Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amoxapine is marketed as an antidepressant. However, its in-vitro profile, receptor occupancy and preclinical effects are very similar to atypical antipsychotics. Amoxapine has also shown efficacy as an atypical antipsychotic in open trials. The objective of this study was to compare the antipsychotic and side effect profile of amoxapine and risperidone in a randomised assignment, standardized dosing, double-blind trial of acutely psychotic patients with schizophrenia. A total of 48 schizophrenic patients were enrolled and randomized in a double-blind 6-week trial to receive either risperidone (up to 5 mg/day) or amoxapine (up to 250 mg/day). Positive, negative, affective symptoms and motor side effects were measured using standardized weekly assessments. Prolactin levels were also determined at baseline and at the end of the study. A total of 39 patients (amoxapine, n=22; risperidone, n=21) completed the trial. Both pharmacological treatments, amoxapine 228.0 mg/day (SD=34.6) and risperidone 4.5 mg/day (SD=0.7), showed equivalent improvement in positive, negative, and depressive symptoms. Amoxapine was associated with less EPS and less prolactin elevation than risperidone. These data support previous reports about the efficacy of amoxapine as an atypical antipsychotic. Since amoxapine is off-patent, it may be a valuable low-cost alternative to new atypical antipsychotics, particularly in low-income countries where the majority of the patients are still treated with typical antipsychotics.
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PMID:Amoxapine as an atypical antipsychotic: a comparative study vs risperidone. 1595 84

Sexual dysfunction is common in people suffering from schizophrenia and is reported by patients to be a significant reason for medication nonadherence. This report contains data for 27 people with schizophrenia who participated in a randomized double-blind 12-week trial of risperidone (4 mg/day), quetiapine (400 mg/day) or fluphenazine (12.5 mg/day). At baseline and endpoint, subjects were rated on the Changes in Sexual Function Questionnaire (CSFQ), the Prolactin-Related Adverse Event Questionnaire (PRAEQ) and had prolactin levels drawn. Endpoint prolactin levels were 50.6 +/- 40.4, 24.4 +/- 18.5, and 8.2 +/- 4.4 mg/dl for risperidone (N = 12), fluphenazine (N = 9) and quetiapine (N=6), respectively (F = 7.5,df = 2, p = 0.005, controlling for sex). Orgasm quality/ability improved significantly for quetiapine as compared to fluphenazine and risperidone (F = 4.41, df = 2, p = 0.033). Seventy-eight percent of patients on fluphenazine reported sexual dysfunction whereas did only 42 and 50% of those on risperidone and quetiapine. Forty percent of quetiapine patients reported they felt better about their sexuality as compared to previous treatment, as did 55% on risperidone. Conversely, only 13% of fluphenazine subjects reported any improvement. Hormonal problems (menstrual problems, gynecomastia, galactorrhea) were predominately observed in risperidone-treated subjects. Overall, quetiapine was associated with a normalization of prolactin levels and had the greatest benefits among these drugs regarding sexual functioning.
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PMID:A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia. 1619 59

The European SOHO (Schizophrenia Outpatient Health Outcome) study is an observational, naturalistic study of the outpatient treatment of schizophrenia. The patient recruitment and assessment began in September 2000 and finished in early 2005. A total of 10 972 adult patients from ten European countries who were initiating or changing antipsychotic medication for the treatment of schizophrenia within the normal course of care have been enrolled. The patients have been followed at regular intervals over the 3-year timeframe of the study. Evaluation includes clinical severity, measured with the Clinical Global Impression (CGI) scale; health-related quality of life; social functioning; and medication tolerability. The 6- and 12-month results have been published so far and have demonstrated that the patients in whom treatment was initiated with olanzapine or clozapine or who were started on more than one antipsychotic of any class at baseline tended to have somewhat greater improvement than patients treated with other atypical or typical antipsychotics, both in terms of symptoms measured with the CGI and quality of life. Numbers of social contacts increased with the treatment, but other aspects of social functioning did not show any significant change. Atypical antipsychotics as a class were associated with a lower frequency of extrapyramidal symptoms (EPS) and anticholinergic use than typical antipsychotics. The frequency of EPS was lowest in the clozapine-, quetiapine- and olanzapine-treated patients, at around 10%. The atypical antipsychotics also conferred a lower risk for tardive dyskinesia than the typical antipsychotics. Weight gain occurred in all treatment cohorts over the first 12 months of treatment and was statistically significantly greater in the patients who started treatment with olanzapine and clozapine. Prolactin- and sexually-related adverse events were frequent at baseline assessment: amenorrhoea was present in around one- third of women, impotence in around 40% of men, and loss of libido in 50% of both male and female patients. Patients treated with olanzapine, clozapine and quetiapine were significantly less likely to have sexual/endocrine-related dysfunctions after 6 months of treatment (the 12-month results of this parameter are yet to be published) than those in the other treatment cohorts (typical antipsychotics, risperidone and amisulpride). Concomitant medication use during the study has been high, ranging from 5% to 29% for anticholinergics, 8% to 23% for antidepressants, 22% to 37% for anxiolytics and 7% to 19% for mood stabilisers, depending on the type of antipsychotic prescribed. Fewer olanzapine-, quetiapine- and clozapine-treated patients used concomitant anticholinergics or anxiolytics/hypnotics. The current results from the SOHO study indicate that differences in effectiveness and tolerability do exist between the antipsychotics. Future results from the study will be published during the coming months and years, and will allow patterns of antipsychotic use in routine clinical practice (including how often and why changes are made) to be determined. This important information is likely to impact on the future use of antipsychotics and will assist clinicians in refining the use of these drugs and improving the outcome of patients to whom they are prescribed.
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PMID:The SOHO (Schizophrenia Outpatient Health Outcome) study: implications for the treatment of schizophrenia. 1659 47

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.
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PMID:A naturalistic, 9-month follow-up, comparing olanzapine and conventional antipsychotics on sexual function and hormonal profile for males with schizophrenia. 1732 96

Hyperprolactinaemia is a common finding in patients treated with antipsychotics. A complete cohort of 194 schizophrenia and bipolar disorder patients receiving antipsychotics in a single community mental health trust in Halifax UK underwent routine prolactin screening in the absence of any reLevant symptomatoLogy. Values above the upper limit of normal were measured in 38% of the cohort and were more common in females (52%) than males (26%). Significantly elevated levels (>1000 mIU/l) were measured in 21% of the cohort. Risperidone monotherapy treatment was associated with hyperprolactinaemia in 69% of patients ( n = 35) and in 100% of female patients (n = 16) and amisulpride monotherapy in 100% (n = 7). Prolactin screening is not currently undertaken routinely in the UK. These data give some indication of prevalence of varying degrees of hyperproLactinaemia that might be found when screening an asymptomatic cohort of schizophrenia and bipolar outpatients. Clinicians may be helped by the reporting of such categorical data from clinical trials in addition to mean cohort values of prolactin. Long-term hyperprolactinaemia may be associated with clinical sequeLae in some patients.
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PMID:Prevalence of hyperprolactinaemia in a naturalistic cohort of schizophrenia and bipolar outpatients during treatment with typical and atypical antipsychotics. 1760 73

Iloperidone, a mixed D2/5-HT2 antagonist, is currently in clinical development for the treatment of schizophrenia. This article assesses the short-term safety of iloperidone using a pooled analysis of 3 phase 2, short-term acute schizophrenia studies conducted between 1998 and 2002 (N = 1943). Patients exposed to 3 dose ranges of iloperidone, another antipsychotic, or placebo were compared on rates of serious adverse events (SAEs), adverse events (AEs), extrapyramidal symptoms, akathisia, prolactin, weight and metabolic parameters, QTc, and other standard safety parameters. The most common treatment-related AEs observed with iloperidone were dizziness, headache, dry mouth, nausea, and insomnia. Discontinuation due to AEs was 4.8% for iloperidone, 7.6% for haloperidol, 6.2% for risperidone, and 4.8% for placebo. Iloperidone groups showed better overall performance on the Extrapyramidal Symptom Rating Scale and Barnes Akathisia Scale than risperidone or haloperidol groups. Patients taking iloperidone experienced a mild weight increase (range, 1.5-2.1 kg) similar to that of risperidone (1.5 kg), whereas those on haloperidol and placebo showed mean weight loss (-0.1 kg and -0.3 kg, respectively). QTc interval significantly increased across all iloperidone groups (least squares mean change from baseline to end point, 2.9-9.1 msec) and for haloperidol (5.0 msec). No significant QTc changes occurred in the risperidone or placebo groups. Iloperidone was associated with no change from baseline in total cholesterol, mild elevation in serum glucose, and slight decrease in triglycerides. Prolactin levels decreased with iloperidone and increased significantly with risperidone and haloperidol. These short-term trials suggest that iloperidone has a reassuring safety profile in many of the areas that are of potential concern, including relatively low dropout rates because of AEs, low extrapyramidal symptoms, akathisia, and prolactin elevation, and a modest short-term effect on weight gain.
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PMID:Safety profile of iloperidone: a pooled analysis of 6-week acute-phase pivotal trials. 1833 8

Using a long-acting antipsychotic to improve adherence early in the illness may reduce relapse rates and promote sustained remission, thereby improving the long-term outcome of schizophrenia. We assessed whether risperidone long-acting injection (RLAI) could be used safely and effectively in the treatment of recent-onset psychosis. Fifty patients aged 15 to 43 years with newly diagnosed schizophreniform disorder or schizophrenia were treated with RLAI 25 to 50 mg every 2 weeks for 2 years. Thirty-six patients (72%) completed the trial. Of 39 (78%) who showed a clinical response of 50%, 4 relapsed. Thirty-two patients (64%) achieved remission. Mean maximum increase in Extrapyramidal Symptoms Rating Scale total score was 1.4 (95% confidence interval, 0.61-2.10; n = 50); 10 patients required anticholinergic medication, and 1 subject developed persistent dyskinesia. Prolactin levels were elevated in 18 patients, 4 of whom reported possible prolactin-related adverse events. Mean increase in body mass index to last visit for all patients was 4.8 kg/m (SD, 3.8 kg/m). The final RLAI dose was 25 mg for 54% of patients, 37.5 mg for 30%, and 50 mg for 16%. This preliminary study suggests that RLAI was overall well tolerated and appears to be effective in recent-onset psychosis. Further investigation is warranted.
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PMID:Long-acting injectable risperidone in the treatment of subjects with recent-onset psychosis: a preliminary study. 1834 32

Elevations in serum prolactin levels (hyperprolactinaemia) are a common side effect of conventional and some atypical antipsychotic treatments. In patients with schizophrenia, the adverse effects of antipsychotic-induced hyperprolactinaemia on physical health (e.g. fertility problems, sexual dysfunction and reduced bone mineral density) are gaining attention. Accumulating evidence shows consistent 'prolactin-raising' effects of conventional antipsychotics and risperidone compared with other current atypical antipsychotics, which are more likely to have 'prolactin-sparing' properties. Prolactin-sparing antipsychotics (for example, aripiprazole and quetiapine) tend to show lower frequencies of hyperprolactinaemia-associated side effects. In recent studies, aripiprazole-treated patients have demonstrated lower prolactin levels compared with patients receiving other prolactin-sparing antipsychotics. There is a lack of robust recommendations for monitoring prolactin elevation among patients receiving antipsychotics. Decreasing the antipsychotic dose or switching to a prolactin-sparing medication are possible management options for antipsychotic-induced hyperprolactinaemia. There is a need to increase awareness and understanding of the impact of antipsychotic-induced hyperprolactinaemia on physical health in schizophrenia.
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PMID:Prolactin awareness: an essential consideration for physical health in schizophrenia. 1834 98

Prolactin (PRL) elevation in patients with prolactin-secreting pituitary tumors has been linked to increased prevalence of thyroid autoantibodies. However, the effects of antipsychotic drug-induced hyperprolactinemia (HPRL) on development of thyroid autoimmunity and also of other autoimmune phenomena have not been previously studied. To examine whether serum PRL levels were associated with the prevalence of thyroid autoantibodies in patients with schizophrenia receiving long-term antipsychotic treatment, we determined serum PRL, thyrotropin, free thyroxine levels, and the presence of antithyroid peroxidase and antithyroglobulin antibodies in 75 consecutive, clinically stable schizophrenic outpatients who had been on stable doses of antipsychotics for at least 3 months, and had no history of overt thyroid disease. We found that the prevalence of hyperprolactinemia was significantly higher in patients positive for thyroid autoantibodies, when compared with patients negative for them (p=0.045). Serum levels of prolactin were also significantly higher in patients with positivity for thyroid autoantibodies (p=0.039). In separate analyses for genders, a trend-level relationship was observed in females between increased levels of prolactin and the presence of thyroid autoantibodies (p=0.060). Our findings suggest that through the associated HPRL, long-term antipsychotic treatment can induce thyroid autoimmunity. Future research is required to investigate, whether other autoimmune processes might be triggered by antipsychotic drug-induced HPRL, and to what extent the immune alterations reported in patients with schizophrenia are related with this phenomenon.
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PMID:Increased incidence of autoimmune thyroiditis in patients with antipsychotic-induced hyperprolactinemia. 1853 8

Schizophrenia is a chronic and debilitating psychotic mental disorder that affects about 1% of the world's population. Antipsychotic drugs are the mainstay of treatment in schizophrenia. Hyperprolactinemia, which is a common side effect of typical antipsychotics, is also associated with the use of some of the newer atypical agents. Antipsychotics may enhance prolactinoma growth as manifested by an increase in serum prolactin concentration. Prolactin-secreting pituitary adenomas possibly related with antipsychotics have been described in the literature. To our knowledge, this is the first series of cases showing a possible relation between pituitary adenomas and amisulpride treatment in patients with schizophrenia.
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PMID:Hyperprolactinemia and possibly related development of prolactinoma during amisulpride treatment; three cases. 1856 8


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