Background

Although antipsychotic maintenance treatment is widely recommended to prevent relapse in chronic psychoses, evidence-based guidelines do not provide clear indications on different maintenance treatment strategies, including continuing the antipsychotic at standard doses, reducing the dose, switching to another antipsychotic, or even stopping the antipsychotic. We aimed to compare the effectiveness of these maintenance treatment strategies, hypothesising the superiority of all strategies over stopping, and of continuing at standard doses over both switching and reducing the dose.

Methods

We did a systematic review and network meta-analysis of randomized controlled trials (RCTs) that investigated antipsychotics for relapse prevention in adults with schizophrenia-spectrum disorders who were clinically stable, and which compared four treatment strategies: continuing the current antipsychotic at standard doses recommended for acute treatment; reducing the current antipsychotic dose; switching to a different antipsychotic; and stopping the antipsychotic and replacing it with placebo. We excluded RCTs with fewer than 25 individuals, a prerandomisation washout period greater than 4 weeks, a follow-up shorter than 6 weeks, and those recruiting treatment-resistant individuals. We searched MEDLINE, EMBASE, PsycINFO, CINAHL, CENTRAL, and online trial registers for published and unpublished RCTs from inception to Sept 1, 2021, combining terms describing all available antipsychotics, and terms describing continuation, maintenance, or long-term treatment for schizophrenia-spectrum disorders. Relative risks (RRs) and standardised mean differences were pooled using random-effects pairwise and network meta-analyses. We assessed risk of bias of each RCT with the Cochrane Risk-of-Bias 2 tool, and confidence of pooled estimates with CINeMA. The primary outcome was relapse prevention. The study protocol was registered in advance in the Open Science Forum registry.

Findings

Of 3936 records identified, 119 records, reporting on 101 RCTs, were eligible, 98 of which (including 13 988 individuals) provided data that could be meta-analysed for at least one outcome. The mean proportion of female participants per study was 38% (range 0–100; median 39%, IQR 29–50), whereas for male participants it was 62% (range 0–100; median 61%, IQR 50–71), and the overall mean age was 38·8 years (range 23·2–63·9; median 39·3, IQR 35·0–43·9). Of the 98 RCTs meta-analysed, 89·8% were done in high-income and upper-middle-income countries. The ethnic group White or so-called Caucasian was the most represented (mean 56% participants per study), although this information was relatively scarce. All continuation strategies were significantly more effective in preventing relapse than stopping antipsychotic treatment, with a large risk reduction for continuing at standard doses (RR 0·37, 95% CI 0·32–0·43; number-needed-to-treat [NNT] 3·17, 95% CI 2·94–3·51) and antipsychotic switching (RR 0·44, 0·37–0·53; NNT 3·57, 3·17–4·25), and moderate risk reduction for dose reduction (RR 0·68, 0·51–0·90; NNT 6·25, 4·08–20·00). Continuing and switching antipsychotics did not differ significantly (RR 0·84, 0·69–1·02; with lower values favouring continuing), whereas reducing antipsychotic dose was outperformed by both continuing (RR 0·55, 0·42–0·71; NNT 4·44, 3·45–6·90) and switching (RR 0·65, 0·47–0·89; NNT 5·17, 3·77–18·18). Results were supported by moderate confidence of evidence and confirmed by secondary analyses and by several sensitivity and subgroup analyses, including removing studies with abrupt antipsychotic discontinuation or fast tapering (≤4 weeks). No tolerability differences emerged between treatment strategies. According to the Cochrane Risk-of-Bias tool, version 2, 16·8% of included RCTs had an overall high risk of bias for the primary outcome. We found moderate heterogeneity (τ²=0·13; I²=61%) and no overall incoherence for the primary analysis. Results were supported by moderate confidence of evidence and confirmed by secondary analyses.

Interpretation

Contrary to our original hypothesis, we found that continuing antipsychotic treatment at standard doses or switching to a different antipsychotic are similarly effective treatment strategies, whereas reducing antipsychotic doses below standard doses is associated with higher risk of relapse than the other two maintenance treatment strategies and should therefore be limited to selected cases. Despite limitations, including moderate heterogeneity and moderate certainty of evidence, these results are of pragmatic relevance for clinicians, and should support the update of evidence-based guidelines.

Funding

None.

