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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypericum perforatum is an herbaceous perennial plant, also known as "St. John's wort", used popularly as a natural antidepressant. Although some clinical and experimental studies suggest it has some properties similar to conventional antidepressants, the proposed mechanism of action seems to be multiple: a non-selective blockade of the reuptake of serotonin, noradrenaline and dopamine; an increase in density of serotonergic and dopaminergic receptors and an increased affinity for GABAergic receptors; moreover, the inhibition of monoaminoxidase enzyme activity has been involved. In any case, the increase of monoamine concentrations in the synaptic cleft resembles several actions exerted by clinically effective antidepressants. In the present article, we review some of the controversial evidence derived from clinical and experimental studies suggesting that H. perforatum exerts antidepressant-like actions, and we also review some of its side effects, such as nausea, rash, fatigue, restlessness, photosensitivity, acute neuropathy, and even episodes of mania and serotonergic syndrome when administered simultaneously with other antidepressant drugs. All of the foregoing suggests that H. perforatum extracts appear to exert potentially significant pharmacological activity involving several neurotransmission systems supposed to be involved in the pathophysiology of depression. However, little information regarding the safety of H. perforatum is available, including potential herb-drug interactions. There is a need for additional research on the pharmacological and biochemical activity of H. perforatum, as well as its side-effects and its several bioactive constituents to further elucidate the mechanisms of antidepressant actions.
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PMID:A review of clinical and experimental observations about antidepressant actions and side effects produced by Hypericum perforatum extracts. 1469 32

High doses of antidepressants are often used for treatment-resistant depression. Venlafaxine, a dual serotonin and noradrenaline reuptake inhibitor, has been shown to have a tolerable side-effect profile in previous studies using doses of up to 375 mg/day. We investigated the tolerability of higher than currently recommended doses of venlafaxine using the UKU side-effect rating scale. Seventy outpatients fulfilling DSM-IV criteria for major depressive disorder were recruited into two demographically matched groups according to their daily dosage of venlafaxine: high dose n = 35 (> or = 375 mg/day, range 375-600 mg, average 437 mg/day) or standard dose n = 35 (< 375 mg/day, range 75-300 mg, average 195 mg/day. Clinical characteristics were noted and the UKU side-effect rating scale was administered to a subsample of patients. The most frequently reported complaints in both groups were increased fatigue (48%), concentration difficulties (48%), sleepiness/sedation (37%), failing memory (44.4%) and weight gain (29.6%). Apart from weight gain, the complaints were found to be experienced significantly more severely by the high-dose group. Six patients discontinued venlafaxine due to intolerable side-effects but only two of these patients were on a high dose. There was a tendency for mildly raised blood pressure in 10% of patients on an average dose of 342 mg/day. However, no difference between the two groups was found. This preliminary open study demonstrates that venlafaxine is tolerated at higher than British National Formulary recommended doses (i.e. up to 600 mg daily). However, increased frequency and severity of reported side-effects in the high-dose group are not associated with increased rates of discontinuation.
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PMID:Tolerability of high-dose venlafaxine in depressed patients. 1526 Sep 8

Catuama is a marketed herbal product currently used as a tonic, especially for the management of mental or physical fatigue. In the present study, we have shown pharmacological and neurochemical evidence for antidepressant-like actions of the product Catuama. Acute and chronic oral treatments with Catuama both resulted in a significant reduction of the immobility time in two models of depression in mice, the forced swimming and the tail suspension tests. Conversely, treatment with the same doses of Catuama did not significantly interfere with motor activity according to assessment in the open-field test. The antidepressant-like effects were comparable to those observed for classical antidepressant drugs. When assessed in vitro, Catuama inhibited, in a concentration-dependent manner, the synaptosomal uptake of noradrenaline and principally of serotonin and dopamine, in rat brain. Likewise, in vitro incubation of Catuama also resulted in a marked increase of the release of serotonin and dopamine in rat brain crude preparation of synaptosomal membranes. Finally, Catuama was found to be effective in interfering with the synaptosomal uptake of serotonin and dopamine following long-term oral treatment of rats. The present findings allow us to suggest that the herbal product Catuama might be useful for the clinical management of moderate and mild depressive states, alone or in association with current antidepressant drugs.
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PMID:Pharmacological and neurochemical evidence for antidepressant-like effects of the herbal product Catuama. 1530 32

