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)

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

Difficulties initiating or maintaining sleep are frequently encountered in patients with schizophrenia. Disturbed sleep can be found in 30-80% of schizophrenic patients, depending on the degree of psychotic symptomatology. Measured by polysomnography, reduced sleep efficiency and total sleep time, as well as increased sleep latency, are found in most patients with schizophrenia and appear to be an important part of the pathophysiology of this disorder. Some studies also reported alterations of stage 2 sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep variables, i.e. reduced REM latency and REM density. A number of sleep parameters, such as the amount of SWS and the REM latency, are significantly correlated to clinical variables, including severity of illness, positive symptoms, negative symptoms, outcome, neurocognitive impairment and brain structure.Concerning specific sleep disorders, there is some evidence that schizophrenic patients carry a higher risk of experiencing a sleep-related breathing disorder, especially those demonstrating the known risk factors, including being overweight but also long-term use of antipsychotics. However, it is still unclear whether periodic leg movements in sleep or restless legs syndrome (RLS) are found with a higher or lower prevalence in schizophrenic patients than in healthy controls.There are no consistent effects of first-generation antipsychotics on measures of sleep continuity and sleep structure, including the percentage of sleep stages or sleep and REM latency in healthy controls. In contrast to first-generation antipsychotics, the studied atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone, ziprasidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity, with an increase in either total sleep time (TST) or sleep efficiency, and individually varying effects on other sleep parameters, such as an increase in REM latency observed for olanzapine, quetiapine and ziprasidone, and an increase in SWS documented for olanzapine and ziprasidone in healthy subjects.The treatment of schizophrenic patients with first-generation antipsychotics is consistently associated with an increase in TST and sleep efficiency, and mostly an increase in REM latency, whereas the influence on specific sleep stages is more variable. On the other hand, withdrawal of such treatment is followed by a change in sleep structure mainly in the opposite direction, indicating a deterioration of sleep quality. On the background of the rather inconsistent effects of first-generation antipsychotics observed in healthy subjects, it appears possible that the high-potency drugs exert their effects on sleep in schizophrenic patients, for the most part, in an indirect way by suppressing stressful psychotic symptomatology. In contrast, the available data concerning second-generation antipsychotics (clozapine, olanzapine, risperidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity in patients and healthy subjects, with an increase in TST and sleep efficiency or a decrease in wakefulness. Additionally, clozapine and olanzapine demonstrate comparable influences on other sleep variables, such as SWS or REM density, in controls and schizophrenic patients. Possibly, the effects of second-generation antipsychotics observed on sleep in healthy subjects and schizophrenic patients might involve the action of these drugs on symptomatology, such as depression, cognitive impairment, and negative and positive symptoms.Specific sleep disorders, such as RLS, sleep-related breathing disorders, night-eating syndrome, somnambulism and rhythm disorders have been described as possible adverse effects of antipsychotics and should be considered in the differential diagnosis of disturbed or unrestful sleep in this population.
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PMID:Sleep disturbances in patients with schizophrenia : impact and effect of antipsychotics. 1884 34

Pyridoxal phosphate and pyridoxamine phosphate, the catalytically active forms of vitamin B(6), influence brain function by participating at stages in metabolism of proteins, lipids, carbohydrates, other coenzymes and hormones. Vitamin B(6) participates in the metabolism of amino acids in the form of decarboxylation, transamination, deamination, racemization and desulfhydration reactions. The crucial roles that these coenzymes play in the maintenance of functional integrity of the brain become evident when one realizes that some compounds implicated as neurotransmitters are synthesized and/or metabolized by the aid of the vitamin B(6)-dependent enzymatic reactions. These include dopamine, norepinephrine and serotonin, tyramine, tryptamine, taurine, histamine, gamma aminobutyric acid, and even acetylcholine indirectly. In recent years, the above-mentioned biogenic amines have become of considerable interest to neurobiologists who are investigating the etiology and the pathological manifestations of many disorders of the central nervous system such as Parkinsonism, Huntington's chorea, minimal brain disfunction, schizophrenia, depression, sleep disorders and seizure disorders. Vitamin B(6) deficiency in these cases is characterized by anemia, growth retardation and alteration in neuronal function, including neuropathies, hyperirritability, hyperexcitability and convulsions. The importance of vitamin B(6) in the study of brain function assumes still greater significance when one considers the effects of nutritional deficiencies on growth and development of the brain and mental processes and in the involvement of vitamin B(6) in some inborn errors of metabolism which result in mental retardation. Vitamin B(6) deficiency results in a lowered concentration of Coenzyme A in blood, in reduced absorption and storage of vitamin B(12), and in increased excretion of vitamin C. Furthermore, vitamin B(6) acts synergistically with vitamin E to control metabolism of unsaturated fats, with vitamin C in tyrosine metabolism and with niacin in its action and participates in niacin synthesis. In addition, vitamin B(6) deficiency results in insufficiency of insulin and in alteration of the functions of adrenal and pituitary glands, since it is involved in the synthesis of growth hormone, follicle-stimulating hormone, luteinizing hormone, aldosterone, glucagon, cortisol, estradiol, testosterone and epinephrine. It is hoped that by understanding the factors that regulate the synthesis, binding, storage and degradation of pyridoxal phosphate in the brain, a better insight into the role of vitamin B(6) in neurobiology may be gained.
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PMID:Regulation and function of pyridoxal phosphate in CNS. 1964 63

