Pharmacological Management of Tardive Dyskinesia

Vernon M Neppe MD, PhD


  1. To provide background as to the enormity of the problem of.
  2. To discuss the pharmacologic management of tardive dyskinesia.
  3. To allow perspectives as to alternative mechanisms of action of drugs such as masking and subsensitization.
  4. Give perspectives for practice on the prevention and the treatment of this condition.


Tardive Dyskinesia (TD) has become the single major epidemiological scourge in the psychopharmacotherapy of the psychotic patient. The threat of development of abnormal, largely irreversible, involuntary movements associated with chronic administration of antipsychotic drugs, has created debates as to whether, at times, continued antipsychotic drug treatment is appropriate and has substantially changed the management of psychoses.

Measures of TD are largely inadequate leading to the development by the author of the STRAW system of evaluation.

There are no FDA approved drugs for Tardive Dyskinesia.

Numerous medications have been attempted for the management of this syndrome, with little success. Previously investigated pharmacologic interventions have included cholinergic agents, amine synthesis inhibitors, amine-depleting agents, gamma-aminobutyric acid (GABA) agonists, calcium antagonists and vitamin E. Most of these agents produced inconsistent or temporary effects or were associated with unacceptable side effects.

Numerous medications accentuate this condition including anticholinergics and neuroleptic withdrawal. Additionally, stress and serotonin modulating drugs influence outcome.

Because TD has been linked to dopamine receptor supersensitivity, and associated tardive psychosis may have similar mechanisms, drugs which may stabilize, this supersensitivity appear appropriate theoretical choices for use in TD. Consequently, the availability of the azapirone, buspirone, may be a breakthrough of profound significance. This drug seems theoretically and empirically to alleviate TD in doses of 120-240 mg/day. The evidence for this is discussed based on the authorís research both in Washington state and St Louis. The need for double blind studies is emphasized.


© Copyright 1997 Pacific Neuropsychiatric Institute.