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

Among the second generation antipsychotics, aripiprazole presents a new pharmacological profile, basically differentiated by a partial agonist effect on the D2 and D3 dopaminergic receptors. Five short-term efficacy studies, conducted on 1648 patients presenting with schizophrenia or acute relapse of schizoaffective disorders, demonstrated the greater efficacy of aripiprazole than the placebo and comparable efficacy to that of haloperidol and risperidone. The short-term tolerance profile was characterised by a lesser incidence of the extrapyramidal side effects and drowsiness than with haloperidol. Two thousand six hundred and eighty five patients were followed-up over a period of 26 to 52 weeks in five clinical trials versus a placebo and haloperidol, olanzapine, quetiapine and risperiodone: demonstrated efficacy in maintaining the response to treatment and on the delay before relapse was comparable to the other antipsychotics. The classical side effects of antipsychotics decreased in the long-term. Versus olanzapine, a glucid and lipid profile, clearly in favour of aripiprazole, was completed by a lesser incidence of hyperprolactinaemia. Aripiprazole is effective on all the dimensions of schizophrenia: the positive and negative and depressive and anxious symptomatology. It appears to be of interest, notably on the cognitive dimension, which should motivate more in-depth exploration of its place in the treatment in the early stages of schizophrenia. Its therapeutic schedule and the methods of initiation are an essential criterion to the success of treatment, notably during the substitution of other antipsychotics. The clinical and pharmacological originality of aripiprazole would justify the terminology of a "third generation antipsychotic".
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PMID:[Present data and treatment schedule of aripiprazole in the treatment of schizophrenia]. 1851 55

We review a growing body of medical and physiological evidence indicating that yawning may be a thermoregulatory mechanism, providing compensatory cooling when other provisions fail to operate favorably. Conditions such as multiple sclerosis, migraine headaches, epilepsy, stress and anxiety, and schizophrenia have all be linked to thermoregulatory dysfunction and are often associated with instances of atypical yawning. Excessive yawning appears to be symptomatic of conditions that increase brain and/or core temperature, such as central nervous system damage, sleep deprivation and specific serotonin reuptake inhibitors. Yawning is also associated with drowsiness, and subjective ratings of sleepiness are correlated with increases in body temperature. This view of yawning has widespread application for the basic physiological understanding of thermoregulation as well as for the improved diagnosis and treatment of diseases associated with abnormal thermoregulation.
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PMID:Yawning and thermoregulation. 1855 Jan 30

Modafinil is a wake-promoting agent that is pharmacologically different from other stimulants. It has been investigated in healthy volunteers, and in individuals with clinical disorders associated with excessive sleepiness, fatigue, impaired cognition and other symptoms. This review examines the use of modafinil in clinical practice based on the results of randomized, double-blind, placebo-controlled clinical trials available in the English language in the MEDLINE database. In sleep-deprived individuals, modafinil improves mood, fatigue, sleepiness and cognition to a similar extent as caffeine but has a longer duration of action. Evidence for improved cognition in non-sleep-deprived healthy volunteers is controversial.Modafinil improves excessive sleepiness and illness severity in all three disorders for which it has been approved by the US FDA, i.e. narcolepsy, shift-work sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure (CPAP). However, its effects on safety on the job and on morbidities associated with these disorders have not been ascertained. Continued use of CPAP in obstructive sleep apnoea is essential. Modafinil does not benefit cataplexy.In very small, short-term trials, modafinil improved excessive sleepiness in patients with myotonic dystrophy. It was efficacious in fairly large studies of attention deficit hyperactivity disorder (ADHD) in children and adolescents, and was as efficacious as methylphenidate in a small trial, but has not been approved by the FDA, in part because of its serious dermatological toxicity. In a trial of 21 non-concurrent subjects, with 2-week treatment periods, modafinil was as effective as dexamfetamine in adult ADHD. Modafinil was helpful for depressive symptoms in bipolar disorder in a trial that excluded patients with stimulant-induced mania. A single dose of modafinil may hasten recovery from general anaesthesia after day surgery. A single dose of modafinil improved the ability of emergency room physicians to attend didactic lectures after a night shift, but did not improve their ability to drive home and caused sleep disturbances subsequently.Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo.Trials of modafinil for excessive sleepiness in Parkinson's disease, cocaine addiction and cognition in chronic fatigue syndrome provided inconsistent results; all studies had extremely small sample sizes. Modafinil cannot be recommended for these conditions until definitive data become available.Modafinil induces and inhibits several cytochrome P450 isoenzymes and has the potential for interacting with drugs from all classes. The modafinil dose should be reduced in the elderly and in patients with hepatic disease. Caution is needed in patients with severe renal insufficiency because of substantial increases in levels of modafinil acid. Common adverse events with modafinil include insomnia, headache, nausea, nervousness and hypertension. Decreased appetite, weight loss and serious dermatological have been reported with greater frequency in children and adolescents, probably due to the higher doses (based on bodyweight) used. Modafinil may have some abuse/addictive potential although no cases have been reported to date.
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PMID:Approved and investigational uses of modafinil : an evidence-based review. 1872 34