Most psychiatric disorders, such as schizophrenia, mood disorders, or neurotic disorders are associated with sleep disorders of various kinds, among which insomnia is most prevalent and important in psychiatric practice. Almost all patients suffering from major depression complain of insomnia. Pharmacological treatment of insomnia associated with major depression shortens the duration to achieve remission of depression. Insomnia has been recently reported to be a risk factor for depression. In patients with schizophrenia, insomnia is often an early indicator of the aggravation of psychotic symptoms. Electroencephalographic sleep studies have also revealed sleep abnormalities characteristic to mood disorders, schizophrenia and anxiety disorders. A shortened REM sleep latency has been regarded as a biological marker of depression. Reduced amount of deep non-REM sleep has been reported to be correlated with negative symptoms of schizophrenia. Recently, REM sleep abnormalities were found in teenagers having post-traumatic stress disorder after a boat accident. Although these facts indicate that insomnia plays an important role in the development of psychiatric disorders, there are few hypotheses explaining the cause and effect of insomnia in these disorders. Here, we reviewed recent articles on insomnia associated with psychiatric disorders together with their clinical managements.
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PMID:[Insomnia associated with psychiatric disorders]. 1976 32

The histamine H(3) receptor is involved in the central and peripheral regulation of levels of histamine and other neurotransmitters (e.g., acetylcholine, noradrenaline, dopamine, serotonin and GABA), which sets it up as a target in the treatment of various CNS (e.g., depression, schizophrenia, ADHD, dementia, neuropathic pain and sleep disorders), metabolic syndrome (e.g., obesity) and allergic disorders. Novel chemical series from the most recent 2 years of patent literature have been reviewed. While overall structural diversity is moderate, these represent or relate to some of the compounds progressing through clinical trials (e.g., GSK-189254). However, an H(3) receptor drug still has yet to reach the market. Patenting activity is likely to remain high in the near future, bolstered by the commercial promise of potential H(3) receptor drugs.
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PMID:Recent advances in the development of histamine H3 antagonists. 2014 64

Patients with schizophrenia may have sleep disorders even when clinically stable under antipsychotic treatments. To better understand this issue, we measured sleep characteristics between 1999 and 2003 in 150 outpatients diagnosed with Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) schizophrenia or schizoaffective disorder and 80 healthy controls using a sleep habits questionnaire. Comparisons between both groups were performed and multiple comparisons were Bonferroni corrected. Compared to healthy controls, patients with schizophrenia reported significantly increased sleep latency, time in bed, total sleep time and frequency of naps during weekdays and weekends along with normal sleep efficiency, sleep satisfaction, and feeling of restfulness in the morning. In conclusion, sleep-onset insomnia is a major, enduring disorder in middle-aged, non-hospitalized patients with schizophrenia that are otherwise clinically stable under antipsychotic and adjuvant medications. Noteworthy, these patients do not complain of sleep-maintenance insomnia but report increased sleep propensity and normal sleep satisfaction. These results may reflect circadian disturbances in schizophrenia, but objective laboratory investigations are needed to confirm subjective sleep reports.
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PMID:Sleep habits in middle-aged, non-hospitalized men and women with schizophrenia: a comparison with healthy controls. 2049 44

