Sumiyoshi Tomiki, Park Sohee, Jayathilake Karu, Roy Ajanta, Ertugrul Aygun, Meltzer Herbert Y
Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
Schizophr Res. 2007 Sep;95(1-3):158-68. doi: 10.1016/j.schres.2007.06.008. Epub 2007 Jul 12.
In previous studies, we demonstrated that tandospirone, a serotonin-5-HT1A partial agonist, added to ongoing treatment with small to moderate doses of typical antipsychotic drugs, improved executive function and verbal learning and memory. However, tandospirone is not available in most countries, and atypical antipsychotic drugs (AAPDs) have largely replaced typical antipsychotic drugs as the primary treatment for schizophrenia. Therefore, the goal of this randomly assigned placebo-controlled double-blind study was to determine if the addition of buspirone, a widely available 5-HT1A partial agonist, would enhance cognitive function, in subjects with schizophrenia treated with AAPDs. Seventy-three patients with schizophrenia, who had been treated with an AAPD for at least three months, were randomly assigned to receive either buspirone, 30 mg/day, or matching placebo. All other medications remained unchanged. Attention, verbal fluency, verbal learning and memory, verbal working memory, and executive function, as well as psychopathology, were assessed at baseline, and 6 weeks, and 3 and 6 months after baseline. A significant Time x Group interaction effect was noted on the Digit Symbol Substitution Test, a measure of attention/speeded motor performance, due to better performance of the buspirone group compared to the placebo group at 3 months. No significant interaction effects were noted for other domains of cognition. Scores on the Brief Psychiatric Rating Scale (Total, Positive) were improved during treatment with buspirone but not placebo, but the effects did not reach statistical significance. The results of this study showed a possible benefit of buspirone augmentation of AAPDs to enhance attention. However, we did not replicate the results of the previous study with tandospirone, which may be due to the differences between tandospirone and buspirone, between typical antipsychotics and AAPDs, or a combination of the above. Further study to determine the usefulness of 5-HT1A agonist treatment in schizophrenia is indicated.
在先前的研究中，我们证明，坦度螺酮（一种5-羟色胺-5-HT1A部分激动剂）添加至小剂量至中等剂量的传统抗精神病药物的持续治疗中，可改善执行功能以及言语学习和记忆。然而，坦度螺酮在大多数国家无法获得，并且非典型抗精神病药物（AAPD）已在很大程度上取代传统抗精神病药物成为精神分裂症的主要治疗药物。因此，这项随机分配的安慰剂对照双盲研究的目的是确定，在接受AAPD治疗的精神分裂症患者中，添加广泛可用的5-HT1A部分激动剂丁螺环酮是否会增强认知功能。73例接受AAPD治疗至少三个月的精神分裂症患者被随机分配接受30毫克/天的丁螺环酮或匹配的安慰剂。所有其他药物保持不变。在基线、6周以及基线后3个月和6个月时评估注意力、言语流畅性、言语学习和记忆、言语工作记忆、执行功能以及精神病理学。在数字符号替换测试（一种注意力/快速运动表现的测量方法）中，观察到显著的时间×组交互效应，这是由于丁螺环酮组在3个月时的表现优于安慰剂组。在其他认知领域未观察到显著的交互效应。简明精神病评定量表（总分、阳性）的得分在丁螺环酮治疗期间有所改善，但在安慰剂治疗期间未改善，不过这些效应未达到统计学显著性。这项研究的结果显示，丁螺环酮增强AAPD可能有助于提高注意力。然而，我们未能重复先前使用坦度螺酮的研究结果，这可能是由于坦度螺酮和丁螺环酮之间、传统抗精神病药物和AAPD之间的差异，或上述因素的综合作用。有必要进行进一步研究以确定5-HT1A激动剂治疗在精神分裂症中的效用。
