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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperprolactinaemia has been associated with a variety of side effects including amenorrhoea, galactorrhoea, sexual dysfunction, breast engorgement and osteoporosis. Since the mid-1970s, the impact of antipsychotics on human prolactin (hPrl) levels has been investigated. Baseline levels of hPrl were found to be similar in healthy controls and patients who were diagnosed as having schizophrenia. Short-term acute studies done after single parenteral or oral doses of phenothiazines found rapid two- to tenfold increases in hPrl. Similar increases were found in longer term studies that reported increases of three times in both men and women after 3 days that doubled again after several weeks of treatment. A study of longer term injectable fluphenazine enanthate found that elevation induced by a single injection lasted up to 28 days. The same results with significant increases have been reported with the butyrophenone, haloperidol. Substantial increases are found after single injections (up to nine times) and after weeks of treatment (up to three times sustained). Thus, early literature believed that there might be an association between these induced changes and response to therapy. However, prolactin is secreted by the anterior pituitary and is under inhibitory control of dopamine released from the tuberoinfundibular neurones. Thus, increases in prolactin are due to antipsychotic impact on tuberoinfundibular tract, one of four dopamine-related tracts. With the application of clozapine and other atypical antipsychotics, it was found that medications can successfully treat psychosis without increasing hPrl. In fact, early single-dose trails found clozapine to reduce hPrl by 16%. Later studies replicated this result and also found that up to 6 weeks of administration led to reductions in hPrl of up to 80%. Risperidone, however, has been found to persistently elevate hPrl in studies, despite its impact on other receptor sites. Olanzapine, quetiapine and ziprasidone have all been found to have little effect or produce decreases in hPrl. Most recently, aripiprazole, in early studies, appears to produce significant reductions in hPrl while maintaining therapeutic efficacy for psychosis.
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PMID:Antipsychotics: impact on prolactin levels. 1238 84

Human sexual function is complex and affected in many different ways by schizophrenia and the antipsychotic drugs used in its treatment. The evaluation of the effects of antipsychotics on sexual function in patients with schizophrenia is also complex because the deleterious effects of conventional antipsychotics are superimposed on the effects of the disease itself. Although not extensively researched, sexual dysfunction seems to be frequent in patients with schizophrenia, especially in men. Sexual dysfunction appears, in significant part, to be a direct consequence of dopamine antagonism, combined with indirect effects due to increased serum prolactin concentration. Atypical antipsychotics have a number of potential advantages over standard agents with regard to their impact on sexual function. Clinical reports indicate that atypical antipsychotics are associated with a lower incidence of sexual adverse events than conventional antipsychotics and that there may also be important differences between them in this regard. For example, dose-related increases in prolactin concentrations occur with risperidone whereas olanzapine is associated with mild and transient increases in long-term treatment. Treatment with clozapine does not result in prolactin elevation and, like olanzapine, only transient increases occur with ziprasidone therapy, but the risk of agranulocytosis with clozapine restricts its use. Quetiapine has no more effect on serum prolactin than placebo across its full dose range. Together with its low frequency of reproductive or hormonal side effects and a low incidence of extrapyramidal symptoms, the tolerability profile of quetiapine may be particularly beneficial for many patients. Sexual dysfunction can be an important source of distress to patients and adversely affects compliance, and is one of the factors that must be taken into account when selecting treatment.
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PMID:Sexual dysfunction and antipsychotic treatment. 1250 73

Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment (< 12 weeks). However, data on longer-term treatment (> 12 weeks) are lacking. Our results suggest that none of the atypical antipsychotics that we studied significantly improved sexual dysfunction and other reproductive side-effects of the conventional antipsychotic, haloperidol, in stabilized patients during long-term treatment. Quetiapine appears to improve this profile during short-term treatment; however, longterm data, with larger samples, are required with this latter drug.
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PMID:Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study. 1262 65

The aim of the present study was to investigate sexual behavior in population of psychiatric patients affected by schizophrenia, schizoaffective disorder or bipolar disorder by means of an ad hoc questionnaire designed to explore the three phases of the sexual response: desire (or interest), arousal, and performance. The study assessed patients' attitude toward sexuality, several aspects of their sexual behavior, including patients' awareness of the risk of sexually transmitted diseases (STD), contraceptive strategy preferred by patients, and sexual effects of psychotropic medication. Patients reported a high frequency of sexual dysfunction, in particular, hyposexuality. Schizophrenia diagnosis and female gender were associated with lower levels of sexual performance. The impact of psychotropic drugs on patients' sexuality was significant, with both positive and negative effects. Although 65.8% of patients reported to be concerned about the risk of contracting infections during sexual intercourse, most of them engaged in sexual behavior at high risk for acquisition and transmission of STD. Patients' compliance with contraceptive measures was poor.
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PMID:Sexual behavior and sexual problems among patients with severe chronic psychoses. 1271 2

This study compared characteristics related to sexual history, sexual activities, sexual functioning, and psychological tendencies associated with sexuality in 45 young adults with schizophrenia treated with novel neuroleptics and in 61 young adults from a comparison group. A smaller proportion of young adults with schizophrenia currently had a sexual partner or had ever engaged in sexual relations. They also had sexual relations and sexual desires less often. Whether affected by schizophrenia or not, a smaller proportion of women had ever masturbated, and a smaller proportion of men currently had a sexual partner. Women masturbated less often, felt less sexual desire, and desired sexual relations less often, compared with men. Proportionally more men with schizophrenia treated with risperidone or olanzapine than men in the comparison group had at least one sexual dysfunction, lacked sexual desire, and reported problems with sexual arousal and ejaculation. Women with schizophrenia were more likely to report problems with sexual arousal and galactorrhea, compared with women in the comparison group. Finally, young adults with schizophrenia were more likely to develop negative psychological tendencies associated with sexuality than were young adults in the comparison group. Sexual problems are highly prevalent among young adults with schizophrenia. Sexuality should occupy the space it deserves within psychosocial rehabilitation programs and the treatment of schizophrenia.
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PMID:Study of sexuality-related characteristics in young adults with schizophrenia treated with novel neuroleptics and in a comparison group of young adults. 1460 49

Prolactin is a polypeptide hormone that exists as a number of isoforms and is involved in a multitude of physiological processes. Prolactin secretion is promoted by various physiological stimuli and pathological processes and is inhibited by the action of dopamine on the lactotroph cells of the hypothalamus. Hyperprolactinaemia, an elevation of prolactin levels above the norm, is a physiological occurrence and is not of concern (including sexual dysfunction and decreased bone mineral density). Treatment of hyperprolactinaemia is usually confined to the removal of the primary cause of the disease, but several dopamine agonists have been investigated. Hyperprolactinaemia is also a side-effect of the conventional, and some of the second-generation, antipsychotics used in the treatment of schizophrenia. These agents rely on their dopamine antagonistic properties to provide their antipsychotic effects. However, this also removes the brake on prolactin secretion, leading to hyperprolactinaemia. While antipsychotic use has been linked to certain hyperprolactinaemia-related side-effects (sexual dysfunction), its link to others (decreased bone mineral density) has proved more controversial. The association of symptoms with antipsychotic use is further complicated by the fact that patients with schizophrenia can suffer from some of these symptoms because of the disease itself. In managing antipsychotic-induced hyperprolactinaemia, the initial step is to exclude other causes of hyperprolactinaemia while monitoring the occurrence of adverse effects. The physician should also engage in close consultation with the patient with regard to the benefits of the antipsychotic medication and the impact of any adverse effects. A regular risk-benefit discussion will allow the clinician to achieve optimal outcomes in each case.
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PMID:Hyperprolactinaemia and antipsychotic therapy in schizophrenia. 1546 98

Medication adherence with antipsychotics is adversely impacted by the burden of untoward adverse effects. In particular, sexual side-effects may interfere with compliance, but are often underreported by patients. Sexual dysfunction related to hyperprolactinemia is commonly described, but ejaculatory disturbance due to potent alpha1 adrenergic antagonism may also occur, and has been reported frequently with certain typical antipsychotics such as thioridazine, but rarely with atypical antipsychotics. Presented here is the case of a 51 year old male with schizophrenia who developed retrograde ejaculation on high dose risperidone therapy (8 mg/day) with prompt resolution of symptoms upon dose reduction. The absence of decreased libido or erectile dysfunction indicates that alpha1 adrenergic antagonism and not low serum testosterone due to hyperprolactinemia is the etiology for this side-effect. This case illustrates another mechanism for sexual adverse effects, and the need for routine inquiry into sexual dysfunction during atypical antipsychotic therapy.
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PMID:Risperidone-induced retrograde ejaculation: case report and review of the literature. 1507 20

