A systematic review on pharmacotherapy of post-traumatic attention impairments

BACKGROUND: Attention impairment is common in post-traumatic brain injury. We synthesized evidence on pharmacological treatments for adults with attention deficits in the acute-to-chronic phases. METHODS: We searched Ovid MEDLINE and Cochrane Library (1946-December 2024). Two reviewers screened studies, extracted data, and assessed study quality. Risk of bias was assessed using the Cochrane Risk of Bias tool and the PEDro scale for RCTs. Levels of evidence (LoE) were determined by the Sackett framework. RESULTS: Twenty-nine studies met inclusion criteria across five drug classes and 14 medications. Results of LoE 1 were mixed: Methylphenidate improved classroom attention/processing speed, and exhibited neutral outcome; amantadine showed no improvement (LoE 1, 4, 5). MLC901 (a multi-herb antioxidant) improved complex attention (LoE 1). Donepezil improved sustained (LoE 1) and divided attention (LoE 4). Physostigmine/lecithin (LoE 1) and antidepressants (LoE 1, 3, 5) had mixed effects; growth hormone (LoE 4), and L-carnitine (LoE 1) showed no effect. Anticonvulsants impaired cognition (LoE 1). CONCLUSION: Methylphenidate showed the strongest evidence at lower doses. Donepezil and MLC901 showed potential benefits. Phenytoin and carbamazepine showed adverse effects on cognition. Standardized attention outcome measures and other high-quality alternative clinical trials with larger study samples are recommended to overcome the current limitations.