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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZMH1-ERB-F (10))
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Chavez, Mark
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University of Maryland Baltimore
Schools of Medicine
United States
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