Pharmacological Management of Tardive Dyskinesia
Vernon M Neppe MD, PhD
- To provide background as to the enormity of
the problem of.
- To discuss the pharmacologic management of tardive
- To allow perspectives as to alternative mechanisms
of action of drugs such as masking and subsensitization.
- 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
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
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 author?s research both in Washington
state and St Louis. The need for double blind studies