background An atypical antipsychotic produces an antipsychotic effect in a dose that is much lower than the dose that causes extrapyramidal side effects. Almost all controlled studies of the new antipsychotics risperidon, olanzapine, and quetiapine are not able to conclude if the drug is atypical, because the dosage of the antipsychotic in the study group is not comparable to the dosage used in the control group.

aims We fomulated four criteria to measure the risk on acute extrapyramidal side-effects. These criteria are: a) the risk on extrapyramidal side effects in animal studies; b) the amount of d2 occupancy on the spect or pet-scans; c) a dose response relationship; and d) the influence of the new antipsychotic on the severity of M. Parkinson.

method A comprehensive search in Medline was done to find the relevant articles about clozapine and the new antipsychotics.

results With the use of these criteria and the data of the controlled trials clozapine seems clearly atypical followed probably by quetiapine. There were no controlled trials of olanzapine compared with an equivalent dose of a classical antipsychotic. However, olanzapine below 15 mg seems to give few acute extrapyramidal side effects. Risperidon 3 to 6 mg gives frequently acute extrapyramidal side effects, however probably less than an equivalent dose of haloperidol. The risk on tardive dyskinesia is very low for clozapine. No conclusions can be given for the risk on tardive dyskinesia with the new antipsychotics.

conclusion Clozapine and probably quetiapine give no acute extrapyramidal side effects. The risk on tardive syndromes is very low for clozapine.