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PubMed2005

Responsiveness of life-threatening refractory emesis to gabapentin-scopolamine therapy following posterior fossa surgery. Case report.

Craniotomy-associated chronic emesis can be refractory to currently approved antiemetic therapy. The authors describe a man who suffered 4 weeks of severe refractory emesis, failure to thrive, and a 40-lb weight loss after he underwent resection of a posterior fossa cholesteatoma. The patient experienced complete resolution of emesis and anorexia in response to combined gabapentin-scopolamine therapy. This case provides anecdotal evidence for the use of gabapentin-scopolamine therapy in patients with chronic, refractory nausea and emesis, particularly following posterior fossa surgery, during which medullary nausea and emesis centers may be affected.

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PubMed1998

Gabapentin in the treatment of refractory partial epilepsy in children with intellectual disability.

Twenty-six children with intellectual disability and six normal children, all suffering from refractory partial seizures, received open-label gabapentin (range = 10-50 mg kg(-1) day(-1); mean = 26.7 mg kg(-1) day(-1) as an add-on medication to their antiepileptic drug regimen. Mean seizure frequency during baseline was 9.5 seizures per week. Both groups had a significant reduction in seizure frequency. Response scores and response ratios did not differ between the intellectually disabled and normal groups (1.67+/-0.67 and 1.25+/-0.69, P = 0.697, and -0.400+/-0.089 and -0.283+/-0.159, P = 0.961, respectively). Behavioural side-effects were more likely to occur in patients with intellectual disability in comparison with the mentally normal group (P = 0.0107). In the present patient population, patients younger than 10 years of age, all of whom had intellectual disability, were more likely to have side-effects than those older than 10 years of age. Observed adverse effects, which were generally mild, occurred in patients with baseline intellectual disability, attention deficit disorder and behavioural problems. Behavioural adverse effects warranted discontinuation of the medication in only three patients. The severity of intellectual disability (mild versus moderate or severe) did not affect the extent of the response or the occurrence of side-effects. It is concluded that gabapentin is equally effective as an add-on medication against partial seizures in patients with or without intellectual disability. However, children with intellectual disability who also are less than 10 years of age with baseline attention deficit appear to be at a higher risk of behavioural side-effects.

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PubMedDate not supplied

[Gabapentin as adjuvant therapy in the treatment of refractory partial epilepsy].

With the aim to evaluate the clinical efficacy and tolerability of gabapentin as an adjuvant therapy in patients with refractory partial epilepsy we conducted an open-randomized study, with 12-weeks follow-up period. The study included 18 epilepsy patients with unsatisfactorily controlled seizures, in spite of the treatment with 1 or 2 first line antiepileptic drug. Gabapentin was administered in a total daily dose between 900-1200 mg. Our results showed seizure frequency reduction by more than 50% in 72.2% patients, while the most frequent adverse effects were vertigo (16.67%) and ataxia (11.11%).

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PubMed1999

Low dose gabapentin for shoulder-hand syndrome induced by phenobarbital: a three-month study.

Both the pathogenetic interpretation and treatment of phenobarbital-induced rheumatism are uncertain. The reflex sympathetic dystrophy syndrome which complicates antiepileptic drug therapy is a problem for rheumatologists. The aim of our study was to test the effect of gabapentin as an additional therapy in patients suffering from phenobarbital-induced shoulder-hand syndrome when these patients were treated with gabapentin instead of receiving phenobarbital only. After a 3-month observation period, the pain and the movement range from the shoulder to the wrist and to the hand improved more than in the control group using acetaminophen. Further studies are required to confirm this observation.

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PubMedDate not supplied

[The effect of gabapentin in bucco-facial allodynia. Experimental correlation of the trigeminal nerve].

INTRODUCTION: Trigeminal neuralgia is an unilateral alteration of the trigeminal nerve, characterized by recurrent paroxysms of pain in one or more of the nerve's branches. Trigger areas are described in points of the facial skin (allodynia). OBJECTIVE: To evaluate the effects of gabapentin (monotherapy) and associated with carbamazepine in allodynia of trigeminal neuralgia. PATIENTS AND METHODS: The effects of these drugs were studied in 14 patients with trigeminal allodynia and with 12 experimental cats, with microelectrodes of multiple connections in the central nervous system and in dental pulp to precipitate pain in injured zones, area of primary hyperalgesia, secondary hyperalgesia and allodynia zone. Unitary registrations and evoked potentials were evaluated in neuronal trigeminal organizations, encephalon, limic system and neocortex. RESULTS: The pairing of innocuous stimulus (allodynia) plus painful stimulus precipitate classic conditioned reflex. Unitary alteration and evoked potentials correlated with learning and memory were evaluated, involving the hippocampus in the results. The allodynia treatment obtains better results with the combined treatment than with the monotherapy. CONCLUSIONS: Allodynia can be the result of a neuronal sensitization due to the increment on intracellular calcium facilitating the exocytosis. Changes in the mechano-receptors of low threshold establish communication with nociceptive neurons by a presynaptic mechanism, considering new synaptic and morphologic contacts associated with learning and memory. The major effectiveness in the combined treatment is the base of an association of the gabaergic mechanism of gabapentin and the blockade of sodium and potassium ionic channels by the carbamazepine.

