Severe Nondiabetic Hypoglycemia After Risperidone Initiation in an Adult With Schizophrenia: A Case Report and Systematic Review.

Hypoglycemia is a rare but potentially serious adverse effect of second-generation antipsychotics (SGAs). Most studies have focused on SGA-induced hyperglycemia and metabolic syndrome, while hypoglycemia in non-diabetic adults remains underreported. We describe a case of severe hypoglycemia following risperidone initiation, demonstrating diagnostic challenges and safety concerns. A 41-year-old woman with treatment-resistant schizophrenia, Asperger's syndrome, and attention-deficit/hyperactivity disorder was admitted for worsening commanding auditory hallucinations and persecutory delusions. Risperidone was started at 2 mg nightly and increased to 3 mg after four days. The patient developed recurrent episodes of severe hypoglycemia (random blood glucose levels 35-50 mg/dL; hypoglycemia defined as <70 mg/dL), accompanied by hypotension, tachycardia, nausea, vomiting, dizziness, and altered mental status, shortly after increasing the dose of risperidone. Extensive laboratory and imaging evaluations were unremarkable except for persistent hypoglycemia. The episodes continued despite aggressive glucose replacement and supportive medical treatment. After risperidone was discontinued, blood glucose levels gradually normalized within 48-72 hours, and no further hypoglycemic episodes occurred. To contextualize this case, a systematic literature search was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using PubMed, PubMed Central, PsycINFO, Embase, and Google Scholar, with keywords including "risperidone", "second-generation antipsychotics", and "hypoglycemia", as well as MeSH terms. Studies involving adult non-diabetic psychiatric patients with antipsychotic-associated hypoglycemia were included. Nine relevant case reports and case series were identified and evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports. Existing literature shows that hypoglycemia associated with SGAs is rare but has been reported with several agents, including risperidone, quetiapine, olanzapine, paliperidone, clozapine, and aripiprazole. Proposed mechanisms include hyperinsulinemia and impaired counter-regulatory responses related to antipsychotic receptor effects. Because symptoms such as confusion, dizziness, and weakness may mimic psychiatric symptoms or medication side effects, diagnosis may be delayed. This case highlights that risperidone can rarely cause severe hypoglycemia even in non-diabetic adults. Although limited by a single case and lack of insulin measurements, this study emphasizes the need for early recognition, glucose monitoring during SGA use, and multidisciplinary care to prevent serious complications. Further research is needed to better understand the underlying biological mechanisms and identify potential risk factors.