Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson’s disease

Abstract

Purpose Altered serotonergic neurotransmission may contribute to the non-motor features commonly associated with Parkinson’s disease (PD) such as sleep disorders. The 5-hydroxytryptophan (5-HTP) is the intermediate metabolite of l-tryptophan in the production of serotonin and melatonin. The purpose of this study was to compare the effects of 5-HTP to placebo on REM sleep behavior disorder (RBD) status in patients with PD. Methods A single-center, randomized, double-blind placebo-controlled crossover trial was performed in a selected population of 18 patients with PD and RBD. The patients received a placebo and 50 mg of 5-HTP daily in a crossover design over a period of 4 weeks. Results 5-HTP produced an increase in the total percentage of stage REM sleep without a related increase of RBD episodes, as well as a marginal, non-significant reduction in both arousal index and wake after sleep onset. The self-reported RBD frequency and clinical global impression (CGI) were improved during 5-HTP and placebo treatment in comparison to baseline. 5-HTP significantly improved our patients’ motor experiences of daily living as rated by the Unified Parkinson’s Disease Rating Scale (UPDRS) part II. Conclusions This study provides evidence that 5-HTP is safe and effective in improving sleep stability in PD, contributing to ameliorate patients’ global sleep quality. Larger studies with higher doses and longer treatment duration are needed to corroborate these preliminary findings.

Current Treatment Options for REM Sleep Behaviour Disorder

“…Results of randomized clinical trials, most of them involving a limited number of patients, have shown the short-term efficacy of the anticholinesterase drugs rivastigmine [67,68] and 5-hydroxytryptophan [75] and the herbal medicine yokukansan [81,82], as well as the lack of efficacy of nelotanserin [74] and cannabidiol [79]. Memantine has shown some degree of medium-term efficacy in the reduction of RBD symptoms in patients with LBD and dementia associated with PD [83].…”

“…Finally, a recent short-term randomized double-blind placebo-controlled crossover trial showed a beneficial effect of 5-hydroxytryptophan (the precursor of serotonin) in the treatment of RBD symptoms in patients with PD and RBD (level I of evidence; >50% of quality score) [75].…”

Patients with Neurodegenerative Proteinopathies Exhibit Altered Tryptophan Metabolism in the Serum and Cerebrospinal Fluid

“…Preliminary data indicate that 5-OH-TRP improves global sleep quality in patients with PD and REM sleep behavior disorder, which are often associated with each other. 30 Moreover, 5-OH-TRP supplementation reportedly reduced depressive symptoms in PD 31 and significantly reduced L-DOPA-induced dyskinesia in PD. 32 Earlier studies examined the use of this aromatic amino acid in the treatment of depression 33,34 and showed that levels of 5-OH-TRP in Alzheimer-type dementia CSF samples were lower than in matched controls.…”

Gut Microbiota and Metabolites may Play a Crucial Role in Sea Cucumber Apostichopus Japonicus Aestivation

“…However, relevant studies on mammals may provide us with a reference, and it was found that 5-HTP supplementation could significantly improve human sleep quality [ 28 ]. Similarly, another study found that inhibition of 5-HTP or 5-hydroxy tryptamine (5-HT) synthesis by tryptophan hydroxylase inhibitors significantly affected sleep in rats.…”