When the treatment for psychogenic polydipsia backfires: the analysis of clozapine-induced neuroleptic malignant syndrome

Abstract: Our case involves a 64-year-old male with a past psychiatric history of schizoaffective disorder (bipolar type; on clozapine 400mg nightly) and who presented to the hospital for evaluation after a near syncopal episode and generalized weakness in the setting of 3-7 days of decreased oral intake. He was found to have orthostatic hypotension, tachycardia, and was febrile at 102.2F. His creatine kinase was found to be elevated at 5,299. CXR revealed consolidation in the left lower lung, indicating aspiration pneumonia. He was admitted to the ICU for the treatment of suspected NMS. His clozapine was held. He was treated supportively and discharged 3 days later. It is possible that the patient’s clozapine therapy led to decreased water intake, causing him to become dehydrated. Dehydration is a risk factor for the development of aspiration pneumonia. Aspiration pneumonia can further exacerbate the degree of dehydration due to pro-inflammatory cytokine release, which also contributed to the patient’s development of NMS due to decreased CYP1A2 expression from these stated pro-inflammatory cytokines, suddenly increasing clozapine’s plasma level. Clozapine has been shown to be an effective treatment for psychogenic polydipsia as it can reduce water drinking behavior. There have been no studies examining water drinking behavior in individuals who are on clozapine therapy but not suffering from psychogenic polydipsia. Such individuals on clozapine may be at risk of developing drug-induced dehydration and secondary adverse effects related to dehydration such as orthostatic hypotension, aspiration pneumonia, and in rare cases, NMS, especially if clozapine’s plasma level becomes supratherapeutic.Short Description: The impact of dehydration on neuroleptic malignant syndrome has been believed to be both a risk factor and symptom of the disorder. The impact of dehydration and sequela of adverse events that took place in a patient with a history of schizoaffective disorder will be discussed. Clozapine may have ignited the patient’s dehydration, as it has been proven to be an effective treatment for psychogenic polydipsia due to its ability to decrease water drinking behavior.Name of Sponsoring Organization(s): N/A