Extrapyramidal symptoms during long-term treatment with antipsychotics: special focus on clozapine and D1 and D2 dopamine antagonists.

In schizophrenic patients in maintenance treatment, clozapine, compared to classic neuroleptics, induces relatively few extrapyramidal syndromes (EPS), especially less akathisia and tremor and usually no dystonia or rigidity. In patients with dyskinetic movements (acute or tardive) 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 seems more likely that this is due to previous treatment with classic neuroleptics. The earlier clozapine is started, the less chance of development of dyskinesia. The low level of EPS with clozapine may be linked to the special receptor-binding profile of this drug: during treatment with therapeutic doses of clozapine, the level of D2 receptor blockade is too low (40% to 50% occupancy by positron emission tomography) to induce EPS, and the D1 receptor blockade (also 40% to 50% occupancy) has a lower EPS potential than D2 blockade. This binding profile may at the same time contribute to the special antipsychotic properties of clozapine. Other receptor affinities may contribute to the beneficial effect of clozapine in EPS and schizophrenia.