The wake of addiction: Pharmacological strategies for sleep disturbances in stimulant use disorders, a systematic review.

Abstract

A systematic review was conducted following PRISMA guidelines to identify human studies investigating pharmacological interventions and reported sleep outcomes among individuals with CUD or MUD. PubMed and APA PsycInfo were searched from inception to January 2025 and risk of bias was assessed. Articles were included if they included human participants with either cocaine or methamphetamine dependence, administered a pharmacological treatment, and reported night-time sleep as an outcome using at least one rigorous measurement tool. Articles were excluded if they included animals, did not include pharmacological intervention (e.g., supplements or behavioral treatments), or only assessed baseline sleep or if sleep was only reported as a side effect rather than as a formal outcome. Eighteen studies (N = 678) met inclusion criteria, eleven in CUD and seven in MUD. The results of the risk-of-bias assessment indicated good-to-excellent interrater reliability (ICC range=0.85-0.90), and overall methodological quality across studies was moderate to high. For CUD, modafinil, buprenorphine, and suvorexant were preliminarily associated with improvements in sleep parameters, with modafinil linked to higher abstinence rates. Results for mirtazapine, lisuride, lorazepam, tiagabine, and cannabidiol were mixed. For MUD, mirtazapine and modafinil demonstrated modest initial benefits, while quetiapine and suvorexant showed preliminary promise in smaller studies. Overall, pharmacological interventions targeting sleep disturbances showed emerging but inconsistent benefits in CUD and MUD, which could be due to small sample sizes, short treatment durations, side effects, or comorbidities. Addressing sleep dysregulation may represent a novel and clinically meaningful pathway to improve recovery outcomes in stimulant use disorders.