Do plasma levels of antipsychotics predict clinical response? Schiz Res.July.2013

04.07.2013

Plasma level monitoring is useful for some psychotropic medications. Plasma levels of Nortriptyline, Lithium and valproate have been known to correlate to clinical response. Haloperidol has been shown to exert maximal clinical effects in acute psychosis at levels between 5.6 and 16.9 μg per liter. Perphenazine is suggested as effective between 1.5–3 nmol per liter.Clozapine has been shown in numerous studies to exhibit evidence for a threshold for clinical efficacy at 350–400 μg per liter.

What about commonly used  antipsychotics (SGA)?

Leonardo V. Lopez and John M. Kane review the evidence for  use of plasma levels in predicting clinical response. Several studies  claim to determine optimal concentration ranges for antipsychotics (SGAs) (risperidone and olanzapine in particular) based PET data on D2-receptor occupancy, rather than on direct correlations between Cps and systematically measured clinical response.

Review identified 12 published articles: five relating to risperidone, five to olanzapine, and one each to quetiapine and aripiprazole.

Risperidone : Of the four studies, three yielded negative results  and one positive. The positive study included 60 patients, was 4 weeks in duration, restricted entry to patients with a diagnosis of schizophrenia, used a fixed-dose design and found a positive correlation between level of drug and rating-scale improvement. All of the studies finding no correlation between drug level and rating-scale change were flexible-dose in nature.

Olanzapine:  The one study which viewed rating-scale scores as continuous variables found a positive, curvilinear relationship between plasma level and response. Two of the remaining studies posited a plasma concentration of 23 ng/mL as predictive of separation between responders and non-responders.The one study in which doses were fixed found a range of 9.3–20.4 ng/mL for response, although again doses were potentially sub-optimal in this study.

Quetiapine: One study of  2 weeks duration with 18 patients, doses ranging from 250 to 1000 mg. Levels of quetiapine were determined 12 h subsequent to the previous dose, revealing a correlation between levels and percentage change in PANSS score.

Aripiprazole: 45 patients, flexible dose schedule, with doses ranging from 5 to 30 mg daily. Plasma levels of aripiprazole were determined 24 h following the once-daily dose.Responders were found to have significantly higher  plasma levels of dehydroaripiprazole and total moiety, with a total moiety of 225 ng/mL having a positive predictive value of 0.78 and a negative predictive value of 0.61 for response.

Conclusions: Only four SGAs  (risperidone, olanzapine, quetiapine, and aripiprazole) have published data relating plasma levels to efficacy. Only three of the eleven studies identified employed a fixed dosing schedule, whereas the remaining studies allowed clinicians to adjust dosing based on perceived response creating systematic bias. There is paucity of literature on this very important question.

Summary of the article:

Plasma levels of second-generation antipsychotics and clinical response in acute psychosis: A review of the literature. Lopez LV, Kane JM. Schizophr Res. 2013 Jul;147(2-3):368-74

One thought on “Do plasma levels of antipsychotics predict clinical response? Schiz Res.July.2013

  1. thank U v much Manoj….

    that was a v useful article….

    keep going….we r with U……

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