Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gabapentin is an antiepileptic drug with an unknown mechanism of action apparently dissimilar to that of other antiepileptic agents, and possessing some desirable pharmacokinetic traits. The drug is not protein bound, is not metabolised and does not induce liver enzymes, diminishing the likelihood of drug interactions with other antiepileptic agents and drugs such as oral contraceptives. Although gabapentin is a structural analogue of the neurotransmitter gamma-aminobutyric acid (GABA), which does not cross the blood-brain barrier, gabapentin penetrates into the CNS and its activity is seemingly distinct from GABA-related effects. Present clinical evaluation is largely restricted to proof of efficacy trials of gabapentin as add-on therapy in patients with partial epilepsy resistant to conventional treatment. Gabapentin (usually 600 to 1800 mg/day) provides notable benefit, reducing seizure frequency by > or = 50% in 18 to 28% of patients with refractory partial seizures, as shown in 3 double-blind, placebo-controlled trials. Overall, seizure frequency decreased by 18 to 32% during 3-month treatment periods. Patients with complex partial seizures, and partial seizures secondarily generalised, are particularly likely to respond to gabapentin. Current experience with the drug in other seizure types, and as monotherapy, is limited. Mild adverse events, commonly somnolence, fatigue, ataxia and dizziness, have been reported in about 75% of gabapentin recipients. While the drug has been well tolerated when administered to a few patients for periods of up to 5 years, its long term tolerability profile has yet to be fully expounded. Thus, with its favourable pharmacokinetic profile, and efficacy in some refractory patients, gabapentin is poised to fill a niche as an adjunct to the treatment of partial epilepsy. Promising results obtained thus far warrant further work to clarify its long term tolerability, its possible efficacy in other seizure types, its position relative to other agents and its use as monotherapy. In the meantime, gabapentin is likely to provide a much-needed option in a therapeutic area requiring complex management.
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PMID:Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy. 769 32

A multicenter, double-blind, randomized, placebo-controlled study evaluated the efficacy and safety of gabapentin (Neurontin, GBP) as add-on therapy in 272 patients with refractory partial seizures who were receiving one to two standard antiepileptic drugs (AEDs). Efficacy assessments compared the frequency of partial seizures during the 12-week treatment phase (T) and the 12-week baseline period (B). The primary analysis compared data for patients receiving GBP 900 mg/day with placebo; the GBP 1,200-mg/day group provided dose-response data. Efficacy criteria were percentage of change in seizure frequency (PCH), responder rate (percentage of patients with > or = 50% reduction in seizure frequency), and response ratio, where RRatio = (T-B)/(T + B). Median PCH was -21.8% in the 900-mg/day group and -17.8% in the 1,200-mg/day group as compared with -0.3% in the placebo group. Responder rate was 22.9% in the 900-mg/day group and 10.1% in the placebo group (p = 0.020, Fisher's exact test). Adjusted mean RRatio was -0.136 in the 900-mg/day group and -0.025 in the placebo group (p = 0.0046, analysis of variance ANOVA). Results showed slightly greater improvement for the 1,200-mg/day than for the 900-mg/day group (RRatio = -0.157, responder rate 28.0%). Adverse events (AE) occurred in 69% of patients in the 900-mg/day group and in 64% in the 1,200-mg/day group as compared with 52% in patients receiving placebo as add-on therapy. The most frequent AE among patients treated with GBP were somnolence, dizziness, and fatigue. Clinical laboratory evaluations showed no clinically important trends and no evidence of hepatic or hematopoietic effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gabapentin (Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. The International Gabapentin Study Group. 808 24

