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Journal of Case Reports
Lurasidone Induced Weight Gain: A Case Report From Oman
Saleha Al-Jadidi1,2,3, Mervat Said1,2, Hazim Mohamed1
1Al Masarra Hospital, Muscat, Oman; 2Oman Medical Speciality Board (OSMB), Muscat, Oman; 3SJMC Mind and Body Clinic, Muscat, Oman.
Corresponding Author:
Dr Saleha Al-Jadidi
Email: Saleha.aljadidi@moh.gov.om
Received: 20-SEP-2025 Accepted: 22-DEC-2025 Published Online: 05-JAN-2026
DOI: http://dx.doi.org/10.17659/01.2026.0001
Abstract
Background: Antipsychotic-induced weight gain (AIWG) is a common and clinically significant side effect of many second-generation antipsychotics. While lurasidone is generally associated with a more favourable metabolic profile, individual variability in response remains a concern. Real-world evidence is still limited regarding its long-term metabolic side effects. Case Report: A 44-year-old woman with a long-standing history of psychotic symptoms, including persecutory delusions, who had previously been stabilized on long-acting injectable paliperidone. She developed hyperprolactinemia and amenorrhea after several doses, prompting a switch to oral lurasidone (40 mg daily). While her menstrual cycle normalized post switch, she experienced significant weight gain of approximately 15 kg over six months, despite no changes in lifestyle or concurrent medications. Conclusion: This case highlights that, although lurasidone is generally considered metabolically neutral, significant weight gain can still occur in certain individuals. Clinicians should remain vigilant for metabolic side effects even when prescribing antipsychotics perceived as lower risk, and personalized monitoring remains essential in long-term management.
Keywords : Amenorrhea, Antipsychotic Agents, Hyperprolactinemia, Psychotic Disorders, Weight Gain.
Introduction 

Antipsychotic-induced weight gain (AIWG) is a well-recognized adverse effect of antipsychotic therapy and represents a major challenge in long-term psychiatric management. The magnitude of weight gain varies widely across antipsychotic agents, with several drugs conferring a high risk of metabolic complications, including obesity, dyslipidemia, type 2 diabetes mellitus, and cardiovascular disease [1]. 
Lurasidone is a second-generation (atypical) antipsychotic approved for the treatment of schizophrenia and bipolar depression and is generally regarded as having a favourable metabolic profile. Evidence from randomized controlled trials and comparative studies suggests that lurasidone is associated with minimal weight gain and a lower risk of metabolic disturbances when compared with many other atypical antipsychotics [2]. Consequently, it is frequently preferred in patients with existing metabolic risk factors. Nevertheless, despite its perceived metabolic safety, AIWG remains a clinically relevant concern. Even modest weight changes can have significant long-term health implications, and emerging real-world data indicate that a subset of patients may experience clinically significant weight gain while receiving lurasidone [3,4]. We report this case to highlight an uncommon but clinically important adverse effect of lurasidone-induced weight gain, particularly in a real-world setting from Oman. This report aims to raise awareness among clinicians, emphasize the need for regular metabolic monitoring even with antipsychotics considered weight-neutral, and contribute to the limited literature on lurasidone’s metabolic effects in diverse populations.

Case Report

A 44-year-old married woman presented to the outpatient psychiatry clinic with a long-standing history of psychotic symptoms. She described persistent persecutory and referential delusions, including a fixed belief that others were aware of and discussing her same-sex attraction. She also believed she had been forced into her marriage and was under continuous pressure from her family to remain with her husband. In addition, she held a firm conviction that a catastrophic event would occur in Oman, specifically an attack by the United States, and believed herself to be personally responsible and deserving of punishment. These symptoms were accompanied by significant sleep disturbance and a marked decline in social and occupational functioning.
The onset of her psychiatric illness dated back to the age of 12 years, following the death of her mother. Although she had been able to cope with her symptoms for many years, there was a notable exacerbation in the months preceding presentation, prompting psychiatric consultation. She had no significant medical comorbidities. Her family history was significant for schizophrenia in her mother and unspecified psychiatric illnesses in two other relatives. During childhood, she had received psychiatric treatment for depression, although details of the medications were unavailable. She also reported a difficult childhood characterized by physical abuse.
Initial treatment with oral antipsychotic medication was limited by poor adherence, leading to a decision to initiate a long-acting injectable (LAI) antipsychotic. She was started on paliperidone palmitate (Invega Sustenna®) 100 mg monthly, which resulted in good symptomatic control and complete remission of psychotic features. To further improve adherence, she was subsequently transitioned to paliperidone palmitate three-monthly formulation (Invega Trinza®) at a dose of 350 mg every three months. Her psychiatric symptoms remained well controlled. However, after three injections of paliperidone Trinza®, the patient developed amenorrhea. Laboratory evaluation revealed elevated serum prolactin levels consistent with hyperprolactinemia, while other investigations were within normal limits. In view of these adverse effects, paliperidone was discontinued and treatment was switched to lurasidone at a dose of 40 mg daily, with close follow-up given her previous adherence issues. Following this change, her menstrual cycle resumed.
Over the subsequent six months of lurasidone therapy, the patient experienced a progressive and significant weight gain of approximately 15 kg. She was not receiving any other psychotropic or medical medications and did not report substantial changes in diet, physical activity, or lifestyle during this period. The weight gain was distressing to the patient and raised concerns regarding an atypical metabolic response to lurasidone, highlighting the variability of weight-related side effects even with antipsychotics considered to have a favorable metabolic profile.

