A Review of Pharmacologic Neurostimulant Use During Rehabilitation and Recovery After Brain Injury

Abstract

Objective: To describe the efficacy and safety of pharmacologic neurostimulants after neurological injuries such as ischemic or hemorrhagic stroke and traumatic brain injury (TBI), critically evaluate the available literature, and make recommendations regarding which neurostimulants should be considered for use in clinical practice. Data Sources: A literature search of PubMed was performed (1953 to October 2020) to identify relevant articles. Search terms included the following: “neurostimulant, neurorehabilitation” AND “traumatic brain injury, cerebrovascular accident, or stroke.” This review is limited to prospective studies and observational trials. Study Selection and Data Extraction: Relevant English-language studies conducted in humans were considered. Data Synthesis: Cognitive and motor deficits caused by stroke and TBI account for high rates of long-term disability. Although not well-established, pharmacologic agents, broadly characterized as neurostimulants, may be prescribed after brain injury to treat these deficits. When prescribing these medications, it is imperative to be aware of the supporting evidence in order to accurately gauge the risk-benefit profile of each agent. Relevance to Patient Care and Clinical Practice: The following presents a literature review critically evaluating clinical studies that investigate neurostimulant use after brain injury. The intent of this review is to serve as an evidence-based guide for clinicians. Conclusions: The pharmacologic agent with the most supporting literature is amantadine used for cognitive improvement after TBI. Other neurostimulants with positive, despite more limited, evidence include methylphenidate, modafinil, levodopa, and citalopram. Caution is warranted with other neurostimulants given higher rates of adverse effects or lack of benefit observed in clinical trials.

2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association

“…In patients with aSAH in a coma, early use of neurostimulants may be reasonable to promote consciousness recovery. [446][447][448] 3: No benefit A 8. In patients with aSAH without depression, fluoxetine therapy is not effective to enhance poststroke functional status.…”

Comment: A Review of Pharmacologic Neurostimulant Use During Rehabilitation and Recovery After Brain Injury

“…Although not included in the literature review by Kakehi and Tompkins 1 because it was published after October 2020, our observational study including 71 patients who received amantadine during the acute phase of post-stroke care further supports its administration. In the study, 34 of 62 (55%) patients receiving amantadine monotherapy and 8 of 24 (33%) receiving both amantadine and modafinil were classified as responders.…”

“…We read the literature review on neurostimulant administration after brain injury by Kakehi and Tompkins 1 with interest. The authors retrieved articles published in the English-language and indexed in PubMed from 1953 through October 2020.…”

Pharmacologic Therapies to Promote Recovery of Consciousness

“…[39][40][41] Improvements in fatigue, processing speed, attention, and depression have been associated with methylphenidate use in mild-to-moderate acquired brain injury, but whether this therapy can hasten recovery or promote recovery of consciousness compared with placebo remains to be determined. 39,[42][43][44][45] An ongoing phase 1 clinical trial is evaluating the safety of intravenous methylphenidate in patients with severe TBI complicated by DoC (NCT03814356). 46 In patients without underlying cardiac comorbidities, methylphenidate can be used off-label to improve arousal as an alternative to amantadine or if the patient-specific therapeutic goal is not achieved during amantadine treatment.…”