Over-the-Counter Cough Medication in Patients with Epilepsy

Mechanism of Action:

Central Nervous System (CNS) Effects:  Dextromethorphan and its active metabolite have numerous pharmacologic actions including activity as a noncompetitive NMDA receptor antagonist, an anticholinergic, a sigma-1 receptor agonist, and a nonselective serotonin-norepinephrine reuptake inhibitor.¹ Dextromethorphan’s central inhibition of the NMDA receptor accounts for its antitussive effects.

Clinical Implication:

Seizure Risk: The combined noncompetitive NMDA receptor antagonism and sigma receptor agonism appears to have inherent antiseizure effects according to preliminary studies.^2-4 However, a small double-blind, crossover, study evaluating the utility of adding on dextromethorphan 120mg/day (therapeutic dose) found a nonsignificant trend towards increase in complex partial seizures.⁵ In overdose settings, dextromethorphan is known to precipitate seizures.¹ In one case report, dextromethorphan toxicity caused sudden tonic-clonic movements and confusion initially thought to be a new onset seizure disorder.⁶ Like ketamine, dextromethorphan also binds to the phencyclidine site (aka PCP) on the NMDA receptor which accounts for its potential for hallucinations, dissociative effects, especially at higher doses.

Drug Interactions: Dextromethorphan can cause drowsiness and confusion, especially if taken with antiseizure medications that have similar side effects. These CNS depressants can have additive effects, increasing the risk of adverse events. Clobazam is an inhibitor of CYP2D6 and may increase the serum concentration of dextromethorphan, a substrate for CYP2D6. Though clinical significance of this increased dextromethorphan exposure is not known, caution may be warranted.⁷ Due to increased risk of serotonin syndrome, which may include seizures if severe, the coadministration of certain medicines with serotonergic effects should be addressed. Avoid concurrent use with monoamine oxidase inhibitors. Use dextromethorphan with caution in persons requiring treatment with serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors or tricyclic antidepressants.

Medication Selection: guaifenesin-containing products for cough relief are a safer option for people with epilepsy, as these are less likely to impact the seizure threshold or current antiseizure medications. 

Patient Education: Advise patients to consider avoiding combination products that contain dextromethorphan and the importance of reading OTC medication labels to avoid products containing this ingredient.