As would be expected in a group of severely brain-injured patients, adverse events were common, with a median number of two events for each patient. The most common events were hypertonia or spasticity (occurring in 21% of amantadine-treated patients and 14% of patients on placebo), insomnia (14% for both groups), and agitation (14% and 11%, respectively).

However, the treatment did not increase the risk for adverse events of particular concern for these patients, such as seizures, and amantadine can be considered safe in this population, according to the researchers.

A limitation of the study was possible selection bias, because participants all were inpatients at rehabilitation centers and thus may have been good candidates for improvement.

In addition, patients all had standard interventions for rehabilitation and other psychoactive drugs, and the course of amantadine was brief.

It therefore is unclear if over the long term, patients who had been given placebo would catch up in their recovery to those given amantadine.

Nonetheless, Giacino and colleagues concluded, “In view of the healthcare cost constraints and declining lengths of stay for inpatient rehabilitation, amantadine-induced acceleration of recovery may represent an important advance.”

Additional work will be needed to identify patients most likely to respond and to establish the optimal dosage and timing of treatment.

The study was supported by the National Institute on Disability and Rehabilitation Research. Many of the investigators also received support from that institute.

Other disclosures included one investigator’s consultancy for Allergan, Merz, Ipsen, and Medtronic, and support for others from the American Academy of Neurology, the Rusk Institute of Rehabilitation, and the Austin Medical Social Workers Association.

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By Nancy Walsh, Staff Writer, MedPage Today
Primary source: New England Journal of Medicine
Source reference: Giacino J, et al “Placebo-controlled trial of amantadine for severe traumatic brain injury” N Engl J Med 2012; 366: 819-826.