Adjunct Aripiprazole Reduces Prolactin and Prolactin-Related Adverse Effects in Premenopausal Women With Psychosis: Results From the DAAMSEL Clinical Trial.

PURPOSE/BACKGROUND: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes. METHODS/PROCEDURES: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored. FINDINGS/RESULTS: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain. IMPLICATIONS/CONCLUSIONS: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.

Schizophrenia clinical symptom differences in women vs. men with and without a history of childhood physical abuse.

BACKGROUND: Childhood abuse has been implicated as an environmental factor that increases the risk for developing schizophrenia. A recent large population-based case-control study found that abuse may be a risk factor for schizophrenia in women, but not men. Given the sex differences in onset and clinical course of schizophrenia, we hypothesized that childhood abuse may cause phenotypic differences in the disorder between men and women. METHODS: We examined the prevalence of childhood physical abuse in a cohort of men and women with schizophrenia and schizoaffective disorder. Specifically, we examined differences in positive, negative, cognitive and depressive symptoms in men and women who reported a history of childhood physical abuse. We recruited 100 subjects for a single visit and assessed a history of childhood physical abuse using the childhood trauma questionnaire (CTQ) and clinical symptoms and cognition using the brief psychiatric rating scale (BPRS), the calgary depression scale (CDS) and the repeatable battery of the assessment of neuropsychological status (RBANS) for cognition. RESULTS: Ninety-two subjects completed the full CTQ with abuse classified as definitely present, definitely absent or borderline. Twelve subjects who reported borderline abuse scores were excluded. Of the 80 subjects whose data was analyzed, 10 of 24 (41.6 %) women and 11 of 56 (19.6 %) men reported a history of childhood physical abuse (χ(2) = 4.21, df = 1, p = 0.04). Women who reported such trauma had significantly more psychotic (sex by abuse interaction; F = 4.03, df = 1.76, p = 0.048) and depressive (F = 4.23, df = 1.76, p = 0.04) symptoms compared to women who did not have a trauma history and men, regardless of trauma history. There were no differences in negative or cognitive symptoms. CONCLUSIONS: Women with schizophrenia and schizoaffective disorder may represent a distinct phenotype or subgroup with distinct etiologies and may require different, individually tailored treatments.

Treating symptomatic hyperprolactinemia in women with schizophrenia: presentation of the ongoing DAAMSEL clinical trial (Dopamine partial Agonist, Aripiprazole, for the Management of Symptomatic ELevated prolactin).

Prolactin elevations occur in people treated with antipsychotic medications and are often much higher in women than in men. Hyperprolactinemia is known to cause amenorrhea, oligomenorrhea, galactorrhea and gynecomastia in females and is also associated with sexual dysfunction and bone loss. These side effects increase risk of antipsychotic nonadherence and suicide and pose significant problems in the long term management of women with schizophrenia. In this manuscript, we review the literature on prolactin; its physiology, plasma levels, side effects and strategies for treatment. We also present the rationale and protocol for an ongoing clinical trial to treat symptomatic hyperprolactinemia in premenopausal women with schizophrenia. More attention and focus are needed to address these significant side effects and help the field better personalize the treatment of women with schizophrenia.