Dystonia triggered by carbamazepine withdrawal in the setting of polypharmacy

Background Dystonia is most often associated with dopamine receptor-blocking agents, but it may also emerge after medication changes that alter antipsychotic exposure or lower the threshold for extrapyramidal symptoms in the setting of polypharmacy. Case presentation We present a male in his 20s with psychiatric history of autism spectrum disorder with behavioral disturbances(ASD), anxiety, mood disorder, intellectual disability(ID), and attention deficit hyperactivity disorder (ADHD), who developed recurrent episodes of neck and jaw stiffness, dysarthria, drooling, gagging, and impaired oral intake after discontinuation of carbamazepine while continuing ziprasidone, sertraline, lamotrigine, atomoxetine, dexmethylphenidate, guanfacine, and memantine. Carbamazepine at 200 mg twice daily was gradually tapered over two weeks before discontinuation. The first episode occurred 4 weeks after the final dose, and two more episodes occurred over the following 11 weeks. EEG, upper endoscopy, and laboratory testing did not reveal seizure, structural swallowing disorder, or metabolic cause. Management and outcome The presentation was interpreted as delayed-onset recurrent dystonic episodes associated with carbamazepine discontinuation, rather than classic acute dystonia following antipsychotic initiation or dose escalation. The most plausible mechanism was increased ziprasidone exposure after loss of carbamazepine-mediated CYP3A4 induction, with broader psychotropic polypharmacy likely increasing susceptibility. Carbamazepine 200 mg twice daily was reintroduced while other psychotropics were unchanged. Episodes resolved completely and did not recur during three months of follow-up. Anticholinergic therapy was deferred because episodes were transient, self-limited, and had resolved before direct assessment; however, standard treatment with anticholinergic therapy would be indicated if symptoms persisted, or failed to resolve promptly. Conclusion This case highlights the complex interplay between pharmacokinetic changes and cumulative pharmacodynamic effects in polypharmacy. Discontinuing a CYP3A4 inducer in patients receiving multiple centrally acting agents can significantly alter antipsychotic exposure and precipitate extrapyramidal symptoms. Causality cannot be proven without antipsychotic serum concentrations, but the timeline, pharmacologic plausibility, and clinical resolution after reinstating carbamazepine support the proposed mechanism. It is essential for clinicians to anticipate these risks, ensure close monitoring during medication changes, and strike a balance between deprescribing goals and maintaining clinical stability.