A novel multimodal pharmacologic approach using guanfacine, N-acetylcysteine, and donepezil in severe TBI: a case series.

The study includes only two patients, which is far too small to draw any conclusions about treatment efficacy. There was no control group. We do not know if the patients would have improved at the same rate without the medication. Both patients received intensive rehabilitation (speech, cognitive, physical, and occupational therapy) alongside the medication. The contribution of the drugs cannot be separated from the contribution of the therapy. Post-treatment comprehensive neuropsychological assessments were not completed due to insurance and cost issues, limiting the depth of the outcome data. The study included no female patients, limiting generalizability. The authors acknowledge that the improvements are anecdotal and that larger, controlled studies are needed.

The authors declare that no financial support was received for the research and/or publication of this article.

Do not interpret the large MoCA score improvements as evidence that the medication worked. Both patients also received intensive speech, cognitive, physical, and occupational therapy, and there was no control group to compare against. The gains could be due to natural recovery, the rehabilitation, or the combination, and this case series cannot separate them.