olanzapine and Hyperprolactinemia

 To evaluate the frequency, validity, and relevance of statistically significant (P<0.05) sex-treatment interactions in randomized controlled trials in Cochrane meta-analyses..  Meta-epidemiological study..  Cochrane Database of Systematic Reviews (CDSR) and PubMed..  Reviews published in the CDSR with sex-treatment subgroup analyses in the forest plots, using data from randomized controlled trials..  Information on the study design and sex subgroup data were extracted from reviews and forest plots that met inclusion criteria. For each statistically significant sex-treatment interaction, the potential for biological plausibility and clinical significance was considered..  Among the 41 reviews with relevant data, there were 109 separate treatment-outcome analyses ("topics"). Among the 109 topics, eight (7%) had a statistically significant sex-treatment interaction. The 109 topics included 311 randomized controlled trials (162 with both sexes, 46 with males only, 103 with females only). Of the 162 individual randomized controlled trials that included both sexes, 15 (9%) had a statistically significant sex-treatment interaction. Of four topics where the first published randomized controlled trial had a statistically significant sex-treatment interaction, no meta-analyses that included other randomized controlled trials retained the statistical significance and no meta-analyses showed statistical significance when data from the first published randomized controlled trial were excluded. Of the eight statistically significant sex-treatment interactions from the overall analyses, only three were discussed by the CDSR reviewers for a potential impact on different clinical management for males compared with females. None of these topics had a sex-treatment interaction that influenced treatment recommendations in recent guidelines. UpToDate, an online physician-authored clinical decision support resource, suggested differential management of men and women for one of these sex-treatment interactions..  Statistically significant sex-treatment interactions are only slightly more frequent than what would be expected by chance and there is little evidence of subsequent corroboration or clinical relevance of sex-treatment interactions.

Topics: Benzodiazepines; Bias; Carotid Stenosis; Endarterectomy, Carotid; Female; Humans; Hyperprolactinemia; Incidence; Lung Neoplasms; Male; Olanzapine; Outcome Assessment, Health Care; Prolactin; Randomized Controlled Trials as Topic; Risperidone; Sex Factors; Stroke

Although atypical antipsychotics have beneficial efficacy and tolerance, non-adherence and partial adherence remain in patients treated for schizophrenia. Long-acting injectable or depot atypical antipsychotics offer better medication adherence and tolerability advantages. Currently, two drugs are available for the treatment of schizophrenia, risperidone long-acting injectable (RLAI) and olanzapine pamoate (OP).. Short- and long-term safety and tolerability data on RLAI and OP from January 2006 through September 2009 were reviewed by performing Medline and PubMed searches, reviewing abstracts and poster presentations, and viewing available material from the FDA and European Medicines Agency.. RLAI and OP show good short- and long-term safety when treating patients with schizophrenia, with uncommon discontinuation due to adverse effects. RLAI and OP data show rare problems with injection site reactions and patients exposed to injectable treatments prefer to continue injections. Infrequent but serious post-injection delirium sedation syndrome occurred after 1% of OP injections. Weight gain was generally higher among patients treated with OP versus RLAI.. Healthcare providers, patients and family members should be made aware of the safety and benefits of long-acting injectable atypical antipsychotics in order to diminish the unnecessary restrictions of these therapies for patients with schizophrenia.

Topics: Administration, Oral; Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Dyslipidemias; Humans; Hyperglycemia; Hyperprolactinemia; Injections; Medication Adherence; Movement Disorders; Olanzapine; Pain; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Weight Gain

The second-generation antipsychotic olanzapine has been shown to be efficacious as a treatment for adults with bipolar disorder and is approved by the United States Food and Drug Administration for the treatment of acute manic or mixed episodes as well as for maintenance treatment in bipolar adults.. This review examines the use of olanzapine for the treatment of children and adolescents with bipolar disorder and presents a discussion of the mechanism of action, pharmacokinetic and pharmacodynamic properties of olanzapine in children and adolescents. In addition, efficacy and safety data are reviewed and the risks and benefits of using olanzapine in bipolar youth are summarized.. Articles published in English were identified using a search of the National Library of Medicine from 1990 to 2007 with manual review of references of each article as well as review of the US Clinical Trials database. Articles describing the use of olanzapine in children or adolescents were included.. Olanzapine appears to have a rapid onset of action for mixed and manic episodes, but is associated with metabolic side effects including hyperprolactinemia, diabetes and weight gain. Therefore, olanzapine may best be used in the acute treatment of children and adolescents experiencing a manic or mixed episode as its side-effect profile may limit its use as a maintenance agent in this population.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Diabetes Mellitus; Humans; Hyperprolactinemia; Olanzapine; Weight Gain

Management of bipolar disorder (BPD) may require multiple medications, including lithium, anticonvulsants, and antipsychotics (both conventional and atypical). Updated treatment guidelines reflect an expanded role for atypical antipsychotics (AAPs) in BPD treatment. Five AAPs--olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole--are approved by the US Food and Drug Administration (FDA) as monotherapy for first-line treatment of acute manic and (except for quetiapine) mixed episodes. Two AAPs--olanzapine (in fixed-dose combination with fluoxetine) and quetiapine--are also FDA approved for bipolar depression. For long-term maintenance therapy, one option is to continue effective, well-tolerated acute phase treatment; however, only olanzapine and aripiprazole are FDA approved for maintenance, based on evidence from randomized, placebo-controlled clinical trials. Although head-to-head comparisons are scarce, meta-analysis data suggest that olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole have similar antimanic efficacy; therefore, AAP selection for this indication should be guided by other considerations such as safety, tolerability, and cost. Safety and tolerability issues to consider when selecting an AAP include metabolic dysfunction (weight gain, type 2 diabetes, and dyslipidemia); hyperprolactinemia; extrapyramidal symptoms; QTc prolongation; and pharmacokinetic drug interactions.

Topics: Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Benzodiazepines; Bipolar Disorder; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Evaluation; Drug Interactions; Drug Therapy, Combination; Dyslipidemias; Humans; Hyperprolactinemia; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome; Weight Gain

Five new antipsychotic drugs introduced in the United States in the last decade offer physicians the ability to treat patients with schizophrenia and bipolar mania without the adverse effects of the first-generation antipsychotics. In this article, the authors discuss the advantages and side effects of these agents and present a guide to help physicians choose the optimal drug in the most favorable formulation for each patient.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Administration Schedule; Humans; Hyperprolactinemia; Mental Disorders; Olanzapine; Patient Compliance; Piperazines; Practice Guidelines as Topic; Prescription Fees; Quetiapine Fumarate; Quinolones; Risk Assessment; Risperidone; Thiazoles; Torsades de Pointes; Treatment Outcome; Weight Gain

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Dyskinesias; Haloperidol; Humans; Hyperglycemia; Hyperprolactinemia; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Thioridazine; Weight Gain

The overall effectiveness of traditional antipsychotics has been hindered by their extrapyramidal side effects, which contribute to noncompliance and relapse in patients with schizophrenia. The side effects associated with traditional antipsychotic treatment are generally minimal in patients who take risperidone, a combined 5-HT2/D2 antagonist, but the literature is sparse on adverse events among the newer atypical antipsychotics. Risperidone is associated with relatively few motor side effects compared with the traditional antipsychotics, and weight gain is less likely with risperidone than with either clozapine or olanzapine. While increased prolactin levels have been reported in patients taking risperidone, little correlation has been found between prolactin levels and adverse events. As antipsychotic treatment options expand to include the new agents, it is important for clinicians to anticipate side effects and to query patients about specific adverse events.

