Phenobarbital for Refractory Behavioral Disturbances in Anti-NMDAR and HSV Encephalitis: A Case Report

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune-mediated disorder with neuropsychiatric manifestations, frequently following herpes simplex virus (HSV) encephalitis. The management of associated behavioral disturbances is challenging, complicated by poor response and tolerability to antipsychotics. This case report describes the use of oral phenobarbital for refractory behavioral disturbances in a patient with concurrent anti-NMDA and HSV encephalitis. A 65-year-old female with a two-year history of anti-NMDAR and HSV encephalitis presented with severe behavioral disturbances, including paranoia, insomnia, hypersexuality, compulsive behaviors, and aggression. Disease-modifying therapies, including IV acyclovir, IV immunoglobulin, prednisone, and rituximab, were ineffective. Multiple psychotropic medications, including fluoxetine, quetiapine, olanzapine, and trazodone, failed to relieve behavioral symptoms. Given previous ineffective pharmacotherapies, oral phenobarbital was initiated at 30 mg every 12 hours and later titrated to 60 mg every 12 hours. Four weeks after phenobarbital dose escalation, behavioral improvements were observed, with reductions in obsessive behaviors, elopement, and insomnia. After 20 weeks of phenobarbital therapy, notable improvements in agitation, redirection, and verbal aggression were documented. No adverse effects were reported. This case suggests that low-dose oral phenobarbital may be a viable option for managing refractory behavioral disturbances in patients and improving quality of life with anti-NMDAR and HSV encephalitis.