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Pilot clinical trial of gabapentin to decrease postoperative delirium in older patients.

In this randomized pilot clinical trial, the authors tested the hypothesis that using gabapentin as an add-on agent in the treatment of postoperative pain reduces the occurrence of postoperative delirium. Postoperative delirium occurred in 5/12 patients (42%) who received placebo vs 0/9 patients who received gabapentin, p = 0.045. The reduction in delirium appears to be secondary to the opioid-sparing effect of gabapentin.

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Gabapentin does not interact with a contraceptive regimen of norethindrone acetate and ethinyl estradiol.

Anticonvulsants that induce hepatic metabolism increase clearance of oral contraceptive hormones and thereby cause contraceptive failure. Gabapentin is not metabolized in humans and has little liability for causing metabolic-based drug-drug interactions. In healthy women receiving 2.5 mg norethindrone acetate and 50 microg ethinyl estradiol daily for three consecutive menstrual cycles, concurrent gabapentin administration did not alter the steady-state pharmacokinetics of either hormone. Thus, gabapentin is unlikely to cause contraceptive failure.

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Gabapentin relieves trigeminal neuralgia in multiple sclerosis patients.

This report describes the effectiveness of gabapentin, a recently approved anticonvulsant, in seven patients with MS experiencing trigeminal neuralgia refractory to treatment with conventional medical therapy. Gabapentin relieved pain completely in six and significantly in the seventh patient. Gabapentin may be a valuable addition to pharmacologic therapy in trigeminal neuralgia, particularly in patients with MS and in refractory cases.

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Gabapentin's effects on hot flashes and hypothermia.

The author describes six cases in which gabapentin treatment reduced the frequency of hot flashes. In addition, gabapentin treatment enhanced the frequency of hypothermic episodes in a separate patient with known hypothalamic dysfunction. Gabapentin may act directly upon temperature regulatory centers.

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Suppression by gabapentin of pain-related mechano-responses in mice given orthotopic tumor inoculation.

In this study, we examined whether several types of non-opioid agents would inhibit the pain-related responses of melanoma-bearing mice. Orthotopic inoculation with melanoma into the hind paw induced marked tactile allodynia and mechanical hyperalgesia. A peroral injection (p.o.) of gabapentin (100-300 mg/kg) inhibited the allodynia and hyperalgesia, without effects on gross behaviors. An intraperitoneal injection (i.p.) of ketamine hydrochloride (30 mg/kg) produced partial inhibition in allodynia and hyperalgesia and prostate posture at 15 min after injection. Diclofenac sodium (10 and 30 mg/kg, i.p), mexiletine hydrochloride (20 mg/kg, i.p.), clonidine hydrochloride (0.1 mg/kg, i.p.) and suramin (100 mg/kg, i.p.) were without effects on allodynia and hyperalgesia. Subcutaneous injections of baclofen (3 mg/kg) and N(G)-nitro-L-arginine methyl ester (100 mg/kg) were also without effects. Repeated administration of gabapentin (150 mg/kg, p.o.) produced constant inhibitions, suggesting no analgesic tolerance. Gabapentin may be useful for the management of cancer pain.

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Antidepressant-induced bruxism successfully treated with gabapentin.

BACKGROUND: Symptoms consistent with bruxism are a common chief complaint in dental practice. The authors describe a case of bruxism likely induced by the antidepressant venlafaxine and successfully treated with gabapentin. CASE DESCRIPTION: A case of bruxism, anxiety, insomnia and tremor is reported in a man with bipolar disorder that developed a few days after he initiated venlafaxine therapy for depression. The patient's psychiatrist prescribed gabapentin for anxiety symptoms, and shortly thereafter the man experienced a complete resolution of the bruxism. CLINICAL IMPLICATIONS: On the basis of this case and the available literature, the authors conclude that bruxism secondary to antidepressant therapy may be common. Thus, dentists should inquire about the use of these medications in patients who have bruxism. Gabapentin may offer promise in the treatment of this condition.

