From the Guidelines
For individuals with Hallucinogen Persisting Perception Disorder (HPPD) who experience anxiety after taking melatonin, immediate-release melatonin would likely be better than slow-release formulations. The immediate-release version typically clears the system more quickly (within 4-8 hours) compared to extended-release formulations that can remain active for 8-10 hours. Starting with a low dose of 0.5-1mg of immediate-release melatonin taken 30-60 minutes before bedtime may help reduce the likelihood of next-day anxiety, as suggested by the management of REM sleep behavior disorder guidelines 1. If melatonin consistently triggers anxiety, alternatives like relaxation techniques, maintaining consistent sleep schedules, or consulting with a healthcare provider about non-hormonal sleep aids might be preferable. The connection between melatonin and anxiety in HPPD patients likely relates to melatonin's effects on neurotransmitter systems that are already dysregulated in HPPD, particularly serotonin pathways, which influence both perception and mood regulation. It is essential to consider the patient’s underlying disease and attendant symptoms when choosing a medication, as patients with neurodegenerative disorders frequently experience other symptoms affecting motor function, cognitive domains, and the autonomic system, as noted in the guidelines for secondary RBD due to a medical condition 1. However, the most recent and highest quality study, which is the 2023 American Academy of Sleep Medicine clinical practice guideline 1, provides the best evidence for the use of immediate-release melatonin in patients with RBD, and by extension, may be applicable to patients with HPPD experiencing anxiety after melatonin use. Key points to consider include:
- The starting dose of immediate-release melatonin is usually 3 mg taken at bedtime, which may be titrated up to address dream enactment in 3-mg increments to 15 mg 1.
- Melatonin is considered a dietary supplement and is available over the counter in the United States and Canada, but its bioavailability and content may be less consistent across formulations 1.
- Combination therapy using clonazepam and melatonin is common in clinical practice if response to monotherapy is inadequate, but there is a paucity of data examining combination therapies 1. Given the potential benefits and risks, immediate-release melatonin is the preferred formulation for patients with HPPD experiencing anxiety, due to its quicker clearance and potentially lower risk of next-day anxiety.
From the Research
Hallucinogen Persisting Perception Disorder (HPPD) and Melatonin Formulation
- There is limited research directly addressing the use of melatonin in patients with HPPD experiencing anxiety.
- However, studies suggest that melatonin can be useful in treating insomnia and circadian sleep disturbances in various psychiatric disorders 2, 3.
- In terms of formulation, a study on jet lag suggests that a short-lived higher peak concentration of melatonin works better, implying that an immediate-release formulation may be more effective than a slow-release formulation 4.
- Another study reviews the use of melatonin in sleep disorders, highlighting its ability to synchronize circadian rhythms and improve sleep quality, but does not specifically address HPPD or the choice of formulation 5.
- A case study on a patient with comorbid HPPD and alcohol use disorder discusses the use of benzodiazepines, but does not mention melatonin or its formulation 6.
- Given the lack of direct evidence, it is unclear whether a patient with HPPD experiencing anxiety would benefit from a slow-release or immediate-release melatonin formulation, but immediate-release melatonin at a low dose (<1 mg) may be considered for treating circadian sleep disturbances 2.