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

One hundred and fifteen patients with definite multiple sclerosis (M.S.) and chronic persistent fatigue were studied. This ten-week cross-over study consisted of a 2-week baseline period and two 3-week treatment periods separated by a 2-week washout. Patients received either amantadine 100 mg bid or matching placebo capsules. Fatigue, the effect of fatigue on an individually pre-selected activity and its effect on activities of daily living, were evaluated. Amantadine produced a small but statistically significant decrease in fatigue. An important placebo effect was noted. Mean fatigue during the washout period was lower than during the placebo run-in period, independently of which treatment had been given first. Side effects were numerous both on amantadine and on placebo. Only insomnia was significantly more common with amantadine.
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PMID:A randomized controlled trial of amantadine in fatigue associated with multiple sclerosis. The Canadian MS Research Group. 288 18

In a double-blind placebo-controlled crossover study of ten patients with multiple sclerosis, we found amantadine hydrochloride therapy to be effective in improving fatigability in six. Administration of the drug was associated with significantly higher levels of beta-endorphin-beta-lipotropin and responders had significantly higher levels than nonresponders. Lactate levels were significantly higher and pyruvate levels lower in nonresponders. Amantadine given for fatigue to patients with multiple sclerosis is associated with measurable changes in levels of metabolites and peptides in the circulation.
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PMID:Amantadine, fatigue, and multiple sclerosis. 297 70

The relative toxicities of amantadine and rimantadine were compared in a double-blind, placebo-controlled study involving healthy adults. In separate studies, drugs were administered at a dosage of 200 mg/day (52 volunteers) or 300 mg/day (196 volunteers) for 4.5 days. Both drugs were well tolerated at the lower dosage. At 300 mg/day amantadine recipients had a greater frequency and severity of central nervous system (nervousness, lightheadedness, difficulty concentrating) and sleep (insomnia, fatigue) complaints compared with rimantadine or placebo recipients. Amantadine recipients also performed less well on an objective test measuring sustained attention and problem-solving ability. Both amantadine and rimantadine recipients reported adverse gastrointestinal symptoms more often than placebo recipients. Because of better tolerance at higher dosage, rimantadine offers more promise than amantadine for treatment of influenza A virus infections.
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PMID:Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in healthy adults. 734 58

Amantadine and rimantadine are recommended for the treatment and prophylaxis of influenza A infections, and constitute an integral component of influenza control measures in the nursing home setting. However, optimal use necessitates a thorough understanding of the toxicity profiles of these agents, as well as strategies to reduce the risk of adverse reactions. Adverse reactions of these compounds predominantly involve the gastrointestinal tract and the central nervous system (CNS), including hyperexcitability, slurred speech, tremors, insomnia, dizziness, mood disturbance, ataxia, psychosis and fatigue. Based on data from comparative trials, rimantadine appears to exhibit a lesser propensity to cause adverse CNS reactions than amantadine, but a similar propensity to cause adverse gastrointestinal reactions. Factors enhancing the risk of adverse reactions to these agents include reduced renal function (especially for amantadine), drug-drug interactions with cationic drugs, which inhibit amantadine renal tubular secretion (e.g. trimethoprim, triamterene, and possibly cimetidine and procainamide), elevated peak and trough plasma concentrations, and a history of seizures. Careful attention to published dosage adjustment guidelines for these compounds, avoidance of interacting drugs and avoiding these agents in patients with a history of seizures may be the best means to reduce the risk of toxicity in elderly patients. Rimantadine may have an advantage over amantadine in the elderly population in light of its lesser propensity to cause adverse reactions, less complex dosage adjustment in the case of renal impairment and probable lack of drug-drug interaction potential with cationic drugs.
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PMID:Amantadine and rimantadine prophylaxis of influenza A in nursing homes. A tolerability perspective. 791 41

Amantadine has found use primarily as an antiviral agent and in the symptomatic treatment of parkinsonism. However, the use of amantadine for the subjective alleviation of fatigue in multiple sclerosis and in the treatment of agitated aggressive behavior in the traumatic brain injured patient has also been described. Side effects of amantadine are primarily related to the central nervous system and include hallucinations, confusion, and nightmares. Toxic manifestations include acute psychosis, coma, cardiovascular toxicity, and death. Amantadine toxicity is a particular problem in patients with renal insufficiency because 90% of an oral dose is excreted unchanged in the urine. We present a case of amantadine-induced coma in a patient with multiple sclerosis and end-stage renal disease. Moreover, this degree of amantadine toxicity was profoundly apparent at a drug level usually not associated with such a severe presentation.
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PMID:Amantadine-induced coma. 821 67

Carnitine is essential for mitochondrial energy production. Disturbance in mitochondrial function may contribute to or cause the fatigue seen in Chronic Fatigue Syndrome (CFS) patients. Previous investigations have reported decreased carnitine levels in CFS. Orally administered L-carnitine is an effective medicine in treating the fatigue seen in a number of chronic neurologic diseases. Amantadine is one of the most effective medicines for treating the fatigue seen in multiple sclerosis patients. Isolated reports suggest that it may also be effective in treating CFS patients. Formal investigations of the use of L-carnitine and amantadine for treating CFS have not been previously reported. We treated 30 CFS patients in a crossover design comparing L-carnitine and amantadine. Each medicine was given for 2 months, with a 2-week washout period between medicines. L-Carnitine or amantadine was alternately assigned as fist medicine. Amantadine was poorly tolerated by the CFS patients. Only 15 were able to complete 8 weeks of treatment, the others had to stop taking the medicine due to side effects. In those individuals who completed 8 weeks of treatment, there was no statistically significant difference in any of the clinical parameters that were followed. However, with L-carnitine we found statistically significant clinical improvement in 12 of the 18 studied parameters after 8 weeks of treatment. None of the clinical parameters showed any deterioration. The greatest improvement took place between 4 and 8 weeks of L-carnitine treatment. Only 1 patient was unable to complete 8 weeks of treatment due to diarrhea. L-Carnitine is a safe and very well tolerated medicine which improves the clinical status of CFS patients. In this study we also analyzed clinical and laboratory correlates of CFS symptomatology and improvement parameters.
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PMID:Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome. 901 19