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Gabapentin: a review of published experience in the treatment of bipolar disorder and other psychiatric conditions.

Successful therapy with valproate and carbamazepine in patients with psychiatric disorders led to investigation of other anticonvulsants for similar indications. Gabapentin is a relatively new anticonvulsant being investigated for potential use in the treatment of bipolar disorder (BD), anxiety disorders, behavioral dyscontrol, and substance use disorders. Its favorable side effect profile, absence of the need for therapeutic drug monitoring, and minimal drug interactions give gabapentin a potential role in these indications. Computer searches of the biomedical literature were undertaken to identify all pertinent case reports, case series, and studies of the drug as monotherapy or adjunctive therapy for BD; 10 reports were retrieved. In the treatment of various anxiety disorders, one study, one case report, and one case series were identified. At least one case series described gabapentin therapy for alcohol withdrawal and one case report of the drug for agitation associated with dementia. Published, well-designed studies evaluating the agent's effectiveness as monotherapy for BD are lacking. Its benefit as an adjunctive treatment with other mood stabilizers is also unestablished. Data regarding its efficacy in the treatment of anxiety disorders or manifestations of substance abuse are limited. These areas may deserve further investigation.

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Gabapentin in the treatment of cocaine dependence: a case series.

BACKGROUND: Although multiple medications have been studied for the treatment of cocaine dependence, no medication has been shown to have a robust effect on craving and use. This pilot project was designed to evaluate the safety and tolerability of gabapentin in subjects with cocaine dependence. METHOD: Thirty cocaine-dependent subjects (DSM-IV criteria) were enrolled in an 8-week, open-label trial of 1,200 mg/day of gabapentin in divided doses. Urine drug screens, subjective measures of craving, and cocaine use interviews were conducted at each weekly visit. RESULTS: Baseline rating of amount and frequency of craving decreased significantly by week 8 (78% vs. 25% for amount, p = .000; 74% vs. 23% for frequency, p = .004). Positive urine drug screens for cocaine decreased from 86% at baseline to 29% at weeks 4 and 8. There were no reports of significant side effects or adverse events. CONCLUSION: This pilot study indicates that gabapentin is safe and well tolerated and may be beneficial in the treatment of cocaine dependence. A placebo-controlled trial would be of interest.

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[Use of gabapentin in glossopharyngeal neuralgia].

Anticonvulsant drugs, especially carbamazepine, are the treatment of choice for glossopharyngeal neuralgia. If no clinical response is obtained, surgical treatment, including nerve section or decompression, may be required. We report the results obtained with a new anticonvulsant, gabapentin, as an alternative for cases of carbamazepine failure. In 7 patients with bouts of glosso-pharyngeal neuralgia refractory to the usual medical treatment, gabapentin produced improvement in 5 patients. Response was poor in patients who had undergone surgical nerve decompression. Gabapentin was concluded to be an effective therapeutic option for neuralgia of the IXth cranial nerve before surgery.

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Antinociceptive effect of gabapentin in the formalin test.

Gabapentin is an adjunctive drug for the treatment of resistant partial seizures. The antinociceptive effect of this drug was assessed by using the formalin pain test in rats. Although low dose gabapentin (10 mg/kg s.c.) was unable to alter pain scores, higher doses (30 and 90 mg/kg s.c.) significantly reduced them. Results suggest that gabapentin may modulate the pain perception produced by chemical irritants like formalin in rats.

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[Monotherapy with gabapentin ++].

