Re-Challenge with Clozapine after Neuroleptic Malignant Syndrome and Seizure in a Patient with Di-George Syndrome: Case Report and Review of Literature

Abstract

Background: Individuals with 22q11.2DS, a genetic subtype of Schizophrenia, respond as well to clozapine as those with other forms of Schizophrenia. It has been reported that serious and rare adverse events like seizures, and myocarditis have been associated with clozapine treatment in this population. To the best of our knowledge, the incidence of neuroleptic malignant syndrome (NMS) as an adverse effect of antipsychotic use in patients with this disorder has not yet been reported. Aim: In this article, we discuss a case of clozapine-induced NMS and subsequent re-challenge in a patient with 22q11.2DSassociated schizophrenia. The aim of this study is to accumulate scientific data about rare presentations, and serve as a major educational tool, and highlight the unique challenges faced when using clozapine in a patient with Di-George Syndrome. Methods: This is a descriptive case report of a patient encountered in the inpatient unit which includes retrospective review of the patient's electronic medical record and a literature review of antipsychotic medications-induced NMS. Conclusion: This study demonstrates a successful re-challenge with clozapine after the patient developed NMS and seizures during the initial treatment and also highlights how, in addition to drug level monitoring, considering pharmacogenetic testing early in treatment might help minimize adverse drug reactions in individuals with known genetic disorders such as 22q11.2DS.

Clozapine Use in 22q11.2 Deletion Syndrome

“…Notably, very few articles in this review reported clozapine levels in general, and levels were reported in only 2 of the individuals who experienced a seizure. Interestingly, neither individual had a supratherapeutic level, 14,32 further demonstrating that individuals with 22q11.2 deletion syndrome may be particularly susceptible to clozapine's seizure threshold lowering effects.…”

“…Leukopenia was reported in one case and agranulocytosis in another, while neuroleptic malignant syndrome was reported in a single case. In patients who experienced a seizure on clozapine, an anticonvulsant was added prophylactically 8,14 or after the occurrence of a first seizure. 9,13,17,22,27,32 While valproate/divalproex was most commonly used, phenytoin was prescribed in one case and a combination of gabapentin/clonazepam was used in another.…”

“…In 7 of 8 cases, no further seizures were reported despite the ongoing use of clozapine. After the initial development of seizures, 1 of 3 approaches was taken: (1) the dose of clozapine was simply reduced or clozapine was stopped and eventually restarted at a lower dose 8,14 ; (2) the dose of clozapine was reduced or clozapine was stopped and eventually restarted at a lower dose in addition to adding valproate/divalproex 9,32 ; or (3) the dose of clozapine was not reduced but an anticonvulsant was started (either valproate/ divalproex or phenytoin). 17,22 With the implementation of these interventions, no further seizures were reported in any of these 6 cases.…”

“…Twenty-six articles were eligible for inclusion 8–33 . Key information for 37 individuals described in 25 of these articles is outlined in Table 1.…”