Is Xcopri (cenobamate) effective for treating Hallucinogen Persisting Perception Disorder (HPPD)?

Xcopri (Cenobamate) is Not Recommended for Treating Hallucinogen Persisting Perception Disorder (HPPD)

There is no evidence supporting the use of Xcopri (cenobamate) for treating Hallucinogen Persisting Perception Disorder (HPPD), and other medications have better evidence for efficacy in this condition.

Understanding HPPD

HPPD is characterized by the re-experiencing of perceptual symptoms (primarily visual) that were initially experienced during hallucinogen intoxication, but which persist after the drug has worn off. Common symptoms include:

• Visual snow
• Floaters
• Palinopsia (visual trailing)
• Photophobia
• Nyctalopia (night blindness)
• Altered motion perception
• Color enhancement

Evidence-Based Treatment Options for HPPD

First-Line Treatments

1. Benzodiazepines

   • Most consistently reported effective treatment in case reports 1
   • Mechanism: May reduce excitability in visual cortex
   • Caution: Risk of dependence and tolerance with long-term use

2. Lamotrigine

   • Considered the "gold standard" for treating perceptual disturbances in HPPD 2
   • Mechanism: Stabilizes neuronal membranes through inhibition of voltage-sensitive sodium channels

3. Clonidine

   • Alpha-2 adrenergic agonist documented as first-line in multiple case reports 3, 2
   • Mechanism: May reduce noradrenergic hyperactivity

Second-Line Treatments

1. Aripiprazole

   • Demonstrated gradual improvement in adolescent HPPD case 3
   • One of the few antipsychotics with documented positive effects

2. Risperidone

   • Mixed evidence: One case report showed significant improvement in a patient with 17-year HPPD symptoms 4
   • Caution: Other reports suggest potential worsening of symptoms in some patients

Why Xcopri (Cenobamate) is Not Recommended

Cenobamate is an anticonvulsant approved for partial-onset seizures that works by:

• Reducing repetitive neuronal firing by inhibiting voltage-gated sodium channels
• Enhancing inhibitory currents through GABA-A receptors

However:

1. No clinical studies or case reports document its use in HPPD
2. No mention in any clinical guidelines for HPPD treatment
3. Other anticonvulsants with similar mechanisms (like lamotrigine) have established evidence for HPPD

Treatment Algorithm for HPPD

1. Initial Assessment

   • Confirm diagnosis by ruling out other causes of visual disturbances
   • Document specific symptoms and severity
   • Screen for comorbid psychiatric conditions (depression, anxiety)

2. First-Line Treatment Options

   • For mild-moderate symptoms: Trial of benzodiazepine (e.g., clonazepam)
   • For moderate-severe symptoms: Consider lamotrigine (starting at low dose with slow titration)
   • For symptoms with anxiety predominance: Consider clonidine

3. If First-Line Treatment Fails

   • Consider aripiprazole (starting at low dose, e.g., 2-5mg)
   • Consider risperidone (with careful monitoring for symptom worsening)

4. Adjunctive Approaches

   • Psychoeducation about the condition
   • Avoidance of substances that may worsen symptoms (cannabis, alcohol, hallucinogens)
   • Cognitive behavioral therapy for associated anxiety/distress

Important Caveats and Pitfalls

1. Misdiagnosis Risk

   • HPPD symptoms overlap with Visual Snow Syndrome (VSS) 1
   • Rule out other neurological and ophthalmological conditions

2. Medication Cautions

   • Some medications may worsen symptoms, including certain SSRIs and typical antipsychotics
   • Benzodiazepines carry risk of dependence with long-term use

3. Prognosis Considerations

   • HPPD can be persistent, with only 25% of cases showing full recovery in literature reviews 1
   • Symptoms may fluctuate over time, with stress often exacerbating symptoms

4. Substance Use

   • Continued use of any psychoactive substances may worsen or perpetuate symptoms
   • Complete abstinence from hallucinogens is essential

In conclusion, while Xcopri (cenobamate) has mechanisms that theoretically could help with neuronal hyperexcitability, there is no evidence supporting its use in HPPD. Treatment should focus on established options like benzodiazepines, lamotrigine, clonidine, or in select cases, aripiprazole.