clozapine and Hyperprolactinemia

The second generation antipsychotic drug clozapine represents the most effective pharmacotherapy for treatment-resistant psychosis. It is also associated with low rates of extrapyramidal symptoms and hyperprolactinemia compared to other antipsychotic drugs. However, clozapine tends to be underutilized in clinical practice due to a number of disabling and serious side-effects. These are characterized by a constellation of metabolic side-effects which include dysregulation of glucose, insulin, plasma lipids and body fat. Many patients treated with clozapine go on to develop metabolic syndrome at a higher rate than the general population, which predisposes them for Type 2 diabetes mellitus and cardiovascular disease. Treatments for the metabolic side-effects of clozapine vary in their efficacy. There is also a lack of knowledge about the underlying physiology of how clozapine exerts its metabolic effects in humans. In the current review, we focus on key studies which describe how clozapine affects each of the main symptoms of the metabolic syndrome, and cover some of the treatment options. The clinical data are then discussed in the context of preclinical studies that have been conducted to identify the key biological substrates involved, in order to provide a better integrated overview. Suggestions are provided about key areas for future research to better understand how clozapine causes metabolic dysregulation.

Topics: Animals; Antipsychotic Agents; Clozapine; Diabetes Mellitus, Type 2; Drug-Related Side Effects and Adverse Reactions; Humans; Hyperprolactinemia; Metabolic Syndrome; Psychotic Disorders; Risk Factors

Topics: Adult; Antipsychotic Agents; Bromocriptine; Clozapine; Dopamine Agonists; Dopamine Antagonists; Drug Antagonism; Female; Haloperidol; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactin; Prolactinoma; Schizophrenia

Schizophrenia is associated with several chronic physical illnesses and a shorter life expectancy, compared with life expectancy in the general population. One approach to improving the health of patients with schizophrenia is to improve the monitoring of physical health that occurs in psychiatric settings. The authors discuss a consensus panel's recommendations for improving the physical health monitoring of patients with schizophrenia who are treated in outpatient settings.. A consensus meeting including psychiatric and other medical experts assembled on October 17-18, 2002, to evaluate the existing literature and to develop recommendations for physical health monitoring of patients with schizophrenia. Conference participants reviewed the literature in the following areas: 1) weight gain and obesity; 2) diabetes; 3) hyperlipidemia; 4) prolongation of the QT interval on the ECG; 5) prolactin elevation and related sexual side effects; 6) extrapyramidal side effects, akathisia, and tardive dyskinesia; 7) cataracts; and 8) myocarditis. Experts for each topic area formulated monitoring recommendations that were discussed by all of the participants until a consensus was reached.. Consensus recommendations included regular monitoring of body mass index, plasma glucose level, lipid profiles, and signs of prolactin elevation or sexual dysfunction. Information from monitoring should guide the selection of antipsychotic agents. Specific recommendations were made for cardiac monitoring of patients who receive medications associated with QT interval prolongation, including thioridazine, mesoridazine, and ziprasidone, and for monitoring for signs of myocarditis in patients treated with clozapine. Patients who receive both first- and second-generation antipsychotic medications should be examined for extrapyramidal symptoms and tardive dyskinesia. Patients with schizophrenia should receive regular visual examinations.. The conference participants recommended that mental health care providers perform physical health monitoring that typically occurs in primary care settings for their patients who do not receive physical health monitoring in those settings. This change in usual practice is recommended on the basis of the conference participants' belief that this additional monitoring will result in the earlier detection of common, serious risk factors that could, without detection and intervention, contribute to impaired health of patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Cataract; Clozapine; Diabetes Mellitus, Type 2; Health Status; Humans; Hyperlipidemias; Hyperprolactinemia; Long QT Syndrome; Monitoring, Physiologic; Myocarditis; Obesity; Practice Guidelines as Topic; Schizophrenia; Sexual Dysfunctions, Psychological; 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

