Amantadine Found to Improve Prolonged Disorders of Consciousness After TBI

The mean age of patients was 36 years and 72% were male. The mean baseline DRS scores in the amantadine group and placebo group were 21.8 and 22.2, respectively, while the mean baseline CRS-R scores were 9.6 and 9.2. Scores on the DRS can range from 0 to 29, and scores on the CRS-R can range from 0 to 23.

Dr. Katz reported that patients who received amantadine had significantly faster functional recovery over 4 weeks of treatment, compared with patients in the placebo group (P = .007). In addition, patients in the amantadine group maintained functional gains during the 2-week washout period, but their recovery slowed, compared with that of patients in the placebo group after the medication was discontinued (P = .02).

Patients treated with amantadine tended to have more rapid recovery, compared with those treated with placebo, regardless of whether they were diagnosed in a vegetative state or a minimally conscious state at enrollment. Treatment with amantadine also was more effective in improving recovery regardless of whether it was administered within 4-10 weeks or 10-16 weeks postinjury.

After 4 weeks of treatment, a lower percentage of patients in the amantadine group remained in a vegetative state or an extreme vegetative state, compared with their counterparts in the placebo group (18% vs. 31%, respectively).

Dr. Katz went on to report that patients in the amantadine group achieved a higher percentage of cognitive behaviors associated with full consciousness based on the CRS-R at week 4, compared with the placebo group, including more consistent following of commands (40% vs. 32%, respectively), object recognition (44% vs. 34%), functional object use (42% vs. 26%), intelligible verbalization (39% vs. 34%), reliable yes/no communication (31% vs. 27%), and sustained attention (35% vs. 29%).

Vomiting and gastrointestinal side effects were the most common adverse events observed, but there were no differences between the two groups in the incidence of adverse events.

"This study demonstrates that amantadine is safe and effective in promoting more rapid functional recovery in patients with disorders of consciousness after severe TBI," Dr. Katz concluded. "Although the rate of improvement slowed, the benefits of amantadine were maintained after the drug was discontinued."

He acknowledged certain limitations of the study, including the limited interval of treatment and assessment, and that it was not controlled for the effects of standard rehabilitation interventions.

The study was funded by the National Institute on Disability and Rehabilitation Research. The project director was Joseph Giacino, Ph.D., of the Spaulding Rehabilitation Hospital in Boston (formerly of the JFK Johnson Rehabilitation Institute, Edison, N.J.). The project codirector was Dr. John Whyte of the Moss Rehabilitation Research Institute, Elkins Park, Pa.

Dr. Katz said that he had no relevant financial disclosures.