Long-term treatment of tardive dyskinesia with presynaptically acting dopamine-depleting agents.

Fourteen patients with TD, all but one also having tardive akathisia, were evaluated on presynaptically acting dopamine-depleting drugs, reserpine, TBZ, and AMT. Initially, the drugs were evaluated individually, but later AMT was used in combination with reserpine and with TBZ, since their different mechanisms of action allowed for increased potency when they were used in this combination. All but one patient responded to this therapeutic approach. Parkinsonism was easily induced, however. Most patients varied during the day between mild parkinsonism and mild dyskinesia-akathisia. It was difficult to have patients at the normal level between these two conditions. The addition of carbidopa/levodopa in one patient not only relieved the side effect of parkinsonism but may have also accelerated a remission from TD and akathisia. Although postural hypotension was a common adverse effect in patients receiving reserpine, especially in combination with AMT, it did not develop in patients taking TBZ, either alone or in combination with AMT. This observation suggests that TBZ may be less effective depleting monoamines in the periphery than in the central nervous system. Since reserpine is available commercially in the United States whereas TBZ is not, reserpine may be the drug of choice in treating patients with TD or tardive akathisia. The addition of AMT will increase the potency of this form of treatment.