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PubMed1997

Isolated ataxia as an idiosyncratic side-effect under gabapentin.

Gabapentin has been accepted worldwide as a novel antiepileptic drug with a favourable tolerability profile. However, movement disorders have been reported previously as rare side-effects in individual patients. We report on two patients who developed isolated severe ataxia under low-dose gabapentin which resolved abruptly after discontinuation of the drug. This side-effect probably resembled a rare idiosyncratic adverse reaction. We propose the gabapentin-specific neuronal binding site which has a high density in the cerebellum as a possible mechanism of action and suggest that the initiation of gabapentin requires caution if pre-existing cerebellar function impairment is evident.

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PubMedDate not supplied

Acute herpetic neuralgia and postherpetic neuralgia in the head and neck: response to gabapentin in five cases.

BACKGROUND AND OBJECTIVES: The clinical presentations and pharmacologic management of three patients with acute herpetic neuralgia (AHN) and two patients with postherpetic neuralgia (PHN), confined to the head and neck region, are described. METHODS: Two patients had pain in the ophthalmic division of the trigeminal nerve, two had pain confined to the C2-C4 dermatomes, and one patient had C2 pain with radiating and referred pain to the second and third divisions of the trigeminal nerve. RESULTS: Gabapentin, an anticonvulsant drug, was effective in treating these patients, including the two cases of AHN. All patients reported complete pain relief after titration with gabapentin up to 1,800 mg/d. The patients noted a dose-dependent decrease in pain almost immediately after starting gabapentin. Specifically, reduction in the frequency and intensity of allodynia, burning pain, shooting pain, and throbbing pain were noted. None of the patients experienced side effects from the drug. CONCLUSIONS: In view of the results in these patients, blinded, controlled studies are needed to determine the efficacy of gabapentin for treating AHN and PHN.

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PubMed2007

A combination of gabapentin and local anaesthetics attenuates acute and late pain after abdominal hysterectomy.

BACKGROUND AND OBJECTIVE: Gabapentin and local anaesthetics may decrease postoperative pain and analgesic needs. The aim of the study was to investigate the effect of the combination of these drugs on the analgesic needs as well as on acute and late pain after abdominal hysterectomy. METHODS: Sixty patients undergoing abdominal hysterectomy were randomly assigned to receive postoperatively oral gabapentin 400 mg 6 hourly for 7 days plus continuous wound infusion of ropivacaine 0.75% for 30 h or placebo capsules identical to those of gabapentin for 7 days and continuous wound infusion of normal saline for 30 h. Morphine consumption (PCA) for 48 h, paracetamol 500 mg plus codeine 30 mg (Lonalgal tablets) intake on days 3-7, visual analogue pain scores at rest and after cough during the first 7 postoperative days, the need for analgesics at home and the presence and incidence of pain after 1 month were recorded. RESULTS: The treatment group consumed less cumulative morphine over the first 48 h (31 +/- 13.2 mg vs. 50 +/- 20.5 mg in controls, P < 0.001) and less Lonalgal tablets on days 3-7 (z = 2.54, P = 0.011). The visual analogue score values at rest and after cough did not differ between the groups during the first 7 postoperative days. One month postoperatively, fewer patients in the treatment group experienced pain due to surgery than in the control group (17/27 vs. 21/24, P = 0.045). CONCLUSION: Gabapentin and continuous wound infusion with ropivacaine 0.75% decreased analgesic needs and late pain in patients undergoing abdominal hysterectomy.

Administration, Oral↗
PubMed1998

Identification of novel ligands for the gabapentin binding site on the alpha2delta subunit of a calcium channel and their evaluation as anticonvulsant agents.

As part of a program to investigate the structure-activity relationships of Gabapentin (Neurontin), a number of alkylated analogues were synthesized and evaluated in vitro for binding to the Gabapentin binding site located on the alpha2delta subunit of a calcium channel. A number of other bridged and heterocyclic analogues are also reported along with their in vitro data. Two compounds showing higher affinity than Gabapentin were selected for evaluation in an animal model of epilepsy. One of these compounds, cis-(1S,3R)-(1-(aminomethyl)-3-methylcyclohexyl)acetic acid hydrochloride (19), was shown to be effective in this model with a profile similar to that of Gabapentin itself.

