Bergman Hanna, Bhoopathi Paranthaman S, Soares-Weiser Karla
Cochrane Response, Cochrane, St Albans House, 57-59 Haymarket, London, UK, SW1Y 4QX.
Cochrane Database Syst Rev. 2018 Jan 20;1(1):CD000205. doi: 10.1002/14651858.CD000205.pub3.
Tardive dyskinesia (TD) is a disfiguring movement disorder, often of the orofacial region, frequently caused by using antipsychotic drugs. A wide range of strategies have been used to help manage TD, and for those who are unable to have their antipsychotic medication stopped or substantially changed, the benzodiazepine group of drugs have been suggested as a useful adjunctive treatment. However, benzodiazepines are very addictive.
To determine the effects of benzodiazepines for antipsychotic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder, or other chronic mental illnesses.
On 17 July 2015 and 26 April 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial registers), inspected references of all identified studies for further trials and contacted authors of each included trial for additional information.
We included all randomised controlled trials (RCTs) focusing on people with schizophrenia (or other chronic mental illnesses) and antipsychotic-induced TD that compared benzodiazepines with placebo, no intervention, or any other intervention for the treatment of TD.
We independently extracted data from the included studies and ensured that they were reliably selected, and quality assessed. For homogenous dichotomous data, we calculated random effects, risk ratio (RR), and 95% confidence intervals (CI). We synthesised continuous data from valid scales using mean differences (MD). For continuous outcomes, we preferred endpoint data to change data. We assumed that people who left early had no improvement.
The review now includes four trials (total 75 people, one additional trial since 2006, 21 people) randomising inpatients and outpatients in China and the USA. Risk of bias was mostly unclear as reporting was poor. We are uncertain about all the effects as all evidence was graded at very low quality. We found no significant difference between benzodiazepines and placebo for the outcome of 'no clinically important improvement in TD' (2 RCTs, 32 people, RR 1.12, 95% CI 0.60 to 2.09, very low quality evidence). Significantly fewer participants allocated to clonazepam compared with phenobarbital (as active placebo) experienced no clinically important improvement (RR 0.44, 95% CI 0.20 to 0.96, 1 RCT, 21 people, very low quality evidence). For the outcome 'deterioration of TD symptoms,' we found no clear difference between benzodiazepines and placebo (2 RCTs, 30 people, RR 1.48, 95% CI 0.22 to 9.82, very low quality evidence). All 10 participants allocated to benzodiazepines experienced any adverse event compared with 7/11 allocated to phenobarbital (RR 1.53, 95% CI 0.97 to 2.41, 1 RCT, 21 people, very low quality evidence). There was no clear difference in the incidence of participants leaving the study early for benzodiazepines compared with placebo (3 RCTs, 56 people, RR 2.73, 95% CI 0.15 to 48.04, very low quality evidence) or compared with phenobarbital (as active placebo) (no events, 1 RCT, 21 people, very low quality evidence). No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, which are outcomes designated important by patients. No trials comparing benzodiazepines with placebo or treatment as usual reported on adverse effects.
AUTHORS' CONCLUSIONS: There is only evidence of very low quality from a few small and poorly reported trials on the effect of benzodiazepines as an adjunctive treatment for antipsychotic-induced TD. These inconclusive results mean routine clinical use is not indicated and these treatments remain experimental. New and better trials are indicated in this under-researched area; however, as benzodiazepines are addictive, we feel that other techniques or medications should be adequately evaluated before benzodiazepines are chosen.
迟发性运动障碍（TD）是一种毁容性的运动障碍，通常累及口面部区域，常由使用抗精神病药物引起。人们已采用多种策略来帮助管理TD，对于那些无法停用或大幅改变抗精神病药物治疗的患者，苯二氮䓬类药物被认为是一种有用的辅助治疗药物。然而，苯二氮䓬类药物极易成瘾。
确定苯二氮䓬类药物对患有精神分裂症、分裂情感性障碍或其他慢性精神疾病的患者因抗精神病药物所致迟发性运动障碍的影响。
2015年7月17日和2017年4月26日，我们检索了Cochrane精神分裂症研究组基于研究的试验注册库（包括试验注册登记），查阅了所有已识别研究的参考文献以查找进一步的试验，并联系了每项纳入试验的作者以获取更多信息。
我们纳入了所有针对精神分裂症患者（或其他慢性精神疾病患者）以及抗精神病药物所致TD的随机对照试验（RCT），这些试验比较了苯二氮䓬类药物与安慰剂、无干预措施或任何其他治疗TD的干预措施。
我们独立从纳入的研究中提取数据，并确保数据选择可靠且进行了质量评估。对于同质二分数据，我们计算随机效应、风险比（RR）和95%置信区间（CI）。我们使用平均差（MD）对有效量表的连续数据进行综合分析。对于连续结局，我们更倾向于终点数据而非变化数据。我们假定提前退出的患者病情无改善。
本综述现纳入四项试验（共75人，自2006年以来新增一项试验，21人），对中国和美国的住院患者和门诊患者进行了随机分组。由于报告质量差，偏倚风险大多不明确。所有证据质量等级均为极低，因此我们对所有效应均不确定。对于“TD无临床重要改善”这一结局，我们发现苯二氮䓬类药物与安慰剂之间无显著差异（2项RCT，32人，RR 1.12，95%CI 0.60至2.09，极低质量证据）。与苯巴比妥（作为活性安慰剂）相比，分配至氯硝西泮的参与者中无临床重要改善的人数显著更少（RR 0.44，95%CI 0.20至0.96，1项RCT，21人，极低质量证据）。对于“TD症状恶化”这一结局，我们发现苯二氮䓬类药物与安慰剂之间无明显差异（2项RCT，30人，RR 1.48，95%CI 0.22至9.82，极低质量证据）。分配至苯二氮䓬类药物的所有10名参与者均经历了任何不良事件，而分配至苯巴比妥的7/11名参与者经历了不良事件（RR 1.53，95%CI 0.97至2.41，1项RCT，21人，极低质量证据）。与安慰剂相比，因苯二氮䓬类药物提前退出研究的参与者发生率无明显差异（三项RCT，56人，RR 2.73，95%CI 0.15至48.04，极低质量证据），与苯巴比妥（作为活性安慰剂）相比也无明显差异（无事件发生，1项RCT，21人，极低质量证据）。没有试验报告社交信心、社会融入、社交网络或个性化生活质量，而这些是患者指定为重要的结局。没有试验比较苯二氮䓬类药物与安慰剂或常规治疗的不良反应。
仅有少数小型且报告质量差的试验提供了极低质量的证据，表明苯二氮䓬类药物作为抗精神病药物所致TD辅助治疗的效果。这些不确定的结果意味着不建议常规临床使用，这些治疗仍处于试验阶段。在这个研究不足的领域需要开展新的、更好的试验；然而，由于苯二氮䓬类药物具有成瘾性，我们认为在选择苯二氮䓬类药物之前应充分评估其他技术或药物。
