Adjunct Aripiprazole for Symptomatic Hyperprolactinemia in Female Schizophrenia

描述（由申请人提供）：利培酮是通用的，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，最近的研究表明，绝大多数女性催乳素水平升高，大约50%的女性也有相应的闭经、少经或溢乳的副作用。随着时间的推移，催乳素升高可能与性功能障碍、生活质量下降、药物依从性下降和骨密度下降有关。在大多数情况下，稳定的患者由于这种副作用而降低剂量或转换药物并不是一个实际的选择。很少有证据指导这一重要领域的治疗，然而，多巴胺激动剂如溴隐肽或金刚烷胺可能会加重症状，缺乏疗效数据，并伴有副作用。我们有相当大的试点数据表明，低剂量的阿立哌唑（10mg /天），一种多巴胺部分激动剂，加入利培酮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，在70名有症状性高泌乳素血症的妇女中检测辅助阿立哌唑（10 mg/天，如果8周无反应则增加到15 mg/天）与安慰剂的对比，并假设它将有效地解决闭经、少经和溢乳。我们还假设阿立哌唑会显著改善生活质量、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。这个应用的意义和创新是很高的，因为这是女性的一个重要抱怨和关注，很少有证据可以指导那些稳定的女性的治疗，抗精神病药物治疗效果很好，但会产生这些明显的副作用。如果获得资助，这项关于阿立哌唑辅助治疗的重要研究将为成千上万患有精神分裂症的妇女提供宝贵的数据和治疗选择，并将帮助该领域朝着更好地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妇女。

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. PUBLIC HEALTH RELEVANCE: At least one in every two women treated with risperidone, the most frequently used dopamine antagonist antipsychotic, will experience hormonal side effects (i.e., menstrual abnormalities, galactorrhea, gynecomastia) and this same percentage will experience sexual dysfunction. These side effects are one of the greatest unmet needs specific to women with schizophrenia and currently no evidence-based treatments for this side effect are available. Our proposed study will test whether adjunctive aripiprazole in women will resolve prolactin related hormonal effects and will improve bone health, psychiatric symptoms, quality of life, wellness and sexual function.