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image of Low-dose Olanzapine and Sertraline Combination Therapy for Metabolic Disturbance in Patients with Schizophrenia: A Large-scale, Open-label Randomized Trial

Abstract

Introduction

Olanzapine-associated metabolic adverse effects lead to medication discontinuation and non-compliance in Schizophrenia (SCZ). This study aimed to examine the efficacy of a low dose of olanzapine in combination with sertraline in mitigating metabolic adverse effects by reducing the olanzapine dose in first-episode SCZ (FE-SCZ) patients.

Methods

This randomized clinical trial with a blinded endpoint design was conducted among FE-SCZ patients. During a 12-week treatment, 196 patients with FE-SCZ were randomly assigned to the combined low-dose olanzapine/sertraline (OS group) or standard-dose olanzapine (control group). The body weight and levels of fasting glucose and blood lipids were determined at baseline and the end of weeks 4, 8, 12, and 24. Additionally, the clinical symptoms were also assessed at baseline and follow-up.

Results

Relative to the control group, the OS group had a lower percentage of weight gain from baseline to week 24 across two thresholds (7% and 10%) for changes in bodyweight (100% 97.8%; 98.7% 28.3%). In addition, combination treatment mitigated olanzapine-associated weight gain and other metabolic abnormalities compared with the control group (all < 0.01). Notably, clinical symptom improvements were similar between the two treatment groups.

Discussion

Our study suggests that low-dose olanzapine/sertraline combination therapy was correlated with significantly less weight gain and improved other metabolic parameter levels than standard-dose olanzapine in patients with FE-SCZ. Clinical symptom improvements in the combination group were comparable to those of the olanzapine monotherapy group.

Conclusion

These findings suggest a potential strategy to improve medication adherence and overall patient outcomes by mitigating metabolic side effects.

Trial Registration

ClinicalTrials.gov, NCT04076371.

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2025-11-03
2026-02-26

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Low-dose Olanzapine and Sertraline Combination Therapy for Metabolic Disturbance in Patients with Schizophrenia: A Large-scale, Open-label Randomized Trial
Bentham Science Publishers ; https://doi.org/10.2174/011570159X395131251008050155
/content/journals/cn/10.2174/011570159X395131251008050155
/content/journals/cn/10.2174/011570159X395131251008050155
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  • Article Type:     Research Article
Keywords: weight gain ; sertraline combination therapy ; first-episode SCZ (FE-SCZ) patients ; Schizophrenia ; olanzapine ; metabolic disturbance

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