Ropinirole for the Treatment of Hyperprolactinemia: A Dose-Escalation Study of Efficacy and Tolerability.

CONTEXT: Treatment of hyperprolactinemia with ergoline dopamine agonists (DAs) can be complicated by intolerance and resistance. OBJECTIVE: This study examines the efficacy and tolerability of the nonergot DA ropinirole for the long-term treatment of hyperprolactinemia. METHODS: Twelve hyperprolactinemic women were treated with ropinirole in a 6-month, open-label, dose-escalation trial; 7 of the 12 continued treatment in an extension study for up to 17 months. Ropinirole doses were uptitrated to achieve normal prolactin (PRL) levels, restore menses, and eliminate galactorrhea. RESULTS: Two of the 12 participants were DA naive; 6 of 12 were ergot DA intolerant; and 1 of 12 had known ergot DA resistance. Baseline PRL levels were 126.2 ± 41.4 ng/mL (SEM). Ropinirole was uptitrated from 0.125 to 0.25 mg/h to a median total daily dose (TDD) of 2 mg/d (1-4 mg/d [interquartile range]). PRL normalization was achieved in 50% of the participants (5 with microadenomas and 1 with idiopathic hyperprolactinemia) at a median effective TDD of 1 mg/d. Of the patients achieving PRL normalization, 83% were ergot DA intolerant. A persistent partial biochemical response (PRL reduction >50% from baseline) was achieved in 17% of the participants. During treatment, menses resumed in 67% of amenorrheic patients; galactorrhea resolved in 67%. Mild adverse effects were reported in 92% of participants; however, ropinirole was not discontinued because of intolerance even among the 50% of individuals with a prior history of ergot DA intolerance and resultant medication discontinuation. CONCLUSION: These data demonstrate the efficacy and tolerability of ropinirole for the treatment of hyperprolactinemia in patients with microprolactinomas and idiopathic hyperprolactinemia and suggest ropinirole may represent a novel therapeutic alternative for treating hyperprolactinemic disorders in patients with ergot DA intolerance.

Antipsychotic-Related Prolactin Levels and Sexual Dysfunction in Mentally Ill Youth: A 3-Month Cohort Study.

OBJECTIVE: Although these agents are used frequently, prospective data comparing serotonin/dopamine antagonists/partial agonists (SDAs) in youth regarding prolactin levels and sexual adverse effects (SeAEs) are scarce. METHOD: Youth aged 4 to 17 years, SDA-naive (≤1 week exposure) or SDA-free for ≥4 weeks were followed for ≤12 weeks on clinician's-choice aripiprazole, olanzapine, quetiapine, or risperidone. Serum prolactin levels, SDA plasma levels, and rating scale-based SeAEs were assessed monthly. RESULTS: Altogether, 396 youth (aged 14.0 ± 3.1 years, male participants = 55.1%, mood spectrum disorders = 56.3%, schizophrenia spectrum disorders = 24.0%, aggressive-behavior disorders = 19.7%; SDA-naive = 77.8%) were followed for 10.6 ± 3.5 weeks. Peak prolactin levels/any hyperprolactinemia/triple-upper-limit-of-normal-prolactin level were highest with risperidone (median = 56.1 ng/mL/incidence = 93.5%/44.5%), followed by olanzapine (median = 31.4 ng/mL/incidence = 42.7/76.4%/7.3%), quetiapine (median = 19.5 ng/mL/incidence = 39.7%/2.5%) and aripiprazole (median = 7.1 ng/mL/incidence = 5.8%/0.0%) (all p < .0001), with peak levels at 4 to 5 weeks for risperidone and olanzapine. Altogether, 26.8% had ≥1 newly incident SeAEs (risperidone = 29.4%, quetiapine = 29.0%, olanzapine = 25.5%, aripiprazole = 22.1%, p = .59). The most common SeAEs were menstrual disturbance = 28.0% (risperidone = 35.4%, olanzapine = 26.7%, quetiapine = 24.4% aripiprazole = 23.9%, p = .58), decreased erections = 14.8% (olanzapine = 18.5%, risperidone = 16.1%, quetiapine = 13.6%, aripiprazole = 10.8%, p = .91) and decreased libido = 8.6% (risperidone = 12.5%, olanzapine = 11.9%, quetiapine = 7.9%, aripiprazole = 2.4%, p = .082), with the least frequent being gynecomastia = 7.8% (quetiapine = 9.7%, risperidone = 9.2%, aripiprazole = 7.8%, olanzapine = 2.6%, p = 0.61), galactorrhea = 6.7% (risperidone = 18.8%, quetiapine = 2.4%, olanzapine = 0.0%, aripiprazole = 0.0%, p = .0008), and mastalgia = 5.8% (olanzapine = 7.3%, risperidone = 6.4%, aripiprazole = 5.7%, quetiapine = 3.9%, p = .84). Postpubertal status and female sex were significantly associated with prolactin levels and SeAEs. Serum prolactin levels were rarely associated with SeAEs (16.7% of all analyzed associations), except for the relationship between severe hyperprolactinemia and decreased libido (p = .013) and erectile dysfunction (p = .037) at week 4, and with galactorrhea at week 4 (p = .0040), week 12 (p = .013), and last visit (p < .001). CONCLUSION: Risperidone, followed by olanzapine, was associated with the largest prolactin elevations, with little prolactin-elevating effects of quetiapine and, especially, aripiprazole. Except for risperidone-related galactorrhea, SeAEs did not differ significantly across SDAs, and only galactorrhea, decreased libido, and erectile dysfunction were associated with prolactin levels. In youth, SeAEs are not sensitive markers for significantly elevated prolactin levels.

