Tardive drug-induced extrapyramidal syndromes

The clinical features, outcomes, differential diagnoses, epidemiology, risk factors, and treatment approaches to tardive drug-induced extrapyramidal syndromes (EPS) are reviewed. Tardive forms of dyskinesia (TD), dystonia (TDt), akathisia (TA), Gilles de la Tourette syndrome (TGTS), myoclonus (TM), and parkinsonism (TP) are described. Moreover, pharmacological and topographical subtypes of TD are discussed. While TD, TDt, and TA are clearly delineated syndromes, there are limited data on TGTS, TM, and the questionable TP. TDt is distinguished from TD by clinical and treatment-related variables. Epidemiological studies provide evidence of better prognosis for TD compared 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 treatment variables and alcohol or drug abuse) and a factor of predisposition (elderly, female, affective disorder diagnosis, presence of EPS, diabetes mellitus type II, and signs of central vulnerability). In contrast, being younger and male was associated with TDt. A significant relationship between the hyperkinetic forms of tardive EPS was confirmed. Therapeutic strategy differs for the mild, moderate, and severe forms of tardive EPS. Using low doses of antipsychotics is a good preventive approach. Reducing the dose or switching to an atypical antipsychotic is the usual, but not yet fully explored, first therapeutic step. Clozapine, an antipsychotic with antidyskinetic and antidystonic effectiveness, is the second treatment step. Various suppressors of tardive movements were tested in controlled trials, mainly in TD. GABAergic benzodiazepines (clonazepam), adrenergic antagonists (propranolol, clonidine), antioxidants (alpha-tocopherol), and calcium channel blockers (nifedipine) are useful in the third step of treatment of more severe tardive EPS. Unlike TD, TDt and (partially) TA improve on higher doses of anticholinergic medication. Local injection of botulinum A toxin markedly ameliorates focal tardive dystonia over several months. Less verified therapeutic interventions are discussed.