Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of moclobemide (300-450 mg/day) was compared with fluoxetine (20-40 mg/day) in a double-blind, multicentre study in 209 patients with new episodes of depression selected from 612 consecutive depressed patients representative of those consulting psychiatric services in Finland. Antidepressant efficacy was assessed with the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale and Clinical Global Impression (CGI). The Medical Outcome Study Short-form General Health Survey (SF-20) and 15D Measure of Quality of Life were used to measure effectiveness in terms of health-related quality of life. Efficacy was evident with both drug treatments, with 67% in the moclobemide group and 57% in the fluoxetine group having a reduction in HDRS of more than 50%. Similarly, 77% of the patients in the moclobemide group and 67% in the fluoxetine group were assessed on the CGI as much better or very much better after 6 weeks of treatment. The most commonly reported adverse events were nausea, other gastrointestinal symptoms, nervousness, dizziness and sleep disorders. Nausea was significantly more common in the fluoxetine group and was found especially in women. Premature terminations of treatment were 18% in the moclobemide and 21% in the fluoxetine group. A significant change for the better in quality of life was found in both treatment groups, even at week 2 but especially after 6 weeks of treatment. Improvement was not only seen in dimensions measuring depression or mental health but also in other dimensions.
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PMID:Antidepressant efficacy and quality of life in depression: a double-blind study with moclobemide and fluoxetine. 808 64

An open, randomized comparison of artemether-benflumetol (CGP 56 697; Novartis) with artesunate-mefloquine was conducted in 617 patients with acute uncomplicated multidrug-resistant falciparum malaria on the western border of Thailand. Both treatments rapidly and reliably cleared fever and parasitemia, and there was no significant difference in the initial therapeutic response parameters. Parasite genotyping was used to distinguish recrudescences from new infections. The 63-day cure rate for artesunate-mefloquine (94%) was significantly higher than the cure rate for artemether-benflumetol (81%) (P < 0.001). Both regimens were well tolerated. Nausea, vomiting, dizziness, sleep disorders, and other neurological side effects were between two and four times more common in the artesunate-mefloquine group than in the artemether-benflumetol group (P < 0.001). Artemether-benflumetol is effective and very well tolerated in the treatment of multidrug-resistant falciparum malaria. A higher dose than that used in the present study may improve efficacy.
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PMID:Randomized comparison of artemether-benflumetol and artesunate-mefloquine in treatment of multidrug-resistant falciparum malaria. 944 73

The authors prospectively assessed symptoms induced by the interruption of antidepressants in 16 patients (11 women and 5 men), aged from 33 to 85 years (mean = 52.4 +/- 16.4), treated with antidepressants since at least two weeks. All patients were free of alcohol abuse or dependence disorder and of other dependence to psychoactive substances. None of them presented medical illness. Diagnosis were made by separate evaluations by two authors and confirmed with a semistructered assessment instrument: the Schedule for Affective Disorders and Schizophrenia (Lifetime Version). All patients were submitted to a brutal discontinuation of their antidepressant agent. Patients were assessed twice, before the interruption of the antidepressant, and 72 hours later. Effects of antidepressant interruption were assessed by several means. Modification of anxiety and depression were evaluated using the Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Scale. Symptoms of withdrawal were assessed with Cassano and al.'s scale SESSH including an evaluation of anxiety, agitation, irritability, anergy, difficulty on concentrating, depersonalization, sleep and appetite disorders, muscle pains, nausea, tremor, sweating, altered taste, hyperosmia, paresthesias, photophobia, motor incoordination, dizziness, hyperacousia pain, delirium. Fourteen of the 16 patients (87.5%) presented modifications of their somatic or psychic state 3 days after the interruption of the antidepressant treatment. Most frequent symptoms were: increase in anxiety (31%), increase in irritability (25%), sleep disorders (19%), decrease of anergia and fatigue (19%). Mean scores of anxiety and depression were not significantly modified by the withdrawal. Following TCAs interruption (7 patients) most frequent symptoms were sleep disorders; increase in anxiety, nausea. Among patients withdrawn from SSRIs (6 patients), most frequent symptoms were increase in anxiety, increase in irritability, headache. Patients also presented a decrease of nausea, and of anorexia.
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PMID:[Prospective evaluation of antidepressant discontinuation]. 969 14

