quetiapine-fumarate and Hyperprolactinemia

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

Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications.. Selective review of endocrine and metabolic effects of psychotropic medications in pediatric populations, with a focus on monitoring and management strategies.. Because youth are still developing at the time of psychotropic drug exposure, most reference values need to be adjusted for gender and age. As in adults, youngsters receiving lithium require monitoring for thyroid dysfunction. Psychostimulants appear to cause mild reversible growth retardation in some patients, most likely because of decreased weight or slowing of expected weight gain; some patients may experience clinically significant reductions in adult height. Although still controversial, valproate use has been associated with an increased risk for polycystic ovary syndrome, in addition to causing weight gain. Although more data are required, children and adolescents appear to be at higher risk than adults for antipsychotic-induced hyperprolactinemia, weight gain, and possibly, associated metabolic abnormalities, which is of particular concern.. Clinicians and caregivers need to be aware of potential endocrine and metabolic adverse effects of psychiatric medications. A careful selection of patients, choice of agents with potentially lesser risk for these adverse events, healthy lifestyle counseling, as well as close health monitoring are warranted to maximize effectiveness and safety.

Topics: Adolescent; Antipsychotic Agents; Child; Dibenzothiazepines; Drug Administration Schedule; Endocrine System Diseases; Female; Humans; Hyperprolactinemia; Life Style; Lithium Compounds; Male; Metabolic Diseases; Polycystic Ovary Syndrome; Psychotic Disorders; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Valproic Acid; 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

Quetiapine is an atypical antipsychotic, licensed in the UK for the treatment of schizophrenia. This review of published literature identifies the evidence that quetiapine is both effective and well-tolerated and highlights the particular indications in which quetiapine will be of most value to clinicians and patients.

Topics: Antipsychotic Agents; Dibenzothiazepines; Forecasting; Humans; Hyperprolactinemia; Patient Satisfaction; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Schizophrenia is a serious and disabling psychiatric disorder affecting approximately 1% of the world's population, with its economic cost in the United States alone estimated to exceed that of all cancers combined. The new generation of atypical antipsychotics introduced over the past decade have comparable or greater efficacy than traditional antipsychotics in treating the psychotic symptoms of schizophrenia and a much improved neurologic side effect profile. Quetiapine, the fourth atypical antipsychotic marketed in the United States, was approved by the U.S. Food and Drug Administration in September 1997 and is also currently approved in over 70 countries worldwide for the treatment of psychosis associated with schizophrenia. This article will review the clinical trials examining the efficacy, safety, and tolerability of quetiapine in the treatment of patients with schizophrenia.

Topics: Affect; Aggression; Antipsychotic Agents; Basal Ganglia Diseases; Cognition; Dibenzothiazepines; Double-Blind Method; Humans; Hyperprolactinemia; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; 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

To evaluate the efficacy and safety of 750 mg/day quetiapine fumarate (Seroquel) in the treatment of Chinese Han patients with schizophrenia.. In this 6-week, multicenter, randomized, rater single-blind study, a total of 119 patients with schizophrenia were randomly assigned to quetiapine (n = 60, 750 mg/day) or risperidone (n = 59, 4 mg/day). The efficacy was assessed by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Change (CGI-C) and the Calgary Depression Scale for Schizophrenia (CDSS). Safety and tolerability assessments included treatment-emergent adverse events, laboratory tests and electrocardiograms.. The primary analysis demonstrated no significant difference between treatment in the two groups (quetiapine vs. risperidone: 31.9 ± 17.5 vs. 33.3 ± 17.3; P = 0.668). Improvements with both treatments were comparable for total PANSS, positive and negative subscores, general psychopathology subscales, and excitement and attack symptoms. Improvements in CGI-S were similar between treatment groups (P = 0.046). A more favorable trend was detected for quetiapine than risperidone in the reduction of CDSS scores from baseline, especially at week 1 (1.1 ± 2.2 vs. 0.3 ± 2.1, P < 0.050). The rate of extrapyramidal symptom (EPS) and hyperprolactinemia-related adverse events was significantly lower in the quetiapine group than the risperidone group (13.3% vs. 43.3%, P < 0.001). Dizziness and somnolence were more common in the quetiapine group than the risperidone group.. Quetiapine fumarate (750 mg/day) has broad clinical efficacy comparable to 4 mg/day risperidone. Dizziness was common in the quetiapine group (P = 0.029), but the rate of somnolence was similar between the two groups (P = 0.114). EPS and hyperprolactinemia rates were significantly higher with risperidone (P < 0.001). Key limitations of this study include small sample size, short treatment periods, and no increase to 6 mg/day for risperidone because of its safety profile.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Asian People; China; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Quetiapine Fumarate; Risperidone; Schizophrenia; Time Factors

The objective of this study was to evaluate the efficacy and tolerability of quetiapine in the treatment of first onset psychosis in older adolescents using risperidone as a comparator. Twenty-two patients with first onset psychosis were randomized to receive quetiapine (up to 800 mg/day) or risperidone (up to 6 mg/day) for 6 weeks. Raters blind to treatment assignment performed outcome symptom ratings. No statistical differences emerged in terms of efficacy or tolerability between the two drugs. However, there were some clinically notable differences that seem to favour the efficacy of risperidone over quetiapine. Patients taking quetiapine, although improved, showed less clinical improvement on scores for total positive and negative symptoms, clinical global severity and depression at 6 weeks than patients taking risperidone. Although both treatments were associated with weight gain and sedation, more patients on quetiapine experienced over 10% weight gain. However, fewer patients who were taking quetiapine required anticholinergic medication or experienced extrapyramidal side effects than patients taking risperidone. Risperidone was significantly more likely to be associated with elevation in serum prolactin levels in this population. In conclusion, the results in this small trial show that adolescent patients may benefit more from treatment with risperidone than quetiapine. However, those susceptible to side effects, particularly hyperprolactinaemia, may be more suitable for treatment with quetiapine.

Topics: Adolescent; Adolescent Behavior; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Male; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome; Weight Gain

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

To compare the efficacy and tolerability of quetiapine and risperidone in the treatment of schizophrenia.. In this 8-week, double-blind, multicenter, flexible-dose study, patients with schizophrenia (DSM-IV diagnosis) were randomly assigned to quetiapine (200-800 mg/day) or risperidone (2-8 mg/day). The primary hypothesis was that quetiapine was not inferior to risperidone. The primary efficacy measure was change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores; secondary outcomes included response rate (> or = 40% reduction in PANSS scores), Clinical Global Impression-Change (CGI-C), and cognitive and social functioning. Tolerability assessments included treatment-emergent adverse events and changes in weight, glucose, and prolactin. Patients were recruited from June 2001 to September 2002.. Patients (N = 673) were randomly assigned to quetiapine (N = 338, mean dose = 525 mg/day) or risperidone (N = 335, mean dose = 5.2 mg/day). The primary analysis demonstrated noninferiority between treatments (p < .05). Improvements with both treatments were comparable on PANSS total, negative, and general psychopathology subscales. Risperidone-treated patients had a significantly (p = .03) greater improvement in PANSS positive subscale score among all patients, but not among completers. Improvements in PANSS response rates, CGI-C, and cognitive function were similar between treatment groups. Changes in serum glucose and weight were minimal and comparable. The rate of extrapyramidal symptom (EPS)-related adverse events was significantly higher with risperidone (22%) than quetiapine (13%; p < .01). Somnolence was more common with quetiapine (26%) than risperidone (20%; p = .04). Prolactin levels increased with risperidone (+35.5 ng/mL), but decreased with quetiapine (-11.5 ng/mL; p < .001).. Quetiapine and risperidone had broadly comparable clinical efficacy. Both agents improved cognitive and social functioning, and neither had a clinically significant effect on weight or glucose. Somnolence was more common with quetiapine; EPS and elevated prolactin rates were significantly higher with risperidone.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Cognition Disorders; Dibenzothiazepines; Disorders of Excessive Somnolence; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hyperprolactinemia; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder.. In an international, multicenter, double-blind, parallel-group, 12-week study, patients with a DSM-IV diagnosis of bipolar I disorder (manic episode) were randomly assigned to treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or lithium. The primary efficacy measure was change from baseline in Young Mania Rating Scale (YMRS) score at day 21. Data were gathered from April 2001 to May 2002.. More patients in the quetiapine (72/107) and lithium (67/98) groups completed the study compared with the placebo group (35/97). Improvement (reduction) in YMRS score was significantly greater for quetiapine than placebo at day 7 (-8.03 vs. -4.89; p < .01), and the difference between groups continued to increase over time to day 21 (-14.6 vs. -6.7; p < .001) and to endpoint at day 84 (-20.3 vs. -9.0; p < .001). Significantly more quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 (53.3% vs. 27.4%; p < .001) and at day 84 (72.0% vs. 41.1%; p < .001). Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures. Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure. The most common adverse events for quetiapine were dry mouth, somnolence, and weight gain, while lithium was associated with tremor and insomnia. The quetiapine and placebo groups had similar, low levels of extrapyramidal symptom-related adverse events.. Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Hospitalization; Humans; Hyperprolactinemia; Lithium; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

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

Topics: Adult; Amenorrhea; Antipsychotic Agents; Drug Administration Schedule; Drug Combinations; Female; Humans; Hyperprolactinemia; Pyridoxine; Quetiapine Fumarate; Schizophrenia; Vitamin B Complex

The aim of this paper is to highlight the association between antipsychotic medication, in this instance paliperidone, and hyperprolactinaemia, and discuss the impact of this adverse effect on patient management.. Four patients with paliperidone-induced hyperprolactinaemia are described with a brief review of the literature.. Four female patients aged between 20 and 50 years developed hyperprolactinaemia 3 weeks to 4 months after commencement of treatment with paliperidone. The levels were significantly raised above the normal upper limit of 500 mIU/L, ranging between 1500 and 3996 mIU/L, and returned to within the normal range after cessation of the medication (82-381 mIU/L). Two of the patients were asymptomatic despite significant elevation of prolactin; two experienced galactorrhoea, a distressing adverse effect. Subsequent management was significantly affected.. Routine standardized monitoring of prolactin levels may guide treatment choice, avoiding potential disruption to the therapeutic relationship, enhancing compliance with future medication and preventing negative treatment outcomes. Detailed education should accompany the monitoring process and include discussion of the risks of associated adverse effects of antipsychotic medications versus the benefit of significant symptom relief.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Female; Galactorrhea; Humans; Hyperprolactinemia; Isoxazoles; Middle Aged; Paliperidone Palmitate; Patient Compliance; Piperazines; Prolactin; Psychotic Disorders; Pyrimidines; Quetiapine Fumarate; Quinolones; Recurrence; Schizophrenia, Paranoid; Young Adult

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

Topics: Adult; Amisulpride; Antipsychotic Agents; Appetite; Dibenzothiazepines; Dose-Response Relationship, Drug; Eating; Female; Humans; Hyperprolactinemia; Hypertriglyceridemia; Quetiapine Fumarate; Recurrence; Schizophrenia, Paranoid; Sulpiride

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

Conventional antipsychotic medications are associated with elevated prolactin levels, resulting in hyperprolactinemia and a number of unwanted side effects. Several atypical antipsychotics, on the other hand, are less likely to evoke hyperprolactinemia. The aim of this study was to investigate the prevalence of hyperprolactinemia induced by conventional antipsychotic drugs, examine changes in serum prolactin levels and psychiatric symptoms after switching to quetiapine, and identify the relevant characteristics of patients who may be suitable to switch to quetiapine.. Sixty-nine of 74 consecutive female patients who had received conventional antipsychotic drugs were initially included in the study. Of these, 49 (71 %) patients suffered from hyperprolactinemia, of which a further 25 were subsequently switched to quetiapine. Psychiatric symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS), and serum prolactin levels were measured just before and at 4 and 8 weeks after switching.. Eight of the 25 (32 %) "switch" patients dropped out due to psychotic exacerbation during the 8 weeks. In the remaining 17 (68 %) patients, serum prolactin levels were significantly decreased without any significant change in PANSS scores after switching. The 17 patients who completed the switch had previously demonstrated significantly lower positive symptom scores compared to the 8 dropout patients.. The present findings suggest that 71 % of female patients receiving conventional antipsychotic drugs may suffer from hyperprolactinemia and that approximately two-thirds of patients can be switched to quetiapine, resulting in an improvement in hyperprolactinemia. The main characteristic of the switched patients may be fewer positive symptoms.

Topics: Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Middle Aged; Prolactin; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

The aim of this study was to report on the serum prolactin levels in 70 male youths at a residential treatment center who were treated with either risperidone or quetiapine. This is a cross-sectional retrospective medical chart review of 50 males (mean age, 13.5+/-2.8 years) treated with risperidone (mean dose, 2.4+/-1.6 mg/day) and 20 males (mean age, 13.5+/-2.4 years) treated with quetiapine (mean dose, 317.5+/-238 mg/day). Serum prolactin levels were drawn according to a protocol, after at least 6 weeks of treatment. Prolactin was above the upper limit of normal for 68% of the patients on risperidone and 20% of the patients on quetiapine (chi2 analysis: R>Q; p<0.001). Both risperidone and quetiapine produced dose-related increases in serum prolactin levels (R, r=0.34, p=0.017; Q, r=0.45, p=0.05). No correlation was found between duration of treatment and prolactin levels. Given that hyperprolactinemia secondary to antipsychotic treatment may result in reproductive and growth irregularities, periodic long-term monitoring during treatment with these two atypical antipsychotics (and perhaps others as well) may be warranted.

Topics: Adolescent; Antipsychotic Agents; Child; Cross-Sectional Studies; Dibenzothiazepines; Drug Therapy, Combination; Humans; Hyperprolactinemia; Male; Quetiapine Fumarate; Residential Treatment; Risperidone

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

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Comorbidity; Depression, Postpartum; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome

To report a case of risperidone-induced hyperprolactinemia that was successfully managed with quetiapine.. A 30-year-old white woman with schizoaffective disorder, depressive type, and comorbid alcohol and cocaine abuse was treated successfully for her psychotic symptoms with risperidone until she developed adverse effects consistent with hyperprolactinemia. This was confirmed by laboratory blood tests, as her prolactin level was 186.9 ng/mL (normal for nonpregnant women 2.8-29.2). The woman had experienced similar effects in the past, which had led to noncompliance and subsequent psychotic relapse. Normalization of prolactin levels and associated adverse effects were achieved upon switching to quetiapine. No psychotic symptoms reoccurred.. Dopamine type 2 (D(2)) receptor blockade in the mesolimbic tract is thought to mediate the therapeutic effects of antipsychotics. This action in the tuberoinfundibular system produces prolactin level elevation. Risperidone has a relatively higher affinity for the D(2) receptor in comparison with other atypical antipsychotics, which may explain why it is associated with a higher incidence of hyperprolactinemia. Quetiapine, which has one of the lowest D(2) receptor affinities, is not known to increase prolactin levels to any significant degree. This pharmacologic property allows quetiapine to be a reasonable treatment option for patients who develop risperidone-induced hyperprolactinemia.. Quetiapine may be a suitable substitute when a patient taking risperidone develops hyperprolactinemia.

Topics: Adult; Comorbidity; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Quetiapine Fumarate; Risperidone; Schizophrenia

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

Novel antipsychotics (clozapine, risperidone, olanzapine, quetiapine) are effective in treating psychotic symptoms, also in neurological disease. Hyperprolactinemia is a side effect related to antipsychotics that can cause galactorrhea, gynecomastia, amenorrhea, anovulation, impaired spermatogenesis, decreased libido and sexual arousal, impotence, and anorgasmia, consequent to removal of tonic dopaminergic inhibition of prolactin secretion via hypothalamic dopaminergic receptor blockade in the tuberoinfundibolar tract. Hyperprolactinemia occurs more frequently during treatment with risperidone and olanzapine compared with clozapine and quetiapine. The therapeutic algorithm to antipsychotic-relatedhyperprolactinemia is the following: reduction in antipsychotic dose, addition of cabergoline, bromocriptine, amantadine, and/or switch to another antipsychotic. We propose switching to quetiapine in symptomatic hyperprolactinemia related to antipsychotics and describe five cases.

Topics: Adolescent; Adult; Antipsychotic Agents; Citalopram; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone