Tardive dyskinesia: nondopaminergic treatment approaches.

The continuing concern about tardive dyskinesia (TD) has stimulated a broad search for therapies for this disorder. Since neuroleptic drugs are thought to be the etiological agents, acting presumably through dopamine receptor blockade, nondopaminergic drugs have been the focus of recent study. However, no uniformly safe and effective drug treatment has been identified. Augmentation of cholinergic function is theoretically attractive, but further research is needed to develop practical and effective compounds. GABA drugs do not consistently suppress TD. The effect of benzodiazepines in TD is unclear, but these agents may be of some temporary benefit in patients with distressing symptoms. Lithium, serotonergic compounds, and numerous neuropeptides all fail to have any consistent effect in TD. Early reports of benefit with alpha- and beta-noradrenergic agents are interesting but require further study. Many other drug types have been tried without benefit. For the majority of patients, it may be best to give no drug treatment. Any drug that is capable of suppressing TD may aggravate the disorder in the long term. The potential for a spontaneous gradual remission of TD is an argument in favor of a patient, nonaggressive, and cautiously optimistic approach to this disorder.