Procyshyn Ric M, Wasan Kishor M, Thornton Allen E, Barr Alasdair M, Chen Eric Y H, Pomarol-Clotet Edith, Stip Emmanuel, Williams Richard, Macewan G William, Birmingham C Laird, Honer William G
Department of Research, Riverview Hospital, Port Coquitlam, BC, Canada.
J Psychiatry Neurosci. 2007 Sep;32(5):331-8.
Investigators have reported that weight gain attributed to clozapine is associated with its clinical response. However, weight gain is a nonspecific physiological variable that, in itself, does not explain the mechanism underlying this relation. Alternatively, other biological variables that are often associated with weight gain, such as serum lipids, may assist in explaining this observation. The primary objective of this study was to determine whether an increase in serum lipids is associated with improvement in schizophrenia symptoms during steady state treatment with clozapine.
The data for this study represent a subset of data from a randomized, double-blinded trial that evaluated subjects with schizophrenia who demonstrated a poor treatment response to clozapine. While continuing their clozapine therapy, subjects were randomly assigned to receive either risperidone 3 mg daily or placebo for 8 weeks. This course of treatment was followed by an optional (open-label) 18 weeks of augmentation with risperidone. In the present study, we included all subjects from the previously reported trial who had fasting lipid analyses and Positive and Negative Syndrome Scale (PANSS) scores from days 7 and 63 (n = 55). For the primary analyses, we used multiple regression to examine the association between serum lipid concentrations and PANSS scores, after controlling for weight.
The analyses showed that the change in serum lipid concentration predicted change in symptoms over that of change in weight. Specifically, an increase in serum triglyceride concentration was associated with a decrease in the total PANSS score (p = 0.037). In addition, an increase in either serum total cholesterol concentration (p = 0.007), serum triglyceride concentration (p = 0.017) or their combined effect (p = 0.010) was associated with a decrease in PANSS negative subscale scores.
Elevation of serum lipids is associated with an improvement in schizophrenia symptoms in subjects treated with clozapine. Although the mechanism is unclear, serum lipids may play a role in influencing clozapine's therapeutic activity.
研究人员报告称，氯氮平所致体重增加与其临床反应相关。然而，体重增加是一个非特异性生理变量，其本身并不能解释这种关系背后的机制。另外，其他常与体重增加相关的生物学变量，如血脂，可能有助于解释这一现象。本研究的主要目的是确定在氯氮平稳态治疗期间，血脂升高是否与精神分裂症症状改善相关。
本研究的数据是一项随机双盲试验数据的子集，该试验评估了对氯氮平治疗反应不佳的精神分裂症患者。在继续氯氮平治疗的同时，患者被随机分配接受每日3mg利培酮或安慰剂治疗8周。此治疗过程之后是一个为期18周的利培酮增效治疗（开放标签）。在本研究中，我们纳入了先前报告试验中所有进行过空腹血脂分析且有第7天和第63天阳性与阴性症状量表（PANSS）评分的受试者（n = 55）。对于主要分析，我们在控制体重后，使用多元回归来检验血脂浓度与PANSS评分之间的关联。
分析表明，血脂浓度变化比体重变化更能预测症状变化。具体而言，血清甘油三酯浓度升高与PANSS总分降低相关（p = 0.037）。此外，血清总胆固醇浓度升高（p = 0.007）、血清甘油三酯浓度升高（p = 0.017）或二者的联合作用（p = 0.010）均与PANSS阴性分量表评分降低相关。
氯氮平治疗的受试者血脂升高与精神分裂症症状改善相关。尽管机制尚不清楚，但血脂可能在影响氯氮平的治疗活性中起作用。