Paliperidone extended-release tablet (paliperidone ER; INVEGA()) is an oral antipsychotic for the treatment of schizophrenia. The recommended dose range is 3-12 mg per day. Paliperidone ER utilizes the OROS((R)) delivery system, which allows for once-daily dosing. Its pharmacokinetic profile results in a more stable serum concentration. Paliperidone is 9-hydroxyrisperidone, the chief active metabolite of risperidone. It undergoes limited hepatic metabolism, thereby minimizing the risks of hepatic drug-drug and drug-disease interactions. Three 6-week trials in patients with acute schizophrenia reported that paliperidone ER was effective, well tolerated, and produced clinically meaningful improvements in personal and social functioning compared with placebo. Post-hoc analysis of these trials in various populations, including recently diagnosed, elderly and more severely ill patients, those with sleep disturbances and those with predominant negative symptoms demonstrated improvement as well. Paliperidone ER was also significantly better than placebo in the prevention of symptom recurrence in a 6-month maintenance study. The most common clinically relevant adverse events associated with paliperidone ER were extrapyramidal symptoms, tachycardia and somnolence. The incidence of Parkinsonism, akathisia and use of anticholinergic medications increased in a dose-related manner. Further, modest QTc interval prolongation was observed but did not produce clinical symptoms. Similar to risperidone, paliperidone ER is associated with increases in serum prolactin levels. Overall, paliperidone ER was effective, well tolerated and provides a new treatment option for patients with schizophrenia.
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PMID:Paliperidone ER: a review of the clinical trial data. 1930 Jun 22

Quetiapine is an atypical antipsychotic agent with well established efficacy and tolerability in the acute and maintenance treatment of adults with schizophrenia. The extended-release formulation of quetiapine (quetiapine XR) was developed to provide more convenient once-daily administration, as well as allowing simple and rapid dose escalation, with the aim of improving compliance (known to be a substantial issue in patients with schizophrenia). In several short-term clinical trials, oral quetiapine XR 400-800 mg once daily was generally effective across a range of symptoms in the acute treatment of schizophrenia. As a long-term maintenance treatment, quetiapine XR prevented relapse in patients with stable disease, with significantly longer times to relapse in patients treated with quetiapine XR compared with placebo. Quetiapine XR was generally well tolerated in clinical trials. According to pooled results from three 6-week trials, events occurring in >or=5% of quetiapine XR recipients with an incidence>or=2-fold that seen in placebo recipients were dry mouth, somnolence and dizziness. A generally low incidence of extrapyramidal symptoms (EPS) is seen in quetiapine XR recipients. The most common potentially EPS-associated adverse events seen with quetiapine treatment were akathisia, restlessness and tremor. Rates of worsening of Simpson-Angus Scale and Barnes Akathisia Rating Scale scores were not dissimilar among quetiapine XR, quetiapine immediate release and placebo.
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PMID:Quetiapine extended release: in schizophrenia. 1932 May 34

Quetiapine has demonstrated efficacy in schizophrenia, bipolar disorder and in the treatment of specific symptom clusters such as agitation and sleep problems in mood disorders. In this review, randomized controlled studies demonstrating efficacy, safety and tolerability of quetiapine in major depressive disorder (MDD) and general anxiety disorder (GAD) are evaluated. The results show that quetiapine monotherapy and quetiapine augmentation of antidepressant treatment in MDD and GAD are efficacious for short-term and maintenance treatment at a dose range between 50 and 300 mg/day. Quetiapine appears to have a specific but overall mild side-effect profile, though, some adverse effects such as sedation and somnolence may lead to withdrawal from treatment in some patients. Overall, the available evidence suggests that there is a significant role for quetiapine in the treatment of MDD and GAD.
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PMID:New developments in the management of major depressive disorder and generalized anxiety disorder: role of quetiapine. 1933 58

Flavin-containing monooxygenase 3 (FMO3) genotype data for European-, Latin-, African- and Asian-American schizophrenia patients administered olanzapine were compared to age-, gender-, and race/ethnicity-matched controls. Single nucleotide polymorphisms and haplotypes associated with case-control status was undertaken to determine the potential role of FMO3 in olanzapine therapeutic response. The relationship between side effects and FMO3 genotype and allele frequencies was also studied. For European Americans, significant differences in individual cases versus controls were observed between FMO3 158 and 257 alleles and genotype frequencies and schizophrenia delusions, hallucinations, and weight gain/increased appetite but this was not observed in a replicated population. For Latin Americans, a significant difference in individual cases versus controls was observed for FMO3 158 and 257 for schizophrenia delusions as well as hallucinations and delusions. Sleepiness and weight gain was associated with allele 308. In African Americans, a comparison of allele frequency and diagnosis showed a significant dependence on allele 158 in individual cases versus controls. FMO3 genotype and allele frequency was not significantly associated with auditory hallucinations or delusions. For Asian Americans, no significant difference in allele or genotype frequency and auditory hallucination and delusions was observed in individual cases versus controls. In female Asian American, allele frequency for FMO3 257 was significantly associated with diagnosis and in males, genotype frequency for FMO3 257 and diagnosis was significantly associated.
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PMID:Analysis of flavin-containing monooxygenase 3 genotype data in populations administered the anti-schizophrenia agent olanzapine. 1935 79