Topics: Antipsychotic Agents; Benzodiazepines; Drug Administration Schedule; Humans; Hyperprolactinemia; Incidence; Movement Disorders; Olanzapine; Pirenzepine; Risperidone; Schizophrenia; Schizophrenic Psychology; Weight Gain

To assess the bioequivalence of two 5-mg olanzapine orally disintegrating tablet (ODT) products, 2 randomized, open-label, single-dose, 2-way crossover studies were carried out under fasting or fed conditions. Blood samples were collected at scheduled times according to the study protocol. Statistical analysis of area under the concentration-time curve from time 0 to 168 hours (AUC

Topics: Administration, Oral; Adult; Antipsychotic Agents; Area Under Curve; Asian People; Cross-Over Studies; Drug Compounding; Fasting; Female; Food-Drug Interactions; Healthy Volunteers; Humans; Hyperprolactinemia; Male; Olanzapine; Therapeutic Equivalency

Objective To observe the efficacy and safety of Shaoyao Gancao Decoction (SGD) in treating olanzapine induced hyperprolactinemia. Methods Totally 120 schizophrenia patients who took Olanzapine Tablet (OT) were assigned to the treatment group and the control group by random number table, 60 in each group. All patients took OT. Those in the treatment group additionally took SGD. The ther- apeutic course for all was 8 weeks. Serum levels of prolactin were measured before treatment and at the end of week 2, 4, and 8 after treatment. The spiritual symptoms of patients were assessed by Positive and Negative Syndrome Scale (PANSS) before treatment and at the end of week 8 after treatment. Adverse reactions were assessed using Treatment Emergent Symptom Scale (TESS) before treatment and at the end of week 8 after treatment. Results Compared with before treatment in the same group, ser- um levels of prolactin were significantly reduced in the treatment group at the end of week 4 and 8 after treatment (P <0. 05). There was no statistical difference in serum levels of prolactin in the control group among each time points (P > 0. 05). Compared with the control group, serum levels of prolactin de- creased significantly in the treatment group at the end of week 4 and 8 after treatment (P <0. 01). There was no statistical difference in PANSS between the two groups at the end of week 8 after treatment (P> 0. 05). Adverse reactions occurred in 5 cases (943%) of the treatment group and 4 cases (7. 14%) in the control group. They were manifested as insomnia, headache, constipation, and incapability of sitting quietly. There was no statistical difference in adverse reaction between the two groups (P'>0. 05). Con- clusions SGD could effectively improve olanzapine-induced hyperprolactinemia, and had no obvious effect on psychotic symptoms. It showed no obvious adverse reactions.

Topics: Antipsychotic Agents; Drugs, Chinese Herbal; Humans; Hyperprolactinemia; Olanzapine; Prolactin; Schizophrenia; Treatment Outcome

This analysis of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (NCT01157351) compared outcomes after administration of once-monthly paliperidone palmitate (PP) vs conventional oral antipsychotics (COAs) or atypical oral antipsychotics (AOAs).. PRIDE was a 15-month study of 444 individuals with schizophrenia and a history of incarceration. They were randomly assigned to PP or to 1 of 7 commonly prescribed OAs. Primary endpoint was time to first treatment failure (TF). Event-free probabilities were estimated using the Kaplan-Meier method; treatment group differences (PP vs COAs, PP vs AOAs, and PP vs oral paliperidone/risperidone) were assessed using a log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No adjustment was made for multiplicity.. Compared with PP, risk for first TF was 34% higher with COAs (HR: 1.34; 95% CI: 0.80-2.25), 41% higher with AOAs (HR: 1.41; 95% CI: 1.06-1.88), and 39% higher with paliperidone/risperidone (HR: 1.39; 95% CI: 0.97-1.99). Incidences of extrapyramidal symptom-related adverse events (AEs) were 45.7%, 13.7%, and 10.6% in the COA, AOA, and oral paliperidone/risperidone groups vs 23.9% in the PP group. Incidences of prolactin-related AEs were 5.7%, 3.8%, and 3.5% vs 23.5%, and incidences of ≥7% weight increase were 11.4%, 14.9%, and 16.0% vs 32.4%.. Results suggest a lower risk of TF but a higher rate of some AEs after treatment with PP vs COAs, AOAs, and paliperidone/risperidone. Deselection of specific OAs and low patient-compliance rates with OAs likely biased the safety results.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Delayed-Action Preparations; Female; Haloperidol; Humans; Hyperprolactinemia; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Perphenazine; Proportional Hazards Models; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Failure; Treatment Outcome

Although hyperprolactinemia carries a long-term risk of morbidity, the threshold of dopamine D2/3 receptor (D2/3R) occupancy for hyperprolactinemia has not been investigated in older patients with schizophrenia. Data were taken from a positron emission tomography (PET) study conducted between August 2007 and August 2015. The present post hoc study included 42 clinically stable outpatients with schizophrenia (DSM-IV) (mean ± SD age = 60.2 ± 6.7 years) taking olanzapine or risperidone. Subjects underwent [¹¹C]-raclopride PET scans to measure D2/3R occupancy before and after reducing their dose of antipsychotic by up to 40%. Blood samples were collected before each PET scan to measure prolactin levels.. The relationship between prolactin levels and D2/3R occupancy was examined using stepwise linear regression analyses. The D2/3R occupancy thresholds for hyperprolactinemia were explored using Fisher exact tests.. Prolactin levels decreased following dose reduction (mean ± SD = 24.1 ± 30.2 ng/mL to 17.2 ± 15.1 ng/mL; P < .001). Prolactin levels were associated with female gender (β = .32, P = .006, vs male), antipsychotics (β = .23, P = .02, risperidone vs olanzapine), and D2/3R occupancy (β = .23, P = .04). Those with D2/3R occupancy of 66% or higher were more likely to have hyperprolactinemia than those with D2/3R occupancy lower than 66% (P = .03). Sensitivity, specificity, positive predictive value, and negative predictive value of this threshold were 0.44, 0.81, 0.78, and 0.48, respectively. We identified a D2/3R occupancy threshold for hyperprolactinemia of 66% in older patients with schizophrenia, which is lower than that reported in younger patients (73%) by other researchers.. Our results suggest a higher sensitivity to antipsychotics in older patients. Prolactin levels could assist in the determination of appropriate antipsychotic dosing to minimize adverse effects.. ClinicalTrials.gov identifier: NCT00716755.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Corpus Striatum; Dopamine Antagonists; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Positron-Emission Tomography; Prolactin; Raclopride; Receptors, Dopamine D2; Receptors, Dopamine D3; Risperidone; Schizophrenia

Large-scale data are still lacking on the relationship between serum prolactin concentration and dopamine D2 receptor occupancy in patients with schizophrenia treated with antipsychotics.. The dataset from 481 subjects (risperidone, N = 172, olanzapine, N = 211, and ziprasidone, N = 98) who participated in Phase 1 of the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) was used in the present analysis. Dopamine D2 receptor occupancy levels on the day of the measurement of serum prolactin level were estimated from plasma antipsychotic concentrations. A multivariate general linear model was used to examine effects of clinical and demographic characteristics, including estimated D2 occupancy levels, on serum prolactin concentrations. Individual subjects were divided into two groups, stratified by the presence of hyperprolactinemia. To evaluate the performance of this binary classification, sensitivity, specificity, and accuracy of consecutive cut-off points in the D2 occupancy were calculated.. The multivariate general linear model revealed that estimated D2 occupancy levels had significant effects on serum prolactin concentrations while any other variables failed to show significant effects. The cut-off point associated with 0.5 or greater, in both sensitivity and specificity with the greatest accuracy, was 73% (sensitivity, 0.58; specificity, 0.68; accuracy = 0.64) (68-70% for risperidone, 77% for olanzapine, and 55% for ziprasidone.).. The threshold for hyperprolactinemia in D2 occupancy may lie somewhat on a lower side of the established therapeutic window with antipsychotics (i.e. 65-80%). This finding highlights the need for the use of the lowest possible dose to avoid this hormonal side effect in the treatment of schizophrenia.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Piperazines; Predictive Value of Tests; Prolactin; Receptors, Dopamine D2; Risperidone; Schizophrenia; Sensitivity and Specificity; Thiazoles