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of tolcapone are reviewed. Tolcapone is the first drug brought to market from the new class of selective and reversible inhibitors of catechol-O-methyltransferase. Tolcapone is indicated for use in the treatment of Parkinson's disease as an adjunct to levodopa-carbidopa therapy in patients who are experiencing fluctuations in symptoms and who are not responding to or are not appropriate candidates for other adjunctive therapies. The absolute bioavailability of tolcapone after an oral dose is about 65%. Clinical trials have demonstrated that tolcapone 50-200 mg three times daily reduces "off" time in patients refractory to levodopa-carbidopa, Unified Parkinson's Disease Rating Scale scores, and the dosage of levodopa-carbidopa required for symptom suppression. The most frequent adverse effects of tolcapone are dyskinesia, nausea, sleep disorders, dystonia, orthostatic hypotension, diarrhea, dizziness, and hallucinations; also, there is a potential for elevation of liver transaminase concentrations in the blood. To date, three deaths from fulminant hepatic failure in association with tolcapone have been reported. Extensive liver function testing is required of all patients before and during therapy. The recommended starting dosage is 100 mg orally three times daily as an adjunct to levodopacarbidopa therapy; a concurrent reduction in the levodopa dosage of about 30% is suggested. Patient response should be monitored carefully during the first three weeks of therapy; treatment should be discontinued in patients failing to respond during this initial use. Tolcapone is of benefit in fluctuating Parkinson's disease, but benefits must be carefully weighed against risks in individual patients.
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PMID:Tolcapone: a novel approach to Parkinson's disease. 1056 98

When peripheral decarboxylation is blocked by carbidopa or benserazide, the main metabolic pathway of levodopa is O-methylation by catechol-O-methyltransferase (COMT). Entacapone and tolcapone are new potent, selective and reversible nitrocatechol-type COMT inhibitors. Animal studies have demonstrated that entacapone mainly has a peripheral effect whereas tolcapone also inhibits O-methylation in the brain. In human volunteers, both entacapone and tolcapone dose-dependently inhibit the COMT activity in erythrocytes, improve the bioavailability and decrease the elimination of levodopa, and inhibit the formation of 3-O-methyldopa (3-OMD). Entacapone is administered with every scheduled dose of levodopa whereas tolcapone is administered 3 times daily. The different administration regimens for these agents are based on their different pharmacokinetic and pharmacodynamic profiles. Both entacapone and tolcapone enhance and extend the therapeutic effect of levodopa in patients with advanced and fluctuating Parkinson's disease. They prolong the duration of levodopa effect. Clinical studies show that they increase the daily ON time by an average 1 to 3 hours, improve the activities of daily living and allow daily levodopa dosage to be decreased. Correspondingly, they significantly reduce the daily OFF time. No comparative studies between entacapone and tolcapone have been performed. Tolcapone also appears to have a beneficial effect in patients with nonfluctuating Parkinson's disease. The main adverse effects of the COMT inhibitors are related to their dopaminergic and gastrointestinal effects. Enhancement of dopaminergic activity may cause an initial worsening of levodopa-induced adverse effects, such as dyskinesia, nausea, vomiting, orthostatic hypotension, sleep disorders and hallucinations. Levodopa dose adjustment is recommended to avoid these events. Tolcapone is associated with diarrhoea in about 16 to 18% of patients and entacapone in less than 10% of patients. Diarrhoea has led to discontinuation in 5 to 6% of patients treated with tolcapone and in 2.5% of those treated with entacapone. Urine discoloration to dark yellow or orange is related to the colour of COMT inhibitors and their metabolites. Elevated liver transaminase levels are reported in 1 to 3% of patients treated with tolcapone but very rarely, if at all, in patients treated with entacapone. The descriptions of acute, fatal fulminant hepatitis and potentially fatal neurological reactions, such as neuroleptic malignant syndrome and rhabdomyolysis, in association with tolcapone led to the suspension of its marketing authorisation in the European Community and Canada. In many other countries, the use of tolcapone is restricted to patients who are not responding satisfactorily to other therapies. Regular monitoring of liver enzymes is required if tolcapone is used. No such adverse reactions have so far been described for entacapone and no laboratory monitoring has been proposed. COMT inhibitors added to levodopa therapy are beneficial, particularly in patients with fluctuating disease. They may be combined with other antiparkinsonian drugs, such as dopamine agonists, selegiline and anticholinergics without adverse interactions. They provide a new treatment possibility in patients with Parkinson's disease who have problems with their present levodopa therapy.
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PMID:Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. 1088 60

The sopite syndrome is a poorly understood response to motion. Drowsiness and mood changes are the primary characteristics of the syndrome. The sopite syndrome can exist in isolation from more apparent symptoms such as nausea, can last long after nausea has subsided, and can debilitate some individuals. It is most likely a distinct syndrome from "regular" motion sickness or common fatigue, and is of potential concern in a variety of situations. The syndrome may be particularly hazardous in transportation settings where other performance challenges (e.g., sleep deprivation) are already present. It is also a potential concern in cases where illnesses such as sleep disorders or depression may interact with the syndrome and confuse diagnosis.
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PMID:The sopite syndrome revisited: drowsiness and mood changes during real or apparent motion. 1154 23