Tolerability of haloperidol, clozapine and risperidone has been studied in 60 women with different psychiatric disorders including schizophrenia (83,2%) and neurotic disorders (16,7%). A spectrum of neurological, mental and somatic side-effects was different in the treatment with typical (haloperidol) and atypical (clozapine and risperidone) antipsychotics. The treatment with haloperidol more often results in movement disorders, sleepiness, inhibition, sexual dysfunction and cholinolytic effects. Sedative effects, reduced sexual drive, somatic-autonomic symptoms (hypersalivation, constipations, dry mouth, orthostatic symptoms, tachycardia), and metabolic endocrine effects (weight gain) were the most characteristic side-effects for clozapine. Risperidone caused less intensive extrapyramidal and somatic-autonomous symptoms but more expressed metabolic endocrine disturbances (weight gain, galactorrhea, menstrual cycle dysfunction). Comparing to clozapine, side effects of risperidone were represented by the less intensive somatic-autonomous symptoms but more intensive weight gain, menstrual dysfunction and galactorrhea. Based on the previous results of the study of men, the authors conclude that frequency and intensity of neuroleptic side-effects are sex-related that should be taken into account in the choice of antipsychotics.
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PMID:[Peculiarities of neuroleptic syndrome in women treated with typical and atypical neuroleptics]. 1936 90

Ziprasidone is a newer "atypical" or "second-generation" antipsychotic. Oral ziprasidone (ziprasidone hydrochloride) has been approved by the US 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). Comparisons with other second-generation antipsychotics in meta-analyses reveal similar efficacy to that observed for quetiapine or aripiprazole, but inferior efficacy to that of olanzapine or risperidone in the treatment of schizophrenia. However, the rate of dose titration and the dose achieved may have an important bearing on ziprasidone's efficacy profile, with a target dose range of 120-160 mg/day being associated with optimal symptom control and greater persistence with treatment. In addition, enhancing ziprasidone's effectiveness requires ensuring that ziprasidone is administered with a 500 kcal meal; otherwise, absorption of oral ziprasidone is substantially reduced and cannot be compensated for by increasing the prescribed dose. 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. Ziprasidone also lacks significant persistent effects on prolactin levels, is not anticholinergic, and only infrequently causes extrapyramidal side effects or postural hypotension; however, it can be associated with somnolence. Ziprasidone may prolong the electrocardiogram (ECG) QT interval but this does not appear to pose a substantial clinical problem. Provided that an adequate dose of ziprasidone is prescribed, and administered with a 500 kcal meal, ziprasidone can be effectively used to control symptoms without the long-term liabilities of metabolic side effects.
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PMID:Using oral ziprasidone effectively: the food effect and dose-response. 1966 31

Delta (1-4 Hz) EEG power in non-rapid eye movement (NREM) sleep declines massively during adolescence. This observation stimulated the hypothesis that during adolescence the human brain undergoes an extensive reorganization driven by synaptic elimination. The parallel declines in synaptic density, delta wave amplitude and cortical metabolic rate during adolescence further support this model. These late brain changes probably represent the final ontogenetic manifestation of nature's strategy for constructing nervous systems: an initial overproduction of neural elements followed by elimination. Errors in adolescent brain reorganization may cause mental illness; this could explain the typical age of onset of schizophrenia. Longitudinal studies of sleep EEG are enhancing our knowledge of adolescent brain maturation. Our longitudinal study of sleep EEG changes in adolescence showed that delta power, which may reflect frontal cortex maturation, begins its decline between ages 11 and 12 years and falls by 65% by age 17 years. In contrast, NREM theta power begins its decline much earlier. Delta and theta EEG frequencies are important to sleep theory because they behave homeostatically. Surprisingly, these brain changes are unrelated to pubertal maturation but are strongly linked to age. In addition to these (and other) maturational EEG changes, sleep schedules in adolescence change in response to a complex interaction of circadian, social and other influences. Our data demonstrate that the daytime sleepiness that emerges in adolescence is related to the decline in NREM delta as well as to altered sleep schedules. These longitudinal sleep data provide guideposts for studying cognitive and behavioral correlates of adolescent brain reorganization.
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PMID:Sleep EEG changes during adolescence: an index of a fundamental brain reorganization. 1988 68


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