Serum neuroleptic concentrations and clinical response: A radioreceptor assay investigation of acutely psychotic patients

Kucharski, L. Thomas; Alexander, Paul; Tune, L.E.; Coyle, Joseph T.

doi:10.1007/bf00427772

Cited by 18 publications

(6 citation statements)

References 20 publications

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“…From their first study, Tune et al (1980) reported a significant correlation between clinical state and neuroleptic serum levels in 30 schizophrenic patients receiving various neuroleptic drugs. The same researchers later reported, from a study including 22 acutely psychotic patients who had been treated for 2 weeks with various neuroleptic drugs, a possible 'therapeutic window' between II and 126 IJ.gJL haloperidol equivalents (Kucharski et al 1984).…”

Section: Neuroleptic Plasma Concentrations By Rra 43mentioning

confidence: 94%

Plasma Level Monitoring of Antipsychotic Drugs Clinical Utility

Dahl

1986

Clinical Pharmacokinetics

145

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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)

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Section: Neuroleptic Plasma Concentrations By Rra 43mentioning

confidence: 94%

Plasma Level Monitoring of Antipsychotic Drugs Clinical Utility

Dahl

1986

Clinical Pharmacokinetics

145

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“…In other words, there is a “therapeutic window” for dose or plasma levels [25,44,64,112,125]. This concept has been discussed in earlier publications by the present author [86,87].…”

Section: Definition In Practice Of Individual Sensitivity To Antipsycmentioning

confidence: 98%

Mechanisms of Action of Antipsychotic Drugs of Different Classes, Refractoriness to Therapeutic Effects of Classical Neuroleptics, and Individual Variation in Sensitivity to their Actions: PART II

Miller

2009

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Rapid-onset psychotic rebound is uncommon on discontinuation of most antipsychotic drugs, as might be expected for antipsychotic drugs with (hypothetically) indirect actions at their final target receptors. Rapid-onset psychosis is more common on withdrawal of clozapine, which might be expected if its action is direct. Drugs other than clozapine (notably thioridazine) may have hitherto unrecognised similarities to clozapine (but without danger of agranulocytosis), and may be useful in treatment of refractory psychosis. Quetiapine fulfils only some criteria for a clozapine-like drug. Clinical response to neuroleptics varies widely at any given plasma level. Haase’s “neuroleptic threshold” concept suggests that the dose producing the slightest motor side effects produces most or all of the therapeutic benefit, but analyses presented here suggest that antipsychotic actions are not subject to a sharp “all-or-none” threshold but increase over a small dose range. This concept could provide a method for quantitative determination of individualized optimal doses.

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“…high-dose HPL in treatment resistant cases must be weighed against the small but notable numbers of sudden deaths on high dose HPL (Flaherty and Lahmeyer, 1978;Ketai, Matthews and Mozdzen, 1979;Modestin, Krapf and Boker, 1981). It has been suggested that serum HPL estimations would be valuable in optimizing the use of this drug (Mendlewicz et al, 1981;Maglozzi et al, 1981;Smith et al, 1982;Mavroidis et al, 1983;Extein, Pottash and Gold, 1983;Kucharski et al, 1984;and Potkin et al, 1985) particularly in 'treatment-resistant' patients (Hollister and Kim, 1982). Our results suggest, however, that there is no advantage in exceeding serum levels of 5-20 ng/ml, and that this therapeutic range is generally achieved with daily doses of 10-40 mg, but that a 'therapeutic window' effect is not usually observed in chronic schizophrenic patients.…”

Section: Discussionmentioning

confidence: 96%

“…High dose HPL treatment does not appear to offer advantages to the majority of acutely ill schizophrenic patients (Ericksen, Hurt and Chang, 1978;Donlon et al, 1980;Modestin et al, 1983) and may cause i unacceptably high levels of unwanted side-effects (Bollini et al, 1984). A curvilinear relationship has been suggested by several authors and a range of 'therapeutic windows' proposed: [8][9][10][11][12][13][14][15][16][17][18] ng/ml (Magliozzi et al, 1981) 5-15 ng/ml (Smith et al, 1982;Extein, Pottash and Gold, 1983) 4.2-11.0 n /ml (Mavroidis et al, 1983) 11-126 ng ml (Kucharski et al, 1984) 4-26 ng/ml (Potkin et al, 1985) 6.5-16.5 ng/ml (Smith et al, 1985) Hollister and Kim (1982) proposed a therapeutic range at a higher level (20-50 ng/ml) for 'treatment-resistant' cases.…”

Section: Introductionmentioning

confidence: 98%

Serum haloperidol levels and clinical response in chronic, treatment-resistant schizophrenic patients

Browne¹,

Cooper²,

Wilson

et al. 1988

J Psychopharmacol

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Eleven chronic treatment-resistant schizophrenic in-patients were treated with haloperidol (HPL) or placebo with a fixed ascending dose schedule for 20 weeks. Seven patients relapsed and were withdrawn and five of these re-entered, single-blind, on known active treatment. Two weekly clinical ratings and weekly serum HPL levels were carried out throughout the study. More patients on placebo dropped out and at an earlier stage than those on active treatment but the difference was not statistically significant. Despite wide individual variations in both serum HPL levels and clinical response, these were positively correlated. HPL appeared to be of more value in the prevention of relapse than in symptom reduction. Overall, the clinical response was poor and a 'therapeutic window' could not be demonstrated either for the group as a whole or in any individual patient. There was no additional therapeutic benefit in exceeding serum HPL levels of 20 ng/ml in any of our patients. Since this serum level was achieved by daily doses of 10-40 mg HPL and the relationship between dose and serum level is linear, the use of serum HPL estimations is not likely to be of value in the routine clinical management of treatment-resistant patients.

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Serum neuroleptic concentrations and clinical response: A radioreceptor assay investigation of acutely psychotic patients

Cited by 18 publications

References 20 publications

Plasma Level Monitoring of Antipsychotic Drugs Clinical Utility

Plasma Level Monitoring of Antipsychotic Drugs Clinical Utility

Mechanisms of Action of Antipsychotic Drugs of Different Classes, Refractoriness to Therapeutic Effects of Classical Neuroleptics, and Individual Variation in Sensitivity to their Actions: PART II

Serum haloperidol levels and clinical response in chronic, treatment-resistant schizophrenic patients

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