title: Adjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: A randomized, double-blind, placebo-controlled, dose-response study.
abstract: Hyperprolactinemia is an unwanted adverse effect associated with several antipsychotics. The addition of partial dopamine receptor agonist aripiprazole may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose effects of adjunctive treatment with aripiprazole on prolactin levels and hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20 ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to fixed dose risperidone treatment. Serum prolactin levels were measured at baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were assessed at baseline and week 8 using the Positive and Negative Syndrome Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%) completed the 8-week study. At study end, all three aripiprazole doses resulted in significantly lower prolactin levels (beginning at week 2), higher response rates (≥30% prolactin reduction) and higher prolactin normalization rates than placebo. Effects were significantly greater in the 10 and 20mg/day groups than the 5mg/day group. No significant changes were observed in any treatment groups regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole treatment was effective and safe for resolving risperidone-induced hyperprolactinemia, producing significant and almost maximal improvements by week 2 without significant effects on psychopathology and side effects.
authors.affiliation: Beijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, China.
authors.forename: Jing-Xu
authors.initials: JX
authors.lastname: Chen
authors.affiliation: Peking University Sixth Hospital/Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China.
authors.forename: Yun-Ai
authors.initials: YA
authors.lastname: Su
authors.affiliation: Beijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, China.
authors.forename: Qing-Tao
authors.initials: QT
authors.lastname: Bian
authors.affiliation: Beijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, China.
authors.forename: Li-He
authors.initials: LH
authors.lastname: Wei
authors.affiliation: Beijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, China.
authors.forename: Rong-Zhen
authors.initials: RZ
authors.lastname: Zhang
authors.affiliation: Beijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Liu
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Correll
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Harris County Psychiatric Center, The University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Jair C
authors.initials: JC
authors.lastname: Soares
authors.affiliation: Beijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, China.
authors.forename: Fu-De
authors.initials: FD
authors.lastname: Yang
authors.affiliation: Beijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, China.
authors.forename: Shao-Li
authors.initials: SL
authors.lastname: Wang
authors.affiliation: Beijing Hui-Long-Guan Hospital, Peking University, Beijing 100096, China; Department of Psychiatry and Behavioral Sciences, Harris County Psychiatric Center, The University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: xiang.y.zhang@uth.tmc.edu.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000068180:Aripiprazole / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood*; D018967:Risperidone / Q000009:adverse effects* / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D000068180:Aripiprazole; D011388:Prolactin; D018967:Risperidone
keywords: Aripiprazole; Dose effect; Hyperprolactinemia; Intervention; Placebo controlled trial; Prolactin; Risperidone