Is phenytoin (an anticonvulsant) effective for managing pain or hallucinations?

Phenytoin for Pain or Hallucinations

Phenytoin is not recommended for pain management and does not treat hallucinations—in fact, it can cause hallucinations as a toxic side effect.

Use in Pain Management

Limited Evidence for Neuropathic Pain

• A 2012 Cochrane systematic review found no evidence of sufficient quality to support phenytoin use in chronic neuropathic pain or fibromyalgia 1
• The American Heart Association/American Stroke Association guidelines classify phenytoin as a second-line treatment option only for central poststroke pain, with the caveat that "its usefulness is not well established" (Level IIb recommendation, Class B evidence) 2
• First-line treatments for central poststroke pain are amitriptyline and lamotrigine (Level IIa, Class B), not phenytoin 2
• Phenytoin may be considered only after failure of amitriptyline, lamotrigine, pregabalin, gabapentin, and carbamazepine 2

Clinical Context

The 2016 stroke rehabilitation guidelines explicitly state that pharmacotherapy for central pain has "relied primarily on antidepressant medications and anticonvulsants," with amitriptyline showing proven efficacy at 75 mg at bedtime for lowering daily pain ratings 2. Phenytoin is mentioned only as an "other option" with unestablished usefulness 2.

A 2020 geriatrics guideline reviewing adjuvant analgesics for neuropathic pain lists gabapentinoids, antidepressants, and newer anticonvulsants but notes that "older drugs, including carbamazepine, phenytoin, and valproate, may be analgesic but have adverse-effect profiles that are less favorable than newer anticonvulsants" 2.

Phenytoin and Hallucinations

Phenytoin Causes Hallucinations (Does Not Treat Them)

• Hallucinations are a manifestation of phenytoin toxicity, particularly in patients with hypoalbuminemia where free phenytoin levels become elevated 3
• A case series documented severe neurological side effects including "disorientation, myoclonia, hallucinations and drowsiness" in a patient with therapeutic total phenytoin levels but toxic free phenytoin levels (4 mg/l; therapeutic range 0.5-2 mg/l) 3
• Phenytoin encephalopathy manifests as cognitive impairment and cerebellar syndrome, developing due to saturation kinetics and individual metabolic differences 4

Mechanism of Toxicity

Phenytoin is 90-95% protein-bound under normal conditions 4. In hypoalbuminemia (albumin <25 g/l), the free fraction increases dramatically, leading to toxic neurological effects even when total serum levels appear therapeutic 3. These effects include hallucinations, confusion, myoclonus, and altered consciousness 3.

Clinical Recommendations

For Pain Management

• Do not use phenytoin as a first-line or even second-line agent for any pain condition 2, 1
• For central poststroke pain: Start with amitriptyline 75 mg at bedtime or lamotrigine 2
• For other neuropathic pain: Use gabapentin or pregabalin as first-line gabapentinoids 2
• Consider phenytoin only after multiple other agents have failed and only in the specific context of central poststroke pain 2

For Hallucinations

• Phenytoin does not treat hallucinations and may cause them 3
• If a patient on phenytoin develops hallucinations, check free phenytoin levels (not just total levels), especially if albumin is low 3
• Discontinue phenytoin if toxic neurological symptoms develop 3
• The therapeutic range for free phenytoin is 0.5-2 mg/l; levels of 4-8 mg/l cause severe toxicity including hallucinations 3

Important Caveats

Phenytoin is not recommended as first-choice therapy for any indication except as a co-drug for managing convulsive status epilepticus 4. In status epilepticus, phenytoin/fosphenytoin is a legitimate second-line option after benzodiazepines, with 84% efficacy but 12% risk of hypotension 5. However, even in this indication, valproate may be superior (88% efficacy, 0% hypotension risk) 5.

For patients with intellectual disability, balance disturbances, or cognitive dysfunction, phenytoin should be replaced with carbamazepine or oxcarbazepine due to its propensity to cause cerebellar symptoms and cognitive impairment 4.