Dose-response relationships for the antipsychotic effects and Parkinsonian side-effects of typical neuroleptic drugs: practical and theoretical implications

1. From a review of published literature it is concluded that the minimum dose of a neuroleptic drug (NLD) required to alleviate psychosis is very similar to that producing minimal parkinsonian side effects (PSE). This conclusion is reached both from group comparisons and individual comparisons of dose/response relations (DRR) for the two effects. 2. A lower dose of NLD is usually sufficient to prevent relapse in well stabilized patients than is needed to check an active psychotic state. 3. Anticholinergic agents used to reduce side effects of typical NLD can retard the therapeutic process during neuroleptic treatment of acute psychosis. Although it is not fully established that this is a central interaction, it is consistent with the idea that minimal side effects are a necessary condition for therapeutic effectiveness with typical antipsychotic drugs. 4. In relapse-free maintenance of psychosis-prone patients, tolerance occurs to PSE. Thus few patients need experience prolonged side effects during maintenance treatment with neuroleptics. 5. The evidence reviewed is discussed with respect to a previous hypothesis of the supposedly "indirect" action of typical neuroleptic drugs in therapy for psychosis. The evidence is consistent with the idea of a close causal relation between minimal PSE of these drugs, and their therapeutic effectiveness in the acute stage of treatment.