Is there a relationship between antipsychotic blood levels and their clinical efficacy? An analysis of studies design and methodology

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Authors
de OIR, Dardennes RM
Abstract
There are now more than 50 studies concerning neuroleptic blood levels and clinical outcome relationships. Haloperidol, the most studied, is the only antipsychotic permitting some conclusions. A number of authors suggest that the striking lack of agreement between different studies results from heterogeneity of their quality. Here, we have proposed a score system for assessing the quality of those studies. According to it, none (0/14) of the studies having a score <0.60 were able to show a therapeutic window, as compared to 53% (10/19) of those having a score >0.60 (P=0.002, Fisher exact test). Also, the studies able to identify the presence of a therapeutic window during haloperidol treatment were those having sample sizes >20 (P=0.60) and those whose patients were treated with fixed doses (P=0.02). The diagnosis of schizophrenia in the studies does not seem to be an exclusive condition, as compared with those also including schizophreniform and schizoaffective disorders (P=0.12). In the stepwise logistic regression, only fixed dose and sample size of the studies were found to significantly explain the presence or absence of a therapeutic window. Our qualitative analysis of haloperidol blood level publications seem to indicate that an upper limit may exist for haloperidol efficacy; values above this limit seem not to provide any supplementary improvement and may even reduce therapeutic effect.