The efficacy of gabapentin (Neurontin), in generalized seizures was evaluated in this 14 week, double-blind, placebo-controlled, parallel-group, add-on, multicenter study. A total of 129 patients with refractory generalized seizures were randomized to receive either placebo or 1200 mg/day gabapentin as add-on therapy. Patients received their standard regimens of antiepileptic drugs (AEDs) during a 12 week baseline period, and gabapentin or placebo was added-on in the subsequent 14 week evaluation period. Results of both an intent-to-treat (ITT) and evaluable-patient analyses showed that gabapentin provided greater reduction in the frequency of generalized tonic-clonic seizures than did placebo; however, the differences between treatments were not statistically significant. Gabapentin did not affect the frequency of absence or myoclonic seizures. Adverse events were reported by 67% of gabapentin-treated patients and by 56% of placebo-treated patients. The most frequently occurring adverse events among patients receiving gabapentin were somnolence, fatigue, and dizziness. Gabapentin is well tolerated by patients with generalized seizures. The results of this study show a trend toward an effect of gabapentin in reducing the frequency of generalized tonic-clonic seizures and suggest that further exploration of high dose gabapentin in generalized epilepsy is warranted.
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PMID:Gabapentin in generalized seizures. 895 16

Gabapentin is a recently introduced antiepileptic drug for the treatment of partial seizures. Although studied extensively in adults, there have been few pediatric studies. It is a unique drug because it has no protein binding, is not metabolized, and is excreted through the kidneys. There are no significant drug interactions with other antiepileptic drugs nor do other antiepileptic drugs alter the pharmacokinetics of gabapentin. The drug is effective in partial seizures, although most studies have used the drug as add-on therapy. It is approved for use of partial seizures with or without secondary generalization in patients over the age of 12 years. The side effect profile of the drug is quite good. No significant idiosyncratic reactions have been reported. The most common side effects have included dizziness, fatigue, and headache. Rarely, children will have adverse behavioral effects, such as hyperactivity and agitated behavior. Usually these children have pre-existing behavioral disturbances. Although the spectrum of efficacy of gabapentin remains to be determined, it is likely to have a major beneficial impact on the treatment of childhood epilepsy.
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PMID:Gabapentin for treatment of epilepsy in children. 932 92

A patient with painful neuropathy developed ocular, facial, and masticatory weakness and fatigue after 3 months of gabapentin (GBP) treatment (400 mg/day). An elevated level of serum acetylcholine receptor antibodies (AChR-Ab) was detected. The patient recovered following pyridostigmine therapy and withdrawal of GBP and, 2 years later, is practically asymptomatic despite positive AChR-Ab. Because of this clinical observation, we gave 150 mg/kg GBP to rats with experimental autoimmune myasthenia gravis (EAMG). Repetitive nerve stimulation at 3-Hz was performed, and the 5th/1st amplitude ratio was used to calculate the decremental response. In all EAMG rats, GBP induced a transient, abnormal decrement (7-20%) 90 to 240 min after administration. No decrement was induced by GBP in normal rats. Thus, GBP aggravates the decrement in EAMG. The mechanism involved in the hitherto unreported possible unmasking of myasthenia gravis (MG) by GBP is unknown. Gabapentin should be used with caution in this disease.
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PMID:Gabapentin may be hazardous in myasthenia gravis. 1091 56

(1) Gabapentin is now licensed for first-line or replacement monotherapy of partial epilepsy, in patients over 12 years of age. (2) The assessment file concurs with current recommendations of medicines agencies. (3) One comparative trial of first-line monotherapy showed a similar efficacy/adverse effects ratio of gabapentin and carbamazepine. Gabapentin has not been compared with valproate sodium. (4) In one trial, involving patients with refractory epilepsy, various doses of gabapentin were added to an ongoing inadequately effective treatment, which was then gradually stopped. Gabapentin monotherapy was considered satisfactory in a minority of patients. (5) The adverse effects of gabapentin are limited to neuropsychological disorders, namely dizzy spells, drowsiness, fatigue and headache. The risk of interactions is also limited. (6) The optimal dose regimen of gabapentin is not yet established.
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PMID:Gabapentin monotherapy: new indication. Sometimes helpful. 1150 84