Fibromyalgia syndrome is a systemic disorder of widespread pain which is thought to result from abnormal pain processing within the central nervous system. There are no currently approved treatments for this indication. Antidepressants appear, however, to be effective, especially those with an action on noradrenergic neurotransmission. The objective of the present study was to test the efficacy of the dual action noradrenaline and serotonin reuptake inhibitor antidepressant, milnacipran, in the treatment of fibromyalgia. The 125 patients, who were enrolled in a double-blind, placebo-controlled, flexible dose escalation trial, were randomized to receive placebo or milnacipran for 4 weeks of dose escalation (up to 200 mg/day), followed by 8 weeks at a constant dose. The study evaluated the efficacy and safety of milnacipran for the treatment of pain and associated symptoms such as fatigue, depressed mood and sleep. 75% of milnacipran-treated patients reported overall improvement, compared with 38% in the placebo group (p < 0.01). Furthermore, 37% of twice daily milnacipran-treated patients reported at least 50% reduction in pain intensity, compared with 14% of placebo-treated patients (p < 0.05). 84% of all milnacipran patients escalated to the highest dose (200 mg/day) with no tolerability issues. Most adverse events were mild to moderate in intensity, and transient in duration. These results suggest that milnacipran may have the potential to relieve not only pain but several of the other symptoms associated with fibromyalgia.
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PMID:A double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgia. 1537 66

Muscle and peripheral nerve development is clearly dependent on their interaction during early postnatal life. Furthermore, muscle or peripheral nerve activity plays a crucial role in the maturation of the neuromuscular system. In this study, the possible involvement of spinal catecholamines in fast muscle recovery after nerve crush is investigated. Sciatic nerve crush was performed on the fourth to fifth postnatal day. Following that, L-Dopa was administered daily [150 mg/kg body weight (BW)] i.p., until the 21st day after birth. L-Dopa-treated and control groups were then examined electrophysiologically for the contractile properties of extensor digitorum longus (EDL) muscles. Two experimental groups were included in this study: (i) rats whose sciatic nerve was crushed and were treated with L-Dopa and (ii) rats whose sciatic nerve was crushed and were not treated with L-Dopa. The number of motoneurones for both groups was estimated by HRP retrograde labelling. The results showed that the operated L-Dopa-treated EDL muscles of the rats exhibited limited atrophy, slighter impairment of maximal tetanic tension, lesser resistance to fatigue, and polyneuronal innervation than the controls. The number of motoneurones was the same for the operated muscles in both groups of animals and was within the normal ranges. Our findings suggest that catecholamines of locomotion during the early stages of development may have a beneficial effect on fast muscle recovery following nerve crush. The action of L-Dopa is attributed to noradrenaline, which acts through descending spinal noradrenergic pathways, possibly via a(2)-adrenergic receptors at the spinal level.
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PMID:Recovery, innervation profile, and contractile properties of reinnervating fast muscles following postnatal nerve crush and administration of L-Dopa. 1546 20

Partial sleep deprivation is clinically associated with fatigue, depressive symptoms and reduced memory. Previously, it has been demonstrated that venlafaxine, an atypical antidepressant, increases the levels of noradrenaline and serotonin in rat hippocampus. The aim of this study was to evaluate the effects of venlafaxine on depression, anxiety, locomotor activity and memory in a model of REM sleep (REMs) deprivation in rats. We have also studied the influence of venlafaxine on monoamine levels in the striatum. Six groups of animals (N=20 each) were treated with saline or venlafaxine (1 or 10 mg/kg) during 10 days, submitted or not to REMs deprivation and studied with the forced swimming test of Porsolt (STP), plus-maze, passive avoidance and open-field tests right after sleep deprivation. Animals were also studied for passive avoidance 24 h later (rebound period). Brain samples for monoamine measurements were collected either immediately after REMs deprivation or after 24 h. Both REMs deprivation and venlafaxine showed an antidepressant effect. An anxiolytic effect was also observed after REMs deprivation. Previous treatment with venlafaxine blocked the antidepressant and anxiolytic effects of REMs deprivation. REMs deprivation alone and treatment with venlafaxine 10 mg/kg increased locomotor activity, and this effect was inhibited by venlafaxine in REMs deprived rats. Both venlafaxine treatment and REMs deprivation induced weight loss. Venlafaxine treatment, but not REMs deprivation, induced an increase in striatal dopamine (DA) levels. The combination of REMs deprivation and venlafaxine treatment was associated with an increase in serotonin turnover 24 h after rebound sleep. In this study, venlafaxine treatment hindered most behavioral effects of REMs deprivation and was associated with an interference on dopamine and serotonin systems in the striatum.
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PMID:The effect of venlafaxine on behaviour, body weight and striatal monoamine levels on sleep-deprived female rats. 1558 21

