Adjunct Aripiprazole for Symptomatic Hyperprolactinemia in Female Schizophrenia

描述（由申请人提供）：利培酮是一种通用的抗精神病药物，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，绝大多数女性的催乳素水平升高，约50%的女性还具有闭经、月经过少或乳汁过多的相应副作用。催乳素升高可能与性功能障碍、生活质量下降、药物不依从和骨密度随时间降低有关。在大多数情况下，由于稳定患者的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。在这一重要领域，几乎没有证据指导治疗，但多巴胺激动剂如溴隐亭或金刚烷胺可能会加重症状，缺乏疗效数据，并与副作用有关。我们有相当大的试点数据表明，低剂量阿立哌唑（10毫克/天），多巴胺部分激动剂，添加到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名有症状的高泌乳素血症女性中检查辅助阿立哌唑（10 mg/天，如果无应答，则在8周时增加至15 mg/天）与安慰剂的对比，并假设其在闭经、月经过少和乳汁过多的解决方面有效。我们还假设阿立哌唑将显着改善生活质量，个人幸福和性功能。并且，我们将检查阳性，阴性和抑郁症状，性激素水平和骨转换措施的改善。该应用的重要性和创新性很高，因为这是女性的重大投诉和关注，并且很少有证据可用于指导稳定且抗精神病药物治疗效果良好但出现这些显著副作用的女性的治疗。如果获得资助，这项重要的阿立哌唑辅助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，并将有助于将该领域推向更好的定制和个性化抗精神病治疗，特别是对于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.