Tardive drug-induced extrapyramidal syndromes

The clinical features, outcomes, differential diagnoses, epidemiology, risk factors, and treatment approaches to tardive drug-induced extrapyramidal s yndromes (EPS) are reviewed. Tardive forms of dyskinesia (TD), dystonia (TD t), akathisia (TA), Gilles de la Tourette syndrome (TGTS), myoclonus (TM), and parkinsonism (TP) are described. Moreover, pharmacological and topograp hical subtypes of TD are discussed. While TD, TDt, and TA are clearly delin eated syndromes, there are limited data on TGTS, TM, and the questionable T P. TDt is distinguished from TD by clinical and treatment-related variables . Epidemiological studies provide evidence of better prognosis for TD compa red with both TDt and TA. Two distinct groups of variables were found to be associated with a higher risk for TD: an exogenous factor (neuroleptic tre atment variables and alcohol or drug abuse) and a factor of predisposition (elderly, female, affective disorder diagnosis, presence of EPS, diabetes m ellitus type II, and signs of central vulnerability). In contrast, being yo unger and male was associated with TDt. A significant relationship between the hyperkinetic forms of tardive EPS was confirmed. Therapeutic strategy d iffers for the mild, moderate, and severe forms of tardive EPS. Using low d oses of antipsychotics is a good preventive approach. Reducing the dose or switching to an atypical antipsychotic is the usual, but not yet fully expl ored, first therapeutic step. Clozapine, an antipsychotic with antidyskinet ic and antidystonic effectiveness, is the second treatment step. Various su ppressors of tardive movements were tested in controlled trials, mainly in TD. GABAergic benzodiazepines (clonazepam), adrenergic antagonists (propran olol, clonidine), antioxidants (a-tocopherol), and calcium channel blockers (nifedipine) are useful in the third step of treatment of more severe tard ive EPS. Unlike TD, TDt and (partially) TA improve on higher doses of antic holinergic medication. Local injection of botulinum A toxin markedly amelio rates focal tardive dystonia over several months. Less verified therapeutic interventions are discussed.