Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India (
J Clin Psychiatry. 2024 May 15;85(2):24f15363. doi: 10.4088/JCP.24f15363.
Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated with many subjective and objective adverse effects. These adverse effects have driven the study of risk-mitigation strategies such as targeted intermittent therapy and dose reduction and drug discontinuation. Randomized controlled trials (RCTs) of these strategies have been synthesized in meta-analysis; both strategies have been associated with no functional benefits and with an increased risk of relapse. The RCTs, however, have been criticized because, in many, patients were abruptly switched to the target dose or too rapidly tapered, thereby predisposing the RCT to failure of the intervention. Two important RCTs examined gradual individualized dose reduction and discontinuation. One, conducted in first-episode psychosis patients who were free from positive symptoms for 6 months, found that, at 18-month follow-up, dose reduction was associated with a higher risk of relapse (number needed to harm [NNH] = 5) and with no functional benefits. However, after return to routine clinical care, at a 7-year follow-up, the dose reduction group had better functional outcomes and similar clinical outcomes relative to the maintenance treatment group. The other RCT, conducted in patients with relapsing psychosis, found that, at a 2-year follow-up, dose reduction was associated with a higher risk of relapse (NNH = 5) and with no improvements in social, cognitive, quality of life, satisfaction, and other domains. Many large nationwide observational studies have found that antipsychotic discontinuation by patients with first-episode psychosis and schizophrenia is associated with increased relapse, rehospitalization, suicide mortality, cardiovascular mortality, and all-cause mortality. There is also the ethical matter that attempts to identify the few who may benefit from antipsychotic dose reduction and discontinuation may compromise the health and stability of the many who require long-term maintenance treatment.
精神分裂症是一种主要的精神疾病，其治疗方法是长期使用抗精神病药物作为标准护理。然而，抗精神病药物会引起许多主观和客观的不良反应。这些不良反应促使人们研究了风险缓解策略，如靶向间歇性治疗、剂量减少和药物停药。这些策略的随机对照试验（RCT）已经在荟萃分析中进行了综合；这两种策略都与没有功能获益和增加复发风险有关。然而，这些 RCT 受到了批评，因为在许多 RCT 中，患者被突然转换为目标剂量或过快地减少剂量，从而使 RCT 容易因干预失败而失败。两项重要的 RCT 研究了逐渐个体化的剂量减少和停药。一项在首发精神病患者中进行的研究，这些患者在 6 个月内没有阳性症状，发现 18 个月的随访中，剂量减少与更高的复发风险（危害比[NNH] = 5）和没有功能获益相关。然而，在回归常规临床护理后，在 7 年的随访中，与维持治疗组相比，剂量减少组的功能结局更好，临床结局相似。另一项 RCT 在复发精神病患者中进行，发现 2 年随访时，剂量减少与更高的复发风险（NNH = 5）和社会、认知、生活质量、满意度和其他领域没有改善相关。许多大型全国性观察性研究发现，首发精神病和精神分裂症患者自行停用抗精神病药物与复发、再住院、自杀死亡率、心血管死亡率和全因死亡率增加有关。还有一个伦理问题，即试图确定少数可能从抗精神病药物剂量减少和停药中获益的患者，可能会损害许多需要长期维持治疗的患者的健康和稳定性。
