The clinical guidelines that underpin the use of drugs for mental disorders are informed by evidence from randomised controlled trials (RCTs). RCTs are performed to obtain marketing authorisation from regulators. The methods used in these RCTs could be appropriate for early phases of drug development because they identify drugs with important harms and drugs that are efficacious for specific health problems and populations. RCTs done before marketing authorisation do not tend to address clinical questions that concern the effectiveness of a drug in heterogeneous and comorbid populations, the optimisation of drug sequencing and discontinuation, or the comparative benefits and harms of different drugs that could be used for the same health problem. This Review proposes an overview of some shortcomings of RCTs, at an individual level and at the whole portfolio level, and identifies some methods in planning, conducting, and carrying out analyses in RCTs that could enhance their ability to support therapeutic decisions. These suggestions include: identifying patient-important questions to be investigated by psychopharmacological RCTs; embedding pragmatic RCTs within clinical practice to improve generalisability to target populations; collecting evidence about drugs in overlooked populations; developing methods to facilitate the recruitment of patients with mental disorders and to reduce the number of patients who drop out, using specific methods; using core outcome sets to standardise the assessment of benefits and harms; and recording systematically serious objective outcomes, such as suicide or hospitalisation, to be evaluated in meta-analyses. This work is a call to address questions relevant to patients using diverse design of RCTs, thus contributing to the development of a patient-centred, evidence-based psychiatry.

支持使用药物治疗精神障碍的临床指南以随机对照试验 (RCT) 的证据为依据。进行 RCT 是为了获得监管机构的上市许可。这些 RCT 中使用的方法可能适用于药物开发的早期阶段，因为它们确定了具有重要危害的药物以及对特定健康问题和人群有效的药物。在上市许可之前进行的 RCT 并不倾向于解决涉及药物在异质和合并症人群中的有效性、药物排序和停药的优化、或可用于相同健康的不同药物的比较益处和危害的临床问题问题。本综述概述了 RCT 的一些缺点，在个人层面和整个投资组合层面，并确定了在 RCT 中规划、实施和执行分析的一些方法，这些方法可以提高他们支持治疗决策的能力。这些建议包括： 确定由精神药理学 RCT 调查的患者重要问题；在临床实践中嵌入务实的 RCT，以提高对目标人群的普遍性；在被忽视的人群中收集有关药物的证据；制定方法以促进招募精神障碍患者并使用特定方法减少辍学患者的数量；使用核心结果集来标准化利弊评估；并系统地记录严重的客观结果，例如自杀或住院，以在荟萃分析中进行评估。