Clinical Pharmacokinetics

, Volume 11, Issue 1, pp 36–61

Plasma Level Monitoring of Antipsychotic Drugs Clinical Utility

  • Svein G. Dahl
Review Article

Summary

The steady-state plasma concentrations of antipsychotic drugs show large interpatient variations but remain relatively stable from day to day in each individual patient. Monitoring of antipsychotic drug concentrations in plasma might be of value provided the patients are treated with only 1 antipsychotic drug. Some studies have reported a relationship between therapeutic response and serum antipsychotic drug ‘concentrations’ as measured using the radioreceptor assay (RRA) method, which measures dopamine receptor-blocking activity in plasma. Most studies, however, have failed to demonstrate such a relationship, and the RRA does not seem to provide the generally useful tool for plasma concentration monitoring of antipsychotic drugs that was hoped for initially. A lack of correlation between dopamine receptor-blocking activity in plasma and therapeutic response may be due to differences in the blood-brain distribution of both antipsychotic drugs and their active metabolites.

Chemical assay methods (e.g. GLC and HPLC) have been used in studies which examined the relationships between therapeutic response and antipsychotic drug concentrations in red blood cells and in plasma. It seems that for these drugs, measuring red blood cell concentrations does not offer any significant advantage over measuring plasma concentrations. Reasonably controlled studies of plasma concentration-response relationships using randomly allocated, fixed dosages of chlorpromazine, fluphenazine, haloperidol, perphenazine, sulpiride, thioridazine and thiothixene have been published but often involve relatively few patients. A correlation between therapeutic response and plasma concentrations of thioridazine and its metabolites has not been demonstrated, and plasma level monitoring of thioridazine and its metabolites therefore appears to have no clinical value. Clinical behavioural deterioration concomitant with high plasma concentrations of chlorpromazine and haloperidol have been reported. A dosage reduction might be considered after 2 to 4 weeks’ treatment in non-responders who have plasma chlorpromazine concentrations above 100 to 150 µg/L or plasma haloperidol concentrations above 20 to 30 µg/L. Non-responders and good responders to chlorpromazine treatment, however, have plasma drug concentrations in the same range, and a therapeutic range of plasma chlorpromazine levels has not been defined. Therapeutic plasma haloperidol concentrations (i.e. ‘window’) in the range of 5 to 20 µg/L have been reported by some investigators, but others have found no such relationship. A generally valid therapeutic plasma concentration range for haloperidol has not yet been defined.

Sulpiride appears to have a therapeutic ‘window’ with an upper limit around 1.5 µmol/L. The interindividual variations in plasma sulpiride concentrations appear to be relatively small compared with other antipsychotic drugs and hence may limit the clinical requirements, if any, of plasma level monitoring.

Measuring steady-state plasma drug concentrations may help to obtain an optimal therapeutic response with fluphenazine, perphenazine and thiothixene. Perphenazine appears to have a therapeutic window of 1.2 to 2.4 µg/L; levels greater than 2.4 µg/L may be associated with extrapyramidal side effects. The reported therapeutic ranges for fluphenazine and thiothixene are 0.2 to 2.0 µg/L and 2 to 15 µg/L, respectively. Dosages of fluphenazine and thiothixene may be adjusted from plasma level measurements after 2 weeks of treatment.

Unfortunately, there is no evidence that plasma concentration monitoring of antipsychotic drugs may significantly reduce the incidence of tardive dyskinesia.

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Copyright information

© ADIS Press Limited 1986

Authors and Affiliations

  • Svein G. Dahl
    • 1
  1. 1.Department of Pharmacology, Institute of Medical BiologyUniversity of TromsøTromsøNorway

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