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PubMed2004

The effects of remifentanil and gabapentin on hyperalgesia in a new extended inflammatory skin pain model in healthy volunteers.

UNLABELLED: We tested the responsiveness of measures of hyperalgesia in a model of UVB-induced inflammatory hyperalgesia with remifentanil, gabapentin, and the combination of both drugs in a double-blinded, active placebo-controlled, 4-way-crossover design in 16 volunteers. A circular skin area was irradiated with UVB-light 20 h before the application of gabapentin (600 mg) and 2 h later remifentanil (0.08 microg.kg(-1).min(-1), 40 min). In the sunburn spots we observed stable decreases of the heat pain perception thresholds (HPPT, mean difference, 4.45 degrees C; 95% confidence interval [CI], 3.32 degrees -5.59 degrees ) and heat pain tolerance thresholds (HPTT; mean difference, 5.43 degrees C; 95% CI, 4.50 degrees -6.35 degrees ) compared with normal skin. Further, large areas of mechanical hyperalgesia to pinprick adjacent to the erythema spots developed in all subjects. Overall remifentanil increased the HPPT (mean increase, 2.47 degrees C; 95% CI, 1.86 degrees -3.09 degrees, P < 0.001) and HPTT (mean increase, 3.18 degrees C; 95% CI, 2.65 degrees -3.71 degrees, P < 0.001) and reduced the area of secondary hyperalgesia by 59% (mean decrease, 5326 mm(2); 95% CI, 4233-6419 mm(2), P < 0.001) compared with placebo. In the sunburn remifentanil markedly increased the HPTT by 86% compared with normal skin (additional increase, 2.57 degrees C; 95% CI, 1.71 degrees -3.43 degrees). This different effect was not seen in the HPPT. With the exception of a small increase of HPTT in the sunburn (P = 0.02) gabapentin had no noticeable effect on either hyperalgesia. In conclusion, opioid analgesia was reliably demonstrated in this new extended pain model. IMPLICATIONS: Opioid analgesia was reliably demonstrated in a new inflammatory model of primary and secondary hyperalgesia. Gabapentin showed no antihyperalgesic and no opioid-enhancing effect in this model.

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PubMed2003

Gabapentin and posttraumatic stress disorder.

OBJECTIVE: To report the effects of gabapentin in a patient with concurrent depression and posttraumatic stress disorder (PTSD) and review the use of antiepileptic drugs (AEDs) in PTSD. CASE SUMMARY: A 37-year-old Latin American woman was being treated for major depression and PTSD. While the depressive symptoms were in remission, she reported a significant reduction in the frequency of her flashbacks after gabapentin was added to venlafaxine. She did not receive any type of psychotherapy. The flashbacks recurred after she discontinued gabapentin. DISCUSSION: While the improvement reported by the patient may have been related to a placebo effect or spontaneous recovery, treatment with gabapentin may have played a role in alleviating the flashbacks. Other published reports suggest that AEDs have a beneficial effect on some PTSD symptoms. CONCLUSIONS: AEDs may be of some therapeutic value in patients with PTSD. Future controlled studies are warranted to investigate the effectiveness of these agents.

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PubMed2005

Gabapentin-induced neurologic toxicities.

Gabapentin is an antiepileptic drug approved for the treatment of postherpetic neuralgia and as adjunctive therapy for partial seizures. The drug has been shown to be safe and nontoxic. The current literature has limited reports of neurologic toxicity associated with gabapentin therapy in patients with or without renal dysfunction. We describe the case of a 75-year-old man with renal dysfunction who developed neurologic toxicity due to gabapentin accumulation. Future studies are warranted to confirm the neurologic adverse effects of gabapentin, including any additional risks in patients with renal dysfunction.

Acute Kidney Injury↗
PubMed1996

Clinical pharmacokinetics of newer antiepileptic drugs. Lamotrigine, vigabatrin, gabapentin and oxcarbazepine.

The clinical pharmacokinetics of the 4 antiepileptic drugs lamotrigine, vigabatrin, gabapentin and oxcarbazepine have been reviewed in this paper. All the drugs have linear kinetics and reliable absorption, although the saturation of transport across the gut may occur at high doses with gabapentin. All the drugs can be conveniently given as a twice daily dosage apart from gabapentin, which has a short half-life and a midday dose is needed. Unlike many of the older drugs, lamotrigine, vigabatrin and gabapentin have a predominantly renal excretion and are not metabolised through the cytochrome P450 system. They do not induce their own metabolism or that of other commonly used anticonvulsants. Similarly, clinically important interactions with other major classes of drugs metabolised this way, such as anticoagulants or steroid hormones, do not occur. Oxcarbazepine, however, can cause oral contraceptive pill failure. Oxcarbazepine is immediately metabolised to a hydroxy metabolite and could be considered a prodrug. It appears to have fewer pharmacokinetic interactions than carbamazepine. Valproic acid (sodium valproate) inhibits the glucuronidation of lamotrigine and increases its half-life; when used together, dosage modification of lamotrigine is needed to avoid toxicity.