Acetates↗
PubMed2003

Gabapentin blocks L-type and P/Q-type Ca2+ channels involved in depolarization-stimulated nitric oxide synthase activity in primary cultures of neurons from mouse cerebral cortex.

PURPOSE: The effect of gabapentin [1-(aminomethyl)cyclohexane acetic acid] on Ca2+ channels involving the activation of nitric oxide synthase (NOS) was investigated in primary neuronal culture of mouse cerebral cortex. METHODS: The expression of alpha2delta subunits of Ca2+ channels was investigated by RT-PCR using specific primer sets. The K(+)-evoked NOS activity was estimated by guanosine 3'5' cyclic monophosphate (cGMP) formation. RESULTS: mRNA for alpha2delta subunits of Ca2+ channels is found in these cells. Gabapentin blocked the K(+)-evoked NOS activity estimated from cGMP formation in a concentration dependent manner. The increase in NOS activity by the K(+)-stimulation was almost completely reversed by the combination of nifedipine, an L-type Ca2+ channel blocker, and omega-agatoxin VIA, a P/Q-type Ca2+ channel blocker. On the other hand, omega-conotoxin GVIA, an N-type Ca2+ channel blocker, was failed to reverse the increase in NOS activity by the K(+)-stimulation, indicating that the activation of NOS by the depolarizing stimulation might be not mediated by N-type Ca2+ channel. Under the presence of nifedipine or omega-agatoxin IVA, gabapentin inhibited the increase in NOS activity concentration-dependently. CONCLUSIONS: These results suggest that gabapentin inhibits depolarization-induced NOS activation in murine cortical neuronal culture via blockade of both P/Q-type and L-type Ca2+ channels.

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PubMed2004

Gabapentin in the management of the recurrent, refractory, idiopathic priapism.

Recurrent idiopathic priapism is a difficult problem to treat and a true emergency for the physicians, and often even invasive therapeutic interventions fail. We recently managed three men with refractory idiopathic priapism with oral gabapentin. They responded to treatment within 48 h. Two men continue not to experience prolonged erections while treated with lower doses of gabapentin for 16 and 24 months, respectively. The third, after a successful treatment for 6 months, stopped gabapentin and priapism recurred. He responded to treatment again and continues to be free of episodes for 9 months. Gabapentin may be a safe alternative for the management of refractory idiopathic priapism.

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PubMed2002

Gabapentin: pharmacology and its use in pain management.

Although its exact mode of action is not known, gabapentin appears to have a unique effect on voltage-dependent calcium ion channels at the postsynaptic dorsal horns and may, therefore, interrupt the series of events that possibly leads to the experience of a neuropathic pain sensation. Gabapentin is especially effective at relieving allodynia and hyperalgesia in animal models. It has been shown to be efficacious in numerous small clinical studies and case reports in a wide variety of pain syndromes. Gabapentin has been clearly demonstrated to be effective for the treatment of neuropathic pain in diabetic neuropathy and postherpetic neuralgia. This evidence, combined with its favourable side-effect profile in various patient groups (including the elderly) and lack of drug interactions, makes it an attractive agent. Therefore, gabapentin should be considered an important drug in the management of neuropathic pain syndromes.

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PubMed2003

The role of gabapentin in treating diseases with cutaneous manifestations and pain.