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PubMed2001

Three-month follow-up of shoulder-hand syndrome induced by phenobarbital and treated with gabapentin.

In the present study we evaluated the 3-month follow-up of 14 subjects with phenobarbital-induced shoulder-hand syndrome after discontinuation of their previous pharmacological treatment (group 1: gabapentin 100 mg/day; group 2: acetaminophen 3 g/day for 3 months). The aim of this study was to evaluate pain and joint function in each group after cessation of treatment and to compare the results in the two groups. The result for pain and joint function was better in the seven patients previously treated with gabapentin.

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PubMedDate not supplied

[Gabapentin and women].

OBJECTIVE: In the management of epilepsy, as a chronic disorder, one should remember the factors which differentiate the patients so that they may be classified into groups with common characteristics. Using gender as a differentiating criterion, we tried to systematize the factors which should be considered when studying and treating a female patient with epilepsy. DEVELOPMENT: The factors to be taken into account are biological such as the sex hormones or of psychosocial type such those related to the stigma, which may have special characteristics depending on gender. Once these factors had been systematized, we reviewed the clinical use of gabapentin from the point of view of the group considered. CONCLUSIONS: We suggest that special guidelines should be used according to the patient s gender. This review considers the female gender. The rational use of gabapentin, as monotherapy or polytherapy plays an important part in fulfilling the requirements described.

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PubMedDate not supplied

[Titration and dosage of gabapentin].

INTRODUCTION: Gabapentin (GBP) is a new anti epileptic drug which is indicated in partial epilepsy as either monotherapy or additional therapy. Unlike most anti epileptic drugs, GBP can be rapidly titrated. DEVELOPMENT: A recent double blind trial has shown that treatment with GBP may start with 900mg from the first day (300 mg every 8 hours). This dose is sufficient to be effective as monotherapy in patients with partial epilepsy of recent onset. It is also known that in patients with drug resistant epilepsy high doses of anti epileptic drugs are often necessary. In the clinical trials carried out before gabapentin was put on the market, the doses used were generally low (almost always below 1,800 mg/day). However, recent experience has shown that doses of up to 4,800 mg/day markedly increase the efficacy without significant increase in the rate of adverse effects. CONCLUSIONS: Recent data suggest that GBP may be rapidly titrated and high doses of GBP show greater efficacy with no increase in adverse effects, so they are advisable in drug resistant patients.

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PubMedDate not supplied

[Monotherapy using gabapentin in epilepsy].

DEVELOPMENT: We report a study of 62 patients with partial seizures treated with gabapentin as monotherapy for two years. After two years 78% of the patients were still on the same treatment. In 67.7% of the patients there was more than 50% reduction in major seizures and 11.1% were free of seizures. There was little difference in efficacy and tolerance when the first and second years were compared. We reviewed the data published in the literature, both in clinical trials and open studies. CONCLUSIONS: Gabapentin is an effective, well tolerated drug used as monotherapy in newly diagnosed epilepsy.

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PubMedDate not supplied

Evaluation of interaction between gabapentin and baclofen in the formalin test in mice.

Gabapentin and baclofen at doses not affecting motor performance, produced dose-dependent inhibition of both phases in the formalin test in mice. Isobolographic analysis revealed an additive interaction between the studied drugs in the second phase of the formalin test. Gabapentin given at doses effective in both phases of the formalin test significantly potentiated baclofen-induced motor impairment.

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PubMed2006

The mechanism of action of gabapentin in neuropathic pain.

Neuropathic pain is a common and potentially treatable cause of considerable lifelong morbidity. Effective pharmacological treatments are scarce, but one group of drugs that has shown promise is the antiepileptics. Gabapentin has become popular as a first-line treatment for neuropathic pain because of its efficacy as an antineuropathic agent and relatively benign side-effect profile. However, its mechanism of action is far from clear. This review discusses the available evidence for the postulated mechanisms of action of gabapentin. Understanding the mechanism of action of this agent may well lead to the development of safer and more effective antineuropathic drugs.

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PubMed1994

Emerging perspectives on the mechanism of action of gabapentin.

Significant advances have been made in understanding the molecular and cellular mechanisms underlying seizure disorders and the actions of antiepileptic drugs. Agents with new mechanisms of action or enhanced activity via known mechanisms might provide improved seizure control or more selective therapy for specific epilepsies. Gabapentin is a new antiepileptic drug that is structurally similar to the neurotransmitter GABA and the endogenous amino acid L-leucine. The mechanism of action of gabapentin is not fully understood, but its distinct profile of anticonvulsant activity in animal seizure models and its lack of activity at many drug binding sites associated with other antiepileptic drugs indicate that its mechanism of action is novel.

