Goff Donald C, Lamberti J Steven, Leon Andrew C, Green Michael F, Miller Alexander L, Patel Jayendra, Manschreck Theo, Freudenreich Oliver, Johnson Steven A
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Neuropsychopharmacology. 2008 Feb;33(3):465-72. doi: 10.1038/sj.npp.1301444. Epub 2007 May 9.
AMPA-receptor-positive modulators (Ampakines) facilitate learning and memory in animal models and in preliminary trials in human subjects. CX516 is the first Ampakine to be studied for cognitive enhancement in schizophrenia. Stable schizophrenia patients treated with clozapine (n=52), olanzapine (n=40), or risperidone (n=13) were randomly assigned to add-on treatment with CX516 900 mg three times daily or placebo for 4 weeks. Subjects were assessed with a cognitive battery at baseline, week 4, and at 4-week follow-up. Clinical scales and safety monitoring were also performed. The primary endpoint was the change from baseline in a composite cognitive score at week 4 for the intent-to-treat sample. Additional analyses examined change in symptom rating scores and examined drug effects on patients treated with clozapine separately from patients treated with either olanzapine or risperidone. A total of 105 patients were randomized and 95 (90%) completed the 4-week trial. Patients treated with CX516 did not differ from placebo in change from baseline on the composite cognitive score, or on any cognitive test at weeks 4 or 8. The between groups effect size at week 4 for the cognitive composite score was -0.19 for clozapine-treated patients and 0.24 for patients treated with olanzapine or risperidone. The placebo group improved more on the PANSS total score than the CX516 group; no other clinical rating differed between treatment groups. CX516 was associated with fatigue, insomnia and epigastric discomfort compared to placebo, but was generally well tolerated. CX516 was not effective for cognition or for symptoms of schizophrenia when added to clozapine, olanzapine, or risperidone.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPA）阳性调节剂（安帕金）在动物模型和人体受试者的初步试验中可促进学习和记忆。CX516是首个用于研究改善精神分裂症认知功能的安帕金。使用氯氮平（n = 52）、奥氮平（n = 40）或利培酮（n = 13）治疗的稳定期精神分裂症患者被随机分配，接受每日三次900毫克CX516或安慰剂的附加治疗，为期4周。在基线、第4周和4周随访时，使用一套认知测试对受试者进行评估。还进行了临床量表评估和安全性监测。主要终点是意向性治疗样本在第4周时综合认知评分相对于基线的变化。额外分析检查了症状评分的变化，并分别检查了药物对接受氯氮平治疗的患者与接受奥氮平或利培酮治疗的患者的影响。共有105名患者被随机分组，95名（90%）完成了为期4周的试验。接受CX516治疗的患者在综合认知评分相对于基线的变化方面，以及在第4周或第8周的任何认知测试中，与安慰剂组没有差异。第4周时，氯氮平治疗患者的认知综合评分组间效应量为-0.19，奥氮平或利培酮治疗患者为0.24。安慰剂组在阳性和阴性症状量表（PANSS）总分上的改善比CX516组更多；各治疗组之间的其他临床评分没有差异。与安慰剂相比，CX516与疲劳、失眠和上腹部不适有关，但总体耐受性良好。当添加到氯氮平、奥氮平或利培酮中时，CX516对精神分裂症的认知或症状均无效。