Anorectics and bulimics often complain sleep onset insomnia and disrupted sleep. During awakenings bulimics can have binges. Conversely, eating disorders can be a clinical expression of a concomitantly occurring sleep disorder. Two clinical entities have been recently described: the Night Eating Syndrome (NES) and the Sleep Related Eating Disorders. The main goal of this literature review was to better characterize the relationships between eating disorders and sleep disturbances. No specific EEG sleep pattern emerges in anorectic and bulimic patients. However, all studies include several methodological limitations: a few number of patients, heterogeneous patient groups, various diagnostic criteria. The results of studies evaluating the impact of depression on sleep EEG in eating disorder patients are also subject to controversy. The only study examining the relationship between sleep EEG and morphological alterations in anorectics and normal weight bulimics shows that patients with enlarged cerebrospinal fluid spaces spent more time in slow wave sleep and that the duration of rapid eye movement (REM) sleep was reduced. The ventricular brain ratio was negatively correlated with REM sleep. The Night Eating Syndrome consists in insomnia, binge eating and morning anorexia. Other criteria are proposed to characterize the NES: more than 50% of the daily energy intake is consumed after the last evening meal, awakenings at least once a night, repetition of the provisional criteria for more than 3 months, subjects do not meet criteria for bulimia nervosa or binge eating disorder. Patients have no amnesia nor alteration of alertness, and no other sleep disorder. There is no modification of sleep EEG except sleep maintenance. The prevalence of the NES is 1.5% in the general population. Some neuroendocrine disturbances have been found in the NES. The delimitation with eating disorders is not yet clearly established. If it shares the compulsive features with eating disorders, particularly the "Binge Eating Disorder", and occurs during full awakenings, the night eating syndrome may be recognized as a specific eating disorder. The sleep related eating syndrome is also characterized by compulsive binge eating during awakenings. But in this case, night eating is linked with a reduced consciousness and sleep disorders, mainly somnambulism. Patients never experience hunger, abdominal pain, nausea or hypoglycemia. Night-eating takes place invariant across weekdays, weekend and vacations. Patients consumed high caloric foods and fluids but never alcohol and purging does not occur. Diurnal bulimia is frequently associated with the sleep-related eating disorder. In conclusion, the sleep related eating disorder seems rather be a clinical subtype of sleep disorders whereas the NES could be considered as an eating disorder.
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PMID:[Correlation between eating disorders and sleep disturbances]. 1176 Jun 92

Forty-one Parkinson's disease patients with dementia (21 galantamine group, 20--control group) with onset of dementia at least two years after the manifestation of parkinsonian symptoms participated in this open-label controlled trial of galantamine in maximum dose 16 mg/day. Cognitive, psychiatric and motor symptoms were assessed before and after 4, 12 and 24 weeks of treatment using clinical assessment as well as rating scales, including the Mini-Mental State Examination (MMSE), ADAS-cog, clock drawing test, Frontal Assessment Battery (FAB), and the Neuropsychiatric Inventory (NPI-12) with assessment of caregiver distress. Patients treated with galantamine had better scores on MMSE (p<0,05), ADAS-cog (p<0,05), clock drawing test (p<0,05) and FAB (p<0,01) to the end of the trial comparing to the control group. NPI scores on individual items changed from baseline at week 12 and 24, showing benefits of galantamine treatment as compared to the controls, with significant difference for hallucinations (p=0,0002), anxiety (p=0,04), sleep disorders (p=0,04) and apathy (p=0,006). Galantamine therapy was associated with a significant reduction in caregiver distress (p=0,007), improvement of daily life activity (p=0,003). Gait, freezing and falls were improved in the galantamine group but a mild worsening of tremor was noted in two patients. Adverse events (drooling, postural hypotension, nausea, dysuria) were observed in 7 (30%) of galantamine treated patients.
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PMID:[Efficacy and safety of galantamine (reminyl) in the treatment of dementia in patients with Parkinson's disease (open-label controlled trial)]. 1842 56

In order to assess the prevalence of Dopaminergic Premonitory Symptoms (DPS) in migraine patients with Restless Legs Syndrome (RLS), we chose migraine patients from a large Italian clinical headache population previously investigated for an association between primary headaches and RLS. We evaluated a total sample of 164 patients with migraine, in particular 114 with migraine without aura (MO), 10 with migraine with aura (MA) and 40 with MO and MA in various combinations between them or with episodic tension-type headache (ETTH), defined as a "mixed group". About 20% of all migraine patients referred at least one of the following DPS: yawning, nausea, somnolence or food craving, confirming data already indicated in the literature. Among migraine patients with RLS (25.6%), DPS were referred from about half of the patients (47.6%) compared to those without RLS (47.6% vs. 13.1%; p<0.001). Based on migraine subtype, patients with MO referred DPS (26.3%) more frequently compared to the MA group and "mixed group" (12.0%, p<0.05), particularly in the presence of RLS (63.0% vs. 20.0%, p<0.01). No statistical differences were found between clinical and demographic data of the subgroups or related to medical conditions investigated (anxiety, depression, sleep disorders, body mass index). It is interesting that the chances of having RLS in migraine patients were more than 5 times higher in the presence of DPS. These results could support a hypothetical dopaminergic imbalance in RLS and migraine, as the dopamine is involved in the pathogenesis of both disorders and it is responsible for the migraine DPS reported above.
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PMID:High prevalence of Dopaminergic Premonitory Symptoms in migraine patients with Restless Legs Syndrome: a pathogenetic link? 1854 25

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


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