Siskind Dan, Bull Claudia, Suetani Shuichi, Warren Nicola, Suraev Anastasia, McGregor Iain, Kisely Steve, De Monte Veronica, Trott Mike, Shine Manju, Moudgil Vikas, Robinson Gail, Parker Stephen, Krishnaiah Ravikumar, Stedman Terry, Drummond Allan, Medland Sarah, Iyer Ravi, Baker Andrea
Faculty of Medicine, The University of Queensland, Woolloongabba, Australia; Metro South Addiction and Mental Health Services, Woolloongabba, Australia; Queensland Centre for Mental Health Research, Wacol, Australia; and Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
Faculty of Medicine, The University of Queensland, Woolloongabba, Australia; and Queensland Centre for Mental Health Research, Wacol, Australia.
BJPsych Open. 2024 Oct 3;10(5):e156. doi: 10.1192/bjo.2024.748.
Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia (TRS), only 40% of people with TRS respond, and there is limited evidence for augmentation agents. Cannabidiol (CBD) reduces positive symptoms in individuals with schizophrenia, but no trials have specifically examined its efficacy in those with clozapine-resistant schizophrenia.
To examine the clinical efficacy of CBD augmentation in people with clozapine-resistant schizophrenia.
This is a 12-week randomised, placebo-controlled, double-blind, parallel-group trial (registration number: ACTRN12622001112752). We will recruit 88 individuals with clozapine-resistant schizophrenia, randomised (1:1) to 1000 mg daily CBD versus placebo. Eligible individuals will be aged between 18 and 64 years, fulfil DSM-IV criteria for schizophrenia or schizoaffective disorder, have a total PANSS (Positive and Negative Syndrome Scale) score ≥60, have received oral clozapine for at least 18 weeks and have a clozapine level of >350 ng/mL. Interim analyses will be conducted at 25, 50 and 75% recruitment; these will also provide an opportunity to reallocate participants dependent on conditional power. The primary endpoint will be the difference in PANSS positive scores at the end of week 12. Secondary endpoints include depression, anxiety, sleep, quality of life, alcohol consumption, change in weight and metabolic syndrome components, and neurocognitive measures, as well as safety and tolerability.
Novel treatments for clozapine-resistant schizophrenia are urgently needed. If found to be effective, CBD may have a role as a novel and safe adjunct to clozapine.
尽管氯氮平是治疗难治性精神分裂症（TRS）最有效的抗精神病药物，但只有40%的TRS患者有反应，且增效剂的证据有限。大麻二酚（CBD）可减轻精神分裂症患者的阳性症状，但尚无试验专门研究其对氯氮平抵抗性精神分裂症患者的疗效。
研究CBD增效治疗氯氮平抵抗性精神分裂症患者的临床疗效。
这是一项为期12周的随机、安慰剂对照、双盲、平行组试验（注册号：ACTRN12622001112752）。我们将招募88名氯氮平抵抗性精神分裂症患者，随机（1:1）分为每日服用1000 mg CBD组和安慰剂组。符合条件的个体年龄在18至64岁之间，符合精神分裂症或分裂情感性障碍的DSM-IV标准，阳性和阴性症状量表（PANSS）总分≥60，口服氯氮平至少18周，且氯氮平水平>350 ng/mL。在招募25%、50%和75%的患者时进行中期分析；这些分析还将提供一个根据条件把握度重新分配参与者的机会。主要终点将是第12周结束时PANSS阳性评分的差异。次要终点包括抑郁、焦虑、睡眠、生活质量、饮酒量、体重变化和代谢综合征成分，以及神经认知指标，以及安全性和耐受性。
迫切需要针对氯氮平抵抗性精神分裂症的新治疗方法。如果被证明有效，CBD可能作为氯氮平一种新型且安全的辅助药物发挥作用。