Recombinant preparations of the cytokine interferon (IFN)-alpha are increasingly used to treat a number of medical conditions, including chronic viral hepatitis and several malignancies. Although frequently effective, IFN alpha induces a variety of neuropsychiatric adverse effects, including an acute confusional state that develops rapidly after initiation of high-dose IFN alpha, a depressive syndrome that develops more slowly over weeks to months of treatment, and manic conditions most often characterised by extreme irritability and agitation, but also occasionally by euphoria. Acute IFN alpha-induced confusional states are typically characterised by disorientation, lethargy, somnolence, psychomotor retardation, difficulties with speaking and writing, parkinsonism and psychotic symptoms. Strategies for managing delirium should be employed, including treatment of contributing medical conditions, use of either typical or atypical antipsychotic agents and avoidance of medications likely to worsen mental status. Significant depressive symptoms occur in 21-58% of patients receiving IFN alpha, with symptoms typically manifesting over the first several months of treatment. The most replicated risk factor for developing depression is the presence of mood and anxiety symptoms prior to treatment. Other potential, but less frequently replicated, risk factors include a past history of major depression, being female and increasing IFN alpha dosage and treatment duration. The available data support two approaches to the pharmacological management of IFN alpha-induced depression: antidepressant pretreatment or symptomatic treatment once IFN alpha has been initiated. Pretreatment might be best reserved for patients already receiving antidepressants or for patients who endorse depression or anxiety symptoms of mild or greater severity prior to therapy. Several recent studies demonstrate that antidepressants effectively treat IFN alpha-induced depression once it has developed, allowing the vast majority of subjects to complete treatment successfully. Recent data suggest that IFN alpha-induced depression may be composed of two overlapping syndromes: a depression-specific syndrome characterised by mood, anxiety and cognitive complaints, and a neurovegetative syndrome characterised by fatigue, anorexia, pain and psychomotor slowing. Depression-specific symptoms are highly responsive to serotonergic antidepressants, whereas neurovegetative symptoms are significantly less responsive to these agents. These symptoms may be more effectively treated by agents that modulate catecholaminergic functioning, such as combined serotonin-noradrenaline (norepinephrine) antidepressants, bupropion, psychostimulants or modafinil. Additional factors to consider in selecting an antidepressant include potential drug-drug interactions and adverse effect profile. Finally, IFN alpha appears capable of inducing manic symptoms. Mania, especially when severe, is a clinical emergency. When this occurs, IFN alpha and antidepressants should be stopped, an emergency psychiatric consultation should be obtained, and treatment with a mood stabilizer should be initiated.
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PMID:Neuropsychiatric adverse effects of interferon-alpha: recognition and management. 1569 25

