TBZ has been in use in countries outside the U.S. since 1960, so many studies have been conducted on the drug.
Mikkelsen (1983) studied the tolerance of TBZ during long-term use. The results of this study showed infrequent and usually mild side effects. Only 5 of 124 participants discontinued the use of TBZ because of adverse effects. The researcher concluded that long-term treatment with TBZ appears to be quite safe.
Pearson & Reynolds (1988) linked TBZ with dopamine depletion by examining brain tissue from people with HD. They looked at people who had been treated with TBZ during their lifetimes, and compared their levels of neurotransmitters to the levels of people who had never been treated with TBZ. They found that those who had received TBZ treatment had lower concentrations of neurotransmitters in all areas of the brain that they studied, compared to those who never received TBZ treatment. These researchers found the greatest decrease of neurotransmitter was dopamine in a part of the striatum called the caudate, an area of the brain important in movement. For more information on HD and the brain, click here. However, the decrease in neurotransmitter was not limited to dopamine, but also included serotonin and similar molecules, which suggested the possibility of side effects. This study confirmed the findings of animal studies that TBZ treats chorea by depleting neurotransmitters in the brain.
Ondo, et al. (2002) tested the efficacy and tolerability of TBZ for treating chorea in 19 people with HD. Participants started with dosages of 25 milligrams per day, with a weekly increase to 150 milligrams per day. These participants had the option of not increasing the dose if they were satisfied with the results at any given stage, or if they began experiencing negative side effects at higher doses. They were evaluated at the beginning and end of the study. These evaluations included a videotaped portion, where they were rated using the motor section of the Abnormal Involuntary Movements Scale (AIMS). The videotapes showed an average improvement of 3.4 points on the AIMS (out of 42 total), with improvements attributable to TBZ in 15 of the 19 participants (two had improved before taking TBZ, one did not change, and one did not return for re-evaluation). When participants were asked to subjectively report their condition, none reported a worsening of their symptoms. Only one participant reported more than mild side effects. For this person, akathisia (feelings of restlessness and urges to move about) improved when the dose was lowered. Before taking part in this study, 13 of the 19 participants had tried at least one medication for chorea that they reported to be ineffective. All of the participants who completed this study, however, decided to continue taking TBZ to treat their chorea. The researchers concluded that TBZ is effective and well-tolerated.
Huntington Study Group (HSG) and Prestwick Pharmaceuticals (2006) collaborated on a clinical trial involving TBZ called TETRA-HD. Led by Dr. Frederick J. Marshall from the University of Rochester Medical Center, TETRA-HD is a phase III clinical trial with the goal of determining the optimal dosage of TBZ in treating chorea and other involuntary movements in people with HD. The trial was carried out at 16 different HSG sites in the United States, involving a total of 84 participants with HD. 54 of the participants were randomly assigned to receive TBZ for 12 weeks with increasing dosages over the first 7 weeks. The other 30 served as the comparison group and received a placebo. The results of the study found that TBZ is effective in treating chorea and that its side effects are less severe than those associated with other anti-choreic drugs. On the CGI Global Improvement Scale, 6.9% of the patients receiving placebo had more than minimal improvement compared to 45.1% of the patients receiving TBZ. Clinical assessments showed that TBZ was associated with drowsiness and insomnia in four patients, depressed mood in two, parkinsonism in two and akathisia in two. Most cases of adverse effects improved after adjusting dosage levels, but the risk of side effects such as increased risk of suicide, must still be acknowledged. These results confirm the benefits of TBZ usage in ameliorating the symptoms of chorea.
Last Modified: 05/22/2009
An educational product of HOPES, not to be used in place of medical care. For more information about HOPES, click on the Logo.
To contact HOPES with comments or questions, click here.
