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Treatment of tardive dyskinesia with bromocriptine. A test of the receptor modification strategy
J A Lieberman1, J Alvir, S Mukherjee
1Hillside Hospital, Division of Long Island Jewish Medical Center, Glen Oaks, NY.
Abstract:
Pathophysiologic theories postulate that tardive dyskinesia arises from the development of chemical denervation supersensitivity of dopamine receptors produced by chronic long-term neuroleptic treatment. To test a dopamine receptor modification strategy, 16 patients with tardive dyskinesia were assigned to treatment with a neuroleptic plus bromocriptine (a dopamine agonist) or placebo for 10 weeks in a rising-dose design. Patients were evaluated weekly during the 10-week treatment period and for 8 weeks after medication withdrawal. No significant treatment effect was found in tardive dyskinesia response in the overall sample. When patients were classified by tardive dyskinesia subtype, patients with choreoathetoid symptoms exhibited only slight improvement with active treatment, which persisted after drug withdrawal; patients with dystonic symptoms showed moderate improvement that was drug and dose dependent. The sustained administration of substantial doses of a dopamine agonist did not produce significant adverse effects, including behavioral toxic effects. These results, although not statistically significant, are of clinical and heuristic interest.
Insights
This study investigated bromocriptine for tardive dyskinesia, finding no overall effect. However, some patients with dystonic symptoms showed moderate improvement with this dopamine agonist treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Clinical Neurology
Background:
- Tardive dyskinesia is theorized to result from dopamine receptor supersensitivity due to long-term neuroleptic use.
- Understanding the pathophysiology of tardive dyskinesia is crucial for developing effective treatments.
Purpose of the Study:
- To test a dopamine receptor modification strategy for tardive dyskinesia using bromocriptine, a dopamine agonist.
- To evaluate the efficacy and safety of bromocriptine in patients with tardive dyskinesia.
Main Methods:
- A randomized, placebo-controlled trial involving 16 patients with tardive dyskinesia.
- Patients received either a neuroleptic plus bromocriptine or placebo over 10 weeks in a rising-dose design.
- Weekly evaluations during treatment and an 8-week follow-up post-withdrawal were conducted.
Main Results:
- No statistically significant treatment effect on tardive dyskinesia was observed in the overall patient sample.
- Patients with choreoathetoid symptoms showed minimal improvement with bromocriptine, which persisted post-treatment.
- Patients with dystonic symptoms demonstrated moderate, dose-dependent improvement during active treatment.
Conclusions:
- Bromocriptine did not yield significant overall efficacy for tardive dyskinesia but showed potential in specific subtypes.
- The treatment was well-tolerated, with no significant adverse effects, including behavioral toxicity.
- These findings, while not statistically significant, offer clinical insights into dopamine agonist therapy for tardive dyskinesia subtypes.