Pharmacy Department, Maudsley Hospital, London, SE5 8AZ, UK.
Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK.
Psychopharmacology (Berl). 2024 Feb;241(2):225-241. doi: 10.1007/s00213-023-06488-3. Epub 2024 Jan 19.
Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce dopaminergic transmission but have limited activity at postsynaptic receptors and so may have antipsychotic activity with lower risk of tardive dyskinesia.
We conducted a systematic database search from inception to September 2022 for articles describing the use of VMAT-2 inhibitors in psychosis. Inclusion criteria were as follows: Population: adults diagnosed with psychosis or schizophrenia; Intervention: treatment with tetrabenazine, deutetrabenazine or valbenazine; Comparison: comparison with placebo or/and antipsychotic drug; Outcomes: with efficacy outcomes (e.g. Brief Psychiatric Rating Scale (BPRS) change or clinician assessment) and adverse effects ratings (e.g. rating scale or clinician assessment or dropouts); and Studies: in randomised controlled trials and non-randomised studies.
We identified 4892 records relating to VMAT-2 inhibitor use of which 5 (173 participants) met our a priori meta-analysis inclusion criteria. VMAT-2 inhibitors were more effective than placebo for the outcome 'slight improvement' (risk ratio (RR) = 1.77 (95% CI 1.03, 3.04)) but not for 'moderate improvement' (RR 2.81 (95% CI 0.27, 29.17). VMAT-2 inhibitors were as effective as active comparators on both measures for-'slight improvement' (RR 1.05 (95% CI 0.6, 1.81)) and 'moderate improvement' (RR 1.11 (95% CI 0.51, 2.42). Antipsychotic efficacy was also suggested by a narrative review of 37 studies excluded from the meta-analysis.
VMAT-2 inhibitors may have antipsychotic activity and may offer promise for treatment of psychosis with the potential for a reduced risk of TD.
多巴胺拮抗剂会引起多巴胺受体超敏。这可能表现为迟发性运动障碍（TD）等晚期出现的运动障碍。VMAT-2 抑制剂可减少多巴胺能传递，但对突触后受体的活性有限，因此可能具有抗精神病作用，且迟发性运动障碍的风险较低。
我们从成立到 2022 年 9 月进行了系统的数据库搜索，以查找描述 VMAT-2 抑制剂在精神病中的应用的文章。纳入标准如下：人群：被诊断患有精神病或精神分裂症的成年人；干预措施：使用四苯嗪、去四苯嗪或 valbenazine 治疗；比较：与安慰剂和/或抗精神病药物比较；结局：有疗效结局（例如，简明精神病评定量表（BPRS）变化或临床医生评估）和不良反应评分（例如，评分量表或临床医生评估或脱落）；研究：随机对照试验和非随机研究。
我们确定了 4892 条与 VMAT-2 抑制剂使用相关的记录，其中 5 条（173 名参与者）符合我们预先设定的荟萃分析纳入标准。VMAT-2 抑制剂在“轻度改善”方面比安慰剂更有效（风险比（RR）=1.77（95%CI 1.03,3.04）），但在“中度改善”方面则不然（RR 2.81（95%CI 0.27,29.17））。VMAT-2 抑制剂在这两种测量方法上与活性对照药物一样有效，“轻度改善”（RR 1.05（95%CI 0.6,1.81））和“中度改善”（RR 1.11（95%CI 0.51,2.42））。荟萃分析排除的 37 项研究的叙述性综述也提示了抗精神病药物的疗效。
VMAT-2 抑制剂可能具有抗精神病活性，并且可能为治疗精神病提供希望，降低迟发性运动障碍的风险。