Discussion 

This case highlights the complexity of antipsychotic selection in patients with chronic psychotic disorders, where clinicians must carefully balance therapeutic efficacy with metabolic and endocrine safety. Lurasidone, a second-generation antipsychotic with high affinity for dopamine D2 and serotonin 5-HT2A receptors, is generally regarded as having a weight-neutral or metabolically favourable profile [5]. However, in the present case, the patient developed a substantial and clinically significant weight gain of approximately 15 kg within six months of treatment. This unexpected outcome emphasizes the need for ongoing, individualized metabolic monitoring even when prescribing antipsychotics considered to carry a low risk of weight gain, particularly in vulnerable populations. Evidence from randomized controlled trials and meta-analyses consistently demonstrates minimal weight gain with lurasidone compared with higher-risk SGAs such as olanzapine and clozapine [6,7]. Nevertheless, real-world experiences may diverge from trial data, as illustrated by this case, suggesting that the metabolic neutrality of lurasidone may not be universal. Several mechanisms may account for this interindividual variability.
Genetic susceptibility is a potential contributing factor. Polymorphisms in genes involved in appetite regulation and energy balance, including melanocortin-4 receptor (MC4R) and serotonin receptor 2C (HTR2C), have been associated with increased vulnerability to antipsychotic-induced weight gain [8,9]. Although genetic testing was not undertaken in this patient, such variants may partially explain the pronounced metabolic response observed. Another possible contributor is the patient’s prior exposure to prolactin-elevating antipsychotic therapy. Long-term treatment with paliperidone, which is known for its potent D2 antagonism and high propensity to cause hyperprolactinemia, may have altered hypothalamic–pituitary regulatory pathways [10,11]. Discontinuation of paliperidone and subsequent normalization of prolactin levels after switching to lurasidone may have triggered a rebound metabolic effect, manifesting as rapid weight gain. Psychosocial factors may also have played a role. The patient’s history of childhood trauma and chronic psychological stress has been linked to long-term metabolic dysregulation through mechanisms involving chronic inflammation, altered cortisol secretion, and hypothalamic–pituitary–adrenal (HPA) axis dysfunction [12]. Such factors may increase susceptibility to weight gain during psychotropic treatment, even with agents typically considered metabolically benign.
Finally, the interaction between gender, endocrine changes, and metabolic outcomes warrants consideration. The development of amenorrhea and hyperprolactinemia during paliperidone treatment is consistent with its known endocrine profile [13]. Although lurasidone is generally associated with minimal and transient prolactin elevation [5], the temporal association between prolactin normalization and subsequent weight gain in this patient raises the possibility of a compensatory or adaptive metabolic response following prolonged dopaminergic suppression [14,15]. This phenomenon may be particularly relevant in female patients, who are more susceptible to antipsychotic-induced endocrine and metabolic adverse effects.
Overall, this case adds to the emerging real-world evidence that clinically meaningful weight gain can occur with lurasidone in select individuals. It reinforces the importance of regular metabolic monitoring, patient education, and individualized risk assessment, even when prescribing antipsychotics with a perceived favourable metabolic profile.

Conclusion

This case shows that even "weight-neutral" antipsychotics like lurasidone can cause significant weight gain in susceptible individuals, despite a favourable metabolic profile. Clinicians should monitor weight and metabolic parameters regularly, individualize antipsychotic selection based on endocrine and psychosocial risks, and remain vigilant for metabolic changes after switching from prolactin-elevating agents. Further research is needed to understand individual susceptibility and optimize long-term safety.

Contributors: SAJ: manuscript writing, data collection, patient management; MS: manuscript editing, patient management; HM: manuscript editing, critical inputs into the manuscript. SAJ will act as a study guarantor. All authors approved the final version of this manuscript and are responsible for all aspects of this study.
Funding: None; Competing interests: None stated.

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Al-Jadidi S, Said M, Mohamed HLurasidone Induced Weight Gain: A Case Report From Oman.JCR 2026;16:1-4
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Al-Jadidi S, Said M, Mohamed HLurasidone Induced Weight Gain: A Case Report From Oman.JCR [serial online] 2026[cited 2026 Mar 14];16:1-4. Available from: http://www.casereports.in/articles/16/1/Lurasidone-Induced-Weight-Gain.html
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Last updated on Mar 11, 2026