in bipolar depression consisting of a combination of lithium, lamotrigine or placebo and paroxetine. Objective: In a previous paper, we reported about the efficacy of the addition of lamotrigine to lithium in patients with bipolar depression. In the second phase of this study paroxetine was added to ongoing treatment in non‐responders. Method: Bipolar depressed patients (n = 124) treated with lithium were randomized to addition of lamotrigine or placebo. In non‐responders after 8 weeks, paroxetine 20 mg was added for another 8 weeks to ongoing treatment. Results: After 8 weeks the improvement in patients treated with lamotrigine vs. patients treated with placebo was significant. After addition of paroxetine this difference disappeared as a result of greater further improvement in the non‐responders to placebo. Conclusion: Addition of lamotrigine to lithium was found effective in bipolar depressed patients. Further addition of paroxetine in non‐responders to lithium plus lamotrigine did not appear to provide additional benefit, while it appeared to do so in non‐responders to lithium plus placebo.