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.

Hippocampal volume in borderline personality disorder with and without comorbid posttraumatic stress disorder: a meta-analysis.

BACKGROUND: Several studies have found a reduction in hippocampal volume in borderline personality disorder (BPD) patients. METHODS: In order to investigate the degree to which comorbid posttraumatic stress disorder (PTSD) could account for reduction in hippocampal volume in these patients, we conducted a systematic review and meta-analysis of studies that compared hippocampal volume in BPD patients with and without PTSD relative to healthy controls. RESULTS: Seven articles, involving 124 patients and 147 controls, were included. We found a statistically significant reduction for the left and right hippocampus. Data from the four studies that discriminated BPD patients with and without PTSD indicate that hippocampal volumes were reduced bilaterally in BPD patients with PTSD, relative to healthy controls, but that results were mixed for BPD patients without PTSD, relative to healthy controls. CONCLUSIONS: Results from this meta-analysis suggest that hippocampal volumes are reduced in patients with BPD, relative to healthy controls, but particularly in cases in which patients are diagnosed with comorbid PTSD.

Risperidone versus haloperidol in the treatment of schizophrenia: a meta-analysis comparing their efficacy and safety.

The aim of this study was to compare the short-term clinical efficacy and safety of risperidone with haloperidol and placebo. A meta-analysis of seven published randomized double-blind controlled trials was carried out. Study quality was assessed. The proportion of patients failing to reach at least 20% improvement on the positive and negative syndrome scale (PANSS) or brief psychiatric rating scale (BPRS), the proportion of patients discontinuing treatment because of adverse effects and the number of patients who needed antiparkinsonian medication were abstracted for use as outcome measures. Treatment failure was present in 50% of risperidone-treated patients compared to 66% in those treated with haloperidol and 83% in those treated with placebo. It would be necessary to treat 11 patients with risperidone to prevent one treatment failure in those patients treated with haloperidol (Odds ratio (OR) = 0.74, 95% CI of 0.58-0.94, P = 0.02). Pooling of the three multicentre trials which included placebo as a treatment arm, showed that one in three patients treated with risperidone 4-16 mg/day (OR = 0.22, 95% CI of 0.13-0.39, P < 0.00001) and one in six treated with haloperidol 10-20 mg/day. (OR = 0.44, 95% CI of 0.22-0.84, P = 0.02) would derive significant benefit. Moreover, there was a highly significant greater need for anticholinergic medication due to extrapyramidal symptoms (EPS) in the haloperidol-treated patients compared to risperidone (OR = 0.54, 95% CI of 0.42-0.70, P < 0.00001). In conclusion, risperidone seems to be more effective and causes less EPS than haloperidol, as suggested by the significantly lower requirement for antiparkinsonian medication.

Haloperidol blood levels and clinical outcome: a meta-analysis of studies relevant to testing the therapeutic window hypothesis.

Haloperidol, the most studied antipsychotic drug, is the only one about which reliable statements on the relationship between blood levels and clinical outcome can be made. A systematic overview was undertaken to determine whether there was an optimum blood concentration range for clinical efficacy. Eighteen published studies which provided individual patient data in tables or graphs were reviewed. Clinical benefits tended to decline when the haloperidol blood concentration was increased above 26 ng/ml. Our data support the existence of a therapeutic window between 4 and 26 ng/ml for haloperidol in the treatment of schizophrenic, schizoaffective and schizophreniform disorders.