Can Phenytoin (antiepileptic medication) cause muscle twitches in a healthy person?

Can Phenytoin Cause Muscle Twitches in a Healthy Person?

Yes, phenytoin can cause motor twitchings (muscle twitches) in healthy individuals, even at therapeutic doses, as this is a recognized dose-related central nervous system adverse effect of the medication. 1

Mechanism and Clinical Presentation

Phenytoin-induced muscle twitches fall under the spectrum of movement disorders associated with this antiepileptic drug:

• Motor twitchings are explicitly listed as a known adverse effect in the FDA drug label, occurring alongside other CNS manifestations like dizziness, insomnia, transient nervousness, and paresthesias 1

• More severe dyskinesias can also occur, including chorea, dystonia, tremor, and asterixis, similar to those induced by phenothiazine and other neuroleptic drugs, though these are rare 1

• These movement disorders can develop during either chronic or initial treatment and may occur even with normal serum phenytoin levels, though they are more common with toxic levels or polytherapy 2

Dose-Related Toxicity Spectrum

The muscle twitches exist on a continuum of dose-related neurological effects:

• The most common CNS manifestations are dose-related and include nystagmus, ataxia, slurred speech, decreased coordination, and mental confusion 1

• Motor twitchings represent a milder manifestation compared to more severe dyskinesias like choreoathetosis, which can be focal or generalized 2

• Phenytoin's saturation (zero-order) pharmacokinetics create special risk for dose-related toxicity, as small dose increases can lead to disproportionate serum level elevations 3

Important Clinical Caveats

The dyskinesia may be the only side effect present, which can delay diagnosis and appropriate management 2. This is particularly important because:

• Patients may not exhibit other classic signs of phenytoin intoxication (nystagmus, ataxia, drowsiness) when muscle twitches occur 2

• The involuntary movements typically resolve completely after phenytoin withdrawal 2

• In a study of acute phenytoin intoxication, unsteady gait was the most common presenting symptom, but the tentative diagnostic accuracy was only 67%, indicating these effects are often under-recognized 3

Risk Factors for Movement Disorders

While muscle twitches can occur in otherwise healthy individuals taking phenytoin, certain factors increase risk:

• Polytherapy with multiple antiepileptic drugs increases the likelihood of dyskinesias 2

• Dosage increases are commonly associated with the onset of movement disorders 2

• Toxic serum levels are the most frequent setting, though normal levels do not exclude the possibility 2