Stinging Nettle (Urtica dioica): An Unusual Case of Galactorrhea.

BACKGROUND The increasing popularity and availability of herbal supplements among patients necessitates a better understanding of their mechanism of action and the effects they have on the body, both intended and unintended. Stinging nettle (Urtica dioica) is an herbaceous shrub found throughout the world that has been used for medicinal purposes for centuries. CASE REPORT A 30-year-old woman with obesity and GERD presented to a primary care clinic with new-onset galactorrhea. A urine pregnancy test was negative. Prolactin, thyroid-stimulating hormone (TSH), and a metabolic panel were all within normal limits. A mammogram demonstrated scattered areas of fibroglandular density and benign-appearing calcifications in the left breast. The breast ultrasound showed no suspicious findings. Her medications included intermittent Echinacea, etonogestrel implant 68 mg subdermal, and the supplement stinging nettle 500 mg, which she had been taking over the past month for environmental allergies. After consultation with a clinical pharmacist, the stinging nettle was discontinued. No additional changes to her medications or supplements were made. One week after discontinuation, she returned to the clinic with complete resolution of the galactorrhea. CONCLUSIONS Stinging nettle (Urtica dioica) is a common supplement and has effects on (1) sex hormone-binding globulin, (2) histamine-induced prolactin release, and (3) serotonin-induced release of thyrotropin-releasing hormone. The local estrogen bioactivity in breast tissue may subsequently lead to gynecomastia and/or galactorrhea. Supplements are an often overlooked but a critical component of medication reconciliation and potential clinical adverse effects.

Chlorpromazine-Induced Hyperprolactinemia on Rat's Uterus.

BACKGROUND: Hyperprolactinemia is a common side effect of antipsychotic drugs that requires further investigation. The current study was designed to evaluate dose-dependent effect of chlorpromazine (CPZ) on hormonal changes and uterine horn histological structure in rats. Moreover, the mammary glands were analyzed to show hyperprolactinemia-induced histological changes. METHODS: Albino Wistar rats (n = 32) were divided into four groups. The first group was set as a control. In the three drug-treated groups (eight rats in each group), CPZ was administered by a gavage at doses of 3, 10, and 30 mg/kg/day for 28 days. One day after the last administration of the drug, the animals were sacrificed. Histopathological and histomorphometrical analyses of the uterine horns and mammary glands were carried out to evaluate dose-dependent effect of CPZ on histological structure. Serum levels of prolactin (PRL), estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also evaluated. RESULTS: Remarkable (P < 0.05) elevation was observed in CPZ-administrated animals' uterine horn endometrium, myometrium, and perimetrium thicknesses, and the mammary glands were observed with galactorrhea features. The serum level of progesterone and PRL significantly (P < 0.05) increased, while the serum concentration of LH, FSH, and estradiol was notably (P < 0.05) decreased depending on administrated CPZ dose. No histological and biological changes were occurred in the control animals. CONCLUSION: The present findings suggest that CPZ-induced disturbances not only depend on PRL level and increased PRL level largely depends on administrated doses of the CPZ.

