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Phenobarbital for Refractory Behavioral Disturbances in Anti-NMDAR and HSV Encephalitis: A Case Report
Lorin J Fisher1, Bryan Struck2, James B Ray1
1Pharmacy Practice & Science, University of Iowa College of Pharmacy, Iowa City, Iowa, USA.
Journal of Pain & Palliative Care Pharmacotherapy
|December 2, 2025
Summary
Oral phenobarbital effectively managed severe behavioral disturbances in a patient with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and herpes simplex virus (HSV) encephalitis. This treatment improved agitation, insomnia, and aggression without adverse effects.
Area of Science:
- Neurology
- Psychiatry
- Immunology
Background:
- Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis presents with neuropsychiatric symptoms, often post-herpes simplex virus (HSV) encephalitis.
- Behavioral disturbances in these patients are challenging to manage, with limited response to standard antipsychotics.
Purpose of the Study:
- To report the efficacy of oral phenobarbital in managing refractory behavioral disturbances in a patient with concurrent anti-NMDAR and HSV encephalitis.
Main Methods:
- A case report of a 65-year-old female with a two-year history of anti-NMDAR and HSV encephalitis.
- Documented failure of disease-modifying therapies (IV acyclovir, IV immunoglobulin, prednisone, rituximab) and multiple psychotropic medications.
- Initiation and titration of oral phenobarbital (30mg to 60mg every 12 hours).
Main Results:
- Significant reduction in obsessive behaviors, elopement, and insomnia within four weeks of phenobarbital dose escalation.
- Notable improvements in agitation, redirection, and verbal aggression after 20 weeks of therapy.
- No adverse effects were reported during phenobarbital treatment.
Conclusions:
- Low-dose oral phenobarbital may be a viable and safe option for refractory behavioral disturbances in patients with concurrent anti-NMDAR and HSV encephalitis.
- Phenobarbital can improve patient quality of life by managing severe neuropsychiatric symptoms.
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