Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Department of Community Health & Psychiatry, University of the West Indies, Mona, Jamaica.
Cochrane Database Syst Rev. 2022 Jul 12;7(7):CD013100. doi: 10.1002/14651858.CD013100.pub2.
BACKGROUND: Whilst antipsychotics are the mainstay of treatment for schizophrenia spectrum disorders, there have been numerous attempts to identify biomarkers that can predict treatment response. One potential marker may be psychomotor abnormalities, including catatonic symptoms. Early studies suggested that catatonic symptoms predict poor treatment response, whilst anecdotal reports of rare adverse events have been invoked against antipsychotics. The efficacy and safety of antipsychotics in the treatment of this subtype of schizophrenia have rarely been studied in randomised controlled trials (RCTs). OBJECTIVES: To compare the effects of any single antipsychotic medication with another antipsychotic or with other pharmacological agents, electroconvulsive therapy (ECT), other non-pharmacological neuromodulation therapies (e.g. transcranial magnetic stimulation), or placebo for treating positive, negative, and catatonic symptoms in people who have schizophrenia spectrum disorders with catatonic symptoms. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, the ISRCTN registry, and WHO ICTRP, on 19 September 2021. There were no language, date, document type, or publication status limitations for inclusion of records in the register. We also manually searched reference lists from the included studies, and contacted study authors when relevant. SELECTION CRITERIA: All RCTs comparing any single antipsychotic medication with another antipsychotic or with other pharmacological agents, ECT, other non-pharmacological neuromodulation therapies, or placebo for people who have schizophrenia spectrum disorders with catatonic symptoms. DATA COLLECTION AND ANALYSIS: two review authors independently inspected citations, selected studies, extracted data, and appraised study quality. For binary outcomes, we planned to calculate risk ratios and their 95% confidence intervals (CI) on an intention-to-treat basis. For continuous outcomes, we planned to calculate mean differences between groups and their 95% CI. We assessed risk of bias for the included studies, and created a summary of findings table; however, we did not assess the certainty of the evidence using the GRADE approach because there was no quantitative evidence in the included study. MAIN RESULTS: Out of 53 identified reports, one RCT including 14 hospitalised adults with schizophrenia and catatonic symptoms met the inclusion criteria of the review. The study, which was conducted in India and lasted only three weeks, compared risperidone with ECT in people who did not respond to an initial lorazepam trial. There were no usable data reported on the primary efficacy outcomes of clinically important changes in positive, negative, or catatonic symptoms. Whilst both study groups improved in catatonia scores on the Bush-Francis Catatonia Rating Scale (BFCRS), the ECT group showed significantly greater improvement at week 3 endpoint (mean +/- estimated standard deviation; 0.68 +/- 4.58; N = 8) than the risperidone group (6.04 +/- 4.58; N = 6; P = 0.035 of a two-way analysis of variance (ANOVA) for repeated measures originally conducted in the trial). Similarly, both groups improved on the Positive and Negative Syndrome Scale (PANSS) scores by week 3, but ECT showed significantly greater improvement in positive symptoms scores compared with risperidone (P = 0.04). However, data on BFCRS scores in the ECT group appeared to be skewed, and mean PANSS scores were not reported, thereby precluding further analyses of both BFCRS and PANSS data according to the protocol. Although no cases of neuroleptic malignant syndrome were reported, extrapyramidal symptoms as a primary safety outcome were reported in three cases in the risperidone group. Conversely, headache (N = 6), memory loss (N = 4), and a prolonged seizure were reported in people receiving ECT. These adverse effects, which were assessed as specific for antipsychotics and ECT, respectively, were the only adverse effects reported in the study. However, the exact number of participants with adverse events was not clearly reported in both groups, precluding further analysis. Our results were based only on a single study with a very small sample size, short duration of treatment, unclear or high risk of bias due to unclear randomisation methods, possible imbalance in baseline characteristics, skewed data, and selective reporting. Data on outcomes of general functioning, global state, quality of life, and service use, as well as data on specific phenomenology and duration of catatonic symptoms, were not reported. AUTHORS' CONCLUSIONS: We found only one small, short-term trial suggesting that risperidone may improve catatonic and positive symptoms scale scores amongst people with schizophrenia spectrum disorders and catatonic symptoms, but that ECT may result in greater improvement in the first three weeks of treatment. Due to small sample size, methodological shortcomings and brief duration of the study, as well as risk of bias, the evidence from this review is of very low quality. We are uncertain if these are true effects, limiting any conclusions that can be drawn from the evidence. No cases of neuroleptic malignant syndrome were reported, but we cannot rule out the risk of this or other rare adverse events in larger population samples. High-quality trials continue to be necessary to differentiate treatments for people with symptoms of catatonia in schizophrenia spectrum disorders. The lack of consensus on the psychopathology of catatonia remains a barrier to defining treatments for people with schizophrenia. Better understanding of the efficacy and safety of antipsychotics may clarify treatment for this unique subtype of schizophrenia.
