阴性症状是精神分裂症精神病理学的核心方面。目前可用的药理学试剂已经证明对治疗阴性症状具有最低限度的效力。有希望的治疗途径是神经肽催产素的鼻内给药。然而,在整个文献中,催产素对阴性症状的影响存在不一致,导致不一致效果的因素尚不清楚。
我们对随机临床试验进行了系统评价和荟萃分析,以比较催产素与安慰剂治疗阴性症状的有效性,并确定治疗效果的调节因素。对阴性症状的平均变化进行随机效应荟萃分析和剂量反应荟萃分析。
在对所有9项确定的随机临床试验的初步分析中,鼻内催产素对阴性症状没有显着影响。对于更高剂量(>40-80IU),发现对阴性症状的有益效果具有中等效果大小,但在排除1个离群值研究后,这种效应消失了.剂量反应荟萃分析预测,较高剂量的催产素可能对阴性症状更有效。对于阳性症状,在主要的荟萃分析中没有发现催产素的有益作用,但剂量-反应荟萃分析提示了高剂量的潜在优势.
本结果显示鼻内催产素对于治疗阴性和阳性症状没有一致的有益效果。剂量反应荟萃分析不能得出任何确切的结论,但表明高剂量的鼻内催产素可能更有效。如果进行未来的研究,需要努力在足够的持续时间内达到足够的CNS浓度。
Negative symptoms are a core aspect of psychopathology in schizophrenia. Currently available pharmacological agents have proven minimally efficacious for remediating negative symptoms. A promising treatment avenue is the intranasal administration of the neuropeptide oxytocin. However, there have been inconsistencies in effects of oxytocin on negative symptoms throughout the literature, and factors leading to inconsistent effects are unclear.
We conducted a systematic
review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect. Random effects meta-analyses and dose-response meta-analysis were performed on mean changes in negative symptoms.
In an initial analysis of all 9 identified randomized clinical trials, intranasal oxytocin showed no significant effect on negative symptoms. For higher doses (>40-80 IU), a beneficial effect on negative symptoms was found with a moderate effect size, but this effect disappeared after exclusion of 1 outlier study. The dose-response meta-analysis predicted that higher doses of oxytocin may be more efficacious for negative symptoms. For positive symptoms, no beneficial effect of oxytocin was found in the main meta-analysis, but the dose-response meta-analysis suggested a potential advantage of higher doses.
The present results show no consistent beneficial effect of intranasal oxytocin for the treatment of negative and positive symptoms. The dose-response meta-analysis does not allow drawing any firm conclusions but suggests that high doses of intranasal oxytocin may be more efficacious. If future studies are conducted, an effort to reach adequate CNS concentrations for a sufficient duration is required.