Trazodone, melatonin, and combination therapy for insomnia, fatigue, and daytime sleepiness following traumatic brain injury: study protocol for a randomized clinical trial.

BACKGROUND: Sleep problems are common and disabling after traumatic brain injury (TBI). They negatively affect cognitive recovery, emotions, and overall quality of life. Fatigue and excessive daytime sleepiness are also frequent and significantly impair daily functioning. Although trazodone and melatonin are used off-label, we still do not know which works better or if they are more effective together for improving sleep quality, fatigue, and daytime sleepiness in TBI patients. This randomized, double-blind clinical trial aims to compare the effectiveness of trazodone, melatonin, and their combination for improving sleep quality, fatigue severity, and daytime sleepiness in adults with moderate to severe TBI.

METHODS: Forty-eight adults with moderate to severe TBI (Glascow Coma Scale (GCS) score of 3-12) and insomnia (insomnia severity index score (ISI) ≥ 8) will be randomly assigned (1:1:1) to receive nightly trazodone (25-100 mg), melatonin (3-5 mg), or both for 4 weeks. Changes in sleep quality (Insomnia Severity Index, ISI), fatigue severity (fatigue severity scale, FSS), and daytime sleepiness (Epworth sleepiness scale, ESS) will be assessed before and after treatment. Recruitment is ongoing. The data will be analyzed via mixed-design ANOVA, with suitable post hoc tests and nonparametric alternatives if the assumptions are not met.

DISCUSSION: This study is one of the first to compare trazodone and melatonin alone and in combination for insomnia, fatigue, and daytime sleepiness in TBI patients. The results will help improve treatment strategies for managing sleep problems, fatigue, and daytime sleepiness in individuals with traumatic brain injury.

TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT) IRCT20241121063793N1. Registered on December 28, 2024.