Adjunct Aripiprazole for Symptomatic Hyperprolactinemia in Female Schizophrenia

描述(由申请人提供)：利培酮是通用的，也是最广泛使用的抗精神病药物之一；但与催乳素升高有关。这种升高在女性中尤其明显，最新的研究表明，绝大多数女性的催乳素水平升高，大约50%的女性也有闭经、月经过少或溢乳的相应副作用。催乳素升高可能与性功能障碍、生活质量下降、药物不依从性以及随着时间的推移骨密度下降有关。对于病情稳定的患者，由于这种副作用，降低剂量或更换药物在大多数情况下都不是一个可行的选择。几乎没有证据来指导这一重要领域的治疗，但多巴胺激动剂，如溴隐亭或金刚烷胺可能会加剧症状，缺乏疗效数据，并与副作用有关。我们有大量的试验数据表明，在利培酮的基础上加入小剂量的多巴胺部分激动剂阿立哌唑(10毫克/天)可以改善症状性催乳素副作用。我们将完成一项为期16周的双盲随机对照试验，检查阿立哌唑(10 mg/天，如果没有反应，在8周内增加到15 mg/天)与安慰剂对70名症状性高催乳素血症患者的影响，并假设它将有效地解决闭经、月经过少和溢乳。我们还假设阿立哌唑将显著改善生活质量、个人幸福感和性功能。此外，我们还将检查阳性、阴性和抑郁症状、性激素水平和骨转换指标的改善情况。这一应用的意义和创新很高，因为这是妇女的重大抱怨和关切，很少有证据可以指导那些病情稳定、抗精神病药物治疗效果良好但出现这些严重副作用的妇女的治疗。如果得到资助，这项关于阿立哌唑辅助治疗的重要治疗研究将为数千名患有精神分裂症的女性提供宝贵的数据和治疗选择，并将有助于推动该领域朝着更好的定制和个性化抗精神病药物治疗的方向发展，特别是对患有这些问题的女性。

DESCRIPTION (provided by applicant): Risperidone is available generically and one of the most widely used antipsychotic medications; but is associated with elevated prolactin. This elevation is particularly pronounced in women and most recent studies show that the vast majority of women have elevated prolactin levels with approximately 50% also having the corresponding side effects of amenorrhea, oligomenorrhea or galactorrhea. Elevated prolactin may be associated with sexual dysfunction, decreased quality of life, medication nonadherence and decreases in bone mineral density over time. Lowering the dose or switching medications due to this side effect in stabilized patients is not a practical option in most cases. There is little evidence to guide treatment in this important area however dopamine agonists such as bromocriptine or amantadine may exacerbate symptoms, have lacking efficacy data and are associated with side effects. We have sizeable pilot data to suggest that a low dose of aripiprazole (10 mg/day), a dopamine partial agonist, added to Risperidone can improve symptomatic prolactin side effects. We will complete a double blind randomized 16-week control trial examining adjunct aripiprazole (10 mg/day with increase to 15 mg/day at 8 weeks if no response) vs. placebo in 70 women with symptomatic hyperprolactinemia and hypothesize it will be effective in the resolution of amenorrhea, oligomenorrhea and galactorrhea. We also hypothesize that aripiprazole will significantly improve quality of life, personal well-being and sexual function. And, we will examine improvements in positive, negative and depressive symptoms, sex hormone levels and measures of bone turnover. The significance and innovation of this application is high as this is a significant complaint and concern of women and very little evidence is available to guide treatment in women who are stabilized and doing well on antipsychotic treatments but develop these significant side effects. If funded, this important treatment research study of adjunct aripiprazole treatment will provide invaluable data and treatment options for thousands of women who suffer from schizophrenia and will help move the field towards better tailoring and personalizing antipsychotic treatment, particularly for women who suffer from these problems.