The extensive pharmacological evaluation of JL 13 as an atypical antipsychotic drug has revealed a close similarity to clozapine, however with some major advantages. JL 13 was characterized as a weak D(2) antagonist, both in vitro and in vivo, with a strong affinity for the D(4) and the 5-HT(2A) receptors. It has no affinity for the 5-HT(2C) receptor. In vivo microdialysis experiments in rat showed that JL 13, like clozapine, preferentially increased extracellular dopamine concentrations in the prefrontal cortex compared to nucleus accumbens or striatum. Behavioral studies showed that JL 13, like clozapine, has the profile of an atypical antipsychotic. Thus, JL 13 did not antagonize apomorphine-induced stereotypy nor did it produce catalepsy, but it antagonized apomorphine-induced climbing in rodents. It was inactive against d-amphetamine-induced stereotypy but antagonized d-amphetamine-induced hyperactivity in the mouse. Likewise, in the paw test, it was more effective in prolonging hindlimb retraction time than prolonging forelimb retraction time. Like other antipsychotic drugs, JL 13 reversed the apomorphine- and amphetamine-induced disruption of prepulse inhibition. In a complex temporal regulation schedule in the dog, JL 13 showed a high resemblance with clozapine without inducing sialorrhea, palpebral ptosis or any significant motor side effects. In rats and squirrel monkeys JL 13 induced a high degree of generalization (70%) to clozapine. Regarding behavioral toxicology, JL 13 did not produce dystonia or Parkinsonian symptoms in haloperidol-sensitized monkeys. After acute administration, again like clozapine, JL 13 induced only a transient increase in circulating prolactin. Last but not the least, regarding a possible hematological toxicity, unlike clozapine, JL 13 did not present sensitivity to peroxidase-induced oxidation. Moreover, its electrooxidation potential was close to that of loxapine and far from that of clozapine. Taking all these preclinical data into account, it appears that JL 13 is a promising atypical antipsychotic drug.

Topics: Animals; Antipsychotic Agents; Brain; Cebidae; Clozapine; Discrimination Learning; Discrimination, Psychological; Dopamine Antagonists; Drug Evaluation, Preclinical; Hematologic Diseases; Hyperprolactinemia; Mice; Oxazepines; Piperazines; Psychotropic Drugs; Pyridines; Rats; Saimiri; Tissue Distribution

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

Hormonally related side effects of antipsychotic drugs, e.g. weight gain, hyperlipidemia and diabetes have come to the forefront in that the use of clozapine and new antipsychotics have increased. Hormones involved are prolactin, growth hormone (GH), insulin-like growth factor I (IGF-I), insulin and leptin. Patients treated with clozapine had lower levels of GH-dependent IGF-I than patients receiving classical antipsychotics. Patients treated with olanzapine had higher serum insulin levels than those receiving classical antipsychotics, indicating a probable influence of olanzapine on insulin secretion. In clozapine-treated patients the insulin levels correlated to the clozapine serum concentration, indicating a likely influence also of clozapine on insulin secretion. The gender difference, i.e. that women normally have higher leptin levels than men, was found in patients receiving classical antipsychotics, but not in patients treated with clozapine or olanzapine.

Topics: Antipsychotic Agents; Clozapine; Diabetes Mellitus; Female; Human Growth Hormone; Humans; Hyperlipidemias; Hyperprolactinemia; Insulin; Insulin-Like Growth Factor I; Lipids; Male; Prolactin; Weight Gain

Antipsychotic medications are among the most widely prescribed class of medications for elderly patients. Despite their high use, few studies document the efficacy, safety, and tolerability of these agents in this patient population. This is unfortunate because, as a group, the elderly are exceptionally sensitive to the adverse effects associated with antipsychotics, in particular, the extrapyramidal side effects (EPS). The atypical antipsychotics with their lower propensity to cause EPS and lower need for augmenting anticholinergic medication have introduced new options for elderly patients who need antipsychotic therapy for a number of psychiatric and neurologic disorders with psychotic manifestations. This review covers the pharmacologic, clinical, and regulatory issues involving antipsychotic use in elderly patients that warrant consideration by the practicing psychiatrist.

