A Comparative Study on the Use of Alprazolam and Melatonin for Sleep Disturbances in Hemodialysis Patients

Abstract

Background and objectives Sleep disorders are prevalent in end-stage renal disease (ESRD) involving the majority of patients undergoing hemodialysis. The main objective of treating sleep disorders in patients of ESRD is to correct subjective and objective sleep quality, decrease fatigue and daytime sleepiness, and enhance daytime functioning. Irrespective of the adverse effects reported, benzodiazepines are widely utilized among patients with sleep disorders in end-stage renal disease. Melatonin is a newer agent being studied for use in hemodialysis patients for improvement of sleep quality. The aim of our observational study is to witness the effectiveness of both benzodiazepine and exogenous melatonin as a treatment of sleep disorders in patients undergoing hemodialysis. Materials and methods We conducted a comparative, observational study in ESRD patients who are on hemodialysis. These patients were selected from attendees of the hemodialysis unit, nephrology department of a tertiary care hospital, including those who were on regular hemodialysis, thrice-weekly in frequency for at least once per year, and taking regular sleep medications for at least three months with frequently reported drug dosages of alprazolam 0.5 mg once daily or melatonin 3 mg once daily (before bedtime). The subjective sleep assessment was done by utilizing four scales, including the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and Stanford Sleepiness Scale (SSS). Results A total of 117 hemodialysis-dependent patients met the inclusion criteria, among whom 79 patients were using alprazolam while 38 were using melatonin for their disturbed sleep. The mean age of the study participants was 49.12 ± 12.75, comprising 72 males (61.53%) and 45 females (38.46%). The duration of the diagnosis of chronic kidney disease (CKD), duration of onset of hemodialysis, and estimated glomerular filtration rate (eGFR) was comparable in both groups. Both groups had similar laboratory markers except for higher hemoglobin in the melatonin group (p=0.028) and high parathyroid hormone (PTH) levels in the alprazolam group (p=0.001). PSQI scores were 8.76 ± 3.09 in the alprazolam group and 7.32 ± 2.65 in the melatonin group (p=0.015). In the sub-scores, there were no differences in sleep latency (p=0.481) and daytime dysfunction (p=0.662) while sleep efficiency (p=0.167) and subjective sleep quality (p=0.132) were not statistically significant. The significant differences were lower scores of sleep duration (p=0.040) and sleep disturbance (p=0.003) in the melatonin group. The ESS scores revealed no significant difference in either group (p=0.074). With respect to the ISI and SSS, higher scores were obtained in the alprazolam group. Overall, 89 study participants had reported poor sleep quality, out of which 81% were using alprazolam, and 65% were using melatonin (p=0.071). A total of 50 study participants exhibited excessive daytime sleepiness with 45% of them were using alprazolam and 36% were using melatonin. About 54% of the alprazolam using hemodialysis patients had moderate insomnia while 50% of the melatonin using patients had sub-threshold insomnia (p=0.062). Conclusion As melatonin use has shown better sleep quality and less insomnia severity as compared to alprazolam use in our study, it is postulated that the sleep-wake cycle should be commonly targeted by pharmacological therapy in ESRD.

Keywords: alprazolam; benzodiazepine; chronic kidney disease; daytime sleepiness; end-stage renal disease (esrd); hemodialysis; insomnia severity index; melatonin; pittsburgh sleep quality index (psqi); sleep-wake disorder.

Figure 1. Comparison of frequency of descriptive sleep parameters among the study groups.

*indicates chi-square test used to compute the p-value. ** indicates fisher's exact test to compute the p-value. Abbreviations: n, number of subjects; PSQI, Pittsburgh Sleep Quality Index; ESS, Epworth Sleepiness Scale; ISI, Insomnia Severity Index