Euprolactinemic galactorrhea secondary to domperidone treatment.

Milk leakage from the breast, which is known as galactorrhea, can be caused by a number of pharmacological, physical, and tumoral factors. Galactorrhea is a well-known side effect of domperidone, and is usually associated with hyperprolactinemia. However, euprolactinemic galactorrhea secondary to domperidone is very rarely seen and has yet to be reported in children before. Here, we report an adolescent with euprolactinemic galactorrhea caused by domperidone.

The risk of elevated prolactin levels in pediatric patients exposed to antipsychotics for the treatment of schizophrenia and schizophrenia spectrum disorders: protocol for a systematic review and meta-analysis.

BACKGROUND: Antipsychotic medications, particularly second-generation antipsychotics, are increasingly being used to alleviate the symptoms of schizophrenia and other severe mental disorders in the pediatric population. While evidence-based approaches examining efficacy and safety outcomes have been reported, no review has evaluated prolactin-based adverse events for antipsychotic treatments in schizophrenia and schizophrenia spectrum disorders. METHODS/DESIGN: Searches involving MEDLINE, EMBASE, CENTRAL, PsycINFO, and clinical trial registries (ClinicalTrials.gov, Drug Industry Document Archive [DIDA], International Clinical Trials Registry Platform [ICTRP]) will be used to identify relevant studies. Two reviewers will independently screen abstracts and relevant full-text articles of the papers identified by the initial search according to the prospectively defined eligibility criteria. Data extraction will be conducted in duplicate independently. Pairwise random effects meta-analyses and network meta-analyses will be conducted on individual drug and class effects where appropriate. DISCUSSION: This systematic review will evaluate prolactin-based adverse events of first- and second-generation antipsychotics in the pediatric population with schizophrenia and schizophrenia spectrum disorders. It will also seek to strengthen the evidence base of the safety of antipsychotics by incorporating both randomized controlled trials and observational studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009506.

[Clinical comparision of alpha dihydroergocryptine against cabergoline in the treatment of the fibrocystic mastopathy]. / Comparación clínica de alfa dihidroergocriptina contra cabergolina en el tratamiento de la mastopatía fibroquística.

BACKGROUND: Fibrocystic breast disease is one of the most frequent conditions of the breast among women from 30 to 49 years, with a frequency of about 60%, hence the interest in studying and treating it with the most advanced and effective resources. OBJECTIVE: To compare the efficacy and adverse events of alpha dihydroergocryptine with cabergoline in patients with fibrocystic breast disease. MATERIAL AND METHODS: A prospective, longitudinal, open, comparative study between alpha-dihydroergocryptine and cabergoline, made in the service of Gynecology and Obstetrics at the Dr. Miguel Silva General Hospital in Morelia, Michoacán. 171 patients diagnosed with fibrocystic breast disease were randomly assigned to the alpha-dihydroergocryptine or the cabergoline group. Assessments were made at baseline and every month subsequently. The following symptoms were evaluated: breast tenderness, breast pain, lumps and nipple discharge. The concentrations of prolactin were determined and an ultrasound was performed at baseline and at 3 and 6 months, patients were questioned about adverse events. RESULTS: 171 patients were included (81treated with alpha-dihydroergocryptine and 90 with cabergoline); 156 completed the study. The age limits were 18 and 51 years. The evolution time prior to study entry was 17.71 +/- 18.3 months for the alpha-dihydroergocryptine group and 18.57 +/- 20.35 for the cabergoline group. 15 patients discontinued treatment due to adverse events (8 of the alpha-dihydroergocryptine group and 7 of the cabergoline group). The most common adverse event was headache. CONCLUSIONS: In this study alpha-dihydroergocryptine was better tolerated and had better clinical response compared with cabergoline; breast pain and breast tenderness disappeared within the first month of treatment. Adverse events were similar for both treatments.