Topics: Accidental Falls; Age Factors; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Clozapine; Drug Costs; Drug Interactions; Dyskinesia, Drug-Induced; Humans; Hyperprolactinemia; Osteoporosis; Psychotic Disorders; Weight Gain

To determine if prolactin levels are associated with glucose-insulin homeostasis in antipsychotic-treated patients with schizophrenia.. Prolactin levels and glucose homeostasis (quantified using oral glucose tolerance testing, insulin measurement, and homeostasis model assessment) were measured in 15 patients with elevated prolactin levels secondary to antipsychotic treatment of schizophrenia (mean age, 30.4 years; SD, 5.3 years). The effect of reducing prolactin levels by switching patients' antipsychotic treatment to clozapine was ascertained by performing the measures before and after the switch to clozapine.. There was no significant correlation between prolactin and glucose-insulin measures at baseline. There was a large reduction in prolactin (593 mIU/L) after switching to clozapine, but this was not associated with changes in glucose-insulin measures.. Prolactin is not a significant determinant of glucose-insulin homeostasis in patients taking antipsychotics for schizophrenia. There was no benefit from lowering prolactin levels using clozapine. This could be because prolactin does not have a major effect on glucose homeostasis or that the effects of prolactin reduction are countered by clozapine.

Topics: Adult; Antipsychotic Agents; Blood Glucose; Clozapine; Follow-Up Studies; Glucose Tolerance Test; Homeostasis; Humans; Hyperprolactinemia; Insulin; Prolactin; Research Design; Schizophrenia; Time Factors; Treatment Outcome

To examine the frequency of hyperprolactinemia and the socio-demographic, clinical, and quality of life (QOL) correlates. The frequency of prolactin-related side effects and associated subjective experiences were also examined.. A cohort of 1364 psychiatric inpatients were consecutively recruited and evaluated. Basic socio-demographic and clinical data were collected. Psychopathology, prolactin-related side effects were measured using standardized instruments. QOL was assessed using the Medical Outcomes Study Short Form 12.. The frequency of hyperprolactinemia was 61.3% in the whole sample; 61.6% in female and 60.8% in male patients. There was no significant association between hyperprolactinemia and any QOL domain. In the whole sample, 15.1% of patients reported moderately severe breast symptoms and lactation, and 53.9% reported moderate or severe discomfort. Nearly a third of female patients (30.4%) reported at least moderate menstrual changes and 50.2% moderate or severe discomfort, while 24.2% of male patients reported at least moderate erectile dysfunction and 52.6% moderate or severe discomfort. Multiple logistic regression analysis revealed that patients with hyperprolactinemia were less likely to be married, diagnosed with mood disorders, or treated with clozapine, aripiprazole, or antidepressants but more likely to receive risperidone.. Effective measures to lower the frequency of hyperprolactinemia and the related side effects should be considered in Chinese psychiatric facilities.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Case-Control Studies; China; Clozapine; Female; Humans; Hyperprolactinemia; Male; Mental Disorders; Quality of Life; Risperidone; Sexual Dysfunction, Physiological; Young Adult

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

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease. The etiology and treatment options of IGM remain controversial. Previous case reports have suggested that hyperprolactinemia may be associated with IGM. In the present report, we describe the first case of IGM associated with risperidone-induced hyperprolactinemia.

Topics: Adult; Antipsychotic Agents; Biopsy; Clozapine; Drug Substitution; Female; Granulomatous Mastitis; Humans; Hyperprolactinemia; Mastectomy; Risperidone; Schizophrenia; Treatment Outcome

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

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

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

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

In cases of treatment-resistant schizophrenic psychoses combined application of atypical antipsychotic drugs is an often-used strategy.. We report the case of a 35-year old man with paranoid schizophrenia, whose symptoms turned out to be resistant to the application of olanzapine, risperidone and quetiapine. After switch to clozapine paranoid delusions remitted, but schizophrenic negative symptoms persisted and side effects limited the patient's compliance. Augmentation with ziprasidone allowed a reduction of the clozapine dose and ameliorated the affective deficits.. Positive and negative symptoms were well controlled. In spite of a transient hyperprolactinaemia and sexual dysfunction the patient was highly content.. The combined application of ziprasidone and clozapine follows a neurobiological rationale, seems able to reduce side effects, and should be further evaluated with respect to risk and benefit in prospective studies.

Topics: Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Interactions; Drug Resistance; Drug Therapy, Combination; Follicle Stimulating Hormone; Humans; Hyperprolactinemia; Male; Piperazines; Prolactin; Psychiatric Status Rating Scales; Schizophrenia, Paranoid; Thiazoles

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

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

Antipsychotic therapy is frequently associated with several side effects such as hyperprolactinemia. The influence of a putative antipsychotic JL 13 on prolactin release was assessed after intraperitoneal injection in gentled male rats in comparison with clozapine and haloperidol. A total of 30 or 150 min after administration, whole blood was collected for preparing serum samples. Prolactin was quantified by radioimmunoassay method. At 30 min, JL 13 like clozapine, increased prolactin concentration only at the higher dose (30 mg/kg) while haloperidol at both tested doses induced a dramatic increase of prolactin concentration. At 150 min after injection, only haloperidol (0.3 mg/kg) significantly increased serum prolactin level. This minimal effect on prolactinemia reinforces the similarity of clozapine and JL 13 regarding the atypical antipsychotic profile.

Topics: Animals; Antipsychotic Agents; Clozapine; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Haloperidol; Hyperprolactinemia; Male; Pituitary Gland, Anterior; Prolactin; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2

Several years ago, we reported that the addition of risperidone to clozapine improved response in some patients with schizophrenia. Risperidone, in general, is well tolerated when administered as monotherapy, but has been linked to a persistent elevation of serum prolactin and associated symptoms. The goal of this study was to determine whether the addition of risperidone to clozapine results in an elevation of serum prolactin levels in patients with chronic schizophrenia or schizoaffective disorder.. Twenty patients on clozapine-risperidone combination therapy were matched for age and gender with 20 patients treated with clozapine monotherapy. Demographic information was gathered along with clozapine and risperidone dose and the length of time on risperidone. Serum prolactin levels were measured from a single blood sample.. The 2 groups did not differ in age, race, gender, diagnosis, age at clozapine initiation, age at onset, Abnormal Involuntary Movement Scale scores, or clozapine dose. The mean +/- SD serum prolactin level was 8.42+/-4.17 ng/mL for clozapine monotherapy patients and 35.76+/-17.43 ng/mL for combination therapy patients. The 2 medication categories showed a significant difference in log prolactin values (t = -7.97, df = 38, p < or = .0001). Sixteen combination therapy patients (80%) exhibited elevated prolactin levels (range for entire group, 9.7-69.8 ng/mL) while only 2 clozapine monotherapy patients (10%) exhibited prolactin elevation levels (range for entire group, 2.4-20.2 ng/mL; df = 1, p < .0001).. The combination of risperidone and clozapine appears to result in a moderate elevation of serum prolactin levels. Additionally, controlled prospective studies are needed to clarify the risks of long-term elevations of serum prolactin level.

Topics: Adult; Age of Onset; Ambulatory Care; Antipsychotic Agents; Chronic Disease; Clozapine; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Prolactin; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology

Hyperprolactinemia is a well-known consequence of conventional antipsychotic therapy. The atypical antipsychotic clozapine is reported to lack this effect. We describe a case of attenuated serum prolactin levels after conversion to clozapine therapy in an adolescent. A 13-year-old female patient developed hyperprolactinemia with galactorrhea and amenorrhea while receiving thioridazine 300 mg daily. These symptoms continued throughout 3 years of treatment with haloperidol 10 mg daily and then fluphenazine 10 mg daily. Subsequently, after an incomplete improvement in her psychiatric symptoms and hyperprolactinemia on thioridazine 150 mg and bromocriptine 15 mg daily, the patient was changed to clozapine at age 16. Clozapine 150 mg twice daily improved her psychiatric status and corrected her serum prolactin concentrations after 2 weeks; bromocriptine was able to be discontinued. We recommend systematic evaluation of atypical neuroleptics as alternative treatments for refractory hyperprolactinemia induced by conventional antipsychotics.

Topics: Adolescent; Amenorrhea; Antipsychotic Agents; Bromocriptine; Clozapine; Female; Fluphenazine; Galactorrhea; Haloperidol; Humans; Hyperprolactinemia; Prolactin; Psychotic Disorders; Thioridazine