Management of Hallucinogen Persisting Perception Disorder (HPPD) with Lamotrigine and Lumateperone
Lamotrigine is the recommended first-line treatment for Hallucinogen Persisting Perception Disorder (HPPD), with lumateperone (Caplyta) considered as a second-line option for patients with comorbid psychotic features or those who fail to respond to lamotrigine therapy.
Understanding HPPD
HPPD is characterized by persistent visual disturbances that continue after hallucinogen use has ceased, including:
- After images
- Perception of movement in peripheral visual fields
- Blurring of small patterns
- Halo effects
- Macro- and micropsia (objects appearing larger or smaller than they are)
Treatment Algorithm
First-Line Treatment: Lamotrigine
Lamotrigine has demonstrated efficacy in treating HPPD, particularly for perceptual disturbances in time and space 1, 2:
- Initial dosing: Start at 25mg daily
- Titration: Increase slowly over 6 weeks to target dose
- Target dose: 200-400mg daily in divided doses
- Mechanism: Likely works through its effects on glutamate and GABA neurotransmission
The evidence supporting lamotrigine comes from case reports showing significant improvement in visual disturbances that had persisted for years after hallucinogen use 2. One case report described almost complete resolution of complex visual disturbances with lamotrigine in a patient who had failed previous treatments with antidepressants and risperidone 2.
Second-Line Treatment: Lumateperone (Caplyta)
For patients who don't respond to lamotrigine or have comorbid psychotic features:
- Dosing: Start at 42mg once daily
- Advantages: Lower risk of metabolic side effects compared to other atypical antipsychotics
- Considerations: May be particularly useful when HPPD is accompanied by psychotic symptoms or severe anxiety
Alternative Treatments
Benzodiazepines (particularly clonazepam):
Risperidone:
- Mixed evidence with some case reports showing improvement 5
- Others report worsening of symptoms
- Consider only if other options have failed
Monitoring and Safety Considerations
For Lamotrigine:
- Monitor for rash: Discontinue immediately if rash appears, particularly if accompanied by fever or flu-like symptoms (risk of Stevens-Johnson syndrome is approximately 0.1% in bipolar studies) 6
- Titrate slowly: Rapid titration increases risk of serious rash
- Dosage adjustments: Required if co-administered with valproate (reduce lamotrigine dose) or carbamazepine (increase lamotrigine dose) 6
For Lumateperone:
- Baseline assessment: Obtain body mass index, waist circumference, blood pressure, fasting glucose, and lipid panel
- Regular monitoring: Though metabolic effects are less pronounced than with other atypical antipsychotics, periodic monitoring is still recommended
Special Considerations
Comorbid substance use disorders:
- Address ongoing substance use as it may worsen HPPD symptoms or interfere with treatment
- Daily substance use, particularly cannabis, can impact treatment response 6
- Consider integrated treatment approach for dual diagnosis
Avoid medications that may worsen symptoms:
- SSRIs and other serotonergic medications may exacerbate symptoms in some patients
- Typical antipsychotics may not be effective and could potentially worsen symptoms
Treatment duration:
- Long-term treatment is often necessary as HPPD can persist for years
- Medication discontinuation should be gradual with close monitoring for symptom recurrence
Conclusion
The treatment of HPPD requires a systematic approach with lamotrigine as the first-line option based on case reports showing significant improvement in visual disturbances. For patients who don't respond adequately or have comorbid psychotic features, lumateperone offers a promising alternative with a favorable side effect profile. Careful monitoring, particularly for rash with lamotrigine, is essential for safe and effective management.