INTRODUCTION AND OBJECTIVE: Gabapentin is an anti-epileptic drug approved in the USA in December 1993 as an additional treatment for patients with crises of partial onset. Recently it has been approved for use as monotherapy. We review the characteristics of this molecule as an anti-epileptic drug and the clinical trials which have permitted approval of the current indications. DEVELOPMENT: We review the particular difficulties of designing trials using monotherapy, both for ethical reasons (problems with the use of a placebo) and for technical reasons and those of interpretation (problems comparing two drugs with equivalent results) and analyze the trials in which attempts were made to overcome these difficulties. A trial designed to replace polytherapy in drug-resistant patients by monotherapy did not show conclusive results, although they were suggestive. A trial of patients admitted for pre-surgical studies permitted verification of the efficacy and safety of higher doses (3,600 mg/day) than those previously used (800-2,400 mg/day). Another trial, this time of newly diagnosed patients, permitted verification of the efficacy and safety of gabapentin used in different dosages. CONCLUSIONS: Gabapentin is effective when used as monotherapy. The dose recommended for the initial treatment of newly-diagnosed patients is 900 mg/day. It has a better safety profile than carbamazepine and is indicated in simple and complex partial crises with or without secondary generalization.

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Gabapentin for the treatment of tinnitus: a case report.

The objective of this article is to discuss the clinically effective use of gabapentin in patients with tinnitus. The author describes the case of a man who came to the office complaining of tinnitus of 10 months' duration. The patient was started on gabapentin and maintained on a regimen of 500 mg/day in divided doses. Subsequently, he reported that he was free of tinnitus approximately 23 days a month and that he experienced a 75% decrease in symptoms during the remaining days. At 2 years' follow-up, he remains noise- and pain-free on 500 mg/day of gabapentin.

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Massive gabapentin and presumptive quetiapine overdose.

Previous reports of gabapentin overdose have described mild symptoms of somnolence, ataxia and slurred speech. Quetiapine has produced a false positive for cyclic antidepressants on immunoassay drugscreens. Quetiapine overdose is associated with coma, QTc prolongation and hypotension. We report a case of massive gabapentin and presumptive quetiapine overdose with the highest recorded serum gabapentin concentration (104.5 u/ml) associated with coma, respiratory depression requiring mechanical ventilation, and hypotension.

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The effect of Vigabatrin, Lamotrigine and Gabapentin on the fertility, weights, sex hormones and biochemical profiles of male rats.

PURPOSE: A case control study was conducted to assess the effect of Sabril (Vigabatrin), Lamictal (Lamotrigine) and Neurontin (Gabapentin) on fertility in male rats. Their effect on the body and organs weight and certain biochemical profiles including total serum protein, cholesterol, triglycerides, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum testosterone, and FSH levels were also measured. METHODS: several parameters, concerning fertility were measured in 40 albino male rats of Sprague Dawley strain, they were divided into 4 groups, group one received vehicle (distilled water), group two received Vigabatrin in a dose of 200 mg/kg body weight, group three received Lamotrigine in a dose of 30 mg/kg body weight, and group four received Gabapentin 100 mg/kg body weight. All the male rats in these groups received the different medications for a complete reproductive cycle (60 days). After 24 hours of the last dose, the animals were weighed and autopsied under light ether anesthesia. Parameter of fertility that has been measured in this study includes: sperm count and motility, weight of different reproductive organs, germ cell and interstitial cell population, serum testosterone and FSH levels and assessment of pregnancies in females mixed with tested males. Biochemical profiles such as serum cholesterol, serum triglycerides, serum bilirubin, SGOT, SGPT level are all measured. The results of the histological, histometerical studies and biochemical profiles were compared to that of the control group, and the significance of these results was measured using student's "t" test. RESULTS: There was significant reduction in the body weight and the weight of the testes, epididymis, seminal vesicles, ventral prostate, and vas deferens in the antiepileptic fed male rats in comparison to the control group (p > 0.001). There was significant reduction in testicular cells population dynamics including both germinal cell types and interstitial cell types in the antiepileptic fed male rats in comparison to the control group. There was also significant reduction in histometrical parameters and sperm dynamics in the antiepileptic fed male rats histologies in comparison to the control group. There was significant reduction in both testosterone and FSH levels (p < 0.001) in the antiepileptics fed male rats in comparison to the control group. There was also significant reduction in pregnancy rate observed in female rats exposed to the tested male rats among antiepileptic fed male rats compared to controls. The results of biochemical profiles assessment showed significant reduction in serum glucose, serum cholesterol, serum triglycerides levels and significant increase in serum bilirubin, SGOT, and SGPT levels in antiepileptics fed male rats in comparison to the control group. CONCLUSIONS: Fertility rate and other parameters concerned with fertility, sex hormones and certain biochemical profiles were significantly disturbed in male rats fed with three of the second-generation antiepileptic drugs Vigabatrin, Lamotrigine, and Gabapentin, indicating a possible toxic effect of these three medications on sexual organs, liver, and lipid metabolism.

