Volume 30, Issue 172, June 2026

Pharmacological and Non- Pharmacological Strategies for the Prevention and Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia: A Narrative Review

Aleksandra Pietrucień^1♦, Agnieszka Mackiewicz¹, Adam Brożyna², Natalia Kursa³, Katarzyna Bielak⁴, Krystian Woźniak³, Julia Witkowska³, Ksenia Jakubiak³, Mikołaj Kurczyński³, Monika Krasoń³

¹Medical Centre of Pabianice, Pabianice, 95-200, ul. Jana Pawła II 68, Poland
²University Clinical Hospital No. 1 of the Medical University of Lodz, Łódź, 90-153, ul. Kopcińskiego 22, Poland
³Central Teaching Hospital of The Medical University of Lodz, Łódź, 92-213, ul. Pomorska 251, Poland
⁴5 Military Clinical Hospital in Cracow, 30-901 Cracow, ul. Wrocławska 1-3, Poland

^♦Corresponding author
Aleksandra Pietrucień, Medical Centre of Pabianice, Pabianice, 95-200, ul. Jana Pawła II 68, Poland

ABSTRACT

Antipsychotic-induced weight gain (AIWG) is a common problem encountered in the treatment of schizophrenia. This side effect often appears soon after starting treatment and can harm physical health and make it harder for patients to stick with their therapy. This review examines current approaches to preventing and managing AIWG, concentrating on practical strategies for clinical use. The pathogenesis of AIWG is complex. The most important pathways are linked to metabolic imbalance, impaired glucose control, and abnormal lipid levels, as well as modulation of appetite mediated by H1, 5-HT2C, and D2 receptors. Inflammation and the gut microbiome are emerging factors. Together, these mechanisms help explain why some antipsychotics carry a higher metabolic risk than others. Early prevention is critical. Choosing lower-risk antipsychotics and monitoring weight from the beginning of treatment are key initial steps. The most established pharmacological option affecting both body weight and metabolic parameters is metformin. Newer approaches, such as GLP-1 receptor agonists, look promising and may lead to greater weight reduction. Other options, including orlistat and the olanzapine/samidorphan combination (OLZ/SAM), may be useful in selected clinical cases. In the future, more experimental strategies such as targeting the gut microbiome or using neuromodulation could become relevant. Both pharmacological and non-pharmacological approaches are used to prevent and treat AIWG. Regardless of which strategy is used, interventions should be individualized. Despite advances in this field, important questions remain about long-term outcomes and optimal treatment options.

Keywords: antipsychotic agents, drug-related side effects, adverse reactions, schizophrenia, weight gain, management of obesity, obesity treatment

Medical Science, 2026, 30, e106ms3884

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Published: 18 June 2026