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PubMed1995

Optimized method for determination of gabapentin in serum by high-performance liquid chromatography.

The anticonvulsant drug gabapentin and its heptaneacetic acid analog-used here as an internal standard--are isolated from serum (pH 9) with an octyldecyl (C-18) solid-phase sorbent column. To enhance analytical detection, trinitrobenzene derivatives of these extracted compounds are prepared quickly within 10 min. To further improve chromatographic selectivity, the derivatives are concentrated on a thin C-18 solid-phase membrane and interferences are washed away. The retained purified derivatives are eluted from the membrane with a small volume of solvent and the eluate is directly injected onto an Ultrasphere C-18 high-performance liquid chromatography column with quantification at 340 nm. No evaporation-concentration steps are necessary. Recoveries (extraction) of gabapentin and the internal standard are 94.2 +/- 2.9% and 98 +/- 2.0%, respectively. Analytical responses are linear from lower limit of sensitivity of 0.05 mg/L up to at least 10 mg/L. Between-run coefficients of variation (CV) range from 2.3 to 2.9% through the concentration range 0.5-4.0 mg/L. To illustrate the rationale for selection of test parameters for a robust method, we present optimization graphs for these processes. Moreover, we discuss the advantage of the packed cartridge and membrane sorbens as companion extraction devices.

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PubMed1994

Gabapentin (NEURONTIN)--a novel anticonvulsant.

Gabapentin represents a significant advance in the management of epilepsy. To date, it appears to be most useful as an add-on therapy for patients with partial seizures uncontrolled by standard anticonvulsants. Side effects are mild and often subside with continued therapy. Unlike traditional anticonvulsants, gabapentin lacks significant drug interactions.

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PubMed1996

Hemodialysis and hemoperfusion for treatment of valproic acid and gabapentin poisoning.

A 31-y-old epileptic man developed coma and shock after suicidally ingesting large amounts of valproic acid and gabapentin. His peak valproic acid, level was 1306.9 micrograms/mL (therapeutic range = 30-100 micrograms/mL). His peak gabapentin level was 60.0 micrograms/mL (therapeutic range = 2.0-8.0 micrograms/mL). His hypotension was refractory to crystalloid and pressor infusions, but resolved during concurrent hemoperfusion and hemodialysis to enhance elimination of valproic acid. Concurrent hemoperfusion and hemodialysis, in series, produced a maximum valproic acid plasma clearance of 55.4 mL/min versus a maximum reported intrinsic valproic acid plasma clearance of 10.6 mL/min. concurrent hemoperfusion and hemodialysis, in series, should be considered in hemodynamically unstable patients with valproic acid poisoning whose clinical condition is worsening in spite of aggressive supportive care.

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PubMed1998

The anti-allodynic effects of amitriptyline, gabapentin, and lidocaine in a rat model of neuropathic pain.

UNLABELLED: The management of patients with neuropathic pain is challenging. There are only a few reports regarding the acute effects of the commonly used adjuvant drugs amitriptyline (AMI), gabapentin (GBP), and lidocaine (LDC) on neuropathic pain behaviors in animal models. Thus, the purpose of this study was to investigate the acute effects of AMI, GBP, and LDC on behavioral signs of mechanical allodynia and the site of action of these drugs using a rat model of neuropathic pain. Under general anesthesia with halothane, neuropathic injury was produced in rats by tightly ligating the left L5 and L6 spinal nerves. In Experiment 1, baseline mechanical allodynia data were recorded, and the animals were randomly divided into five groups: Group 1 received saline intraperitoneally (IP), Group 2 received AMI (1.5 mg/kg IP); Group 3 received GBP (50 mg/kg IP), Group 4 received an IV saline infusion for 10 min, and Group 5 received LDC (10-mg/kg IV infusion) for 10 min. Measurements of mechanical allodynia were repeated 0.5, 1, 2, and 4 h and 1, 3, and 7 days after treatment. In Experiment 2, rats were prepared similarly to the first experiment, and a single unit activity of continuous discharges of injured afferent fibers was recorded from the left L5 fascicles before and until 1 h after treatment. All animals developed neuropathic pain behavior within 7 days after surgery. All three tested drugs were effective in increasing the threshold for mechanical allodynia as early as 30 min after treatment, and the effect lasted for at least 1 h. Furthermore, AMI and LDC reduced the rate of continuing discharges of injured afferent fibers, whereas GBP did not influence these discharges. Our findings clearly demonstrate an attenuation of neuropathic pain behavior in rats treated with AMI, GBP, or LDC. Finally, the site of action of LDC seems to be primarily in the periphery, and that of GBP is exclusively central, whereas that of AMI seems to have both peripheral and central components. IMPLICATIONS: In the present study, we examined the effectiveness of three drugs commonly used for the treatment of neuropathic pain. Systemic injections of amitriptyline, gabapentin, or lidocaine produced pain-relieving effects in this established model for neuropathic pain in rats, which supports their clinical use in managing patients with neuropathic pain syndromes.

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