Amantadine May Hasten Functional Recovery in Patients With Severe TBI

Fewer patients receiving amantadine remained in a vegetative state compared with patients receiving placebo.

Patients with post-traumatic disorders of consciousness who received amantadine hydrochloride experienced a more rapid rate of functional recovery than those treated with a placebo, according to an article published in the March 1 New England Journal of Medicine. The benefit of the drug was evident in patients diagnosed with a vegetative or minimally conscious state at baseline, regardless of when they were enrolled in the trial.

Fewer patients who received amantadine, a drug used to treat Parkinson’s disease, remained in a vegetative state, compared with patients who received placebo, according to Joseph T. Giacino, PhD, Director of Rehabilitation Neuropsychology at Spaulding Rehabilitation Hospital and Associate Professor at Harvard Medical School in Boston. In addition, a greater percentage of patients receiving amantadine met key behavioral milestones for recovery (eg, consistent following of commands and object recognition) by the end of the treatment period, compared with the control group. Treatment did not increase patients’ risk of adverse medical events.

After patients stopped receiving amantadine, their level of improvement continued to increase, albeit at a significantly slower rate. Two weeks after treatment ended, the disability scores of the experimental and control groups were similar.

Treating Post-Traumatic Disorders of Consciousness
Dr. Giacino and his colleagues conducted a prospective, double-blind, randomized trial to evaluate the effectiveness of amantadine in helping patients with post-traumatic trauma recover from a vegetative or minimally conscious state. The study followed 184 patients at 11 clinical sites in three countries.

Eligible patients had experienced traumatic brain injury four to 16 weeks before enrollment, and they were receiving care at in-patient facilities. Participants had disability rating scores (DRS) greater than 11, could not follow commands, and could not engage in functional communication. Nearly 87% of patients were white, and approximately 72% were male.

After randomization, the experimental group received 100 mg of amantadine twice daily for 14 days. The dose was increased to 150 mg twice daily at week three, and to 200 mg twice daily at week four for any patient in the group whose DRS had not improved by two points from baseline. After four weeks, treatment ceased, but DRS scores continued to be assessed for two additional weeks. The control group received a placebo for four weeks.

Amantadine May Shorten In-Patient Stays
“We conclude that amantadine is effective in accelerating the pace of recovery during acute rehabilitation in patients with prolonged post-traumatic disturbances in consciousness,” said Dr. Giacino. “The favorable neurobehavioral effects of amantadine may reflect enhanced neurotransmission in the dopamine-dependent nigrostriatal, mesolimbic, and frontostriatal circuits that are responsible for mediating arousal, drive, and attentional functions.”

The researchers limited the length of the treatment period for practical and ethical reasons. Therefore, the study results leave open the question of whether amantadine improves patients’ long-term outcome or accelerates recovery to the end point that an untreated patient would reach. “In view of health care cost constraints and declining lengths of stay for in-patient rehabilitation, amantadine-induced acceleration of recovery may represent an important advance,” said Dr. Giacino. Future studies should identify which patients are likely to respond to amantadine, the effective dose, and the optimal duration of treatment, he concluded.   

Fewer patients receiving amantadine remained in a vegetative state compared with patients receiving placebo.

Patients with post-traumatic disorders of consciousness who received amantadine hydrochloride experienced a more rapid rate of functional recovery than those treated with a placebo, according to an article published in the March 1 New England Journal of Medicine. The benefit of the drug was evident in patients diagnosed with a vegetative or minimally conscious state at baseline, regardless of when they were enrolled in the trial.

Fewer patients who received amantadine, a drug used to treat Parkinson’s disease, remained in a vegetative state, compared with patients who received placebo, according to Joseph T. Giacino, PhD, Director of Rehabilitation Neuropsychology at Spaulding Rehabilitation Hospital and Associate Professor at Harvard Medical School in Boston. In addition, a greater percentage of patients receiving amantadine met key behavioral milestones for recovery (eg, consistent following of commands and object recognition) by the end of the treatment period, compared with the control group. Treatment did not increase patients’ risk of adverse medical events.

After patients stopped receiving amantadine, their level of improvement continued to increase, albeit at a significantly slower rate. Two weeks after treatment ended, the disability scores of the experimental and control groups were similar.

Treating Post-Traumatic Disorders of Consciousness
Dr. Giacino and his colleagues conducted a prospective, double-blind, randomized trial to evaluate the effectiveness of amantadine in helping patients with post-traumatic trauma recover from a vegetative or minimally conscious state. The study followed 184 patients at 11 clinical sites in three countries.