Hyperprolactinemia, an adverse effect associated with the use of typical antipsychotics and the atypical antipsychotic risperidone, has both acute and chronic clinical consequences. One option for clinical management is switching to an agent with a lower liability for inducing hyperprolactinemia. This post-hoc sub-analysis of an 8-week, open-label study in outpatients with schizophrenia (CN138-215) examined short-term effects on prolactin levels during a switch from risperidone or olanzapine to aripiprazole 30 mg/day. Three switch strategies were used: (I) immediate aripiprazole initiation with simultaneous immediate discontinuation of olanzapine/risperidone; (II) immediate aripiprazole initiation while tapering off olanzapine/risperidone over 14 days; (III) titrating aripiprazole upwards while tapering off olanzapine/risperidone over 14 days. Changes in prolactin levels from baseline to each last observation carried forward time point were compared with t-tests using Bonferroni correction for multiple comparisons. This sub-analysis included 269 subjects: 105 previously treated with risperidone; 164 previously treated with olanzapine. Mean baseline prolactin levels (ng/mL) were within normal range for the three olanzapine groups (Group-I, 11.7; Group-II, 13.2; Group-III, 11.2), but above normal for the risperidone groups (Group-I, 39.7; Group-II, 48.5; Group-III, 33.5). Following aripiprazole initiation, mean prolactin levels decreased significantly (p<0.001) at week-1 and were maintained to week-8 in all groups irrespective of prior treatment. Previously elevated prolactin levels in the risperidone groups were reduced to within normal range within 1 week, irrespective of switching strategy. Tolerability was good regardless of prior medication or switching strategy. Overall, rapid decreases of prolactin levels were achieved safely with all three aripiprazole switching strategies. Reversal of hyperprolactinemia during the crossover period indicates the safety and potential utility of aripiprazole addition in patients with elevated prolactin.

Topics: Administration, Oral; Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Piperazines; Prolactin; Psychotic Disorders; Quinolones; Risperidone; Schizophrenia; Sex Factors; Substance Withdrawal Syndrome; Young Adult

Second generation antipsychotics have less influence on prolactin levels than conventional antipsychotics (CA), which are commonly associated with sexual dysfunction and hyperprolactinaemia. However, only a few studies have been conducted assessing these newer antipsychotics and sexual function/dysfunction. The aim of this study is to evaluate the sexual function and hormonal profile of male schizophrenic patients taking olanzapine or CA. Sixty-three inpatients with acute episodes of schizophrenia were randomly assigned to take either olanzapine, or go on conventional antipsychotic treatment. The Dickson-Glazer sexual functioning questionnaire was used to assess sexual functioning where serum prolactin, luteinizing hormone, follicle-stimulating hormone, total testosterone, free testosterone, and sex hormone-binding globulin concentrations were measured. All measurements were taken on discharge from the inpatient unit (baseline), and again at 3 and 9 months after discharge. Prolactin levels in the olanzapine group decreased more rapidly and were significantly lower than in the CA group after 3 months (12.1+/-6.3 microg/l, p=0.01; 18.1+/-11.2 microg/l, p=0.564, respectively). After nine months, there was a tendency toward normal levels in both groups, and the frequency of sexual complaints did not differ between the groups. This study showed no difference between olanzapine and conventional antipsychotics regarding sexual complaints in the treatment of schizophrenia, but did show a difference in the hormone level normalization rate.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Follow-Up Studies; Hormones; Humans; Hyperprolactinemia; Male; Olanzapine; Prolactin; Schizophrenia; Sexual Dysfunction, Physiological; Surveys and Questionnaires

The main objective was to evaluate the effect of five second-generation antipsychotics (amisulpride, quetiapine, olanzapine, risperidone, and zotepine) on prolactinaemia during 6 week therapy in 433 female in-patients with mainly schizophrenic disorders. Secondary objectives included identification of dynamics of change in serum prolactin levels and correlations of changes of prolactinaemia with some demographic and clinical parameters.. The trial was a prospective, open-label, single-center one with a flexible dosing of SGAs. The therapeutic effect of SGAs was assessed by a change of scores of CGI-S and CGI-I scales from a baseline to the endpoint. Blood samples were taken in the morning under fasting condition.. Amisulpride and risperidone increased prolactinaemia significantly in 100% of patients, as early as after week 1 of the therapy. Quetiapine and zotepine relatively reduced prolactinaemia significantly, as early as from week 1 of the quetiapine treatment. Olanzapine led to a transient mild prolactin elevation. The much lower prevalence of hyperprolactinaemia over 2 000 mIU/l differentiates olanzapine from amisulpride and risperidone. Prolactin elevation did not correlate with age, menopausal condition, therapeutic efficacy, antipsychotic daily dose, serum levels of lipids and glucose. There was significant correlation with first vs. subsequent psychotic episodes, weight, EPS and serum levels of thyroid hormones.. Amisulpride and risperidone had marked and early prolactin elevating effects, requiring, therefore, more frequent monitoring of prolactinaemia and associated undesirable effects and risks than olanzapine, quetiapine and zotepine.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amisulpride; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dibenzothiepins; Female; Humans; Hyperprolactinemia; Middle Aged; Olanzapine; Prolactin; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Statistics, Nonparametric; Sulpiride

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cross-Over Studies; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Prolactin; Risperidone; Schizophrenia; Sex Distribution; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Amenorrhea; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Female; Galactorrhea; Humans; Hyperprolactinemia; Menstruation Disturbances; Middle Aged; Olanzapine; Pirenzepine; Prolactin; Prospective Studies; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Treatment Outcome

Prolactin elevation is both a common and a persistent event with the currently marketed antipsychotics, excluding clozapine. Elevations have been associated with both acute (galactorrhea, amenorrhea) and chronic (predisposition to osteoporosis) treatment-emergent adverse events. One of the defining criteria for an atypical antipsychotic is the relative lack of persistent prolactinemia. A double-blind, placebo- (N = 68) and haloperidol- (Hal: 15 +/- 5 mg/day, N = 69) controlled trial of three dose ranges of olanzapine (Olz-L: 5 +/- 2.5 mg/day, N = 65; Olz-M: 10 +/- 2.5 mg/day, N = 64; Olz-H: 15 +/- 2.5 mg/day, N = 69) in the treatment of schizophrenia afforded the opportunity to assess the temporal course of the influence of olanzapine and haloperidol on serum prolactin concentration. Consistent with its potent D2 antagonism, haloperidol was associated with a statistically significantly higher incidence of treatment-emergent prolactin elevation (72%) than seen with placebo (8%; p < 0.001) at week 2 of therapy. Expectedly, this elevation was also persistent at weeks 4 and 6. In contrast, olanzapine-associated treatment-emergent prolactin elevations were both lower in magnitude and transient. At week 2, 38% of the Olz-H, 24% of the Olz-M, and 13% of the Olz-L treatment groups exhibited a treatment-emergent prolactin elevation, with a mean increase of 0.35, 0.52, and 0.61 nmol/l, respectively; for haloperidol the mean increase was 1.23 nmol/l. For only the Olz-M and the Olz-H treatment groups did the week 2 incidence of treatment-emergent prolactin elevations differ statistically significantly from placebo. Both the incidence of elevations and the mean increase, in prolactin concentration were less than that seen with haloperidol. Furthermore, by treatment week 6, all three olanzapine groups exhibited incidences of treatment-emergent prolactin elevation that were comparable to placebo and were statistically significantly less than observed with haloperidol. Rapid adaptation was observed in the temporal course of prolactin elevations associated with olanzapine based on both the categorical analysis of treatment-emergent high values and the analyses of temporal change in mean concentrations. In contrast to haloperidol, the magnitudes of the treatment-emergent elevations associated with olanzapine were minimal. The rates of elevation were approximately one-half to one-third those observed with haloperidol and were significantly more transient. Olanzapine, even a

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chi-Square Distribution; Cross-Sectional Studies; Dopamine Antagonists; Double-Blind Method; Female; Haloperidol; Humans; Hyperprolactinemia; Longitudinal Studies; Male; Olanzapine; Pirenzepine; Schizophrenia; Sex Distribution; Time Factors

Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no established guidelines for antipsychotic switching. This naturalistic study explored the association between antipsychotic switching, baseline clinical status, metabolic changes, and relapse in patients with schizophrenia. In total, 177 patients with amisulpride-induced hyperprolactinemia and 274 with olanzapine-induced metabolic disturbance were enrolled. Relapse was determined by assessing changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to 6 months (increased over 20% or 10% reaching 70). Metabolic indices were measured at baseline and 3 months. Patients with baseline PANSS >60 were more likely to relapse. Further, patients switching to aripiprazole had a higher risk of relapse regardless of their original medication. Participants who originally used amisulpride had reduced prolactin levels following medication change, while switching to olanzapine caused increased weight and blood glucose levels. In patients originally using olanzapine, only switching to aripiprazole reduced insulin resistance. Adverse effects on weight and lipid metabolism were observed in patients who switched to risperidone, while amisulpride improved lipid profiles. Changing schizophrenia treatment requires careful consideration of multiple variables, particularly the choice of substituted drug and the patient's baseline symptoms.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Chronic Disease; Humans; Hyperprolactinemia; Olanzapine; Piperazines; Quinolones; Recurrence; Schizophrenia

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.. 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.. 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).. 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.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cohort Studies; Erectile Dysfunction; Female; Galactorrhea; Humans; Hyperprolactinemia; Male; Mentally Ill Persons; Olanzapine; Pregnancy; Prolactin; Prospective Studies; Quetiapine Fumarate; Risperidone

This study identified discrepant therapeutic outcomes of antipsychotics.. A total of 5191 patients with schizophrenia were enrolled, 3030 as discovery cohort, 1395 as validation cohort, and 766 as multi-ancestry validation cohort. Therapeutic Outcomes Wide Association Scan was conducted. Types of antipsychotics (one antipsychotic vs other antipsychotics) were dependent variables, therapeutic outcomes including efficacy and safety were independent variables.. In discovery cohort, olanzapine related to higher risk of weight gain (AIWG, OR: 2.21-2.86), liver dysfunction (OR: 1.75-2.33), sedation (OR: 1.76-2.86), increased lipid level (OR: 2.04-2.12), and lower risk of extrapyramidal syndrome (EPS, OR: 0.14-0.46); risperidone related to higher risk of hyperprolactinemia (OR: 12.45-20.53); quetiapine related to higher risk of sedation (OR = 1.73), palpitation (OR = 2.87), increased lipid level (OR = 1.69), lower risk of hyperprolactinemia (OR: 0.09-0.11), and EPS (OR: 0.15-0.44); aripiprazole related to lower risk of hyperprolactinemia (OR: 0.09-0.14), AIWG (OR = 0.44), sedation (OR: 0.33-0.47), and QTc prolongation (β = -2.17); ziprasidone related to higher risk of increased QT interval (β range: 3.11-3.22), nausea (OR: 3.22-3.91), lower risk of AIWG (OR: 0.27-0.46), liver dysfunction (OR: 0.41-0.38), and increased lipid level (OR: 0.41-0.55); haloperidol related to higher risk of EPS (OR: 2.64-6.29), hyperprolactinemia (OR: 5.45-9.44), and increased salivation (OR: 3.50-3.68). Perphenazine related to higher risk of EPS (OR: 1.89-2.54). Higher risk of liver dysfunction in olanzapine and lower risk of hyperprolactinemia in aripiprazole were confirmed in validation cohort, and higher risk of AIWG in olanzapine and hyperprolactinemia in risperidone were confirmed in multi-ancestry validation cohort.. Future precision medicine should focus on personalized side-effects.

Topics: Antipsychotic Agents; Aripiprazole; Humans; Hyperprolactinemia; Lipids; Olanzapine; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Treatment Outcome

Antipsychotics often induce hyperprolactinemia. The transforming growth factor (TGF)-beta1 signaling in the pituitary and hypothalamus inhibits prolactin synthesis and secretion, and its impairment is implicated in neuropsychiatric disorders. Longdan Xiegan Tang (LXT) alone or together with antipsychotics have been used to treat various neuropsychiatric diseases and hyperprolactinemia-associated disorders.. To investigate the effect of LXT on hyperprolactinemia and involvement of the TGF-beta1 signaling.. Male rats were co-administered with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) (p.o., × 8 weeks). Plasma concentrations of prolactin and TGF-beta1 were determined by ELISA. Protein expression was analyzed by Western blot.. Treatment of rats with LXT extract suppressed olanzapine-induced increase in plasma prolactin concentration and overexpression of pituitary and hypothalamic prolactin protein. Importantly, LXT restored olanzapine-induced decrease in protein expression of the key components of the TGF-beta1 signaling, TGF-beta1, type II TGF-beta receptor, type I TGF-beta receptor and phosphorylated SMAD3 in the pituitary and hypothalamus. Further, it antagonized downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein level, and inhibited pituitary estrogen receptor (ER) alpha and ERbeta protein expression.. The present results suggest that LXT ameliorates antipsychotic-induced hyperprolactinemia in rats by repairing the pituitary and hypothalamic TGF-beta1 signaling possibly via D2R, ERs or/and other pathways. Our findings may also provide scientific elucidation for use of the ancient Chinese formula to treat the impaired TGF-beta1 signaling-associated neuropsychiatric disorders.

Topics: Animals; Antipsychotic Agents; Drugs, Chinese Herbal; Estrogen Receptor alpha; Estrogen Receptor beta; Hyperprolactinemia; Hypothalamus; Male; Olanzapine; Pituitary Gland; Prolactin; Rats; Receptors, Dopamine D2; Signal Transduction; Transforming Growth Factor beta1

Antipsychotic medication, stress, gender, and age are factors that influence prolactin levels in patients with psychosis. The aim of the study was to investigate the level of prolactin response to antipsychotic treatment in acute patients, taking into account the total duration of psychosis.. The study was conducted on 170 acute patients with schizophrenia spectrum disorders and bipolar disorder. Subjects were divided into three subgroups according to the duration of the psychosis (less than 5 years, between 5 and 10 years and more than 10 years of disorder duration). The initial prolactin response under antipsychotic treatment was measured, while the severity of the psychiatric symptoms was assessed with the BPRS (Brief Psychiatric Rating Scale). Hyperprolactinemia was found in 120 (70.6%) patients, amongst which 80 (66.7%) were females and 40 (33.3%) were males. The average increase in prolactinemia was 2.46 times the maximum value in women, and 1.59 times in men. Gender (β = 0.27, p<0.0001), type of antipsychotic medication according to potency of inducing hyperprolactinemia (β = -0.23, p<0.003), and the duration of psychosis over 10 years (β = -0.15, p = 0.04) significantly predicted prolactin levels, when age, diagnosis, antipsychotic category (conventional/atypical/combinations of antipsychotics), and BPRS total scores were controlled for.. Prolactin levels in patients treated with antipsychotic medication appeared to depend on patients' gender, on the type of antipsychotic medication according to potency of inducing hyperprolactinemia, and on the duration of the psychosis. An increase in prolactin levels was associated with female gender, while the use of prolactin sparing antipsychotics and a duration of psychosis over 10 years were associated with lower prolactin levels.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Hyperprolactinemia; Inpatients; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Risperidone; Schizophrenia; Sex Factors; Time Factors

Paeoniflorin, a prominent component in some Chinese formulas for hyperprolactinemia-associated disorders, has been found to inhibit prolactin secretion in prolactinoma cells.. To examine the efficacy of paeoniflorin on hyperprolactinemia and the underlying mechanisms of action.. Hyperprolactinemia in female rats was generated by administration of olanzapine (5 mg/kg, by a gavage method, once daily, × 13 weeks). The rats were co-treated with paeoniflorin (10 and 50 mg/kg). Prolactin and TGF-β1 concentrations were detected by ELISA. Protein expression was determined by Western blot. The effect in MMQ cells was also examined.. Paeoniflorin inhibited olanzapine-induced increases in plasma prolactin concentration and prolactin protein overexpression in the pituitary and hypothalamus of rats. Further, paeoniflorin restored olanzapine-induced downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein expression. More importantly, paeoniflorin attenuated olanzapine-suppressed protein expression of transforming growth factor (TGF)-β1 and its downstream genes, type II TGF-β receptor, type I TGF-β receptor and phosphorylated SMAD3 in the tissues. However, paeoniflorin did not affect plasma TGF-β1 concentration and hepatic TGF-β1 protein expression. In accord, olanzapine-induced increase in prolactin concentration, upregulation of prolactin protein expression, and downregulation of protein expression of the D2R and TGF-β1 signals in MMQ cells were attenuated.. This study demonstrates that paeoniflorin ameliorates olanzapine-induced hyperprolactinemia in rats by attenuating impairment of the D2R and TGF-β1 signaling pathways in the hypothalamus and pituitary. Our findings may provide evidence to support the use of paeoniflorin-contained Chinese herbs and formulas for hyperprolactinemia and its associated disorders.

