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.

Pathological postpartum breast engorgement: prediction, prevention, and resolution.

BACKGROUND: Severe breast engorgement can cause substantial discomfort for mothers and interfere with an infant's ability to feed at the breast. This study explored the possibility of prediction of pathological postpartum breast engorgement in lactating women in relation to intense breast engorgement at the end of the luteal phase of the menstrual cycle and the possibility of prevention and resolution of postpartum breast engorgement with expression with a breast pump of colostrum before the appearance of transitional milk. SUBJECTS AND METHODS: The first group included 70 women with pathological postpartum breast engorgement. The second group included 52 postpartum women, with 24 women having colostrum extracted by the breast pump from each breast once or twice for a duration of 20-25 minutes sequentially in the first 2-3 days after delivery in addition to the removal of colostrum by the baby, before engorgement developed. Twenty-eight women had colostrum removed only by the baby. The degree of breast engorgement was assessed using the previously published Robson four-level scale. RESULTS: Of the 70 patients with severe postpartum engorgement studied in the first group, 90% showed intense breast engorgement in the late luteal phase of the menstrual cycle. Expression of colostrum milk in the first experimental group from each breast eliminated excessive breast engorgement in breastfeeding mothers. CONCLUSIONS: Presence of intense breast engorgement at the end of the luteal phase of the menstrual cycle may be one of the most important indicators useful for predicting severe postpartum breast engorgement. Extraction of colostrum before the appearance of transitional milk lowers the risk of excessive engorgement in breastfeeding women.

Effects of olanzapine on prolactin levels of female patients with schizophrenia treated with risperidone.

BACKGROUND: This study was conducted to prospectively examine the effect of switching from risperidone to olanzapine on female schizophrenia patients who experienced menstrual disturbances, galactorrhea, and/or sexual dysfunction. METHOD: Twenty female patients with DSM-IV schizophrenia who were taking risperidone and were suffering from menstrual disturbances, galactorrhea, and/or sexual dysfunction were enrolled. Patients were switched from risperidone to olanzapine over a 2-week period, then treated with olanzapine for 8 additional weeks. The serum prolactin concentrations were examined every 2 weeks. The Positive and Negative Syndrome Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale for Extrapyramidal Symptoms (SAS), and questions from the Dickson-Glazer Sexual Functioning Scale were administered to evaluate efficacy, extrapyramidal side effects, and sexual and reproductive functioning at baseline and the endpoint of 10 weeks. RESULTS: Serum prolactin levels decreased significantly (p < .01) following the switch from risperidone to olanzapine. Scores of PANSS, AIMS, and SAS at the endpoint were also significantly decreased (p < .01) compared to those of baseline. Patients experienced improvements in menstrual functioning and perceptions of sexual side effects. CONCLUSION: Olanzapine reversed hyperprolactinemia in risperidone-treated female schizophrenic patients. This was associated with a decrease in amenorrhea, improved cycle regularity, and a decrease in sexual side effects that the women attributed to antipsychotic medication. This study suggests that switching to olanzapine is a safe and effective alternative method for patients with antipsychotic-induced hyperprolactinemia associated sexual and/or reproductive dysfunction. Long-term follow-up studies are warranted, with particular attention to the course of sexual and reproductive dysfunction.

Hormonal side effects in women: typical versus atypical antipsychotic treatment.

Neuroleptic-induced hyperprolactinemia can cause menstrual disorders, impaired fertility, galactorrhea, and sexual dysfunction, as well as hypoestrogenism secondary to disruption of the hypothalamic-pituitary-ovarian axis. The development of the prolactin-sparing atypical antipsychotic drugs offers prevention and resolution of these adverse reactions. Thus far, this property of the new medications has received insufficient clinical attention. The authors use case vignettes to discuss assessment and management of clinical situations that arise as a result of antipsychotic-induced endocrine changes.

Long-term considerations after switching antipsychotics.

The so-called "atypical" antipsychotics are rapidly becoming the de facto standard pharmacologic treatment of schizophrenia. This article reviews some common psychopharmacologic and psychological issues that may arise after an outpatient with schizophrenia is switched to one of the newer antipsychotics. Important issues to consider in the first few months after switching include assessment of response to the new medication, dealing with subsequent psychological reactions, and management of an unsatisfactory response. Once the response is established, there are other pharmacologic and psychological issues that arise during the next year or two. Pharmacologic issues that emerge later on include the role of long-term combination antipsychotics, management of new side effects, and deciding whether and when to switch again. Some of the long-term psychological issues include changes in self-image that arise from being less visibly ill, sexuality and intimacy concerns, and recovery issues.

The efficacy, tolerability and safety of Parlodel LAR versus Parlodel in hyperprolactinemia.

A double blind, double dummy study on the efficacy, tolerability and safety of Parlodel LAR versus oral Parlodel was carried out in 13 hyperprolactinemic women. Six patients received active from of Parlodel LAR (1 intramuscular injection at a dose of 50 mg) and placebo for oral Parlodel simultaneously. Seven other patients received active form of Parlodel orally (up to 7.5 mg daily) and placebo for Parlodel LAR injection. In all patients the marked reduction in serum prolactin level was observed. In normalization of prolactinemia was achieved in 8 patients (2 LAR, 6 oral). Galactorrhea disappeared in 7 of 8 patients (4 LAR, 3 oral), menstrual bleeding occurred in 5 of 10 amenorrheic patients (3 LAR, 2 oral). Tumor shrinkage was shown in 1 case (oral therapy). The improvement of slightly narrowed visual field was documented in 3 cases (2 LAR, 1 oral). The adverse effect during the therapy were mild and transient. We conclude that both froms of bromocriptine are very useful for treatment of hyperprolactinemia but Parlodel LAR is better tolerated and more convenient in application because of its prolonged activity.