Page synopsis: The drug I'm most interested in using. Given reports that it helps both my  conditions (CFS and pTBIcf) and that it has helped many patients significantly, I'm excited for treatment

Skill Level  5

Relevance:5 Technical Level:2

This page has the most 'bang for the buck' in that Amantadine may make all the difference to CFS patients (even though it is not a cure), while the page contains few technically challenging sections


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Amantadine interacts with venlafaxin where the risk or severity of QTc prolongation can be increased when Venlafaxine is combined with Amantadine. A good alternative to Venlafaxine (and perhaps to SSRI's and SSNRI's) may be Amisulpride


QT prolongation is a measure of delayed ventricular repolarisation. Excessive QT prolongation can predispose the myocardium to the development of early after-depolarisations, which in turn can trigger re-entrant tachycardias such as TdP


The following conditions can also increase the likelihood of QT prolongation causing TDP:

  • dehydration.
  • conditions that cause electrolyte imbalances.
  • raised blood cholesterol.
  • diabetes.
  • thyroid disorders.
  • left ventricular hypertrophy


Neuropharmacology In TBI: What We Know & What We Don’t - ppt download

  • Meythaler et al 2002 found amantadine improved neurorecovery in TBI with DAI in Double-Blind randomized crossover 6 week trial
  • 35 patients with TBI, GCS of 10 or less
  • Amantadine 200mg/day/placebo given in first 6 weeks or 2^nd 6 weeks
  • Improved MMSE, DRS, GOS, and FIM cognitive Score in amantadine group in first 6 weeks, and no improvement in next 6 on placebo. No sig effect on GOAT
  • In group on amantadine in weeks 6-12, statistical sig improvment in MMSE, DRS, GOS, an FIM cog after active drug
  • No sig effect on GOAT


Conclusion: rapid functional improvement on amantadine when given in first 3 months after injury


There exits evidence to support use of amantadine.


Kraus et al 2005 found improvements of tests of executive function after treatment with amantadine in patients with chronic TBI

(N=22, amantadine 200mg BID Outcome measures: neuropsychological testing (pre and post-12 week treatment) and PET scanning on 6 participants)



  • Significant improvements on tests of executive function
  • Analysis of PET data demonstrated significant increase in left prefrontal and medial temporal cortex glucose metabolism
  • This correlated with improvement in measures of executive function


Memory and attention did not significantly improve


Amantadine improved global outcome on DRS (Maythaler 2002).

Amantadine has most support for improving executive function after TBI, but is not supported in memory or attentional recovery.

From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment'


Dr David Bell found amantadine 25 mg to 50 mg twice daily helps ME/CFS, but says higher doses can exacerbate symptoms.1(


From: Drug Speeds Recovery After Traumatic Brain Injury - MedicineNet


A drug that's typically used to treat the flu and Parkinson's disease appears to speed recovery in traumatic brain injury patients, a new study indicates.


Traumatic brain injury (TBI) victim who weren't fully conscious and were discharged to rehabilitation facilities after hospitalization were given amantadine hydrochloride
The drug is already given "off-label" to such patients, but if and how much it helps has remained unclear.


While taking the drug, the patients given amantadine scored better on behavioral tests that measure how well the brain is functioning compared to a group of patients given a placebo, researchers report in the March 1 issue of *The New England Journal of Medicine*.


"Amantadine appeared to increase the rate of recovery compared to placebo. Patients got better faster while they were on the drug," said study co-author Joseph Giacino, director of rehabilitation neuropsychology at the Spaulding Rehabilitation Hospital, in Boston, and an associate professor in the department of physical medicine and rehabilitation at Harvard Medical School.


Study co-author Dr. John Whyte, director of the Moss Rehabilitation Research Institute at Albert Einstein Healthcare Network, in the Philadelphia area, said previous observational studies had suggested amantadine improved the rate of recovery. While the medicine is already commonly prescribed off-label to treat people suffering from prolonged disorders of consciousness, he said this is the first placebo-controlled trial of the drug in patients who were either in a vegetative state (wakeful but not aware) or a minimally conscious state (able to track with their eyes).


"There were many hypotheses out there about what this drug should do, but there was very little data to support or refute those hypotheses," Whyte explained.


For the study, 184 patients from 11 medical centers in three countries were enrolled. They had all suffered a TBI within the previous one to four months. Half received amantadine while the other half were given a placebo for the first four weeks of the six-week study. Both groups were followed up for two additional weeks, Whyte said.


The researchers used the Disability Rating Scale (DRS) to monitor patients' progress during the treatment and follow-up period. The test measures eye opening, verbal ability and motor response, among other functions, Giacino said.


"During the four-week treatment period, recovery was significantly faster in the amantadine group than the placebo group," said Giacino.


Whyte said during his 25-year career as a brain trauma rehabilitation physician there have been no groundbreaking treatments for these patients. TBI rehabilitation can take months, or years, and many patients do not have the health insurance or private funds to access good rehabilitative care, so a drug that could speed recovery would be a boon, he said.


The ability of patients in a vegetative state or those in the MCS "to access rehab has gotten less and less," Whyte said. "Many of these patients go straight to a nursing home or home with family." He noted that TBI remains the most common cause of death and disability in people between the ages of 15 and 30.


The new finding "is very exciting because we have a new tool to help improve these patients in their early outcome," said one expert, Dr. J. Javier Provencio, director of the Neurocritical Care Fellowship Program at the Cerebrovascular Center of the Cleveland Clinic Neurological Institute.


"The take-home message is that this medicine is promising for patients in a very certain setting. I think the results have to be taken very strictly and not extrapolated to other conditions," said Provencio.


He noted that the rate of improvement in the drug group slowed in weeks five and six. By the study's end, the overall improvement from baseline between the placebo group and the amantadine group was identical.


That means that, "it is still unclear whether the effects last," Provencio said. "In the study, by week six, the effect difference was getting smaller. I hope they follow these patients out to a year to see how they do."


Co-author Giacino said the researchers were surprised when they saw an immediate leveling off between the two groups in the final two weeks.


"But when I take a step back, it is even stronger evidence that this drug was doing something," he added.


Neurologist Dr. Daniel Labovitz, of Montefiore Medical Center in New York City, believes hope should remain in check despite the promising results. "It's not a home run. It's a small change and it was temporary, and I think that would be the message that has to come through."


Labovitz said the drug appears to be gently waking the patients. "If this trial holds up in larger, longer-term studies, maybe you can enhance the ability of rehabilitation therapists to interact with patients while they're on the drug."


Giacino said they researchers also aimed to look at side effects of amantadine.


"There was not a single category where the amantadine group had a higher rate of side effects than the placebo group," he said.


Whyte said that while this research may influence more rehabilitation experts to use amantadine for this type of patient, more challenges remain before the drug's impact is completely understood.


"This study isn't the end of the story," Whyte said.

Amantadine recommended by Clearfield hormone therapy as used in conjunction with HRT, Statins, Bromocriptine and Selegiline




 Taken together with



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