Age and adverse drug reactions from psychopharmacological treatment: data from the AMSP drug surveillance programme in Switzerland.

QUESTION UNDER STUDY: The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years. METHODS: Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP. RESULTS: A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients' age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions. CONCLUSION: The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.

Domperidone induced galactorrhea: an unusual presentation of a common drug.

Domperidone is a prokinetic drug used for diabetic gastro paresis, hiccoughs, and vomiting. It is a peripheral D2 receptor antagonist with selective peripheral activity restricted to the upper gastro intestinal tract. It is not known to cross the blood brain barrier and hence, lacks neurological side effects. We would like to report a case of domperidone induced galactorrhea in a young female who presented with galactorrhea and other symptoms suggestive of prolactinoma.

Hyperprolactinemia in a patient with a pituitary adenoma receiving antipsychotic drug therapy.

Hyperprolactinemia is a common consequence of treatment with an antipsychotic medication. It can result in hypogonadism due to the inhibitory effect of elevated prolactin levels on the hypothalamic-pituitary-gonadal hormonal axis. We present a case of hypogonadism secondary to hyperprolactinemia in a patient taking antipsychotic medication, with radiological evidence of a pituitary microadenoma. The relevance and investigation of hyperprolactinemia in patients being treated with antipsychotic medications are discussed.

Reliability and validity of a new sexual function questionnaire (Nagoya Sexual Function Questionnaire) for schizophrenic patients taking antipsychotics.

OBJECTIVE: This study aims to validate a new user-friendly sexual function questionnaire (Nagoya Sexual Function Questionnaire [NSFQ]) for schizophrenic patients taking antipsychotics. METHODS: Schizophrenic outpatients (men = 30, women = 30) were asked to fill out the NSFQ at initial entry into the research program (Time1) and again 1 to 2 weeks later (Time2). To assess the convergent validity of the NSFQ, at Time1, subjects were asked to fill out the Japanese version of the Udvalg for Kliniske Undersogekser Side Effect Rating Scale (UKU). To assess the discriminant validity of the NSFQ, at Time1, subjects were also asked to fill out the Japanese version of Epworth Sleepiness Scale. RESULTS: Results from Cronbach's alpha analysis indicated that the NSFQ demonstrated excellent internal consistency and scale reliability. The NSFQ also demonstrated strong test-retest reliability. The NSFQ total score was highly correlated with the UKU total score. The NSFQ was shown to have good convergent validity with the UKU. The NSFQ total score was not correlated with the Japanese version of Epworth Sleepiness Scale total score. CONCLUSIONS: This study revealed the internal consistency, test-retest reliability, and convergent and discriminant validities of the NSFQ.

Euprolactinemic gynecomastia and galactorrhea with risperidone-fluvoxamine combination.

Risperidone is associated with hyperprolactinemia and its consequent symptoms such as gynecomastia, galactorrhea and sexual dysfunction in adults, and less so in adolescents. Rarely, serotonin reuptake inhibitors are also associated with such adverse effects. We report a case of gynecomastia and galactorrhea in an adolescent male while on a combination of risperidone and fluvoxamine, although the serum prolactin was within normal range.

Oral versus injectable antipsychotic treatment in early psychosis: post hoc comparison of two studies.

BACKGROUND: Few studies have compared long-acting injectable second-generation antipsychotics with oral antipsychotics. Long-acting injectable antipsychotics-developed specifically to address the problem of adherence-might have an important role to play in treating early psychosis. OBJECTIVE: The effects of oral antipsychotics versus risperidone long-acting injection (RLAI) were compared between 2 similar studies lasting 2 years each that were conducted at our site in South Africa. METHODS: Results of an open-label study in which patients were treated with flexible doses of RLAI were compared with the results of a randomized controlled trial of flexible doses of oral risperidone or haloperidol. Inclusion criteria for both studies were age 16 to 45 years; confirmed diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder;

Risperidone-induced polydipsia and polyphagia associated with galactorrhea, abdominal pain, and rapid weight gain in an adolescent Hispanic female.

A 15-year-old Hispanic female was started on risperidone for new-onset psychosis. The patient responded well to the gradual dose increase but developed rapid weight gain secondary to polydipsia and polyphagia. She also began complaining of nipple discharge and griping abdominal pain on the left lower quadrant by the third week of treatment. Her prolactin level escalated to three times normal with a weight gain of 12 pounds in 16 days. Risperidone was switched to another antipsychotic. Her prolactin level then dropped to a normal level within 7 days and she lost 7 pounds in the next 2 weeks. Her abdominal pain, galactorrhea, polydipsia, and polyphagia subsided within the first few days of the cessation of risperdione.

[A naturalistic, observational study of outpatients with schizophrenia: efficacy and safety results after 6 months. The International Schizophrenia Outpatient Health Outcomes study, IC-SOHO]. / Nyílt megfigyeléses vizsgálat szkizofré- niás járóbetegek körében: hatékonysági és biztonságossági adatok 6 hónapot követoen. A Nemzetközi Szkizofrénia Járóbeteg Egészségi Kihatás vizsgálat (The Intemational Schizo- phrenia Outpatient Health Outcomes study, IC-SOHO).

The International Schizophrenia Outpatient Health Outcomes study, IC-SOHO is a three-year international observational study that investigates clinical and health outcomes of antipsychotic treatments. 7658 outpatients treated for schizophrenia were enrolled in the study, who needed an antipsychotic therapy to initiate or switch. The primary analysis compared the group taking olanzapine with the group taking any other antipsychotics, while the secondary comparison was performed between those treated with olanzapine and those with risperidone. Efficacy analysis was carried out based on changes in Clinical Global Impression of Severity scale (CGI-S), which was performed at a global symptom level, as well as with respect to the patients' positive, negative, cognitive and depressive symptoms. In addition, adverse events were also evaluated. Results of the analysis of the 3- and 6-month data from Hungary are disclosed in this publication. 200 patients were enrolled in the country. Demographics of the treatment groups were not significantly different. At 3 and 6 months after treatment initiation, there were no significant between-group differences in improvement of global symptomatology, however, cognitive symptoms improved more in the Olanzapine-group compared to those taking other antipsychotics (p<0.05). In patients showing Extrapyramidal Symptoms (EPS) at baseline, these symptoms finished to a greater extent among those receiving olanzapine than in those receiving other antipsychotics (after 6 months D<0.0001). Half a year later, significantly less patients showed extrapyramidal adverse events (p=0,0007), and the previous EPS terminated to a greater extent (p=0.0016) in the olanzapine group, as compared to those taking risperidone. No between-group differences were found in changes of sexual functions, as well as of weight and Body Mass Index measures. Switching antipsychotic initiated at study baseline, and adding-on one or more other antipsychotic to the initial one, were significantly less frequent in the Olanzapine-group compared to those initiated other antipsychotics. In the first 3 months, treatment compliance was significantly higher with olanzapine therapy than with other antipsychotic treatments, and with risperidone respectively. Results from the Hungarian sample correspond with results from higher analysis levels of wider patient populations of IC-SOHO study. Olanzapine showed outstanding efficacy in lessening cognitive disturbances and global clinical symptomatology associated with schizophrenia. Extrapyramidal symptoms of patients treated with olanzapine improved significantly better compared with those patients who received other antipsychotics and risperidone respectively.

Gynaecomastia in a man and hyperoestrogenism in a woman due to ingestion of nettle (Urtica dioica).

Nettle (Urtica dioica) is commonly sold as a herbal tea in Turkey. We report a case of gynaecomastia in a man (in which the only aetiologic factor identified was nettle tea consumption) and a case of galactorrhoea in a woman (in which the only aetiologic factor identified was also nettle tea ingestion).