Eligible patients had experienced traumatic brain injury four to 16 weeks before enrollment, and they were receiving care at in-patient facilities. Participants had disability rating scores (DRS) greater than 11, could not follow commands, and could not engage in functional communication. Nearly 87% of patients were white, and approximately 72% were male.

After randomization, the experimental group received 100 mg of amantadine twice daily for 14 days. The dose was increased to 150 mg twice daily at week three, and to 200 mg twice daily at week four for any patient in the group whose DRS had not improved by two points from baseline. After four weeks, treatment ceased, but DRS scores continued to be assessed for two additional weeks. The control group received a placebo for four weeks.

Amantadine May Shorten In-Patient Stays
“We conclude that amantadine is effective in accelerating the pace of recovery during acute rehabilitation in patients with prolonged post-traumatic disturbances in consciousness,” said Dr. Giacino. “The favorable neurobehavioral effects of amantadine may reflect enhanced neurotransmission in the dopamine-dependent nigrostriatal, mesolimbic, and frontostriatal circuits that are responsible for mediating arousal, drive, and attentional functions.”

The researchers limited the length of the treatment period for practical and ethical reasons. Therefore, the study results leave open the question of whether amantadine improves patients’ long-term outcome or accelerates recovery to the end point that an untreated patient would reach. “In view of health care cost constraints and declining lengths of stay for in-patient rehabilitation, amantadine-induced acceleration of recovery may represent an important advance,” said Dr. Giacino. Future studies should identify which patients are likely to respond to amantadine, the effective dose, and the optimal duration of treatment, he concluded.   

Fewer patients receiving amantadine remained in a vegetative state compared with patients receiving placebo.

Patients with post-traumatic disorders of consciousness who received amantadine hydrochloride experienced a more rapid rate of functional recovery than those treated with a placebo, according to an article published in the March 1 New England Journal of Medicine. The benefit of the drug was evident in patients diagnosed with a vegetative or minimally conscious state at baseline, regardless of when they were enrolled in the trial.

Fewer patients who received amantadine, a drug used to treat Parkinson’s disease, remained in a vegetative state, compared with patients who received placebo, according to Joseph T. Giacino, PhD, Director of Rehabilitation Neuropsychology at Spaulding Rehabilitation Hospital and Associate Professor at Harvard Medical School in Boston. In addition, a greater percentage of patients receiving amantadine met key behavioral milestones for recovery (eg, consistent following of commands and object recognition) by the end of the treatment period, compared with the control group. Treatment did not increase patients’ risk of adverse medical events.

After patients stopped receiving amantadine, their level of improvement continued to increase, albeit at a significantly slower rate. Two weeks after treatment ended, the disability scores of the experimental and control groups were similar.

Treating Post-Traumatic Disorders of Consciousness
Dr. Giacino and his colleagues conducted a prospective, double-blind, randomized trial to evaluate the effectiveness of amantadine in helping patients with post-traumatic trauma recover from a vegetative or minimally conscious state. The study followed 184 patients at 11 clinical sites in three countries.

Eligible patients had experienced traumatic brain injury four to 16 weeks before enrollment, and they were receiving care at in-patient facilities. Participants had disability rating scores (DRS) greater than 11, could not follow commands, and could not engage in functional communication. Nearly 87% of patients were white, and approximately 72% were male.

After randomization, the experimental group received 100 mg of amantadine twice daily for 14 days. The dose was increased to 150 mg twice daily at week three, and to 200 mg twice daily at week four for any patient in the group whose DRS had not improved by two points from baseline. After four weeks, treatment ceased, but DRS scores continued to be assessed for two additional weeks. The control group received a placebo for four weeks.

Amantadine May Shorten In-Patient Stays
“We conclude that amantadine is effective in accelerating the pace of recovery during acute rehabilitation in patients with prolonged post-traumatic disturbances in consciousness,” said Dr. Giacino. “The favorable neurobehavioral effects of amantadine may reflect enhanced neurotransmission in the dopamine-dependent nigrostriatal, mesolimbic, and frontostriatal circuits that are responsible for mediating arousal, drive, and attentional functions.”

The researchers limited the length of the treatment period for practical and ethical reasons. Therefore, the study results leave open the question of whether amantadine improves patients’ long-term outcome or accelerates recovery to the end point that an untreated patient would reach. “In view of health care cost constraints and declining lengths of stay for in-patient rehabilitation, amantadine-induced acceleration of recovery may represent an important advance,” said Dr. Giacino. Future studies should identify which patients are likely to respond to amantadine, the effective dose, and the optimal duration of treatment, he concluded.