Englisch Susanne, Jung Hanna Sophie, Eisenacher Sarah, Lewien Antje, Becker Anna, Nowak Ulrike, Braun Hanna, Thiem Jascha, Meyer-Lindenberg Andreas, Zink Mathias
Municipal Hospital Karlsruhe, Department of Psychiatry and Psychotherapy, Karlsruhe.
Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen, Göttingen.
J Clin Psychopharmacol. 2018 Aug;38(4):357-361. doi: 10.1097/JCP.0000000000000909.
Cognitive impairment in schizophrenia is highly disabling and remains one of the major therapeutic challenges. Agomelatine (AGO), an agonist at melatonergic MT1/MT2 receptors and antagonist at 5-HT2C receptors, increases dopamine and norepinephrine in the prefrontal cortex and may therefore have the potential of improving neurocognition in patients with schizophrenia.
Twenty-seven patients with schizophrenia and comorbid depression were treated with AGO in addition to stable doses of antipsychotic drugs. Cognitive abilities were assessed with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) at study entry and after 12 weeks of AGO treatment after the intention-to-treat principle.
We observed statistically significant yet clinically negligible increases of the MCCB composite score and the reasoning/problem solving subscore. Patients with unimpaired sleep at baseline showed greater improvements over time than those with sleep disturbances. Changes on the MCCB were not correlated with other psychometric variables.
Despite statistically significant, cognitive improvements after 12 weeks of AGO treatment were clinically irrelevant. Our findings may be limited by baseline properties of the study sample and the study design. In particular, lacking a control group, it cannot be ruled out that improvements were unrelated to AGO treatment. That is why randomized controlled trials are needed to validate the relevance of AGO as a cognitive enhancer in schizophrenia.
精神分裂症中的认知障碍具有高度致残性,仍然是主要的治疗挑战之一。阿戈美拉汀(AGO)是褪黑素能MT1/MT2受体激动剂和5-HT2C受体拮抗剂,可增加前额叶皮质中的多巴胺和去甲肾上腺素,因此可能具有改善精神分裂症患者神经认知的潜力。
27例患有精神分裂症合并抑郁症的患者在稳定剂量抗精神病药物基础上接受AGO治疗。根据意向性治疗原则,在研究开始时以及AGO治疗12周后,使用精神分裂症认知改善测量与治疗研究共识认知成套测验(MCCB)评估认知能力。
我们观察到MCCB综合评分以及推理/解决问题子评分在统计学上有显著提高,但临床意义不大。基线睡眠未受损的患者随时间推移比有睡眠障碍的患者改善更大。MCCB的变化与其他心理测量变量无关。
尽管在统计学上有显著意义,但AGO治疗12周后的认知改善在临床上并无关联。我们的研究结果可能受到研究样本的基线特征和研究设计的限制。特别是,由于缺乏对照组,不能排除改善与AGO治疗无关的可能性。这就是为什么需要进行随机对照试验来验证AGO作为精神分裂症认知增强剂的相关性。