Medication adherence with antipsychotics is adversely impacted by the burden of untoward adverse effects. In particular, sexual side-effects may interfere with compliance, but are often underreported by patients. Sexual dysfunction related to hyperprolactinemia is commonly described, but ejaculatory disturbance due to potent alpha1 adrenergic antagonism may also occur, and has been reported frequently with certain typical antipsychotics such as thioridazine, but rarely with atypical antipsychotics. Presented here is the case of a 51 year old male with schizophrenia who developed retrograde ejaculation on high dose risperidone therapy (8 mg/day) with prompt resolution of symptoms upon dose reduction. The absence of decreased libido or erectile dysfunction indicates that alpha1 adrenergic antagonism and not low serum testosterone due to hyperprolactinemia is the etiology for this side-effect. This case illustrates another mechanism for sexual adverse effects, and the need for routine inquiry into sexual dysfunction during atypical antipsychotic therapy.
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PMID:Quetiapine-induced diabetes with metabolic acidosis. 1510 61

Risperidone is one of the second-generation antipsychotics (SGAs). Use of SGAs or so-called atypical antipsychotics is becoming more frequent because they are more efficacious and safer than typical antipsychotics. This is due to their ability to occupy some other receptors as well as dopamine type 2 (D(2)) receptors in the brain. Risperidone has more affinity for serotonin type 2 (5-HT(2)) than for D(2) receptors. This accounts for its better treatment of negative symptoms of schizophrenia and fewer extrapyramidal side effects when compared with typical antipsychotics. Common side effects associated with risperidone include extrapyramidal symptoms, dizziness, nausea, weight gain, sleep disturbance, and sexual dysfunction. We describe here a case of risperidone-induced hypothermia. Body temperature is regulated by the preoptic anterior hypothalamus with involvement of dopamine, serotonin, norepinephrine, and alpha-adrenergic receptors. Experimental data suggest that stimulation of 5-HT(2) and dopamine receptors can increase the body temperature. Additional clinical evidence indicates potent antagonists of 5-HT(2) are more likely to cause hypothermia. Risperidone has higher potency for occupying 5-HT(2) than D(2) receptors.
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PMID:A case of risperidone-induced hypothermia. 1513 39

Hyperprolactinaemia is an important but neglected adverse effect of antipsychotic medication. It occurs frequently with conventional antipsychotics and some atypical antipsychotics (risperidone and amisulpride) but is rare with other atypical antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, ziprasidone). For this reason the terms 'prolactin-sparing' and 'prolactin-raising' are more useful than 'atypical' and 'conventional' when considering the effect of antipsychotic drugs on serum prolactin. During antipsychotic treatment prolactin levels can rise 10-fold or more above pretreatment values. In a recent study approximately 60% of women and 40% of men treated with a prolactin-raising antipsychotic had a prolactin level above the upper limit of the normal range. The distinction between asymptomatic and symptomatic hyperprolactinaemia is important but is often not made in the literature. Some symptoms of hyperprolactinaemia result from a direct effect of prolactin on target tissues but others result from hypogonadism caused by prolactin disrupting the normal functioning of the hypothalamic-pituitary-gonadal axis. Symptoms of hyperprolactinaemia include gynaecomastia, galactorrhoea, sexual dysfunction, infertility, oligomenorrhoea and amenorrhoea. These symptoms are little researched in psychiatric patients. Existing data suggest that they are common but that clinicians underestimate their prevalence. For example, well conducted studies of women treated with conventional antipsychotics have reported prevalence rates of approximately 45% for oligomenorrhoea/amenorrhoea and 19% for galactorrhoea. An illness-related under-function of the hypothalamic-pituitary-gonadal axis in female patients with schizophrenia may also contribute to menstrual irregularities. Long-term consequences of antipsychotic-related hypogonadism require further research but are likely and include premature bone loss in men and women. There are conflicting data on whether hyperprolactinaemia is associated with an increased risk of breast cancer in women. In patients prescribed antipsychotics who have biochemically confirmed hyperprolactinaemia it is important to exclude other causes of prolactin elevation, in particular tumours in the hypothalamic-pituitary area. If a patient has been amenorrhoeic for 1 year or more, investigations should include bone mineral density measurements. Management should be tailored to the individual patient. Options include reducing the dose of the antipsychotic, switching to a prolactin-sparing agent, prescribing a dopamine receptor agonist and prescribing estrogen replacement in hypoestrogenic female patients. The efficacy and risks of the last two treatment options have not been systematically examined. Antipsychotic-induced hyperprolactinaemia should become a focus of interest in the drug treatment of psychiatric patients, particularly given the recent introduction of prolactin-sparing antipsychotics. Appropriate investigations and effective management should reduce the burden of adverse effects and prevent long-term consequences.
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PMID:Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. 1545 28


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