(133) Neuroleptic Malignant Syndrome from Oxcarbazepine & Topiramate Withdrawal: A Rare Case Report

Abstract: Background/Significance: Neuroleptic malignant syndrome(NMS) is a dose-independent idiosyncratic reaction from dopamine modulating medications with estimated mortality rates of 15%. Although frequently linked to antipsychotics and direct dopaminergic agents, there are paucity of literature describing other etiologies of NMS. We present a novel case of NMS from oxcarbazepine and topiramate withdrawal, in the absence of antipsychotics and direct dopamine modulators.

Case: A 20-yo-male with a history of autism, disruptive mood dysregulation disorder, generalized anxiety disorder, spastic cerebral palsy, and morbid obesity was admitted for altered mental status. Home psychotropic regimen included oxcarbazepine, topiramate, lorazepam, and clonidine. Collaterals confirmed compliance with medication, but stopped within the past week due to poor oral intake. Initially, inpatient consultation-liaison was consulted for management of agitations, where patient was noted to be non-verbal with bilateral upper extremities stiffness, intermittently high spiking fevers, and signs of autonomic instability. Labs were significant for leukocytosis, transaminitis, elevations in CPK, lactate, and CRP. Amid clinical suspicion for NMS and benzodiazepine withdrawal, lorazepam was recommended in the setting of agitation while holding all psychotropic medications. After a battery of negative diagnostic tests that ruled out numerous etiologies, including intracranial pathologies, tonic seizures, infectious meningoencephalitis, lethal catatonia, and malignant hyperthermia, the NMS research criteria was met by diagnosis of exclusion. The administration of dantrolene, amantadine, and aggressive fluid therapy provided gradual return of the patient’s baseline mentation along with normalization in laboratory reassessments.

Discussion: This case highlights the need for having a high suspicion of NMS, even in the absence of antipsychotics and when it is masked by concurrent medical conditions(e.g., cerebral palsy and autism spectrum). Clinicians should not only be vigilant of the various direct, but also indirect dopamine modulators with capability of triggering NMS. Currently, limited literature recognizes oxcarbazepine and topiramate withdrawal as causation of NMS, however, these medications are well-recognized in promoting and indirectly increasing the release of dopamine within the CNS (Clinckers2005, Huang2010, Huang2017). As a result, abrupt discontinuation of this antiepileptics can lead to a central hypodopamingergic state that physician should preventatively warn their patients about.

Conclusion/Implications: In this rare case of NMS, oxcarbazepine and topiramate withdrawal are possible attributing factors. This article emphasizes the need for hypervigilance in cases with high suspicion of NMS, in addition to raising a broader clinical awareness for other potential etiologies of NMS that is not restricted to antipsychotic medications.

References:
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HuangS, WangH, XuY. The protective action of topiramate on dopaminergic neurons. Med Sci Monit. 2010;16(9):BR307-BR312.

HuangY, MaH, WangY. Topiramate add-on treatment associated with normalization of prolactin levels in a patient with schizophrenia. Neuropsychiatr Dis Treat. 2017;13:1395-1397.https://doi.org/10.2147/NDT.S1