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PubMed1996

A pilot study of gabapentin as treatment for acquired nystagmus.

The effects of the anticonvulsant gabapentin were measured on vision and eve movements in three patients with acquired pendular nystagmus. In two patients, the nystagmus was associated with multiple sclerosis and, in the other, it followed brainstem stroke. A single oral 600 mg dose of gabapentin produced improvement of vision due to changes in ocular oscillations in all three patients. The effect was sustained after five weeks of treatment in two patients who elected to continue taking gabapentin 900-1500 mg/day. The results of this pilot study suggest that a controlled trial of gabapentin should be conducted to evaluate its role in the treatment of acquired forms of nystagmus.

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PubMed1998

Gabapentin treatment of mood disorders: a preliminary study.

OBJECTIVE: To determine if gabapentin is effective either as adjunctive treatment or as monotherapy for major affective disorders in a naturalistic setting. METHOD: All charts of patients meeting DSM-IV criteria for bipolar disorder or unipolar major depressive disorder treated with gabapentin in a private psychiatric practice were reviewed and clinical response was assessed retrospectively using the Clinical Global Impressions scale for Improvement (CGI-I). RESULTS: Gabapentin was moderately to markedly effective in 30% (15/50) of patients, with statistically nonsignificant differences between patients with bipolar disorder type I, bipolar disorder type II and NOS, and unipolar major depressive disorder. 70% reported side effects, mainly sedation, with 16% of the total sample discontinuing treatment due to adverse events. CONCLUSION: Gabapentin appears to be somewhat effective as add-on treatment in a subgroup of patients with mood disorders in a naturalistic setting. Prospective, controlled studies are required to clarify these pilot data.

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PubMed2004

Gabapentin reduces cocaine use among addicts from a community clinic sample.

BACKGROUND: Individuals with chronic psychiatric conditions display a high rate of cocaine use. Gabapentin was hypothesized to reduce cocaine use by restoring inhibitory GABAergic feedback on ascending dopaminergic projections to nucleus accumbens neurons. METHOD: Nine participants with DSM-IV cocaine dependence were selected from patients attending a large community psychiatric clinic. During a 24-week open-label trial of gabapentin (800-2400 mg/day), qualitative urine drug screens were collected from the participants up to 3 times per week. Data were collected from September 1999 to May 2001. RESULTS: With gabapentin, the mean +/- SD number of cocaine-positive urine screens decreased from 53.11 +/- 13.23 to 35.22 +/- 14.84 (t = 3.58, N = 9, p <.01). The number of weeks of abstinence from cocaine increased from 2.1 +/- 1.5 to 8.0 +/- 5.5 (t = 3.21, N = 9, p <.01). CONCLUSION: Gabapentin appeared to be a safe and efficacious medication to reduce cocaine usage in a community sample of psychiatric patients.

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PubMed2006

Pharmacokinetics and bioequivalence evaluation of two gabapentin preparations after a single oral dose in healthy Korean volunteers.

OBJECTIVE: To evaluate the bioequivalence of a single oral 400 mg dose of 2 gabapentin preparations in healthy male Korean volunteers. SUBJECTS, MATERIALS AND METHODS: The study was conducted as a randomized, 2-period crossover design in 26 healthy male Korean volunteers who received a single oral dose of 400 mg gabapentin capsule in each study period. There was a 7-day washout period between the doses. Serum concentrations of gabapentin up to 24 hours after the administration were determined using a validated HPLC method with fluorescence detection. In addition, in vitro dissolution profiles of both preparations were examined. The pharmacokinetic parameters such as AUC(0.t) (the area under the curve from zero to the time), AUC(0-infinity) (the area under the curve from zero to infinity), C(max) (maximum serum concentration), t(max) (time to reach C(max)) and t1/2 (terminal half-life) were analyzed by noncompartmental analysis, and the analysis of variance (ANOVA) was carried out using logarithmically transformed AUC(0-t), AUC(0-infinity) and C(max) and untransformed t(max). RESULTS: In vitro dissolution profiles were very similar at all media. There were no significant differences between the two preparations in AUC(0-t), AUC(0-infinity) and C(max). The point estimates (90% confidence intervals) for AUC(0-t), AUC(0-infinity) and C(max) were 1.0319 (0.9142 - 1.1647), 1.0127 (0.8458 - 1.2127) and 0.9796 (0.8670 - 1.1069), respectively, satisfying the bioequivalence criteria of 0.80 - 1.25 as proposed by the US FDA and the Korean legislation. No statistically significant difference was found for tmax and t1/2 values. CONCLUSION: From the results of the present study, it is indicated that the two preparations of gabapentin are bioequivalent and it can be assumed that they are therapeutically equivalent and exchangeable in clinical practice.

