Conditions: Bipolar Disorder
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 4
Healthy volunteers: no

Brief summary:
Primary Aim: To estimate the antidepressant efficacy of simvastatin versus placebo as an adjunct to lithium, valproate, and/or other atypical antipsychotic therapy among individuals with bipolar I disorder in a nonpsychotic major depressive episode.

Hypothesis: Simvastatin will be superior to placebo in improvement of depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale (MADRS).

Detailed description:
(see brief summary)

Arms:
arm 1: Subjects will receive simvastatin in phase 1 (4 weeks) and phase 2 (4 weeks) arm 2: Placebo non-responders after the 1st 4 weeks will be re-randomized 1:1 to placebo or simvastatin for the next 4 weeks arm 3: Placebo nonresponders for the 1st 4 weeks will be re-randomized 1:1 to placebo or simvastatin for the subsequent 4 weeks

Interventions: intervention 1: Simvastatin intervention 2: Placebo
Intervention descriptions: intervention 1: The study uses the Sequential Parallel Comparison design (SPCD), with two 4-week phases: n=30 subjects are randomized 1:1 to simvastatin versus placebo add-on for 4 weeks, with the nonresponders re-randomized 1:1 for a further 4 weeks. The SPCD will allow us to pool data from both phases to estimate the simvastatin treatment effect. Subjects who respond in phase 1, and all subjects who receive simvastatin in phase 1, continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed. Dosage for simvastatin or matched placebo 20mg daily for 8 weeks. intervention 2: Subjects (n=15) are randomized to placebo add-on for 4 weeks, with the nonresponders re-randomized 1:1 to statin vs placebo for a further 4 weeks. Subjects who respond in phase 1 continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed. Dosage for simvastatin or matched placebo 20mg daily for 8 weeks.

Protocol document: