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)

Extended-release paliperidone is a new atypical antipsychotic chemically related to the well-known antipsychotic risperidone. It has been formulated in an osmotic controlled-release oral delivery system that minimizes peak-trough fluctuations and, by obviating dose-titration, allows once-daily dosing with a therapeutically active dose from the first day. Its pharmacokinetic profile is characterized by a mean time-to-peak plasma concentration of 24.1 hours and an elimination half-life of approximately 24 hours. A dose of 6 mg of paliperidone extended-release (ER) provides a mean striatal D2 receptor occupancy of 64%, approaching the accepted lower receptor occupancy threshold required for optimal antipsychotic activity without causing extrapyramidal symptoms. It undergoes minimal hepatic biotransformation and is mainly excreted unchanged in the urine with four metabolic products. Three pivotal randomized, double-blind, placebo-controlled, parallel-group six-week trials investigated the efficacy, safety and tolerability of paliperidone ER at doses of 3-15 mg/day. All doses produced a significant reduction in schizophrenia symptomatology, with an onset of effect as of day 4. Personal and social functioning also improved as measured by the Personal and Social Performance scale. A prevention of recurrence study showed that paliperidone ER effectively prolonged the time-to-recurrence versus placebo. Paliperidone ER was efficacious in young, elderly and recently diagnosed schizophrenia patients. Beneficial effects on sleep assessed objectively and subjectively with minimal daytime somnolence were demonstrated. Overall, it was well-tolerated and had placebo-like discontinuation rates for adverse events. There were some dose-related extrapyramidal symptoms, mostly mild to moderate in intensity and associated with minimal changes in the rating scales that assessed extrapyramidal symptom severity. Although prolactin elevation occurred with paliperidone ER, only few prolactin-related adverse events were reported. There were no signals for metabolic dysfunction in terms of glucose, insulin, lipid or triglyceride changes or any indicators of clinically relevant cardiac events. Body weight increased slightly, but the changes were acceptable in the context of the doses likely to be used clinically, and patients with higher initial body mass index gained less weight as has been reported for other antipsychotics.
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PMID:Extended-release paliperidone: efficacy, safety and tolerability profile of a new atypical antipsychotic. 1746 Jul 86

Ziprasidone is a newer "atypical" or "second-generation" antipsychotic. Oral ziprasidone (ziprasidone hydrochloride) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia, and acute manic or mixed episodes associated with bipolar disorder (with or without psychotic features). Ziprasidone intramuscular (ziprasidone mesylate) is FDA-approved for acute agitation in patients with schizophrenia. Oral ziprasidone appears efficacious, and has been shown to have some limited clinical advantages over chlorpromazine and haloperidol in ameliorating negative symptoms of schizophrenia. In Phase 2 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) for schizophrenia, ziprasidone did not match the clinical performance of olanzapine and risperidone, appearing closer in overall effectiveness to quetiapine. The rate of dose titration and the dose achieved may have an important bearing on ziprasidone's efficacy profile. In studies of usage for acute agitation in individuals with schizophrenia, intramuscular ziprasidone has been shown to be efficacious and relatively well tolerated. Regarding tolerability, ziprasidone, has important advantages in that it is not associated with clinically significant weight gain or adverse changes in cholesterol, triglycerides, or glycemic control, and patients may experience moderate improvement in these measures when switching to ziprasidone from a different antipsychotic agent. It also lacks significant persistent effects on prolactin levels, is not anticholinergic, and only infrequently causes extrapyramidal side effects or postural hypotension, although it can be associated with somnolence. This tolerability profile may be quite valuable in the treatment of some patients. Ziprasidone may prolong the electrocardiogram (ECG) QTc interval (QT interval corrected for heart rate by a standard algorithm), but after 5 years' clinical availability ziprasidone (by itself) does not appear to pose a substantial clinical problem in this regard. Therefore, ziprasidone may be considered a first-line drug option in the treatment of schizophrenia or manic episodes, but, in view of the differences among antipsychotic medications, drug selection should be guided by the patient's individual characteristics and situation.
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PMID:Ziprasidone for schizophrenia and bipolar disorder: a review of the clinical trials. 1762 70

The effects of paliperidone extended-release on sleep architecture in patients with schizophrenia-related insomnia were evaluated in this multicenter, double-blind, randomized, placebo-controlled study. Patients received paliperidone extended-release 9 mg/day or matching placebo during the 14-day double-blind phase. Sleep architecture and sleep continuity were evaluated using polysomnograms. Subjective sleep measures were evaluated daily using the Leeds Sleep Evaluation Questionnaire. Efficacy and safety were also assessed. Thirty-six patients (17 on paliperidone extended-release, 19 on placebo; mean age 32.2 years) completed the study. Paliperidone extended-release treatment vs. placebo resulted in clinically and statistically significant differences in sleep measurements from baseline to endpoint including a reduction in: persistent sleep latency (41 min), sleep onset latency (35 min), number of awakenings after sleep onset (7), time awake in bed (50 min), and stage 1 sleep duration (12 min); prolongation in: total sleep time (53 min), sleep period time (42 min), stage 2 sleep duration (51 min), and rapid eye movement sleep duration (18 min); and an increase in sleep efficiency index (11%). Paliperidone extended-release, compared with placebo, did not exacerbate daytime somnolence and improved symptoms of schizophrenia. Paliperidone extended-release was well tolerated and improved sleep architecture and sleep continuity in patients diagnosed with schizophrenia and concomitant insomnia.
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PMID:A double-blind, placebo-controlled, randomized study evaluating the effect of paliperidone extended-release tablets on sleep architecture in patients with schizophrenia. 1769 May 99

Frequent readmissions of people with schizophrenia pose considerable pressure on the psychiatric service provision of Amanuel Psychiatric Hospital. The purpose of the study was to ascertain factors mainly contributing to the rate of readmissions of people with schizophrenia. Descriptive survey methods and qualitative focus group interviews were employed to conduct the study. Random sampling techniques were used to select 43 respondents of people with schizophrenia from 231 people with schizophrenia who were readmitted for two or more times in the last two years and who gained access during the time of the study. Structured interviews were used for respondents of people with schizophrenia. Fourteen (N=14) family members/caregivers were selected using purposive sampling methods for focus group discussions. Quantitative data was analyzed using the SPSS Version 11.00 program and the qualitative data was analyzed by generating themes and categories. The results suggest that alcohol and khat abuse were contributing factors for the rate of readmissions of people with schizophrenia into the Amanuel Psychiatric Hospital. It was found that communities contribute to the problems of substance abuse by providing and/or selling it to those mentally ill people. The study also revealed that patients use alcohol and khat in order to tolerate the severe side effects of the anti-psychotic drugs, to suppress hunger due to shortage of food and to avoid drowsiness. Raising community awareness, psycho-education, strengthening the capacities of caretakers and laws to prevent substance abuse, as well as campaigning to prevent people from abusing mentally ill sufferers, should be established.
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PMID:Substance abuse and the risk of readmission of people with schizophrenia at Amanuel Psychiatric Hospital, Ethiopia. 1770 25

The aim of this study was to investigate, in healthy subjects, the modulation of amplitude and phase precision of the auditory steady-state response (ASSR) to 40 Hz stimulation in two resting conditions varying in the level of arousal. Previously, ASSR measures have shown to be affected by the level of arousal, but the findings are somewhat controversial. Generally, ASSR is diminished in sleep but it may be increased in drowsiness. Besides, ASSR reduction has been observed in schizophrenia. However, schizophrenic patients are known to have a disturbance of arousal level, what makes it pertinent to know the effects of fluctuations in arousal on passive response to gamma-range stimulation. In nine healthy volunteers trains of 40 Hz click stimuli were applied during two conditions: in the "high arousal" condition subjects were sitting upright silently reading a book of interest; in the "low arousal" condition subjects were sitting in a reclined position with eyes closed and the lights turned off. The 64-channel EEG data was wavelet transformed and the amplitude and phase precision of the wavelet transformed evoked potential were decomposed by the recently proposed multi-subject non-negative multi-way factorization (NMWF) (Morup et al. in J Neurosci Methods 161:361-368, 2007). The estimates of these measures were subjected to statistical analysis. The amplitude and phase precision of the ASSR were significantly larger during the low arousal state compared to the high arousal condition. The modulation of ASSR amplitude and phase precision by differences in the arousal level during recording warrants caution when investigating oscillatory brain activity and interpreting the findings of reduced ASSR in schizophrenia. It also emphasizes the necessity of standardized recording procedures and monitoring the level of arousal during ASSR testing.
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PMID:The amplitude and phase precision of 40 Hz auditory steady-state response depend on the level of arousal. 1782 30

The aim of the present paper was to clarify the factors influencing subjective daytime sleepiness in patients with obstructive sleep apnea syndrome (OSAS). Subjects included 230 adult male OSAS patients aged 20-73 years. Single and multiple linear regression analyses were performed to estimate the association between the Epworth Sleepiness Scale (ESS) and the following variables: Minnesota Multiphasic Personality Inventory (MMPI), Self-Rating Depression Scale (SDS), age, body mass index (BMI), sleep duration during the preceding month and apnea-hypopnea index (AHI). Single linear regression analysis showed that age had a negative association with ESS score, while BMI, AHI, SDS, hypochondriasis (Hs), hysteria, psychopathic deviant, psychasthenia, schizophrenia and hypomania on the MMPI had a positive association with ESS score. However, the other remaining parameters such as nocturnal sleep duration during the preceding month, depression, masculinity-femininity, paranoia, social introversion on the MMPI had no statistical association with ESS score. Multiple linear regression analysis with stepwise elimination method was applied to choose the significant factors associated with ESS. It was found that three variables including age, AHI and Hs scores were independent factors influencing ESS score. The R(2) for the model was 0.14, suggesting that these factors account for 14% of possible variance of subjective daytime sleepiness of OSAS patients. These results suggest that subjective daytime sleepiness in patients with OSAS may be influenced not only by the severity of respiratory disorder indices but also by certain personality characteristics affecting Hs score and by age.
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PMID:Factors influencing subjective sleepiness in patients with obstructive sleep apnea syndrome. 1787 36

Risperidone (Risperdal), a psychotropic atypical antipsychotic agent, is thought to act via dopamine D(2) and serotonin (5-HT [5-hydroxytryptamine])(2A) receptor antagonism. The clinical efficacy of oral risperidone in the treatment of bipolar mania and schizophrenia in adult patients is well established. In the US, risperidone is also approved for the treatment of irritability associated with autistic disorder in children and adolescents aged 5-16 years, for the treatment of schizophrenia in adolescents aged 13-17 years and, as monotherapy, for the short-term treatment of acute manic and mixed episodes associated with bipolar I disorder in children and adolescents aged 10-17 years. Oral risperidone treatment was better than placebo treatment in reducing irritability and other behavioral symptoms associated with autistic disorder in children and adolescents in two well designed short-term trials, with these benefits maintained in those receiving risperidone for up to 6 months. The drug had a clinically manageable tolerability profile, with most adverse events being of mild to moderate intensity. There are some aspects of treatment, such as weight gain, somnolence, and hyperglycemia, that require monitoring, and the long-term safety of risperidone in children and adolescents with autistic disorder remains to be fully determined. With these issues in mind, risperidone offers a valuable emerging option for the treatment of irritability associated with autistic disorder in children and adolescents.
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PMID:Risperidone: a review of its use in the treatment of irritability associated with autistic disorder in children and adolescents. 1827 80

Risperidone (Risperdal), a psychotropic atypical antipsychotic agent, is thought to act via dopamine D(2) and serotonin 5-HT(2A) receptor antagonism. The clinical efficacy of oral risperidone in the treatment of bipolar mania and schizophrenia in adult patients is well established. In the US, risperidone is also approved for the treatment of irritability associated with autistic disorder in children and adolescents aged 5-16 years, for the treatment of schizophrenia in adolescents aged 13-17 years and, as monotherapy, for the short-term treatment of acute manic and mixed episodes associated with bipolar I disorder in children and adolescents aged 10-17 years. Oral risperidone treatment was better than placebo treatment in reducing irritability and other behavioural symptoms associated with autistic disorder in children and adolescents in two well designed short-term trials, with these benefits maintained in those receiving risperidone for up to 6 months. The drug had a clinically manageable tolerability profile, with most adverse events being of mild to moderate intensity. There are some aspects of treatment, such as weight gain, somnolence and hyperglycaemia, that require monitoring, and the long-term safety of risperidone in children and adolescents with autistic disorder remains to be fully determined. With these issues in mind, risperidone offers a valuable emerging option for the treatment of irritability associated with autistic disorder in children and adolescents.
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PMID:Spotlight on risperidone in irritability associated with autistic disorder in children and adolescents. 1792 5