BACKGROUND: Gabapentin was first approved by the FDA in 1993 as an add-on treatment for partial epileptic seizures. In May of 2002, it was approved as treatment for post-herpetic neuralgia by the Food and Drug Administration. It appears to be a promising agent in the treatment of pain, alterations of sensation and pruritus associated with dermatological disease, but no review of these uses exists. METHODS: Medline and Google searches were performed for the words "Gabapentin" and "Neurontin." The articles found were reviewed. Article identified that contained references to the treatment of skin disease and neuropathic pain were examined and their contents surveyed. RESULTS: Approximately 1200 articles were located in Medline that referred to Garbapentin or Neurontin. Over 150 articles reviewed its use for neuropathic pain, neuritis or neuralgia of various sorts. Approximately 20 articles reviewed its use for a variety of dermatological conditions or diseases with dermatological manifestations that included: pain control associated with wound dressing changes, erythromelagia, piloleiomyoma related pain, brachioradial pruritus, Glossodynia, vulvodynia, and reflex sympathetic dystrophy. Over 100 articles that related to Gabapentin side effects were reviewed. CONCLUSIONS: Gabapentin is a very promising medication in the treatment of post-herpetic neuralgia and pain. Because dermatological patients suffer pain from painful tumors, after surgery, in conjunction with neuropathic ulcers, during dressing changes involving serious medical conditions, its applications seem manifold. Future studies must assess its role in the treatment of pruritus and other dermatological conditions involving pain or alteration of sensation.

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PubMed2005

Gabapentin-induced myopathy in 2 patients on short daily hemodialysis.

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.

Adult↗
PubMedDate not supplied

Gabapentin for the treatment and prophylaxis of cluster headache.

BACKGROUND AND OBJECTIVES: Cluster headache is an uncommon debilitating condition for which effective management remains a challenge. We describe the use of gabapentin in the treatment and prophylaxis of cluster headache in a patient who was refractory to other treatments. CASE REPORT: A 38-year-old man had a history of intermittent right-side headaches for 24 years, diagnosed as cluster headache. He received only partial relief from a range of conventional treatments. A trial with gabapentin 300 mg twice daily was tried and found to be effective in treatment and prophylaxis of his headaches. CONCLUSION: Gabapentin was effective in the treatment of a patient with cluster headache. Further investigation of gabapentin compared with conventional treatments and placebo is warranted.

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PubMed1999

Treatment of alcohol withdrawal syndrome with gabapentin.

Four in-patients with moderate alcohol-withdrawal syndromes benefited from treatment with gabapentin administered in an add-on fashion to clomethiazole. In comparison with the amount of clomethiazole required as estimated using a specially developed score during previous detoxifications of these patients at our hospital, gabapentin (400 mg q.i.d.) clearly reduced the amount of clomethiazole needed now Gabapentin, an anticonvulsant with favorable pharmacokinetic properties and tolerability, and with no known risk of dependence, may therefore be a useful new drug in the treatment of alcohol withdrawal. We believe that the potential value of gabapentin in alcohol withdrawal deserves further controlled studies.

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PubMed2003

Gabapentin for the treatment of ethanol withdrawal.

Benzodiazepines (BZDs) are the drug of choice for the suppression of alcohol withdrawal symptoms. Gabapentin, a drug approved for use as adjunctive therapy in the treatment of partial seizures, has none of the BZD-type difficulties (drug interactions, abuse potential). We retrospectively report on the use of gabapentin for ethanol withdrawal in 49 patients. Thirty-one patients were treated in the outpatient program and 18 in the general inpatient psychiatric unit. Positive outcomes as evidenced by completion of gabapentin therapy were achieved in 25 out of 31 outpatients and 17 out of 18 inpatients. Statistical significance was reached regarding the positive relationship between prior ethanol use and inpatient "as needed" benzodiazepine use. Both sets of data suggest that gabapentin works well for the mild to moderate alcohol withdrawal patient.

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PubMed2005

A randomized, open-label pilot comparison of gabapentin and bupropion SR for smoking cessation.

This 6-week, randomized, open-label pilot study estimated the treatment effect size of gabapentin (n = 17) compared with bupropion SR (n = 19) for smoking cessation, thereby allowing sample size calculations for a definitive comparison study. The primary outcome measure was smoking cessation. Secondary outcome measures included smoking reduction and withdrawal severity. Gabapentin was less efficacious than bupropion for smoking cessation but was associated with fewer dropouts from adverse effects. Withdrawal severity was less with bupropion. Bupropion remains the first-line non-nicotine pharmacotherapy for smoking cessation. Further study is required to determine if gabapentin has any useful role in smoking cessation. Based on our primary outcome measure, 79 subjects would be required in each treatment group of a two-armed study to achieve 90% power for detecting a difference in efficacy between gabapentin and bupropion.

Adolescent↗
PubMed2005

Gabapentin is effective in the treatment of cancer-related neuropathic pain: a prospective, open-label study.

BACKGROUND: Gabapentin has been evaluated in the treatment of nonmalignant neuropathic pain, however, there is little direct evidence evaluating its efficacy in cancer-related neuropathic pain. OBJECTIVE: This study evaluated the effectiveness of gabapentin to treat cancer-related neuropathic pain. DESIGN: This was an open-label study. Two parallel groups of patients were recruited with either treatment-related (radiotherapy, surgery, chemotherapy) or tumor-related neuropathic pain. Gabapentin was dose-escalated from 300 mg/d to 1.8 g/d. MEASUREMENTS: The primary outcome, pain, was assessed using the modified brief pain inventory. In addition patient descriptors of pain and scores of activities of daily living were collated together with demographic data. RESULTS: We recruited 62 patients with treatment-related (n = 25) or tumor-related (n = 37) neuropathic pain. There was a significant reduction in the worst, average, and current pain scores (p < 0.002), but not the least pain score (p = 0.21). Twenty-eight of 62 (45.2%) of patients achieved at least a one third reduction in pain score (95% confidence interval [CI] 32.5-58.3); the number needed to treat to obtain this benefit is 2.2 (95% CI 1.7-3.1). There was a significant reduction in all scores measuring the impact of pain on daily living (p < 0.003). There was no significant difference in pain scores at day 8 compared to day 15. Analysis of variance suggested that gender, but not etiology, or type of neuropathic pain, was a significant predictor of analgesic response and this warrants further investigation. CONCLUSION: We conclude that gabapentin is an effective treatment for cancer-related neuropathic pain.

Aged↗
PubMed1995

Gabapentin and lamotrigine: novel antiepileptic drugs.

The pharmacokinetics, efficacy, and adverse effects of gabapentin and lamotrigine, two new antiepileptic drugs (AEDs), are reviewed. Gabapentin and lamotrigine are promising advances in the treatment of epilepsy, which has not been satisfactorily controlled by available agents in 25-41% of patients. Gabapentin is chemically similar to gamma-aminobutyric acid, but it is able to pass into the central nervous system. It is effective for the treatment of partial-onset seizures that are refractory to other AEDs. It has no known drug-drug interactions and a relatively benign adverse effect profile, but its short half-life necessitates at least thrice-daily dosing. Lamotrigine is structurally unrelated to the other available AEDs. Its role is currently limited to add-on therapy in patients with partial seizures, with or without secondary generalization, that are resistant to current treatment. The efficacy of lamotrigine in patients with primary generalized tonic-clonic seizures, absence seizures, and Lennox-Gastaut syndrome remains to be validated. The adverse effect profile also remains to be determined. A rash may appear in up to 5% of patients, possibly necessitating discontinuation of the drug. Although lamotrigine does not seem to affect the pharmacokinetics of the other AEDs, the other AEDs affect lamotrigine pharmacokinetics. Lamotrigine can be given once or twice daily. Gabapentin and lamotrigine may be useful in treating patients whose epilepsy is not controlled by other available AEDs; however, further research is needed to confirm their roles in epilepsy treatment.

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PubMed1999

Gabapentin and lamotrigine in bipolar disorder.

The utility of gabapentin and lamotrigine for the treatment of bipolar disorder is reviewed. Bipolar disorder is characterized by extreme mood fluctuations, including mania, hypomania, depression, and mixed episodes. Extrapolation of postulated mechanisms of anticonvulsant activity in bipolar disorder has led to the use of the newer anticonvulsants gabapentin and lamotrigine for therapy. Both agents appear promising on the basis of limited (often anecdotal) evidence. They may prove effective in patients with difficult cases of bipolar disorder, such as patients with rapid cycling, mixed episodes, and illness refractory to other treatments. Lamotrigine may offer a much-needed treatment alternative for bipolar depression and could be found effective for acute mania, but the need for slow dosage adjustment and the risk of rash may limit overall clinical utility. Gabapentin may offer significant advantages for acute mania: The dosage can be adjusted rapidly, adverse effects are generally minimal, the therapeutic index is high, there is no required laboratory monitoring, and there is minimal potential for interactions with other psychotropics. Until the results of randomized controlled trials are known, however, these two agents should be reserved for patients with bipolar disorder unresponsive to traditional therapies and for patients who cannot tolerate traditional agents. Preliminary evidence indicates that gabapentin and lamotrigine may be useful for the treatment of bipolar disorder.