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Evaluation of encephalotropic and psychotropic properties of gabapentin in man by pharmaco-EEG and psychometry.

In a double-blind, placebo-controlled study the encephalotropic and psychotropic properties of gabapentin - a new gaba-analogue with anticonvulsant and antispastic properties penetrating the blood brain barrier easily - were studied in 10 normal subjects by means of quantitative pharmaco-EEG and psychometric analyses. They received randomized and in weekly intervals single oral doses of 50 mg, 100 mg, 200 mg and 400 mg gabapentin as well as placebo. EEG recordings and evaluation of pulse, blood pressure and side effects were carried out after 0, 1, 2, 4, 6 and 8 hours; psychometric tests were done at the same times except for the first hour. Computer-assisted spectral analysis of the EEG showed moderate though significant central effects of gabapentine in doses of 200-400 mg as compared with placebo, which were maximally pronounced in the 2nd hour post drug. These alterations were generally characterized by an attenuation of total power, augmentation of delta and theta activity and a decrease of alpha activity indicating CNS-inhibitory properties. Only at the late hours did the type of changes shift towards a vigilance-promoting one. Beta activity showed alternating changes. Psychometric and psychophysiological evaluations demonstrated subtle psychotropic effects as compared with placebo characterized mostly by an improvement in concentration, numerical memory, complex reaction and performance in the alphabetical reaction test while performance variability increased as well. Subjectively experienced well-being changed dose-dependently. CFF decreased after 100 mg as did pupil size after 50-200 mg. Evaluation of pulse, blood pressure and side effects demonstrated good tolerability of the drug.

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Choreoathetosis as a side effect of gabapentin therapy in severely neurologically impaired patients.

OBJECTIVE: To evaluate the relationship of gabapentin therapy with choreoathetotic movements in mentally retarded patients treated with intractable epilepsy. DESIGN: Case reports of 2 institutionalized patients who developed choreoathetosis temporally related to adjunctive therapy with gabapentin at dosages of 1200 to 1800 mg/d. RESULTS: Both patients experienced resolution of abnormal movements on discontinuation of the therapy. One patient developed recurrent choreiform movements after drug rechallenge. CONCLUSION: We suggest that, in patients with mental retardation and epilepsy, involuntary movements may either occur as reversible side effects of gabapentin therapy or result from a previously undescribed adverse drug interaction with other antiepileptic agents.

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[Treatment of neuropathic pain with gabapentin ++].

INTRODUCTION: The antiepileptic drug gabapentin has begun to be used successfully in some cases of neuropathic pain. Its mechanism of action is still unknown, but seems to be related to a positive effect on the synthesis and liberation of the neurotransmitter GABA. CLINICAL CASES: Based on the observations of other authors, we used this drug in dosage varying between 900 and 1,200 mg/day, in three patients with neuropathic pain, of both central and peripheral origin, and in whom the usual treatments had been unsatisfactory or could not be tolerated because of side-effects. The patients had been diagnosed as having trigeminal neuralgia, post-herpetic neuralgia in the area of the first branch of the trigeminal nerve and a thalamic infarct which gave rise to a contralateral Déjerine-Roussy syndrome, respectively. In all three cases, administration of gabapentin was followed by such a striking improvement of the pain that co-adjuvant treatment could be reduced or stopped, with excellent tolerance and a minimal incidence of side-effects. CONCLUSIONS: Gabapentin should be borne in mind in the treatment of this type of pain, particularly when the usual treatment cannot be given or is insufficient to control pain, especially in elderly patients in whom there is often reduced tolerance of drugs.

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