背景:虽然抗精神病药是精神分裂症谱系障碍治疗的主要方法,但已经有许多尝试来确定可以预测治疗反应的生物标志物。一个潜在的标志物可能是精神运动异常,包括紧张症症状。早期研究表明紧张症症状预示着治疗反应不佳,而罕见的不良反应的传闻报告则被用来反对使用抗精神病药。抗精神病药治疗这种精神分裂症亚型的疗效和安全性在随机对照试验(RCT)中很少被研究。
目的:比较任何一种单一抗精神病药物与另一种抗精神病药物或其他药物、电惊厥治疗(ECT)、其他非药物神经调节治疗(如经颅磁刺激)或安慰剂在治疗有紧张症症状的精神分裂症谱系障碍患者的阳性、阴性和紧张症症状方面的效果。
检索方法:我们检索了 Cochrane 精神分裂症组的试验注册库,该库基于 CENTRAL、MEDLINE、Embase、CINAHL、PsycINFO、PubMed、ClinicalTrials.gov、ISRCTN 登记处和世卫组织 ICTRP,检索日期为 2021 年 9 月 19 日。注册库中纳入的记录没有语言、日期、文件类型或出版状态的限制。我们还手动检索了纳入研究的参考文献,并在相关时联系了研究作者。
纳入排除标准:所有比较任何一种单一抗精神病药物与另一种抗精神病药物或其他药物、ECT、其他非药物神经调节治疗或安慰剂在有紧张症症状的精神分裂症谱系障碍患者中的疗效的 RCT。
数据收集和分析:两名综述作者独立检查引用文献、选择研究、提取数据和评估研究质量。对于二分类结局,我们计划按意向治疗原则计算风险比及其 95%置信区间(CI)。对于连续性结局,我们计划计算组间平均差异及其 95%CI。我们评估了纳入研究的偏倚风险,并创建了一个发现总结表;然而,由于纳入研究中没有定量证据,我们没有使用 GRADE 方法评估证据的确定性。
主要结果:在 53 份报告中,有 1 项 RCT 包括 14 名住院的患有紧张症的精神分裂症患者,符合综述的纳入标准。这项在印度进行的研究持续了仅三周,比较了利培酮与 ECT 在初始劳拉西泮试验无反应的患者中的疗效。虽然两组在 Bush-Francis 紧张症评定量表(BFCRS)上的紧张症评分都有所改善,但 ECT 组在第 3 周的终点(均数 +/- 估计标准差;8 例为 0.68 +/- 4.58;6 例为 6.04 +/- 4.58;N = 8;P = 0.035 的双因素方差分析(ANOVA))的改善明显大于利培酮组。同样,两组在阳性和阴性症状量表(PANSS)上的评分都在第 3 周有所改善,但 ECT 在阳性症状评分上的改善明显大于利培酮(P = 0.04)。然而,ECT 组的 BFCRS 评分似乎存在偏倚,且未报告平均 PANSS 评分,因此根据方案无法进一步分析 BFCRS 和 PANSS 数据。尽管没有报告神经阻滞剂恶性综合征的病例,但在利培酮组报告了 3 例锥体外系症状作为主要安全性结局。相反,在接受 ECT 的人中报告了 6 例头痛、4 例记忆丧失和 1 例延长的癫痫发作。这些不良反应分别被评估为抗精神病药和 ECT 的特异性不良反应,是研究中报告的唯一不良反应。然而,两组中出现不良事件的确切人数都没有明确报告,因此无法进一步分析。我们的结果仅基于一项样本量非常小、治疗持续时间短、由于随机方法不清楚或高风险、可能存在基线特征不平衡、数据偏倚和选择性报告的 RCT。没有报告结局的一般功能、总体状态、生活质量和服务利用情况,以及紧张症症状的具体表现和持续时间的数据。
结论:我们只发现了一项小型的短期试验,该试验表明利培酮可能改善精神分裂症谱系障碍伴紧张症患者的紧张症和阳性症状量表评分,但 ECT 可能在治疗的前 3 周导致更大的改善。由于样本量小、方法学缺陷和研究持续时间短以及偏倚风险,本综述的证据质量非常低。我们不确定这些是否是真实的效果,限制了从证据中得出任何结论的能力。尽管没有报告神经阻滞剂恶性综合征的病例,但我们不能排除在更大的人群样本中发生这种或其他罕见不良反应的风险。需要高质量的试验来区分治疗精神分裂症谱系障碍伴紧张症患者的方法。对紧张症的精神病理学缺乏共识仍然是定义精神分裂症患者治疗方法的障碍。对抗精神病药疗效和安全性的更好理解可能会阐明对这种独特精神分裂症亚型的治疗方法。
Cochrane Database Syst Rev. 2022-7-12
Cochrane Database Syst Rev. 2005-7-20
Cochrane Database Syst Rev. 2018-1-25
Cochrane Database Syst Rev. 2018-4-10
Cochrane Database Syst Rev. 2022-11-24
Cochrane Database Syst Rev. 2018-7-9
Cochrane Database Syst Rev. 2018-2-6
Cochrane Database Syst Rev. 2018-1-18
Cochrane Database Syst Rev. 2018-3-5
Cochrane Database Syst Rev. 2021-12-17
SAGE Open Med Case Rep. 2024-1-31
Case Rep Psychiatry. 2023-11-21
Front Psychiatry. 2023-11-6
Harv Rev Psychiatry. 2023
Clin Psychopharmacol Neurosci. 2021-2-28
Cochrane Database Syst Rev. 2019-3-19
Gen Hosp Psychiatry. 2017-6-24
Schizophr Res. 2017-8-14