Topics: Animals; Antipsychotic Agents; Biomarkers; Cell Line, Tumor; Disease Models, Animal; Female; Glucosides; Hyperprolactinemia; Hypothalamus; Monoterpenes; Olanzapine; Pituitary Gland; Prolactin; Rats, Sprague-Dawley; Receptors, Dopamine D2; Signal Transduction; Transforming Growth Factor beta1

To study a relationship between plasma levels of antipsychotics (AP) and severity of side-effects (SE) during the treatment of inpatients with exacerbation of schizophrenia.. The study included 39 patients treated with risperidone, haloperidol, zuclopenthixol, clozapine, aripiprazole or olanzapine as monotherapy or in combination of two AP. Blood sampling to measure the AP plasma level was performed twice (at 7-10 and 26-30 day from start of treatment), the levels of prolactin and glucose were determined once (at 26-30 day from start of treatment). Patients were assessed by psychometric scales PANSS and NSA and the side-effects scale UKU.. The increased concentration of AP was noted in 33% of the patients. The high concentration of AP was significantly associated with akathisia and hyperkinesia (by UKU scale), NSA retardation factor and hyperprolactinemia. Patients with severe hyperprolactinemia were twice as likely to have a clinically significant depression. Increased blood glucose levels were observed in 18% of the patients, there was no significant association with AP plasma levels. Mental SE were most prominent, with a drift towards the neurological SE in the group with higher AP plasma levels. Chlorpromazine equivalent didn't significantly differ in the groups with normal, high and low AP concentrations.. Elevated AP plasma levels, which were associated with some clinically significant SE and some negative symptoms, were found in most patients. In this regard, therapeutic drug monitoring is a promising method for the individualization of schizophrenia exacerbation treatment in routine clinical practice.. Цель работы - изучение связи концентрации антипсихотических препаратов (АП) и выраженности побочных эффектов (ПЭ) при лечении обострения шизофрении в условиях стационара. Материал и методы. В исследование были включены 39 пациентов обоего пола, поступивших в психиатрический стационар в связи с обострением шизофрении, получающие лечение АП (рисперидон, галоперидол, зуклопентиксол, клозапин, арипипразол или оланзапин) в виде монотерапии или комбинации из 2 АП, где второй использовался для седации или коррекции инсомнии. Дважды проводился забор крови для определения концентрации АП (на 7-10-й и на 26-30-й дни от начала лечения), однократно - для определения уровней пролактина и глюкозы (на 26-30-й дни от начала лечения). Пациенты оценивались по психометрическим шкалам PANSS и NSA (на 2-5-й и 26-30-й дни от начала лечения) и по шкале побочных эффектов UKU (на 26-30-й дни от начала лечения). Результаты. Повышенная концентрация АП отмечалась у 33% пациентов. Статистически достоверно связанными с повышенной концентрацией АП в нашем исследовании оказались акатизия и гиперкинезия (по шкале UKU), фактор заторможенности по шкале NSA и гиперпролактинемия. В свою очередь у пациентов с выраженной гиперпролактинемией (уровень пролактина выше 90 нг/мл) в два раза чаще (28% против 14%) возникала клинически значимая депрессия (оценка по пункту PANSSG6 'депрессия' 4 балла и выше). Повышение уровня глюкозы крови отмечалось у 18% пациентов, достоверной связи с концентрацией АП в плазме крови отмечено не было. В структуре ПЭ преобладали психические ПЭ, с тенденцией к смещению в сторону неврологических в группе с повышенной концентрацией АП. Хлорпромазиновый эквивалент статистически достоверно не различался в группах нормальной, повышенной и пониженной концентрации АП. Заключение. У значительной части пациентов был обнаружен повышенный уровень АП в плазме крови, который был связан как с некоторыми клинически значимыми ПЭ, так и с частью негативных симптомов. В связи с этим терапевтический лекарственный мониторинг является перспективным методом персонализации терапии пациентов с обострением шизофрении в повседневной клинической практике.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Clozapine; Depression; Drug Therapy, Combination; Female; Haloperidol; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Prolactin; Risperidone; Schizophrenia; Schizophrenic Psychology; Young Adult

Topics: Antipsychotic Agents; Benzodiazepines; Biomarkers; Drug Combinations; Drugs, Chinese Herbal; Female; Glycyrrhiza; Humans; Hyperprolactinemia; Olanzapine; Paeonia; Prolactin; Schizophrenia, Paranoid; Treatment Outcome; Young Adult

This study consisting of two subprojects was undertaken to evaluate the effects of hyperprolactinemia on cardiovascular disease (CVD) risk parameters such as anthropometric measures, insulin sensitivity and blood lipids in patients with schizophrenia or related psychoses on long term treatment with antipsychotics.. In subproject Ι, 45 patients receiving the 2nd generation antipsychotics risperidone, clozapine or olanzapine were compared regarding prolactin (PRL), body mass index (BMI), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and blood lipids. In subproject Π, 24 patients receiving 1st or 2nd generation antipsychotics were investigated with diurnal profile of PRL and oral glucose tolerance test (OGTT).. Elevated PRL levels were found in about 45% of the patients and occurred more often in patients receiving risperidone or haloperidol, compared to patients receiving clozapine or olanzapine. In contrast, in subproject Ι, insulin and HOMA-IR were higher and high density lipoprotein cholesterol was lower in patients receiving clozapine or olanzapine, compared with patients receiving risperidone. However, PRL levels did not correlate to BMI, insulin, HOMA-IR or lipids in any of these three treatment groups. In subproject Π, OGTT showed impaired glucose tolerance in 25% and new-onset diabetes in 4% of the 24 patients investigated. Additionally, the PRL (median 24 h) levels correlated positively to the 2 h glucose level at OGTT (rs=0.42, p=0.04).. Our findings point to that hyperprolactinemia due to 1st and 2nd generation antipsychotics may decrease insulin sensitivity, whereas other mechanisms probably underlie insulin resistance induced by PRL-sparing antipsychotics such as clozapine and olanzapine.

Topics: Adult; Anthropometry; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Clozapine; Female; Glucose Intolerance; Humans; Hyperprolactinemia; Insulin Resistance; Lipids; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Risperidone; Schizophrenia; Young Adult

Body weight gain, sexual/reproductive dysfunction and hematological abnormalities are serious consequences of atypical antipsychotics treatment. No attempts however have been made preclinically to elucidate the adverse hematological impacts. Presently, effects of lactational exposure of olanzapine (4, 8 and 10 mg/kg) and risperidone (1 and 2 mg/kg) on hematology as well as lymphoid organ histopathology of mice neonates were investigated. Both olanzapine and risperidone transfers through milk and make the neonates susceptible to their adverse side effects. Corticosterone elevation tendency of both the drugs further enhance the susceptibility for immune dysfunction. Analysis of total and differential leukocytes counts revealed neutropenia with all the doses of olanzapine but only with risperidone 2mg/kg. Weight analysis and histopathology of thymus and spleen indicated a state of suppression; less in the risperidone-exposed groups. Significant plasma corticosterone elevation occurred on 4 and 8 mg/kg olanzapine exposures but not with 10 mg/kg as well as with both the risperidone doses. Elevation of plasma prolactin levels occurred dose-dependently for both the drugs. Hematological toxicity (neutropenia) might be the direct toxic effects of the drugs/unstable metabolites on circulating neutrophils and/or on the bone marrow hemopoietic cells. Direct toxicity of the drugs might also have suppressed the lymphoid organs thymus and spleen. Further, it could be associated to hormonal imbalance induced by adverse pharmacological effects of the drugs on the endocrine system. Suppression of lymphoid organs in olanzapine groups might have resulted because of corticosteronemia and hyperprolactinemia, while in risperidone it could be mediated by pronounced hyperprolactinemic effect alone.

