Journal Article Annotations
2024, 1st Quarter
Annotations by Nathan Praschan, MD, MPH, Laura Duque, MD
April, 2024
The finding:
Thirty seven patients who had experienced within 1-6 months an aneurysmal rupture leading to subarachnoid hemorrhage and disordered consciousness were randomized to placebo or amantadine (doubled weekly until 200 mg twice daily) for six weeks. Participants, researchers, and clinicians were blinded to the allocation. Participants were similar across demographics, baseline Glasgow Coma Scale (GCS), clinical severity indices, and important clinical events (eg need for surgery), although sepsis was more common in the placebo group and CNS infection more common among the amantadine group. At all time points through 6 months, amantadine did not produce a significant change in the Coma Recovery Scale-Revised, the Rappaports Disability Rating Scale, or mortality.
Strength and weaknesses:
This study was well controlled and achieves high external validity. The small N may have limited the study’s ability to detect an effect from amantadine. Patients were deemed eligible for amantadine 30 days after the hemorrhage, and so it is possible that earlier use may provide some benefit.
Relevance:
Consultation-liaison psychiatrists—particularly neuropsychiatrists who liaise with neurointensive care units—are often called upon to help diagnose and manage patients with disorders of consciousness (DoC) or similar presenting complaints. This study evaluates the use of a commonly prescribed medication, amantadine, to promote cognitive recovery in DoC due to a specific etiology: subarachnoid hemorrhage. Amantadine has historically been used and found effective among patients with DoC related to traumatic brain injury. The findings of this study call into question the broad use of this agent for all DoC; CL psychiatrists should thus be judicious in recommending its use in these settings, keeping in mind that the etiology of the DoC may influence amantadine’s effectiveness.
The finding:
Transcranial Magnetic Stimulation (TMS) improves both global and specific cognitive functions in patients with mild cognitive impairment (MCI) or dementia attributable to Alzheimer’s Disease (AD), non-Alzheimer’s dementia, cognitive impairment without dementia, and healthy older adults. This improvement was noted across various TMS protocols, which, despite their variability, all demonstrated safety and tolerability with minimal serious adverse events. In the meta-analysis component of the study, TMS was found to improve cognitive function in patients with MCI and AD compared to sham stimulation, across global cognitive outcome measures.
Strength and weaknesses:
The study has a robust sample size, incorporating data from 5,800 patients across 143 studies, lending considerable weight to its findings. There was significant heterogeneity in study designs and a wide variation in stimulation parameters (including targets) and cognitive outcome assessments. This variability restricts the establishment of a definitive TMS protocol for widespread clinical application. Additionally, there was limited long-term outcome data.
Relevance:
The management of patients with cognitive impairment, including dementia and MCI, often falls within the practice of C-L psychiatry, hence the need for nuanced understanding and management strategies of these patients. This study’s findings illuminate the potential of TMS as a safe and effective treatment modality for cognitive function.