Olanzapine induced paresthesia

Dear Editor, Olanzapine is a widely used atypical antipsychotic for schizophrenia, bipolar disorder, and treatment-resistant depression. Its efficacy is related to antagonism at dopaminergic, serotonergic, muscarinic, histaminergic, and adrenergic receptors.[1] Although generally well tolerated, olanzapine is associated with adverse effects such as metabolic disturbances, sedation, and anticholinergic symptoms. Neurological sensory side effects are rarely reported. Paresthesia, characterized by tingling, prickling, or itching without external stimulus, is distressing and may contribute to poor adherence, yet is not commonly associated with olanzapine.[2] Other antipsychotics, including quetiapine, have been implicated in producing paranesthesia and restless legs–like symptoms.[3] We report two cases of schizophrenia where olanzapine induced paresthesia. A 40-year-old male with a 5-year history of schizophrenia, continuous course, presented with suspiciousness and aggressive behavior. Olanzapine 10 mg/day was initiated. Within one week, he developed persistent bilateral tingling and numbness in the feet, described as a continuous pin-pricking sensation. Family members discontinued the drug without consultation, after those symptoms resolved. On rechallenge, paresthesia reappeared within 4 days. Neurological examination, metabolic workup, vitamin B12 levels, and nerve conduction studies were normal. The Naranjo adverse drug reaction (ADR) probability score was 8, indicating a probable relationship. The patient was switched to aripiprazole, following, which paresthesia did not recur. The second case involved a 38-year-old male with schizophrenia, admitted with worsening paranoia, auditory hallucinations, and poor sleep. He was restarted on olanzapine 10 mg/day and titrated to 15 mg/day over 1 week. By day 10, he reported bilateral tingling and burning sensations in the soles progressing to calves. Neurological evaluation and laboratory tests, including nerve conduction studies, were normal. Dose reduction to 10 mg resulted in improvement, but escalation back to 15 mg/day reproduced symptoms within 4 days. The Naranjo ADR score was 9, suggesting a definitive causal relationship. The pathophysiological mechanism of olanzapine-induced paresthesia remains unclear. Antagonism at dopamine D2 and serotonin 5-HT2 receptors, which are involved in sensory modulation, may underlie these abnormal sensations.[4] Restless leg syndrome has been reported with olanzapine,[5] but unlike typical restless leg symptoms, the paresthesia in our patients was persistent, not relieved by movement, and occurred throughout the day. The absence of metabolic, nutritional, or neurological abnormalities further supports a drug-induced etiology. These cases emphasize the importance of recognizing paresthesia as a rare but clinically significant adverse effect of olanzapine. While not life-threatening, such symptoms can be distressing, compromise adherence, and increase relapse risk. Early identification, dose modification, or switching to alternative agents may prevent unnecessary investigations and improve treatment outcomes. Reporting such cases adds to pharmacovigilance data and helps refine the safety profile of antipsychotics. Ethics committee details The study was approved by the Institutional Ethics Committee of Mahatma Gandhi Memorial Medical College, Indore (Approval No. IEC/MGMMC/2025/48, dated 12 June 2025). Data sharing statements Data will share via Corresponding Email on request. Authors’ contributions VM: Supervised the work and final approval of manuscript. AK: Collected data and conceptualized the manuscript. PG: Manuscript writing and case management. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.