Administration, Oral↗
PubMed2000

Interstitial cystitis and the potential role of gabapentin.

Gabapentin, an antiepileptic agent, is a safe and versatile medication also used in the adjunctive treatment of painful disorders. These include neuropathic pain, such as postherpetic neuralgia, diabetic neuropathy, and the pain of reflex sympathetic dystrophy. Interstitial cystitis, a painful disease entity, shares many common features of these chronic pain states, and the use of gabapentin can assist in pain control. Gabapentin, as an adjunctive agent, may reduce use of cotherapeutics such as narcotics. Two patients with interstitial cystitis improved functional capacity within their activities of daily living and received adequate pain control with the addition of gabapentin to their medication regimen.

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PubMedDate not supplied

[Clinical response of gabapentin for glossopharyngeal neuralgia].

INTRODUCTION: The analgesic effect of the antiepileptic drug gabapentin makes it useful as an alternative for neuropathic pain. Its structural resemblance to other GABAergic antiepileptic drugs does not explain its mechanism of action, which seems not to depend on the activation of GABA receptor. Glossopharyngeal neuralgia is a rare entity which presents paroxystic crisis of pain, often with unknown etiology and poor response to treatment. CLINICAL CASES: Nine patients bearing of IX root neuralgia resistant to other therapies and ages ranged from 43 to 71 years old are being treated with gabapentin at doses between 800 and 3,600 mg daily in a period of time between two and sixteen months. Four cases in which magnetic resonance detected a compression of the nerve by posterior inferior cerebellar artery were submitted to a decompression surgery, but it was not effective. Gabapentin, alone or in association to carbamazepine, reduced the frequency and severity of crisis in seven patients, but in those with vascular compression the response was poorer. CONCLUSION: Gabapentin can be considered as an useful option for the management of glossopharyngeal neuralgic crisis, associated or not to other agents, for a short and long time, because of its good tolerance and lack of interactions.

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PubMed2000

Reversible acute renal allograft dysfunction due to gabapentin.

BACKGROUND: The use of gabapentin as an effective analgesic agent for neuropathic pain has expanded considerably. Its lack of both anticholinergic side effects and interference with the metabolism of drugs via the cytochrome P450 pathway make it especially useful for transplant recipients. METHODS AND RESULTS: We describe the case of a renal transplant recipient with a long-term stable functioning allograft who developed reversible acute renal dysfunction after beginning gabapentin therapy for chronic pain due to diabetic neuropathy. CONCLUSIONS: We suggest that gabapentin may cause acute renal dysfunction by a mechanism involving renal afferent vasoconstriction. Caution should be employed when considering the use of gabapentin in transplant recipients, especially when combined with other agents that may potentiate renal vasoconstriction.

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PubMed2001

[Gabapentin--yet another antiepileptic agent for the treatment of neuropathic pain?].

Gabapentin is a recently introduced anti-epileptic drug used as an adjuvant in partial and secondarily generalised tonic-clonic seizures. Its mechanism of action has not been fully elucidated, but it seems that gabapentin may regulate voltage-dependent calcium channels, presumably on a spinal level, in the nociceptive system. Two large, controlled clinical trials of painful diabetic neuropathy and postherpetic neuralgia have demonstrated its analgesic efficacy. The adverse effects associated with gabapentin treatment are relatively harmless, mild to moderate in severity, and usually transient, with tolerance developing 2-3 weeks after start of treatment. Gabapentin and tricyclic antidepressants are efficacious in the treatment of painful diabetic neuropathy and postherpetic neuralgia.

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PubMedDate not supplied

[Gabapentin in 50 patients with epilepsy].