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PubMed1998

The effect of intrathecal gabapentin and 3-isobutyl gamma-aminobutyric acid on the hyperalgesia observed after thermal injury in the rat.

UNLABELLED: Gabapentin is an anticonvulsant that may represent a novel class of drugs, which has novel spinal antihyperalgesic activity. We sought to characterize this spinal action in a model of hyperalgesia that involves a mild thermal injury to the hind paw of the rat. Rats were prepared with chronic spinal catheters. Under brief halothane anesthesia, a thermal injury was induced by applying the left hind paw to a thermal surface (52.5 degrees C) for 45 s. This exposure results in mild erythema but no blistering. Thermal escape latency of the hind paw was determined using an underglass thermal stimulus with which response latencies of the injured and uninjured (normal) paw could be obtained. Thirty minutes after thermal injury, the response latency in all groups decreased from 10-12 s to 5-7 s. Uninjured paw withdrawal latency was unaltered. The intrathecal injection of gabapentin (30-300 microg) produced a dose-dependent reversal of the hyperalgesia but had no effect on the response latency of the normal hind paw, even at the largest doses. A similar reversal was observed after intrathecal delivery of the structural analog S(+)-3-isobutyl gamma-aminobutyric acid (GABA) (30-300 microg), but not after the largest dose of its stereoisomer R(-)-3-isobutyl GABA (300 microg). The effects of both intrathecal gabapentin and S(+)-3-isobutyl GABA were reversed by intrathecal D-serine, but not L-serine. All effects were observed at doses that had no significant effect on motor function. These observations, in conjunction with the accumulating data on binding and transmitter release, emphasize that these gabapentinoids can selectively modulate the facilitation of spinal nociceptive processing otherwise generated by persistent small afferent input generated by tissue injury. IMPLICATIONS: Gabapentin and its analog, 3-isobutyl gamma-aminobutyric acid, given spinally, produce a dose-dependent, D-serine-sensitive reversal of the thermal hyperalgesia evoked by mild thermal injury.

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PubMedDate not supplied

Gabapentin for relief of spasticity associated with multiple sclerosis.

The use of a recently released anticonvulsant, gabapentin, in the treatment of spasticity in two patients with multiple sclerosis is reported. Gabapentin was chosen because of its GABA-ergic effect and because previously reported studies have shown that it is well tolerated compared with other GABA-mimetic medication. Satisfactory release of spasticity with significant improvement of functional outcome was noted in both cases. Both patients were first treated with gabapentin for one month at 300 mg per day and then, with no reported side-effects, at 400 mg per day. Before treatment, spasticity (graded with modified Ashworth Scale) in one patient was 3 for left lower and 2 for right lower limbs, and Expanded Disability Status Scale (EDSS) was 7; ambulation was limited to a few steps with a standard walker. After two weeks of treatment, spasticity was 2 and 1 for the left and right lower limbs, respectively. At three-month intervals, spasticity was +1 for left and 1 for right lower limbs, and EDSS was 6; the patient could ambulate 75 to 100 m with a standard walker. In the second patient, spasticity before treatment was 2 for both lower and left upper limbs. EDSS was 5.5, and ambulation was confined to 100 m with a cane. Spasticity improved to +1 in lower and 1 in left upper limbs after two weeks and to 1 and normal after three months. At three months, EDSS was 3 and the patient could ambulate for long distances without an assistive device. We suggest that gabapentin can be used effectively to decrease spasticity without significant side effects in patients with multiple sclerosis.

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