Although the precise function of sleep is unknown, decades of research strongly implicate that sleep has a vital role in central nervous system (CNS) restoration, memory consolidation, and affect regulation. Slow-wave sleep (SWS) and rapid eye movement (REM) sleep have been of significant interest to psychiatrists; SWS because of its putative role in CNS energy recuperation and cognitive function, and REM sleep because of its suggested involvement in memory, mood regulation, and possible emotional adaptation. With the advent of the polysomnogram, researchers are now beginning to understand some of the consequences of disrupted sleep and sleep deprivation in psychiatric disorders. The same neurochemistry that controls the sleep-wake cycle has also been implicated in the pathophysiology of numerous psychiatric disorders. Thus it is no surprise that several psychiatric disorders have prominent sleep symptoms. This review will summarize normal sleep architecture, and then examine sleep abnormalities and comorbid sleep disorders seen in schizophrenia, as well as anxiety, cognitive, and substance abuse disorders.
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PMID:Sleep in psychiatric disorders: where are we now? 2070 66

Two case examples and a review of the sleep literature illustrate the potential of antipsychotic medication to trigger sleepwalking episodes in the context of schizophrenia. Causative hypotheses are briefly reviewed, as well as risk factors, differential diagnosis, and management. Sleepwalking may contribute to delusions, aggression, and accidental suicide. It is important to investigate sleep disorders in schizophrenia. They are not rare and may contribute to behavior that increases the stigma and isolation of individuals with schizophrenia.
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PMID:Sleepwalking, a possible side effect of antipsychotic medication. 2073 37

Sleep disorders are becoming more prevalent. There is an overlap of symptoms related to obstructive sleep apnea syndrome (OSAS) and many psychiatric conditions. Complaints of excessive sleepiness, insomnia, cognitive dysfunction, and depressive symptoms can be related to both disease states. Obstructive sleep apnea syndrome is characterized by repetitive disruption of sleep by cessation of breathing and was first described in the 19th century by bedside observation during sleep. Physicians observed this cessation of breathing while the patient slept and postulated that these episodes were responsible for subsequent complaints of sleepiness. OSAS can coexist with major depressive disorder, exacerbate depressive symptoms, or be responsible for a large part of the symptom complex of depression. Additionally, in schizophrenia, sleep apnea may develop as a result of chronic neuroleptic treatment and its effect on gains in body weight, a major risk factor for the development of OSAS.It is important to recognize the signs and symptoms of sleep apnea, namely excessive daytime sleepiness, snoring, and witnessed apneas. Recognition of the existence of sleep apnea, prompt referral to a sleep specialist, and ultimately treatment of an underlying sleep disorder, such as OSAS, can ameliorate symptoms of psychiatric disease.
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PMID:Sleep-disordered breathing: in depression and schizophrenia. 2097 18

Most psychiatric disorders, such as schizophrenia, mood disorders, or neurotic disorders are associated with sleep disorders of various kinds, among which insomnia is most prevalent and important in psychiatric practice. Almost all patients suffering from major depression complain of insomnia. Pharmacological treatment of insomnia associated with major depression shortens the duration to achieve remission of depression. Insomnia has been recently reported to be a risk factor for depression. Hypersomnia is also a major sleep problem in patient suffering from depression. There have been no clinical guide to treat the symptoms of hypersomnia in depression, but some clinical trials treating them with NDRI or adjunctive administration of psychostimulants. In patients with schizophrenia, insomnia is often an early indicator of the aggravation of psychotic symptoms. Electroencephalographic sleep studies have also revealed sleep abnormalities characteristic to mood disorders, schizophrenia and anxiety disorders. A shortened REM sleep latency has been regarded as a biological marker of depression. Reduced amount of deep Non-REM sleep has been reported to be correlated with negative symptoms of schizophrenia. Recently, REM sleep abnormalities were found in teenagers having post-traumatic stress disorder after a boat accident. Although these facts indicate that insomnia plays an important role in the development of psychiatric disorders, there are few hypotheses explaining the cause and effect of insomnia in these disorders. Here, we reviewed recent articles on insomnia and hypersomnia associated with psychiatric disorders together with their clinical managements.
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PMID:[Management of insomnia and hypersomnia associated with psychiatric disorders]. 2107 97


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