Is there a relationship between antipsychotic blood levels and their clinical efficacy? An analysis of studies design and methodology.
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 used a scoring system for assessing the quality of those studies. According to this system, none (0/14) of the studies having a score < 0.60 was able to show a therapeutic window, as compared to 53% (10/19) of those having a score > or = 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 size > 20 (p = 0.06) and those whose patients were treated with fixed doses (p = 0.02). The diagnosis of schizophrenia in the studies seems not to be an exclusive condition, as compared with those also including schizophreniform and schizoaffective disorders (p = 0.12). 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 clinical improvement and may even reduce therapeutic effect.
de Oliveira
I R
IR
Department of Pharmacology and Physiology, Federal University of Bahia, Salvador-Bahia, Brazil.
Dardennes
R M
RM
Amorim
E S
ES
Diquet
B
B
de Sena
E P
EP
Moreira
E C
EC
de Castro-e-Silva
E J
EJ
Payan
C
C
Fermanian
J
J
Marcílio
C
C
D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000097:blood* / Q000627:therapeutic use*; D006801:Humans; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D006220:Haloperidol