Efficacy and safety of olanzapine for treatment of patients with bipolar depression: Chinese subpopulation analysis of a double-blind, randomized, placebo-controlled study

Abstract

BackgroundDepression in bipolar I disorder responds to the atypical antipsychotic olanzapine. This subpopulation analysis assessed whether olanzapine is superior to placebo specifically in the treatment of Chinese patients with bipolar I depression.MethodsThis was a subpopulation analysis of a 6-week, multicenter, double-blind, parallel, randomized, placebo-controlled trial among 12 Chinese study centers. Eligible inpatients and outpatients were randomized to olanzapine (5 to 20 mg/day) or placebo. Patients were primarily assessed by the Montgomery-Åsberg Depression Rating Scale total score. Secondary assessments used a range of other efficacy and safety measures. This subpopulation analysis was underpowered to show statistically significant differences between treatment groups.ResultsIn total, 210 patients (mean age 32.9 years at baseline, 54.3% females) were random-ized. Similar proportions of patients treated with olanzapine (75.0%) and placebo (72.9%) completed the double-blind phase. Baseline-to-endpoint least-squares mean ± standard error decrease in the Montgomery-Åsberg Depression Rating Scale total score in the olanzapine group (−13.55±0.80) was similar to that noted in the parent trial (−13.82±0.65). However, the difference between olanzapine and placebo groups was not statistically significant (P=0.44); this finding was also true for the secondary efficacy measures. A post hoc analysis showed a greater emergence of mania in the placebo group, which likely reduced the treatment difference between olanzapine and placebo in the primary efficacy measure. Safety data were consistent with the known safety profile of olanzapine, including a higher incidence of weight gain (≥7%) in the olanzapine group (24.1% vs 1.4%, P<0.001).ConclusionOlanzapine provides similar improvement in depression among Chinese and non-Chinese bipolar I patients. The lack of a statistically significant difference between the olanzapine and placebo groups in this Chinese subpopulation analysis may relate to an a priori lack of study power, and underestimation of the effect of olanzapine because of a greater emergence of mania in placebo-treated patients and missing data associated with a high early discontinuation rate.

Samidorphan/olanzapine combination therapy for schizophrenia: Efficacy, tolerance and adverse outcomes of regimen, evidence-based review of clinical trials

“…In view of the adverse effects of olanzapine which are evident from various studies, such as weight gain, obesity, dyslipidemia, diabetes mellitus, and metabolic syndrome; U.S. FDA approved a combination dose of OLZ/SAM (LYBALVI™) to mitigate the effects of weight gain by olanzapine for the treatment of schizophrenia and bipolar I disorder [ [26] , [27] , [28] , [29] , [30] ]. It received its first approval on May 28, 2021 in the USA for treating not only schizophrenia but also bipolar I disorder (including acute treatment of manic or mixed episodes as monotherapy and as an adjunct to lithium or valproate, and maintenance monotherapy treatment) in adults [ 30 ].…”

“…One of the most recurring adverse effects of olanzapine is weight gain and obesity which has been reiterated in several studies. A study conducted by Cheng et al indicated that after six weeks of treatment with olanzapine (5–20 mg/d) in Chinese patients with bipolar I disorder, significantly more patients receiving olanzapine experienced a clinically relevant weight gain (CRW) (24.1% vs. 1.4%), as well as a significantly higher, mean weight increase (2.44 vs. 0.16 kg) compared to placebo [ 28 ]. In a study by Shen, Zhao, Rosenzweig-Lipson et al olanzapine caused significantly more weight gain (average mean weight change: 4.04 kg [2.51; 5.57]) over a course of six weeks compared to placebo (p < 0.001).…”