Neurostimulants for disorders of consciousness in the intensive care unit: A systematic review
In brief
Amantadine linked to short-term gains in consciousness for ICU coma patients
A systematic review of 35 studies found that amantadine was associated with modest improvements in arousal and earlier transfer to rehabilitation among critically ill adults with disorders of consciousness. Other stimulants such as methylphenidate showed similar signals, while modafinil's effects were mixed, but most data are observational and heterogeneous, underscoring the need for rigorous placebo-controlled trials.
- Journal
- General hospital psychiatry (Q1)
- Published
- 29 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Matthew Gunther, Nathan Tran, Katherine Prothro, Boglarka Huddleston, Shixie Jiang
- PMID
- 42679710
- DOI
- 10.1016/j.genhosppsych.2026.08.012
Why clinicians should know about it
- Picked for Critical Care and Intensive Care Medicine (top studies of the week, 6 September 2026): Neurostimulants improve consciousness in ICU patients
Abstract
BACKGROUND: Disorders of consciousness (DoC; encompassing coma, unresponsive wakefulness syndrome, and minimally conscious state) are sequelae of critical illness that prolong hospitalization and interfere with engagement in care. Due to heterogeneous and incompletely understood pathophysiology, no pharmacologic standard of care has been established. We aimed to systematically examine the efficacy, safety, and dosing of neurostimulants among adult ICU patients with DoC. METHODS: We conducted a systematic search of PubMed, Embase, CINAHL, and Web of Science from inception to December 2025. Studies that examined the use of neurostimulants for DoC in critically ill adults were included. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and used the Effective Public Health Practice Project framework to appraise bias. RESULTS: 35 studies met inclusion criteria: 11 randomized controlled trials, 19 observational, and 5 case-based studies. Amantadine was the most studied agent (N = 2743), with several studies reporting improvements in standardized measures of consciousness and earlier transition to rehabilitation. Modafinil (N = 1776) was primarily evaluated for hypersomnolence and demonstrated mixed effects on Glasgow Coma Scale (GCS) scores. Methylphenidate (N = 1044) demonstrated signals of benefit in both randomized studies and augmentation strategies with amantadine. Apomorphine was evaluated in one placebo-controlled ICU trial and carbidopa-levodopa in one case series. Despite inclusion in our search strategy, no studies examined caffeine, amphetamines, or bromocriptine. CONCLUSIONS: Neurostimulants were associated with short-term improvements in measures of arousal and recovery, although evidence remains heterogeneous and largely observational. Amantadine has the largest ICU evidence base; methylphenidate has been studied as monotherapy and augmentation; modafinil has primarily been evaluated for hypersomnolence. Further placebo-controlled trials are needed to establish efficacy across different causes of DoC; head-to-head studies are needed to clarify comparative effectiveness among available neurostimulants.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.