Pharmacological Treatment of Hallucinogen Persisting Perception Disorder (HPPD): A Systematic Review

Learning Objectives: After participating in this CME activity, the psychiatrist should be better able to: Hallucinogen persisting perception disorder (HPPD) is characterized by perceptual phenomena that either linger after substance-use cessation or recur as reperceptions or flashbacks. These symptoms may be either mild and transient or long-lasting and severely burdening. Since evidence for pharmacological treatment of HPPD is unclear, we seek to provide treatment advice based on a systematic review of existing medication studies. Our search yielded 31 studies with 87 participants treated for HPPD with different types of medication. Three observational studies reported substantial symptom reduction for regimens with clonidine, clonazepam, and levetiracetam. The other 28 studies, which consist of case reports and small case series, found largely similar results for benzodiazepines, antiepileptics, antidepressants, and alpha agonists. Of those who received these pharmacological treatments, 28% showed full recovery and 61% partial recovery within a year. When HPPD was triggered by lysergic acid diethylamide, benzodiazepines were ineffective. Notably, several studies described HPPD symptom aggravation upon treatment with the antipsychotic agent risperidone. Although not statistically significant, our analysis suggests that HPPD can be treated to good effect with the aforementioned groups of medicines. On the basis of our findings, we provide a list of practice-based treatment methods and make suggestions for further research. In particular, epidemiological studies are needed to investigate the natural course of HPPD. Likewise, randomized controlled pharmacological studies are necessary to evaluate the efficacy of medications in different, well-defined HPPD subgroups.