Neuroleptic Malignant Syndrome (NMS) Induced by Clozapine at a Very Low Dose

INTRODUCTION

Clozapine, a dibenzodiazepine atypical antipsychotic, is a mainstay treatment for treatment-resistant schizophrenia. Despite its efficacy, clozapine carries a rare but potentially life-threatening side effect: neuroleptic malignant syndrome (NMS). NMS is a clinical emergency characterized by a constellation of symptoms, including fever, muscle rigidity, autonomic dysfunction, and altered mental status. While the exact mechanisms remain unclear, NMS is thought to be associated with dopamine receptor blockade, a key pharmacological action of clozapine.

CASE REPORT

The patient was a 25-year-old Muslim married female, primary pass, suffering from treatment-resistant schizophrenia for the last 10 years, with no family history of psychiatric illness. She had been under regular treatment and follow-up for the last 5 years, and she was on tab clozapine 200 mg in two divided doses over the last 2–3 months but discontinued medications because of her psychopathology for the last 10 days. Following the stoppage of medication, the patient developed catatonic symptoms characterized by rigidity, mutism, and refusal of food and fluid for the next 7 days. Because of her symptoms, she was admitted to our hospital, and after stabilizing her vitals, relevant investigations were sent. A psychiatric referral was taken. After suspecting catatonia, she was given inj Lorazepam 2 mg IV BD, and clozapine was restarted after a detailed history of taking and review of past medications. She was started on Tab Clozapine 12.5 mg on D1, and after 2 days, the dose was increased to 25 mg per day. On D4, she suddenly developed high-grade fever, low oxygen saturation, and disorientation. There was an elevated heart rate (130 bpm) and low BP (90/60 mmHg). She was quickly shifted to the ICU, and relevant investigations were sent (as mentioned below in Table 1). A high total leukocyte count and raised serum creatine phosphokinase (CPK) level were noted. She was provisionally diagnosed with NMS. Clozapine was stopped. She was monitored closely. Her vitals were stabilized. She was managed with an infusion of paracetamol 1 g for her fever, an injection of cefuroxime for sepsis coverage, and Moist O2 for breathing difficulties. Her fever subsided, and she was oriented within 2 days. She was started on Tab Olanzapine 5 mg at night, and the dose of Tab Lorazepam was increased to 2 mg in two divided doses. No autonomic instability or fever was noted after that details of his vitals and investigations reports are summarized in Table 1. However, mutism and poor oral intake persisted.

DISCUSSION

CONCLUSION

Clozapine-induced NMS, though rare, remains a serious complication requiring prompt recognition and intervention. The atypical presentations associated with clozapine-induced NMS pose a diagnostic challenge. Clinicians should maintain a high index of suspicion, considering a broader spectrum of symptoms beyond the classical triad. While the exact dose-dependent relationship is unclear, the index case report emphasizes the fact that NMS can occur with a Clozapine dose as low as 25 mg/day. Further research is crucial to elucidate the underlying mechanisms, identify reliable risk factors, and establish definitive dose thresholds. The goal is to ensure the safe and effective use of clozapine while minimizing the risk of this life-threatening side effect.