Response to placebo among bipolar I disorder patients experiencing their first manic episode


Corresponding author: KN Roy Chengappa, MD, Western Psychiatric Institute and Clinic, Special Studies Center at Mayview State Hospital, 3811 O'Hara Street, Pittsburgh, PA 15213-2593, USA. Tel: +1 412 624 2634; fax: +1 412 624 0493; e-mail:


Background: The first episode of an illness may respond differently to any treatment compared to multiple episodes of the same illness. This study details the treatment response of six first-episode manic patients who participated in a previously reported study of 139 subjects comparing olanzapine to placebo in bipolar I mania (Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KNR, Daniel DG. Olanzapine versus placebo in the treatment of acute mania. Am J Psychiatry 1999; 156: 702–709).

Methods: Six first-episode subjects participated in a 3-week double-blind, random assignment, parallel group, placebo-controlled study of olanzapine for bipolar mania. The Young Mania Rating Scale (Y-MRS), Clinical Global Impression, and Hamilton Depression ratings were administered weekly. Lorazepam as rescue medication was permitted for the first 10 days.

Results: Five subjects were randomized to placebo and one to olanzapine. Two subjects (40%) with psychotic mania (who also had their first-illness episode) were assigned to placebo and responded with greater than 50% reduction in the Y-MRS score and also remitted in 3 weeks. Another placebo-assigned subject had a 46% reduction in the Y-MRS scores, and two placebo-assigned subjects worsened. The olanzapine-assigned subject had a 44% reduction in the Y-MRS score. In contrast, 34 of 69 (48.6%) multiple-episode olanzapine subjects responded and 14 of 61 (23.0%) of placebo-treated subjects did.

Conclusions: This preliminary data set suggest there may be differences in treatment response between first-illness episode versus multi-episode bipolar manic subjects. Larger numbers of subjects with these illness characteristics are needed to either confirm or refute this suggestion.