Gabapentin is an antiepileptic medication that also has been used for restless legs syndrome. The mechanism of action is unknown. The most commonly reported adverse effects of this medication include somnolence, dizziness, ataxia, fatigue, nystagmus, and tremor. Myalgia has been reported in 2% of gabapentin users compared with 1.9% of patients in placebo-controlled add-on trials. Two patients on short daily hemodialysis therapy developed neuromuscular symptoms and an elevation in creatine kinase levels after starting gabapentin therapy. To our knowledge, this is the first case report of an increase in creatine kinase level after the administration of gabapentin.
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PMID:Gabapentin-induced myopathy in 2 patients on short daily hemodialysis. 1595 20

A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400 mg/day. The study comprised a run-in period of two weeks, two treatment periods of five weeks separated by a three weeks' washout period. The primary efficacy variable was the change in the mean pain intensity score from baseline to the last week of treatment. Other variables included pain relief, health related quality of life (SF-36), interference of sleep by pain, Clinician and Patient Global Impression of Change, and adverse effects. Nine centers randomized a total of 120 patients, 22 of whom withdrew. There was no statistically significant difference between the treatments for the primary outcome efficacy variable. However, gabapentin provided significantly better pain relief (p=0.015) compared with placebo. More patients had at least a 30% pain reduction with gabapentin compared with placebo (p=0.040) and pain interfered significantly less with sleep during gabapentin treatment compared with placebo (p=0.0016). Both the Patient (p=0.023) and Clinician (p=0.037) Global Impression of Change indicated a better response with gabapentin compared with placebo. Gabapentin was well tolerated. The most common adverse effects were dizziness and tiredness.
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PMID:Gabapentin in traumatic nerve injury pain: a randomized, double-blind, placebo-controlled, cross-over, multi-center study. 1825 68

Hot flashes occur frequently in menopausal women and in women with breast cancer, diminishing their quality of life. A report from the Women's Health Initiative published in 2002 raised concerns about the long-term safety of estrogen therapy. As a result, nonhormonal alternatives have emerged as preferred treatments. Gabapentin is an anticonvulsant that the United States Food and Drug Administration approved as an adjunct therapy for partial seizures and postherpetic neuralgia. Somnolence, dizziness, ataxia, fatigue, nystagmus, and peripheral edema are adverse effects commonly associated with gabapentin in the treatment of epilepsy and postherpetic neuralgia. The North American Menopause Society and the American College of Obstetricians and Gynecologists recommend the use of gabapentin as an option for managing hot flashes in women who are unwilling to take estrogen-containing supplements. To evaluate the efficacy and safety of gabapentin for the treatment of hot flashes in women with menopause and/or breast cancer, we performed a search of the MEDLINE database (1966-March 2008) and International Pharmaceutical Abstracts, as well as manually searching reference articles for relevant articles and abstracts; 10 clinical studies were identified. Although the studies were few, all showed gabapentin to be safe and effective in the treatment of hot flashes. At doses used to control hot flashes, gabapentin was well tolerated, with drowsiness as its most reported adverse effect. Gabapentin can be considered effective in the treatment of hot flashes and should be considered a reasonable alternative when estrogen therapy is not desired.
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PMID:Use of gabapentin in patients experiencing hot flashes. 1911 98

Gabapentin (GBP) is a drug which is frequently used in diabetic neuropathy. Common adverse effects of GBP include drowsiness, dizziness, ataxia, somnolence, and fatigue. Rhabdomyolysis is an extremely rare side effect of GBP. In this report we describe a case of GBP-induced rhabdomyolysis in a 63-year-old diabetic woman. She presented with severe muscle pain in her extremities, fatigue, decreased urine output and urine discoloration within 3 weeks after starting treatment with GBP (900 mg/day) for diabetic neuropathy. Laboratory tests revealed extreme elevations of muscle enzymes, increased creatinine and potassium levels. She required hemodialysis as a result of anuria. Investigation confirmed the diagnosis of rhabdomyolysis, and discontinuation of GBP resulted in resolution of clinical and biochemical features of rhabdomyolysis.
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PMID:Gabapentin-induced rhabdomyolysis in a patient with diabetic neuropathy. 1952 4


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