Twenty-one patients (mean age 70 yrs) with restless legs syndrome (RLS) were treated with amantadine in an open-label trial. Amantadine was started at 100 mg per day and was increased every 3-5 days by 100 mg (up to a maximum of 300 mg per day) until significant relief of symptoms or intolerable side effects were experienced. Patients were rated pre- and posttreatment using an RLS rating scale (0-10). Each patient also rated the degree of response in a continuous scale from 0% (no improvement) to 100% (complete improvement). Eleven of 21 (52%) had subjective benefit to amantadine, with degree of response ranging from 25%-100% (mean 69%) among responders. Six had 95%-100% improvement. The RLS score for all 21 patients dropped from a mean (+/- standard deviation) of 9.8 +/- 0.6 (range, 8-10) pretreatment to 6.6 +/- 3.8 (range, 0-10) posttreatment (p = 0.001). The duration of response was 0-13 months (mean, 3.6 +/- 4.5), with nine responders still remaining on the drug as of last follow up. The mean effective dose was 227 mg per day. The most common side effects were drowsiness (3), fatigue (2), and insomnia (2); only two stopped amantadine because of side effects. We conclude that amantadine is an effective and well-tolerated drug for RLS.
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PMID:Amantadine is beneficial in restless legs syndrome. 1075 86

In primary interferon-alpha (IFN-alpha) nonresponders with chronic hepatitis C, retreatment with IFN-alpha has only limited efficacy with sustained response rates below 10%. Therefore, the aims of the present study were to compare the efficacy and safety of IFN-alpha alone or in combination with amantadine sulphate in nonresponders to previous IFN-alpha monotherapy. Fifty-five IFN-alpha nonresponders with chronic hepatitis C (mean age: 46.6 years) received IFN-alpha 6 MIU thrice weekly for 24 weeks followed by 3 MIU thrice weekly for additional 24 weeks. Amantadine sulphate (n=26) or a matched placebo (n=29) was given orally twice daily for 48 weeks. Because of a low initial response rate at week 12 (13/55 patients) and a high breakthrough rate (8/13 patients) after IFN-alpha dose reduction in week 24, a virological end-of-treatment response with undetectable serum HCV-RNA (< 1000 copies/mL) was achieved in only five patients (IFN-alpha/amantadine sulphate, one patient; IFN-alpha/placebo, four patients). After 24 weeks follow-up a sustained virological response was observed in only two patients receiving IFN-alpha and placebo. Health-related quality-of-life analysis showed a substantial improvement of the Profile of Mood States (POMS) scale concerning the subscales fatigue (P < 0.05) and vigor (P < 0.05) in patients receiving combined IFN-alpha/amantadine sulphate treatment compared with those treated with IFN-alpha alone. IFN-alpha/amantadine sulphate combination therapy was well tolerated without any serious adverse events. In conclusion, retreatment with IFN-alpha and amantadine sulphate does not increase the low sustained virological response rates of IFN-alpha therapy in primary IFN-alpha nonresponders with chronic hepatitis C, but may lead to a sustained improvement of health-related quality-of-life.
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PMID:Randomized, placebo-controlled, double-blind trial with interferon-alpha with and without amantadine sulphate in primary interferon-alpha nonresponders with chronic hepatitis C. 1145 79

Fatigue is a common complaint in patients affected by multiple sclerosis. Its mechanisms are poorly understood and are likely diverse. The term "fatigue" has been used for asthenia at rest but also for fatigability during exercise. Amantadine is the only drug that has a proven therapeutic benefit in randomized, double blind, controlled trials. Inhibitors of serotonin re-uptake are used pragmatically because of the relationship between fatigue and depression. Aminopyridins may improve fatigability, mainly at the level of lower limbs.
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PMID:[Therapeutic indications for managing symptoms: fatigue]. 1178 38

Fatigue is a very common symptom of multiple sclerosis (MS). Theoretically, fatigue may be related to neuromodulation by soluble products of the autoimmune process or by disruption of central nervous system pathways necessary for sustained activity, but little empirical evidence supports these possibilities. Amantadine, pemoline, and modafanil improved fatigue in placebo-controlled clinical trials, but these studies all had significant limitations. Difficulty measuring fatigue has impeded studies of its characteristics, mechanisms, and therapeutics. Most studies have relied on self-report questionnaires. These may be inappropriate, however, because they can be easily confounded by other symptoms of MS, they are entirely subjective, and they require patients to make difficult retrospective assessments. Studies of fatigue would be improved by including measures of more rigorously defined, quantifiable components of fatigue. For example, motor fatigue can be measured as the decline in strength during sustained muscle contractions. Cognitive fatigue can be measured as the analogous decline in cognitive performance during tasks requiring sustained attention. Lassitude is defined as a subjective sense of reduced energy, and it can be measured with the use of a visual analog diary. These measures provide reproducible results and demonstrate significant differences between MS patients and healthy controls. Dividing fatigue into these components can provide objective assessments that are less likely to be confounded by other symptoms of MS, such as weakness, spasticity, cognitive impairment, and depressed mood.
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PMID:Fatigue in multiple sclerosis: current understanding and future directions. 1205 65


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