1 Addiction and Mental Health Services and MIRT, Metro South Health, Brisbane, QLD, Australia.
2 MIRT, Woolloongabba Community Health Centre, Metro South Health, Woolloongabba, QLD, Australia.
Aust N Z J Psychiatry. 2018 Aug;52(8):751-767. doi: 10.1177/0004867418772351. Epub 2018 May 6.
Although clozapine is the most effective medication for treatment refractory schizophrenia, only 40% of people will meet response criteria. We therefore undertook a systematic review and meta-analysis of global literature on clozapine augmentation strategies.
We systematically reviewed PubMed, PsycInfo, Embase, Cochrane Database, Chinese Biomedical Literature Service System and China Knowledge Resource Integrated Database for randomised control trials of augmentation strategies for clozapine resistant schizophrenia. We undertook pairwise meta-analyses of within-class interventions and, where possible, frequentist mixed treatment comparisons to differentiate treatment effectiveness Results: We identified 46 studies of 25 interventions. On pairwise meta-analyses, the most effective augmentation agents for total psychosis symptoms were aripiprazole (standardised mean difference: 0.48; 95% confidence interval: -0.89 to -0.07) fluoxetine (standardised mean difference: 0.73; 95% confidence interval: -0.97 to -0.50) and, sodium valproate (standardised mean difference: 2.36 95% confidence interval: -3.96 to -0.75). Memantine was effective for negative symptoms (standardised mean difference: -0.56 95% confidence interval: -0.93 to -0.20). However, many of these results included poor-quality studies. Single studies of certain antipsychotics (penfluridol), antidepressants (paroxetine, duloxetine), lithium and Ginkgo biloba showed potential, while electroconvulsive therapy was highly promising. Mixed treatment comparisons were only possible for antipsychotics, and these gave similar results to the pairwise meta-analyses.
On the basis of the limited data available, the best evidence is for the use of aripiprazole, fluoxetine and sodium valproate as augmentation agents for total psychosis symptoms and memantine for negative symptoms. However, these conclusions are tempered by generally short follow-up periods and poor study quality.
氯氮平是治疗难治性精神分裂症最有效的药物，但只有 40%的患者会达到应答标准。因此，我们对氯氮平增效策略的全球文献进行了系统评价和荟萃分析。
我们系统地检索了 PubMed、PsycInfo、Embase、Cochrane 数据库、中国生物医学文献服务系统和中国知识资源综合数据库，以寻找氯氮平抵抗性精神分裂症增效策略的随机对照试验。我们对同类干预措施进行了成对荟萃分析，并在可能的情况下进行了似然混合治疗比较，以区分治疗效果。
我们共确定了 46 项 25 种干预措施的研究。在成对荟萃分析中，针对总体精神病症状最有效的增效剂为阿立哌唑（标准化均数差：0.48；95%置信区间：-0.89 至 -0.07）、氟西汀（标准化均数差：0.73；95%置信区间：-0.97 至 -0.50）和丙戊酸钠（标准化均数差：2.36；95%置信区间：-3.96 至 -0.75）。美金刚对阴性症状有效（标准化均数差：-0.56；95%置信区间：-0.93 至 -0.20）。然而，这些结果大多包含低质量的研究。某些抗精神病药物（奋乃静）、抗抑郁药（帕罗西汀、度洛西汀）、锂和银杏叶的单药研究显示出一定的潜力，而电惊厥治疗则非常有前景。仅对抗精神病药物进行了混合治疗比较，结果与成对荟萃分析相似。
根据现有有限的数据，最好的证据是使用阿立哌唑、氟西汀和丙戊酸钠作为总体精神病症状的增效剂，以及美金刚作为阴性症状的增效剂。然而，这些结论受到随访时间短和研究质量差的影响。
