EXTRAPYRAMIDAL SYMPTOMS DURING LONG-TERM TREATMENT WITH ANTIPSYCHOTICS - SPECIAL FOCUS ON CLOZAPINE AND D-1 AND D-2 DOPAMINE ANTAGONISTS

In schizophrenic patients in maintenance treatment, clozapine, compare d to classic neuroleptics, induces relatively few extrapyramidal syndr omes (EPS), especially less akathisia and tremor and usually no dyston ia or rigidity. In patients with dyskinetic movements (acute or tardiv e) induced by other neuroleptics, clozapine may reduce or even remove dyskinesia or permit it to disappear. It cannot, however, be excluded that clozapine can induce dyskinesia in extremely rare cases, but it s eems more likely that this is due to previous treatment with classic n euroleptics. The earlier clozapine is started, the less chance of deve lopment of dyskinesia. The low level of EPS with clozapine may be link ed to the special receptor-binding profile of this drug: during treatm ent with therapeutic doses of clozapine, the level of D-2 receptor blo ckade is too low (40% to 50% occupancy by positron emission tomography ) to induce EPS, and the D-1 receptor blockade (also 40% to 50% occupa ncy) has a lower EPS potential than D-2 blockade. This binding profile may at the same time contribute to the special antipsychotic properti es of clozapine. Other receptor affinities may contribute to the benef icial effect of clozapine in EPS and schizophrenia.