Tardive Dyskinesia (TD) can occur in people exposed to dopamine receptor antagonists (DRAs). Its clinical management remains challenging. We conducted a systematic review/random-effects network meta-analysis (NMA) searching PubMed/MEDLINE/PsycINFO/ClinicalTrials.gov/Cochrane Central Register (22/05/2023, pre-defined protocol https://osf.io/b52ae/), for randomized controlled trials (RCTs) of pharmacological/brain stimulation interventions for DRA-induced TD in adults with schizophrenia or mood disorders. Primary outcomes were TD symptom change (standardized mean difference/SMD) and all-cause discontinuation (acceptability-risk ratio/RR). Sensitivity analyses were conducted. Global, local inconsistencies, risk of bias (RoB-2 tool), and confidence in evidence (CINeMA) were measured. We included 46 trials (n = 2844, age = 52.89 ± 9.94 years, males = 59.8%, schizophrenia = 84.6%, mood disorders = 15.4%), all testing pharmacological interventions versus placebo. We identified three subnetworks. In network 1, several treatments outperformed placebo on TD symptoms with large effect sizes (k = 34, n = 2269), encompassing 22 interventions versus placebo, but 18 had 1 RCTs only, and 15 had n ≤ 20. High heterogeneity (I² = 57.1%; tau² = 0.0797), and global inconsistency (Q = 32.64; df = 14; p = 0.0032) emerged. No significant differences emerged in acceptability. When restricting analyses to treatments with trials with n > 20 and >1 RCT, only valbenazine (k = 5, SMD = −0.69; 95% CI = −1.00, −0.37) and vitamin E (k = 7, SMD = −0.49; 95% CI = −0.87, −0.11) were superior to placebo. Deutetrabenazine outperformed placebo considering AIMS score and in low risk of bias trials only and with a moderate effect size for 24/36 mg (k = 2, SMD = −0.57/−0.60). Confidence in findings was low for deutetrabenazine and valbenazine, very low for all others. In network 2 (k = 2, n = 63), switch to molindone (k = 1, n = 9) versus switch to haloperidol worsened TD (SMD = 1.68; 95% CI = 0.61,2.76). In network 3 (k = 3, n = 194), antipsychotic wash-out+placebo (k = 1, n = 25) versus TAU+placebo (k = 1, n = 27) worsened TD (SMD = 1.30; 95% CI = 0.36,2.23). Despite large effect sizes for some treatments with very low quality/confidence, when considering higher quality evidence only valbenazine or deutetrabenazine are evidence-based first-line treatments for TD, and potentially vitamin E as second-line. Switching to molindone and antipsychotic washout should be avoided. More treatment options and higher-quality trials are needed.

迟发性运动障碍 （TD） 可发生在暴露于多巴胺受体拮抗剂 （DRA） 的人群中。其临床管理仍然具有挑战性。我们进行了一项系统评价/随机效应网络荟萃分析 （NMA），检索了 PubMed/MEDLINE/PsycINFO/ClinicalTrials.gov/Cochrane Central Register （22/05/2023，预定义方案 https://osf.io/b52ae/），以查找药物/脑刺激干预治疗成人精神分裂症或情绪障碍患者 DRA 诱导的 TD 的药物/脑刺激干预的随机对照试验 （RCT）。主要结局是 TD 症状变化 （标准化均数差/SMD） 和全因停药 （可接受风险比/RR）。进行了敏感性分析。测量了整体、局部不一致、偏倚风险 （RoB-2 工具） 和证据可信度 （CINeMA）。我们纳入了46项试验（n=2844，年龄=52.89±9.94岁，男性=59.8%，精神分裂症=84.6%，情绪障碍=15.4%），所有试验均测试了药物干预与安慰剂的比较。我们确定了三个子网络。在网络 1 中，几种治疗在 TD 症状上优于安慰剂，效应量大 （k = 34，n = 2269），包括 22 项干预措施与安慰剂相比，但 18 项仅有 1 项 RCT，15 项有 n ≤ 20。出现了高异质性 （I² = 57.1%;tau² = 0.0797） 和全局不一致性 （Q = 32.64;df = 14;p = 0.0032）。可接受性没有出现显著差异。当将分析限制在使用 n > 20 和 >1 RCT 的试验的治疗时，只有缬苯那嗪（k = 5，SMD = -0.69;95% CI = -1.00，-0.37）和维生素 E （k = 7，SMD = -0.49;95% CI = -0.87，-0.11）优于安慰剂。考虑到 AIMS 评分和仅在低偏倚风险试验中，氘代丁苯那嗪的表现优于安慰剂，并且在 24/36 mg 的效应量中等 （k = 2，SMD = -0.57/-0.60）。 氘代丁苯那嗪和缬苯那嗪的研究结果可信度低，所有其他研究结果的可信度极低。在网络 2 （k = 2， n = 63） 中，改用莫林酮 （k = 1， n = 9） 与改用氟哌啶醇恶化的 TD （SMD = 1.68;95% CI = 0.61,2.76）。在网络 3 （k = 3， n = 194） 中，抗精神病药洗脱 + 安慰剂 （k = 1， n = 25） 与 TAU+安慰剂 （k = 1， n = 27） 相比，TD 恶化 （SMD = 1.30;95% CI = 0.36,2.23）。尽管一些治疗的质量/可信度很高，但当考虑更高质量的证据时，只有缬苯那嗪或氘代丁苯那嗪是TD的循证一线治疗，而维生素E可能是二线治疗。应避免改用莫林酮和抗精神病药洗脱。需要更多的治疗选择和更高质量的试验。