Reactions to noise-induced communication disturbance of 42 men during a seminar were investigated. Stress reactions with or without road traffic noise (Lm = 60 dBA) were compared. Traffic noise was played back via loudspeakers during one day in the seminar room. The following parameters were measured: Fatigue and mental tension by questionnaire; blood pressure and heart rate; excretion of adrenaline, noradrenaline and cAMP from the collected urine. The same subjects participated in a laboratory test where the blood pressure was measured during 5 minutes of rest and after 5 minutes of exposure to intermittent white noise (Lm=97 dBA). It was found that the noise in the field experiment caused psychological and physiological stress effects in half of the subjects. Increased mental tension was correlated to increases as well as decreases of the blood pressure. Systolic blood pressure reactions were stronger than the reactions of diastolic blood pressure. Noise sensitive subjects reacted stronger than the others. In the short-term laboratory test, systolic blood pressure increases were smaller than the diastolic increases. At the end of the 5 minutes noise exposure only the diastolic blood pressure increases were significant. There was no correlation between the blood pressure reactions in the two different noise exposure experiments. There existed a positive correlation between noise sensitivity and the systolic blood pressure increases during the seminar, whilst the correlation, between noise sensitivity and systolic blood pressure increases in the laboratory exposure, was negative. From these results we conclude that short-term noise exposure experiments do not provide information about the effects of long-term real life exposure to environmental noise. Potential health effects of chronic noise-induced disturbances of activities are discussed.
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PMID:Stress effects of noise in a field experiment in comparison to reactions to short term noise exposure in the laboratory. 1570 36

The primary aims of this paper were to examine the effect of heat stress on working memory, choice reaction time and mood state, and to investigate the relationship between heat induced changes in plasma concentrations of selected neurotransmitters and hormones, and cognition. Heat stress resulted in a deterioration of performance on a central executive task (random movement generation) but not on verbal and spatial recall, and choice reaction time tasks. Perceptions of vigour decreased and fatigue increased following exposure to heat stress. Plasma concentrations of cortisol and 5-hydroxytryptamine significantly increased following exposure to heat. Regression analyses showed that percent body mass loss and change from baseline (Delta) concentrations of cortisol, post-exposure to heat, were significant predictors of Delta random movement generation and Delta fatigue. A secondary purpose was to examine the effect of recovery on cognition and mood. Following recovery, the performance of the central executive task was poorer than pre-treatment. Mood states, catecholamines and 5-hydroxytryptamine concentrations returned to pre-treatment values, but cortisol fell to a level significantly lower. Regression correlations showed that Delta adrenaline and Delta scores, post-recovery, on the central executive task were significantly correlated. Delta noradrenaline correlated significantly with Delta fatigue. It was concluded that heat stress results in deterioration in the performance of central executive tasks and perceptions of mood state, and that this can be predicted by changes in body mass loss and plasma concentrations of the hormones cortisol and adrenaline.
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PMID:Heat stress, plasma concentrations of adrenaline, noradrenaline, 5-hydroxytryptamine and cortisol, mood state and cognitive performance. 1630 71

Being awake, alert, and able to function in our 24-7 world is a challenge in the face of the fatigue and sleepiness engendered by long work hours, unusual work schedules, sickness, and other factors. Development of effective treatments to combat fatigue and sleepiness requires an understanding of the neurobiology of wakefulness. In this brief review, we examine the neuroanatomical, neurochemical, and molecular basis of the wakeful state to provide a framework for understanding current and future pharmacologic approaches to modification of wakefulness. The spontaneously awake state can be defined as a natural state of vigilance or arousal differing from natural sleep in both behavior and neural activity. These differences have long intrigued researchers and largely have been characterized in the brain areas and neurochemical systems affecting the sleep and wake states. Many of the strategies for promoting the awake condition involve manipulation or modulation of specific neurochemical systems with the ultimate goal of enhancing wakefulness, diminishing sleepiness, or both. Wakefulness is an important cortical function that depends on the coordinated effort of multiple brain areas including the thalamus, hypothalamus, and basal forebrain to integrate and relay information from the brainstem to the cortex. Norepinephrine and serotonin-long considered arousal-enhancing transmitters as well as glutamate, acetylcholine, histamine, and the neuromodulators hypocretin-orexins and adenosine, are known to affect the signal transduction in these brain areas and initiate, promote, or enhance wakefulness. Use of molecular tools to evaluate the awake, asleep, and sleep-deprived state has revealed novel insights concerning the gene expression events associated with wakefulness. Understanding wakefulness at this level undoubtedly will contribute to the development of pharmacologic approaches to promote or enhance the wakeful state. We caution, however, that sleep may have a necessary, restorative function for the brain; therefore, prolonging wakefulness for long periods through artificial means could have unexpected and perhaps detrimental consequences on brain health.
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PMID:The pharmacology of wakefulness. 1697 20


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