Refractory tardive dyskinesia in the critical care setting: A case report of successful use of phenobarbital

Tardive dyskinesia is a hyperkinetic movement disorder most often induced by chronic antipsychotic use. It can be challenging to treat, particularly when symptoms persist despite standard therapies such as vesicular monoamine transporter 2 inhibitors. We describe a 37-year-old male with schizoaffective disorder and persistent tardive dyskinesia involving oro-buccal-lingual and axial movements. Despite withdrawal of antipsychotics, a trial of deutetrabenazine, and high-dose tetrabenazine (150 mg/day for several weeks), symptoms persisted and significantly impaired critical care management. On hospital day 46, phenobarbital was initiated (dose and route here), resulting in rapid improvement of dyskinetic movements within 3 days. By hospital day 54, complete resolution of tardive dyskinesia was observed, and notably, symptoms did not recur after phenobarbital discontinuation. The patient maintained clinical improvement during long-term follow-up, with Abnormal Involuntary Movement Scale score improving to 2 at 18 months. This case illustrates a potential novel role for phenobarbital in refractory tardive dyskinesia, particularly when conventional therapies fail. The sustained response beyond the drug's pharmacokinetic profile raises the possibility of a disease-modifying or prolonged therapeutic effect. Given phenobarbital's activity on Gamma Aminobutyric Acid B receptors, its mechanism may involve modulation of GABAergic pathways implicated in the pathophysiology of tardive dyskinesia. Further investigation in clinical studies is warranted.