Topics: Animals; Animals, Newborn; Benzodiazepines; Female; Hematologic Diseases; Hyperprolactinemia; Lactation; Male; Mice; Olanzapine; Risperidone; Spleen; Thymus Gland

Hyperprolactinemia is a common side effect of antipsychotic drugs used in the treatment of schizophrenia. However, the magnitude of hyperprolactinemia differs among antipsychotics, and there is no reliable mechanism-related marker for the risk of hyperprolactinemia that would allow us to characterize antipsychotics.. In this study, 11 healthy male subjects taking different doses of sulpiride and 24 male patients with DSM-IV-diagnosed schizophrenia taking different antipsychotic drugs (risperidone, olanzapine, haloperidol, and sulpiride) participated. Positron emission tomography scanning using [¹¹C]FLB 457 was performed on all subjects. The dopamine D₂receptor occupancy of antipsychotics in the pituitary and temporal cortex was calculated. Correlations between plasma concentration of prolactin and dopamine D₂receptor occupancies were evaluated. The ratio of drug concentration of cerebral receptor site to that of pituitary receptor site (brain/plasma concentration ratio; B/P ratio) was calculated from the receptor occupancies in the 2 regions. Data were collected between November 2001 and September 2007.. Significant positive correlation was observed between the plasma concentration of prolactin and dopamine D₂receptor occupancy in the pituitary by all 4 antipsychotics (P = .001). Dopamine D₂receptor occupancies of sulpiride were markedly different between the pituitary and temporal cortex, and the B/P ratio for sulpiride (0.34) was significantly lower than for olanzapine (P = .007) and risperidone (P = .015). Olanzapine had a relatively high B/P ratio (2.70), followed by haloperidol (2.40) and risperidone (1.61).. Dopamine D₂receptor occupancy in the pituitary is a good indicator of hyperprolactinemia. B/P ratio, indicating the penetrating capability across the blood-brain barrier, seems to be a good characteristic biomarker of each antipsychotic drug for the risk of hyperprolactinemia at therapeutic dose.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Carbon Radioisotopes; Cerebellar Cortex; Cerebral Cortex; Computer Graphics; Dopamine Antagonists; Dose-Response Relationship, Drug; Haloperidol; Humans; Hyperprolactinemia; Male; Mathematical Computing; Middle Aged; Olanzapine; Pituitary Gland; Positron-Emission Tomography; Prolactin; Pyrrolidines; Receptors, Dopamine D2; Risperidone; Salicylamides; Schizophrenia; Statistics as Topic; Sulpiride; Temporal Lobe; Young Adult

Hyperprolactinemia is a frequent consequence of treatment with some antipsychotic agents. Although prolactin secretion varies over the course of a day and during psychological circumstances, there is little information in the literature regarding the time dependence of the prolactin response to antipsychotics. We evaluated prolactin levels in schizophrenic patients receiving risperidone (3 mg twice daily), olanzapine (10 mg twice daily), or perospirone (16 mg twice daily) for at least 4 weeks. The subjects were compared to matched healthy controls. Plasma sample collection for quantification of drug and prolactin levels was conducted before and 2, 4, 6, 8, and 12 h after the morning dosing. Prolactin concentrations before dosing during risperidone treatment were significantly higher than during treatment with olanzapine and perospirone in females. The daily fluctuation of prolactin concentration after perospirone treatment was larger than that observed after risperidone and olanzapine treatments. Areas under the plasma concentration-time curves was greatest in subjects treated with risperidone, followed by perospirone and finally by olanzapine. These findings suggest that daily fluctuations in prolactin concentration after perospirone treatment are larger than following treatment with risperidone and olanzapine. The plasma concentration of prolactin during perospirone treatment therefore depends on the time of sampling.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Circadian Rhythm; Drug Administration Schedule; Drug Monitoring; Female; Humans; Hyperprolactinemia; Isoindoles; Male; Middle Aged; Olanzapine; Prolactin; Risperidone; Schizophrenia; Thiazoles; Time Factors; Treatment Outcome

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Female; Follow-Up Studies; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Middle Aged; Olanzapine; Pituitary Gland; Pituitary Neoplasms; Prolactinoma; Psychotic Disorders; Remission, Spontaneous; Sulpiride; Thyrotropin-Releasing Hormone

Topics: Adenoma; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bromocriptine; Dopamine Antagonists; Female; Hormone Antagonists; Humans; Hyperprolactinemia; Olanzapine; Piperazines; Pituitary Neoplasms; Quinolones; Risperidone; Schizophrenia; Serotonin Antagonists; Trifluoperazine

To study the effect of drugs on the hypothalamo-pituitary-gonadal (HPG) axis we compared the endocrine actions of two neuroleptics with different receptor affinity profiles-risperidone and olanzapine in male schizophrenic patients.. We investigated the levels of prolactin, estradiol, testosterone, LH, FSH and testicular peptide hormone-inhibin B, and we assessed psychopathology (PANSS), sexual function (ASEX) and treatment adherence (DAI-10) in 89 male schizophrenic inpatients treated with olanzapine or risperidone administered orally. The initial and final evaluations were carried out at weeks 3 and 8 after the onset of treatment, respectively.. At initial evaluation the mean serum prolactin and inhibin B levels were markedly higher, whereas testosterone level was lower in patients treated with risperidone, than in those treated with olanzapine. In 5 out of 50 subjects from risperidone group (10%) and in 1 from olanzapine group (2.6%) testosterone levels were below the lower limit (<241ng/ml), which reflected Leydig's cell impairment. In one patient receiving risperidone and in three receiving olanzapine, inhibin B level was below 80pg/ml, indicating Sertoli's cell dysfunction. At the final evaluation the mean serum prolactin level was markedly higher in patients taking risperidone, whereas their FSH levels were lower than in patients receiving olanzapine. In all investigated groups, except for the risperidone-hyperprolactinemic group inhibin B levels were negatively correlated with serum FSH. The mean LH, FSH, testosterone and estradiol levels were within the normal reference range at initial and final evaluation. The non-adherence to medications and ASEX scores were significantly higher in risperidone groups. Sexual dysfunction and medication non-adherence was not related to prolactin or gonadal hormone levels.. Risperidone elicited higher PRL elevation than olanzapine. Treatment with this medication can be associated with disturbances in reproductive hormones (testosterone) and gonadotropins (FSH). The cause of olanzapine-elicited reduction of inhibin B level and the lack of negative correlation between FSH and inhibin B in patients with risperidone-induced hyperprolactinemia require further investigation. Patients receiving risperidone showed higher level of sexual dysfunction and treatment non-adherence than those treated with olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Estradiol; Gonadotropins, Pituitary; Hormones; Humans; Hyperprolactinemia; Inhibins; Male; Olanzapine; Patient Compliance; Prolactin; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sexual Dysfunction, Physiological; Testosterone

Many dopamine antagonists are proven acute migraine treatments. Genetic studies also imply that polymorphisms in dopamine genes (DRD2 receptors) in persons with migraine may create dopamine hypersensitivity. However, treatment is limited by the adverse event profiles of conventional neuroleptics including extrapyramidal symptoms, anticholinergic and antihistaminergic effects, hyperprolactinemia, and prolonged cardiac QT interval. Atypical neuroleptics cause less extrapyramial symptoms and some atypical neuroleptics, including olanzapine and quetiapine, may be beneficial as both acute and preventive migraine treatment. The combination of prochlorperazine, indomethacin, and caffeine is effective in the treatment of the acute migraine attack. The mechanism of action by which neuroleptics relieve headache is probably related to dopamine D2 receptor antagonist. Other actions via serotonin (5HT) receptor antagonists may also be important, particularly for migraine prevention. Additional studies to clarify the mechanism of action of neuroleptics in migraine could lead to new drugs and better management of migraine.

