Plasma Level Monitoring of Antipsychotic Drugs Clinical Utility

Abstract

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 micrograms/L or plasma haloperidol concentrations above 20 to 30 micrograms/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 micrograms/L have been reported by some investigators, but others have found no such relationship.(ABSTRACT TRUNCATED AT 400 WORDS)

A cross-validation study on the relationship between central D2 receptor occupancy and serum perphenazine concentration

“…Previously, many studies have failed to show a quantitative relationship between serum or plasma drug concentration and clinical effects (for references, see Dahl 1986;Baldessarini et al 1988;Garver 1989). One reason for this may be that the relationships have been searched for at treatment with high doses of antipsychotics, where the occupancy in most patients exceeds the suggested optimal interval.…”

“…The use of serum drug concentrations has been suggested to provide such a tool. However, in most studies, no consistent relationship between serum drug concentration and antipsychotic effect has been demonstrated (Dahl 1986;Baldessarini et al 1988;Garver 1989). Difficulties in finding such a relationship may be related to inclusion primarily of patients treated with high doses and no or few patients with subtherapeutic doses.…”

Pharmacokinetic Optimisation of the Treatment of Psychosis

“…For more details on analytical methods and the clinical pharmacokinetics of antipsychotics, reviews are available (Balant-Gorgia & Balant 1987a;Dahl 1986;J0rgensen 1986;Simpson & Yadalam 1985). Accordingly, the bibliography in the present article is restricted to a minimum.…”

Simultaneous determination of haloperidol and bromperidol and their reduced metabolites by liquid–liquid extraction and automated column-switching high-performance liquid chromatography

“…There are numerous references for quantification of either haloperidol or bromperidol by GC, HPLC or LC/MS/MS [6][7][8][9][10][11][12][13][14]. Among them, a successful separation of its reduced metabolite from haloperidol [9,10,12] or bromperidol [8] and a successful separation of bromperidol from haloperidol [9][10][11]13,14] have been reported.…”