中文翻译：

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对临床稳定的精神分裂症谱系障碍患者继续、减少、转换或停止使用抗精神病药物：系统评价和网络荟萃分析

背景

尽管抗精神病药物维持治疗被广泛推荐用于预防慢性精神病的复发，但循证指南并未对不同的维持治疗策略提供明确的指示，包括以标准剂量继续使用抗精神病药物、减少剂量、换用另一种抗精神病药物，甚至停药。抗精神病药。我们的目的是比较这些维持治疗策略的有效性，假设所有策略都优于停止，以及继续使用标准剂量优于切换和减少剂量。

方法

我们对临床稳定的精神分裂症谱系障碍患者预防复发的随机对照试验 (RCT) 进行了系统回顾和网络荟萃分析，并比较了四种治疗策略： 以推荐的标准剂量继续使用当前的抗精神病药物用于急性治疗；减少目前的抗精神病药剂量；换用不同的抗精神病药；并停止抗精神病药并用安慰剂代替。我们排除了人数少于 25 人、随机化前清除期大于 4 周、随访时间短于 6 周的随机对照试验，以及招募耐药个体的随机对照试验。我们在 MEDLINE、EMBASE、PsycINFO、CINAHL、CENTRAL 和在线试验注册库中搜索了从开始到 2021 年 9 月 1 日已发表和未发表的 RCT，结合描述所有可用抗精神病药物的术语，以及描述精神分裂症谱系障碍的持续、维持或长期治疗的术语。使用随机效应成对和网络荟萃分析汇总相对风险 (RR) 和标准化平均差。我们使用 Cochrane Risk-of-Bias 2 工具评估每项 RCT 的偏倚风险，并使用 CINeMA 评估汇总估计的置信度。主要结果是预防复发。研究方案已提前在开放科学论坛注册表中注册。我们使用 Cochrane Risk-of-Bias 2 工具评估每项 RCT 的偏倚风险，并使用 CINeMA 评估汇总估计的置信度。主要结果是预防复发。研究方案已提前在开放科学论坛注册表中注册。我们使用 Cochrane Risk-of-Bias 2 工具评估每项 RCT 的偏倚风险，并使用 CINeMA 评估汇总估计的置信度。主要结果是预防复发。研究方案已提前在开放科学论坛注册表中注册。

发现

在确定的 3936 条记录中，119 条报告了 101 项 RCT 的记录符合条件，其中 98 条（包括 13 988 人）提供了可以对至少一项结果进行荟萃分析的数据。每项研究中女性参与者的平均比例为 38%（范围 0-100；中位数 39%，IQR 29-50），而男性参与者的平均比例为 62%（范围 0-100；中位数 61%，IQR 50-71） ，总体平均年龄为 38·8 岁（范围 23·2–63·9；中位数 39·3，IQR 35·0–43·9）。在荟萃分析的 98 项 RCT 中，89·8% 是在高收入和中高收入国家进行的。种族群体白人或所谓的高加索人是最有代表性的（每项研究平均有 56% 的参与者），尽管这些信息相对稀缺。所有继续策略在预防复发方面都比停止抗精神病药物治疗更有效，继续使用标准剂量的风险大大降低（RR 0·37, 95% CI 0·32–0·43；需要治疗的次数 [NNT] 3·17, 95% CI 2·94–3· 51) 和抗精神病药物转换 (RR 0·44, 0·37–0·53; NNT 3·57, 3·17–4·25)，以及减少剂量的中度风险降低 (RR 0·68, 0·51– 0·90；NNT 6·25, 4·08–20·00)。继续使用和更换抗精神病药没有显着差异（RR 0·84, 0·69-1·02；较低的值有利于继续使用），而减少抗精神病药剂量的效果优于继续使用（RR 0·55, 0·42-0· 71；NNT 4·44, 3·45–6·90) 和转换 (RR 0·65, 0·47–0·89; NNT 5·17, 3·77–18·18)。结果得到中等可信度证据的支持，并得到二次分析以及一些敏感性和亚组分析的证实，包括取消抗精神病药物突然停药或快速减量（≤4 周）的研究。治疗策略之间没有出现耐受性差异。根据 Cochrane 偏倚风险工具第 2 版，16·8% 的纳入 RCT 对主要结局总体偏倚风险较高。我们发现中等异质性（τ² =0·13；I ² =61%) 并且主要分析没有整体不一致。结果得到中等可信度证据的支持，并得到二次分析的证实。

解释

与我们最初的假设相反，我们发现以标准剂量继续抗精神病药物治疗或换用不同的抗精神病药物是同样有效的治疗策略，而将抗精神病药物剂量减少到低于标准剂量与其他两种维持治疗策略相比，复发风险更高，应该因此仅限于选定的案例。尽管存在局限性，包括中等的异质性和中等的证据确定性，但这些结果对临床医生具有实用意义，并应支持循证指南的更新。

资金

没有任何。