Neuroleptic dosing and neuroleptic plasma levels in schizophrenia: determining the optimal regimen.

Abstract

To recommend dose range and therapeutic plasma concentration for several neuroleptics, and to discuss conditions under which neuroleptic plasma levels are clinically useful. Neuroleptic drug therapy is a major component of the acute and maintenance treatment of schizophrenia. However, there is no consensus on what constitutes an appropriate or optimal dose of antipsychotic drug in individual patients. Low-dose medication has the potential to improve psychosocial function and reduces the frequency of side effects but can lead to an increase in positive symptoms and schizophrenic relapse. High doses may be associated with behavioural toxicity, symptom exacerbation, a worsening of secondary deficit symptoms, impaired social functioning and increased adverse effects such as acute extrapyramidal symptoms and tardive dyskinesia. Numerous clinical studies have attempted to determine the degree of correlation between dose, neuroleptic blood levels, and clinical response. To date, this approach has met with only limited success: neuroleptic dose overall appears to be a poor predictor of clinical outcome, and the suggested therapeutic plasma level concentrations of some antipsychotic drugs cannot be regarded as established by any means. Furthermore, the ability to conduct neuroleptic plasma levels is not readily accessible in the usual clinical setting. In the acute treatment phase, titrating the dose until the onset of minimal cogwheel rigidity or hypokinesia (neuroleptic threshold dose) has met with some success and is preferable to standard dosing as a means of individualizing pharmacotherapy. During the maintenance phase, a slow and gradual dosage reduction with adjunctive psychosocial and psychotherapeutic intervention is the preferred strategy. Reinforcing patient and physician compliance is a key element in achieving an optimal treatment regimen.