Topics: Antipsychotic Agents; Benzodiazepines; Brain; Caffeine; Dibenzothiazepines; Dopamine; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Drug Interactions; Female; Humans; Hyperprolactinemia; Indomethacin; Male; Migraine Disorders; Neural Pathways; Olanzapine; Prochlorperazine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Serotonin 5-HT2 Receptor Antagonists; Serotonin Receptor Agonists; Treatment Outcome

To analyse the prescribing pattern and the safety profile of different atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs) during the years 2002-2003 in paediatric setting.. Two Child Neurology and Psychiatry Divisions of Southern Italy (University of Messina and "Oasi Institute for Research on Mental Retardation and Brain Aging" of Troina).. A retrospective chart review of all children and adolescents starting an incident treatment with atypical antipsychotics or SSRIs was performed. Within the first 3 months of therapy, any potential adverse drug reaction (ADR) was identified and the clinical outcome of psychotropic drug treatment was assessed.. Rate of ADR in the first 3 months of therapy with atypical antipsychotics and SSRIs in children and adolescents.. On a total of 97 patients' charts being reviewed, 73 (75%) concerned atypical antipsychotics and 24 (25%) SSRIs. Risperidone (N=45, 62%) was the most frequently prescribed antipsychotic drug, followed by olanzapine (24, 32%). Overall, 50 (68%) antipsychotic users reported a total of 108 ADRs during the first 3 months of therapy, leading to drug discontinuation in 23 patients (31%). Among 24 users of SSRI, 12 (50%) received paroxetine, 6 (25%) sertraline, 5 (21%) citalopram and 1 (4%) fluoxetine. Only paroxetine users (21%) reported at least one ADR, however, none of SSRI users withdrew drug treatment within first 3 months.. ADRs occurred frequently during first 3 months of treatment with atypical antipsychotics and, to a lesser extent, with SSRIs in children and adolescents. Further investigations are urgently needed to better define the benefit/risk ratio of psychotropic medications in paediatric setting.

Topics: Adolescent; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Child; Citalopram; Drug Utilization Review; Female; Fluoxetine; Humans; Hyperprolactinemia; Italy; Male; Medical Records; Mental Disorders; Olanzapine; Paroxetine; Practice Patterns, Physicians'; Retrospective Studies; Risperidone; Sertraline; Treatment Outcome

The receptor binding affinities of the three drug candidates 1 (SLV310), 2 (SLV313), and 3 (SLV314) were positioned against the results from nine (a)typical antipsychotic drugs. The receptor binding data from sixteen monoaminergic receptors served as the input in a principal component analysis (PCA). The PCA outcome revealed a unique binding profile of 1, 2, and 3 as compared with the reference compounds 4-8 and 10-12. The weight gain inducing antipsychotics 6-8 clustered in the PCA by scoring strongly negative for factor 1. The hyperprolactinaemia related antipsychotics 4, 5, 10, and 12 clustered by their negative scores for factor 2.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzoxazines; Biogenic Monoamines; Humans; Hyperprolactinemia; Indoles; Metabolic Diseases; Phthalimides; Piperazines; Principal Component Analysis; Pyridines; Radioligand Assay; Receptors, Biogenic Amine; Weight Gain

Hyperprolactinemia is a frequent side-effect in the use of atypical antipsychotics. The propensity to induce hyperprolactinemia is highly substance dependent and hyperprolactinemia is not always associated with clinical side-effects. We report a case in which hyperprolactinemia and amenorrhea under the treatment with olanzapine gets normalized after the addition of aripiprazole.

Topics: Adult; Amenorrhea; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Olanzapine; Piperazines; Quinolones

To analyze the disproportionality of reporting of hyperprolactinemia, galactorrhea, and pituitary tumors with seven widely used antipsychotic drugs.. Retrospective pharmacovigilance study.. United States Food and Drug Administration's Adverse Event Reporting System (AERS) database.. We initially identified higher-than-expected postmarketing reports of pituitary tumors associated with risperidone, a potent dopamine D2-receptor antagonist antipsychotic, by analyzing reporting patterns of these tumors in the AERS database. To further examine this association, we analyzed disproportionate reporting patterns of pituitary tumor reports for seven antipsychotics with different affinities for blocking D2 receptors: aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and haloperidol.. To conduct both of these analyses, we used the Multi-item Gamma Poisson Shrinker (MGPS) data mining algorithm applied to the AERS database. The MGPS uses a Bayesian model to calculate adjusted observed:expected ratios of drug-adverse event associations (Empiric Bayes Geometric Mean [EBGM] values) in huge drug safety databases. The higher the adjusted reporting ratio, or EBGM value, the greater the strength of the association between a drug and an adverse event. Risperidone had the highest adjusted reporting ratios for hyperprolactinemia (EBGM 34.9, 90% confidence interval [CI] 32.8-37.1]), galactorrhea (EBGM 19.9, 90% CI 18.6-21.4), and pituitary tumor (EBGM 18.7, 90% CI 14.9-23.3) among the seven antipsychotics, and one of the highest scores for all drugs in the AERS database. Some tumors were associated with visual field defects, hemorrhage, convulsions, surgery, and severe (>10-fold) prolactin elevations. The EBGM values for risperidone for these adverse events were higher in women, but high EBGM values for these events were also seen in men and children. Moreover, the rank order of the EBGM values for pituitary tumors corresponded to the affinities of these seven drugs for D2 receptors.. Treatment with potent D2-receptor antagonists, such as risperidone, may be associated with pituitary tumors. These findings are consistent with animal (mice) studies and raise the need for clinical awareness and longitudinal studies.

Topics: Adolescent; Adverse Drug Reaction Reporting Systems; Amenorrhea; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Clozapine; Dibenzothiazepines; Female; Galactorrhea; Gynecomastia; Haloperidol; Humans; Hyperprolactinemia; Male; Olanzapine; Piperazines; Pituitary Neoplasms; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Sex Factors; Thiazoles; United States; United States Food and Drug Administration

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bromocriptine; Drug Therapy, Combination; Female; Galactorrhea; Hormone Antagonists; Humans; Hyperprolactinemia; Olanzapine; Prolactin; Psychotic Disorders

The aim of this cross-sectional study was to investigate the degree and frequency of prolactin (PRL) elevation and related symptoms in patients treated with 3 different atypical antipsychotics: clozapine, olanzapine, and risperidone.. Twenty-eight patients receiving clozapine, 29 patients receiving olanzapine, and 18 patients receiving risperidone (all meeting DSM-IV criteria for schizophrenia, schizophreni-form disorder, or schizoaffective disorder) were studied. The median daily dose was 400 mg of clozapine, 10 mg of olanzapine, and 3 mg of risperidone. Fasting morning blood samples were analyzed for PRL, and the occurrence of hyper-prolactinemic symptoms in the patients was evaluated.. Elevated PRL levels were found in 16 (89%) of the patients receiving risperidone and in 7 (24%) of the patients receiving olanzapine, but in none of the patients receiving clozapine. In addition, there was a significant difference in median PRL level among the treatment groups (p < .0001), in that the PRL level was higher both in the patients treated with risperidone and in the patients treated with olanzapine, compared to those treated with clozapine. Moreover, hyperpro-lactinemic symptoms-menstrual disturbances, galactorrhea, impotence, oligospermia, and decreased libido-were reported in 8 (44%) of the risperidone-treated patients and in 1 (3%) of the olanzapine-treated patients, but in none of the clozapine-treated patients.. Treatment with risperidone was frequently associated with hyperprolactinemia and related symptoms, whereas the occurrence of PRL elevation and related symptoms was modest in patients receiving olanzapine and nonexistent in those receiving clozapine. Thus, atypical anti-psychotics in therapeutic doses differ with regard to effect on PRL secretion.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Clozapine; Cross-Sectional Studies; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Prevalence; Prolactin; Risperidone; Schizophrenia; Treatment Outcome