Iloperidone is a mixed D2/5-HT2 antagonist in development for treatment of schizophrenia. This trial aimed to evaluate the efficacy and safety of a fixed dose of iloperidone in patients with acute exacerbations of schizophrenia. This randomized, placebo-controlled, multicenter study comprised a 1-week titration period and a 3-week double-blind maintenance period. Eligible patients (n = 593) were randomized to iloperidone 24 mg/d, ziprasidone 160 mg/d as an active control, or placebo. Primary efficacy variable was change from baseline in the Positive and Negative Syndrome Scale Total (PANSS-T) score, using a mixed-effects model repeated measures analysis. Iloperidone demonstrated significant reduction versus placebo on the PANSS-T score (P< 0.01). Significant improvement versus placebo was also demonstrated with ziprasidone (P < 0.05). Compared with ziprasidone, iloperidone was associated with lower rates of many adverse events (AEs) that are particularly troublesome with antipsychotics, including sedation, somnolence, extrapyramidal symptoms, akathisia, agitation, and restlessness; iloperidone was associated with higher rates of weight gain, tachycardia, orthostatic hypotension, dizziness, and nasal congestion as reported as an AE. Most AEs were mild to moderate. A similar amount of QT prolongation was observed with both active treatments, although no patient had a treatment-emergent postbaseline corrected QT interval of 500 msec or greater. The incidence of clinically relevant changes in laboratory parameters was comparable between iloperidone and ziprasidone. Iloperidone was associated with a low incidence of extrapyramidal symptoms. Overall, there was improvement in akathisia with iloperidone treatment. Iloperidone treatment was effective, safe, and well tolerated in patients with acute exacerbation of schizophrenia.
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PMID:Four-week, double-blind, placebo- and ziprasidone-controlled trial of iloperidone in patients with acute exacerbations of schizophrenia. 1833 9

Schizophrenia may reflect a sensitization of dopaminergic (DA) function. Apomorphine (Apo), a DA receptor agonist, induces both sensitization and tolerance of DA function in rodents depending on dose intervals. We investigated sensitization and tolerance to Apo in healthy male volunteers. After a period of acclimatization to the experimental setting (Day 1) subjects were assigned randomly to two groups: Group A subjects received seven injections of placebo (physiological saline) (PLA) and Group B subjects received seven injections of Apo HCl (7 microg/kg sc) under double-blind conditions at 2 h intervals commencing at 0930 hours (Day 2) after an overnight fast. Twelve hours after the seventh injection, i.e. on Day 3, after an overnight fast all subjects received an injection of Apo. Serial samples of blood commencing at 0900 hours were drawn after the first and last injection in both groups for assay of growth hormone (GH), prolactin (PRL) and cortisol by radioimmunoassay; sleepiness was measured using the Analog Sleepiness Rating Scale and yawning recorded by video recorder. The GH response in Group B (N = 8) was (a) decreased after the eighth injection of Apo compared with the first injection of Apo (P = 0.03) and (b) decreased after the eighth injection of Apo compared with the first injection of Apo in Group A (N = 10) (P = 0.001). The number of yawns in Group B was significantly decreased after the eighth injection of Apo compared with the first injection of Apo (P = 0.042). PRL, cortisol and sleepiness were not significantly different between the first and eighth injection of Apo. Sensitization was not observed in any of the measures studied. These results are compatible with induction of acute tolerance of DA-mediated GH and yawning responses. The method used provides a safe pharmacological paradigm to examine plasticity of DA mechanisms in man. Results are discussed in the context of possible therapeutic implications for schizophrenia.
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PMID:Induction of tolerance of dopaminergic responses in man. 1850 87


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