Section for Evidence Based Medicine in Psychiatry and Psychotherapy, Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany.
Department of Clinical and Experimental Medicine, Psychiatry Unit, University of Catania, Catania, Italy.
Cochrane Database Syst Rev. 2022 Aug 30;8(8):CD014383. doi: 10.1002/14651858.CD014383.pub2.
In clinical practice, different antipsychotics can be combined in the treatment of people with schizophrenia (polypharmacy). This strategy can aim at increasing efficacy, but might also increase the adverse effects due to drug-drug interactions. Reducing polypharmacy by withdrawing one or more antipsychotics may reduce this problem, but must be done carefully, in order to maintain efficacy.
To examine the effects and safety of reducing antipsychotic polypharmacy compared to maintaining people with schizophrenia on the same number of antipsychotics.
On 10 February 2021, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, CINAHL, ClinicalTrials.Gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed and WHO ICTRP.
We included randomised controlled trials (RCTs) that compared reduction in the number of antipsychotics to continuation of the current number of antipsychotics. We included adults with schizophrenia or related disorders who were receiving more than one antipsychotic and were stabilised on their current treatment.
Two review authors independently screened all the identified references for inclusion, and all the full papers. We contacted study authors if we needed any further information. Two review authors independently extracted the data, assessed the risk of bias using RoB 2 and the certainty of the evidence using the GRADE approach. The primary outcomes were: quality of life assessed as number of participants with clinically important change in quality of life; service use assessed as number of participants readmitted to hospital and adverse effects assessed with number of participants leaving the study early due to adverse effects.
We included five RCTs with 319 participants. Study duration ranged from three months to one year. All studies compared polypharmacy continuation with two antipsychotics to polypharmacy reduction to one antipsychotic. We assessed the risk of bias of results as being of some concern or at high risk of bias. A lower number of participants left the study early due to any reason in the polypharmacy continuation group (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.29 to 0.68; I = 0%; 5 RCTs, n = 319; low-certainty evidence), and a lower number of participants left the study early due to inefficacy (RR 0.21, 95% CI 0.07 to 0.65; I = 0%; 3 RCTs, n = 201). Polypharmacy continuation resulted in more severe negative symptoms (MD 3.30, 95% CI 1.51 to 5.09; 1 RCT, n = 35). There was no clear difference between polypharmacy reduction and polypharmacy continuation on readmission to hospital, leaving the study early due to adverse effects, functioning, global state, general mental state and positive symptoms, number of participants with at least one adverse effect, weight gain and other specific adverse effects, mortality and cognition. We assessed the certainty of the evidence as very low or low across measured outcomes. No studies reported quality of life, days in hospital, relapse, depressive symptoms, behaviour and satisfaction with care. Due to lack of data, it was not possible to perform some planned sensitivity analyses, including one controlling for increasing the dose of the remaining antipsychotic. As a result, we do not know if the observed results might be influenced by adjustment of dose of remaining antipsychotic compound.
AUTHORS' CONCLUSIONS: This review summarises the latest evidence on polypharmacy continuation compared with polypharmacy reduction. Our results show that polypharmacy continuation might be associated with a lower number of participants leaving the study early, especially due to inefficacy. However, the evidence is of low and very low certainty and the data analyses based on few study only, so that it is not possible to draw strong conclusions based on the results of the present review. Further high-quality RCTs are needed to investigate this important topic.
在临床实践中，不同的抗精神病药物可以联合用于治疗精神分裂症患者（联合用药）。这种策略可以提高疗效，但也可能因药物相互作用而增加不良反应。减少抗精神病药物的联合使用（撤回一种或多种抗精神病药物）可能会减少这个问题，但必须谨慎进行，以维持疗效。
研究减少抗精神病药物联合用药与维持精神分裂症患者使用相同数量的抗精神病药物相比的效果和安全性。
我们于 2021 年 2 月 10 日检索了 Cochrane 精神分裂症组的试验注册库，该数据库基于 CENTRAL、CINAHL、ClinicalTrials.Gov、Embase、ISRCTN、MEDLINE、PsycINFO、PubMed 和 WHO ICTRP。
我们纳入了比较减少抗精神病药物数量与继续使用当前数量抗精神病药物的随机对照试验（RCT）。我们纳入了正在接受一种以上抗精神病药物且病情稳定的成年精神分裂症或相关障碍患者。
两名综述作者独立筛选所有确定的参考文献以确定是否纳入，并对所有全文进行筛选。如果我们需要任何进一步的信息，我们会联系研究作者。两名综述作者独立提取数据，使用 RoB 2 评估偏倚风险，并使用 GRADE 方法评估证据的确定性。主要结局包括：生活质量评估为生活质量有临床意义改善的参与者数量；服务使用评估为因住院而再次入院的参与者数量；不良事件评估为因不良事件而提前退出研究的参与者数量。
我们纳入了五项 RCT，共 319 名参与者。研究持续时间从三个月到一年不等。所有研究均比较了继续使用两种抗精神病药物与减少至一种抗精神病药物的联合用药。我们评估了结果的偏倚风险为存在一些关注或高风险。继续使用抗精神病药物的参与者因任何原因提前退出研究的比例较低（RR 0.44，95%CI 0.29 至 0.68；I = 0%；5 项 RCT，n = 319；低质量证据），因疗效不佳而提前退出研究的比例也较低（RR 0.21，95%CI 0.07 至 0.65；I = 0%；3 项 RCT，n = 201）。继续使用抗精神病药物会导致更严重的阴性症状（MD 3.30，95%CI 1.51 至 5.09；1 项 RCT，n = 35）。继续使用抗精神病药物与减少抗精神病药物联合用药在再次入院、因不良事件提前退出研究、功能、总体状态、一般心理状态和阳性症状、至少有一个不良事件的参与者数量、体重增加和其他特定不良事件、死亡率和认知方面没有明显差异。我们评估了所有测量结果的证据确定性为非常低或低。没有研究报告生活质量、住院天数、复发、抑郁症状、行为和对护理的满意度。由于缺乏数据，无法进行一些计划好的敏感性分析，包括一项控制剩余抗精神病药物剂量增加的分析。因此，我们不知道观察到的结果是否会受到剩余抗精神病药物化合物剂量调整的影响。
本综述总结了最新的关于继续使用抗精神病药物与减少抗精神病药物联合用药的证据。我们的结果表明，继续使用抗精神病药物可能会导致较少的参与者提前退出研究，特别是因为疗效不佳。然而，证据的确定性为低和非常低，并且数据分析仅基于少数几项研究，因此我们无法根据本综述的结果得出强有力的结论。需要进一步开展高质量的 RCT 来研究这一重要课题。