The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study was designed to provide information regarding use and outcome of antipsychotic treatments in a large, diverse population in real practice settings.. Outpatients with schizophrenia (ICD-10 or DSM-IV) who initiated or changed to a new antipsychotic entered this 3-year, naturalistic, prospective observational study. Four monotherapy treatment groups were defined according to the antipsychotic prescribed at baseline, namely olanzapine, risperidone, quetiapine, and haloperidol. Efficacy was assessed using the Clinical Global Impressions-Severity of Illness rating scale (CGI-S), inclusive of subscales for positive, negative, depressive, and cognitive symptoms. Tolerability was assessed by adverse event questionnaires and weight measurements. Six-month findings are described.. At baseline, 5833 participants were prescribed monotherapy and the mean severity of illness was moderate to marked (CGI-S). At 6 months, olanzapine resulted in significantly greater improvements in overall, positive, negative, depressive, and cognitive symptoms compared with quetiapine, risperidone or haloperidol (p <.001). Improvements in overall, negative, and cognitive symptoms were significantly higher for risperidone compared with haloperidol (p <.001), whereas improvements across all symptoms were comparable for quetiapine and haloperidol. Extra-pyramidal symptoms and tardive dyskinesia decreased compared with baseline in the olanzapine, quetiapine, and risperidone groups but increased in the haloperidol group (p <.001, likelihood of extrapyramidal symptoms with haloperidol compared with olanzapine, quetiapine, or risperidone). Sexual function adverse events were most prominent in the haloperidol and risperidone treatment groups. Weight change was significantly greater for olanzapine compared with the other antipsychotics (p <.001).. Our results support the previously reported positive impact of atypical antipsychotics, particularly olanzapine, in patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Hyperprolactinemia; International Classification of Diseases; Male; Observation; Olanzapine; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Sexual Dysfunction, Physiological; Surveys and Questionnaires; Weight Gain

Hyperprolactinaemia induced by D(2) dopamine receptor antagonist antipsychotic medication can result in significant health problems.. To examine the role of DRD2 polymorphism on prolactin levels in patients treated with antipsychotic medication.. Antipsychotic drugs with different degrees of D(2) receptor binding were given to 144 patients with schizophrenia. Serum prolactin levels were obtained and Taq1A DRD2 alleles were determined.. Prolactin levels increased across medication groups reflecting increasingly tight D(2) receptor binding (clozapine, olanzapine, typical antipsychotics and risperidone). In the combined medication group, patients with the DRD2(*)A1allele had 40% higher prolactin levels than patients without this allele. In patients treated with clozapine (the loosest D(2) receptor binding agent), patients with the DRD2(*)A1allele had prolactin levels twice those of patients without this allele.. Patients with the DRD2A1 allele receiving antipsychotic medications had higher prolactin levels and were overrepresented among those with hyperprolactinaemia, suggesting greater functional D(2) receptor binding in this group.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Clozapine; Dopamine Antagonists; Female; Genotype; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Prolactin; Receptors, Dopamine D2; Risperidone; Schizophrenia; Sex Factors

Topics: Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hyperprolactinemia; Olanzapine; Patient Dropouts; Patient Selection; Prolactin; Research Design

Topics: Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Middle Aged; Olanzapine; Psychotic Disorders; Thromboembolism; Venous Thrombosis

We attempt to demonstrate the association between neuroleptic-induced hyperprolactinemia and sexual dysfunction in schizophrenic patients treated with prolactin-elevating antipsychotics. Our findings indicate that sexual function improved with euprolactinemia in patients switched from treatment with prolactin-elevating antipsychotics to olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Ejaculation; Female; Humans; Hyperprolactinemia; Male; Olanzapine; Prolactin; Psychotic Disorders; Risperidone; Sex Characteristics; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological

Atypical antipsychotic drugs for the treatment of schizophrenia provide effective treatment of psychotic symptoms with a safety profile superior to conventional antipsychotic medications. Neuroendocrine abnormalities in patients with schizophrenia, such as chronic hyperprolactinemia, may now potentially be minimized by the use of newer prolactin-sparing antipsychotic drugs. A discrimination of prolactin-sparing versus prolactin-elevating antipsychotic drugs may provide the clinician with treatment choices in order to avoid or mitigate hyperprolactinemia-associated morbidity.. Results from five clinical trials were used to characterize factors that may influence antipsychotic drug effects on levels of serum prolactin. Factors investigated included drug treatment, gender, time course, potential for reduction or reversibility, and age.. Factors that influenced the risk of hyperprolactinemia included gender, with females appearing to be more sensitive than males, and drug treatment, with risperidone and conventional antipsychotic agents increasing prolactin more than olanzapine. Patients of all ages demonstrated sensitivity to increased prolactin. Furthermore, patients with hyperprolactinemia sustained the effect over time. Hyperprolactinemia reversed when patients were switched to a prolactin-sparing antipsychotic medication.. Effects of antipsychotic medications on serum prolactin are multi-factorial. Evidence for sexual, reproductive, and general medical consequences of antipsychotic-induced hyperprolactinemia is developing, and identifying antipsychotic drugs with a favorable prolactin profile would be important in mitigating these consequences. Most notably for women, atypical or novel antipsychotic drugs with a prolactin-sparing profile may offer effective clinical treatment with preservation of physiological hormonal function.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Estrogens; Female; Haloperidol; Humans; Hyperprolactinemia; Male; Olanzapine; Pirenzepine; Prolactin; Risk Factors; Risperidone; Schizophrenia; Sex Characteristics

Elevations in prolactin plasma concentration occur with antipsychotics due to their dopamine D2 receptor antagonism. Hyperprolactinemia may be associated with both acute (galactorrhea, amenorrhea, decreased libido etc.) and chronic (predisposition to osteoporosis and cardiovascular disease) treatment emergent effects in both men and women associated with apparently impaired compliance. The aim of our study was to investigate these supposed effects regarding clinically relevant endocrinologic symptoms under routine treatment conditions with newer, atypical antipsychotics. Our findings confirm that amisulpride frequently leads to a remarkable elevation of prolactin plasma concentration, same--in minor degree--for risperidone. Under treatment with quetiapine and olanzapine just temporary elevated prolactin levels were registered. However, no correlation between prolactin levels and dosage could be found. In females treated with amisulpride acute hormonal side effects were seen in a clinically relevant manner. Features of illness itself, stress factors, concomitant medication or other patient's conditions are supposed to be relevant factors for acute endocrine symptomatology.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Pirenzepine; Product Surveillance, Postmarketing; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride

Some, but not all, antipsychotics elevate serum prolactin. Antipsychotic-induced hyperprolactinemia is thought to account for high rates of menstrual dysfunction and diminished estrogen levels in women with schizophrenia. However, few studies have directly assessed the relationships between prolactin, menstrual function, and ovarian hormone levels in this population. Sixteen premenopausal women with schizophrenia and schizoaffective disorder, eight treated with an antipsychotic with prolactin-elevating potential (five with typical antipsychotics and three with risperidone) and eight treated with an antipsychotic with prolactin-sparing potential (seven with olanzapine and one with clozapine), were studied for eight weeks. Data were collected on menstrual functioning and on serum prolactin, estradiol, and progesterone levels, and were compared between subjects who received an antipsychotic with prolactin-elevating potential and an antipsychotic with prolactin-sparing potential, and between subjects with hyperprolactinemia (N=6) and normoprolactinemia (N=10). Additionally, peak ovarian hormone levels were compared to normal values. While mean prolactin levels of subjects who received an antipsychotic with prolactin-elevating potential were significantly greater than those of subjects who received an antipsychotic with prolactin-sparing potential, there were no differences in rates of menstrual dysfunction or in ovarian hormone values between the two groups. Additionally, similar rates of menstrual dysfunction and ovarian hormone values were observed between the hyperprolactinemic and normoprolactinemic subjects. Moreover, irrespective of medication type or prolactin status, most subjects had peak estradiol levels below normal reference values for the periovulatory phase of the menstrual cycle. While our sample size is small, warranting the need for further investigation, the findings of this preliminary study suggest that antipsychotic-induced hyperprolactinemia, alone, may not adequately explain the observed ovarian dysfunction in women with schizophrenia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Estradiol; Female; Humans; Hyperprolactinemia; Menstrual Cycle; Menstruation Disturbances; Olanzapine; Pirenzepine; Progesterone; Prolactin; Prospective Studies; Risperidone; Schizophrenia

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Humans; Hyperprolactinemia; Male; Olanzapine; Pirenzepine; Prolactin; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Testosterone

Topics: Adult; Amenorrhea; Antipsychotic Agents; Benzodiazepines; Female; Galactorrhea; Humans; Hyperprolactinemia; Middle Aged; Olanzapine; Perphenazine; Pirenzepine; Risperidone; Schizophrenia