Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson's disease and sleep disorders: a randomized, double-blind trial.

Abstract

Sleep disturbances are common non-motor symptoms of Parkinson's disease (PD). We aimed to compare the safety and efficacy of trazodone with melatonin and clonazepam in patients with PD and sleep complaints. This single-center, double-blind, randomized clinical trial was conducted on PD patients with subjective sleep complaints. Eligible patients were randomized 1:1:1 to receive melatonin 3mg/day, clonazepam 1mg/day, or trazodone 50mg/day for 4weeks. The primary outcome measure was the changes in Pittsburgh Sleep Quality Index (PSQI) scores. The mean change in Epworth Sleepiness Scale (ESS) and RBD screening questionnaire (RBDSQ) was considered as the secondary outcome measures. A total of 112 eligible patients were randomized and 93 participants, melatonin (n = 31), trazodone (n = 31), and clonazepam (n = 31), completed the study. There was a significant decrease in PSQI scores after 4weeks of treatment in all groups. The mean changes of PSQI from baseline were similar among the treatment arms (P = 0.325). Mean changes of RBDSQ and ESS from baseline were significantly different between study arms (P < 0.05). Melatonin intake was associated with a higher decrease in RBDSQ score compared to trazodone (P = 0.011) and clonazepam (P = 0.004). Trazodone intake was associated with a higher decrease in ESS score compared to clonazepam (P = 0.010). Mild adverse events were reported in three patients in the clonazepam, two patients in the trazodone group, and none in the melatonin group. Trazodone 50mg/day, clonazepam 1mg/day, and melatonin 3mg/day were all tolerable and effective in improving sleep quality in patients with PD. Iranian Registry of Clinical Trials (registration number; IRCT20170821035819N2).