OBJECTIVE: To evaluate monotherapy treatment with the anticonvulsant drug gabapentin, its efficacy and tolerability when used in patients with partial and secondary generalized partial epileptic seizures of recent onset who had not received treatment or who, in spite of treatment with other antiepileptic drugs failed to attain control over their seizures. PATIENTS AND METHODS: We made an open prospective study of 50 patients diagnosed as having partial and secondarily generalized partial epileptic seizures. The patients were given treatment at their first visit and them regularly followed up for two years. Treatment was given progressively until a maintenance dose of 1.200 mg/day was reached, and the dose them adjusted individually. RESULTS: We included 50 patients in the study; 78% were treated with gabapentin. Ten percent stopped this treatment because it was ineffective. All the patients who continued their treatment with gabapentin had their seizures reduced by over 50%. This reduction in the number of seizures is statistically significant (p < 0.05) for patients with partial and secondarily generalized partial seizures. Twelve percent of the group of patients stopped their treatment because of side-effects. CONCLUSIONS: When the results of our study are evaluated and compared with those published in the literature, it may be seen that gabapentin is a safe, effective drug which is well tolerated when used as monotherapy for the treatment of patients with partial seizures.

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PubMedDate not supplied

[GABApentin--new therapeutic possibilities].

The paper is a review of current experience with use of gabapentin--a new antiepileptic drug--in neurologic conditions others than epilepsy. Mechanism of action of the drug is not fully elucidated yet. However it proved to be effective in therapy of chronic pain, especially in neuropathic pain, neuralgia, low back pain, reflex sympathetic dystrophy and erythromelalgia. Gabapentin is also effective in pain and spasticity in multiple sclerosis. Clinical studies of gabapentin in movement disorders, such as Parkinson disease, essential tremor and atrophic lateral sclerosis are discussed in the paper. It can be summarized that gabapentin is a valuable medication and the use thereof in neurology is not limited to epilepsy.

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PubMedDate not supplied

[Gabapentin in the treatment of tremor].

PATIENTS AND METHODS: We evaluated the efficacy of gabapentin added to basal tremor treatment by means of a 16 month non randomized open study conducted at our Unit on treated and monitored patients. Efficacy was evaluated by means of the following scales: Tremor Scale (TS), Global Disability Examiner Scale (GDE) and Global Disability Patient Scale (GDP). For the GDE and GDP scales we constructed a dichotomic result evaluation variable (improvement vs. non improvement) and adjusted a logistic regression model (independent variables: age, gender, tremor duration and number of antitremor drugs associated with gabapentin). Two multiregression models were adjusted for the TS (12 month score result variable). Model 1: TS (items 1 14) and model 2: TS (items 15 21). INDEPENDENT VARIABLES: age, gender, tremor duration, initial test score and number of antitremor drugs associated with gabapentin. We studied 63 patients aged 59.4 years (SD, 16 years): 34 essential tremor, 16 Parkinson s disease tremor, 10 multiple sclerosis tremor, 4 writing tremor and 3 orthostatic tremor. RESULTS: At 12 months gabapentin improved the clinical results. The largest decrease (absolute terms) was observed in multiple sclerosis tremor, and in percentage terms the largest decrease was in orthostatic tremor. Logistic regression showed that masculine gender and a shorter tremor duration predicted a better result. Multiregression showed association between end and basal score, on the one hand, and a better result in males and shorter tremor duration, on the other

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PubMedDate not supplied

[Gabapentin: its mechanisms of action in the year 2003].

AIMS: The purpose of our study was to survey the data from the main research work published about the mechanisms of action of gabapentin. DEVELOPMENT: In addition to an unquestionable Gabaergic effect, gabapentin is the first antiepileptic that has been shown to have an effect on the a2d subunit of the voltage dependent calcium channels and on hyperpolarization activated cationic (Ih) currents. Gabapentin also exerts an indirect effect on the voltage dependent sodium channels, slightly inhibits glutamate and reduces the excretion of certain neurotransmitters, such as serotonin, dopamine and noradrenalin. CONCLUSIONS: Gabapentin has a number of original mechanisms of action with which to account for its effects in epilepsies and in many other clinical entities.

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PubMed2003

[Gabapentin in the treatment of neuropathic pain in patients with type 2 diabetes mellitus].

STUDY AIM: Assessment of pain relief in type 2 diabetes mellitus patients with neuropathic pain treated with gabapentin at daily dose 2400 mg. MATERIAL AND METHODS: 26 patients with type 2 diabetes mellitus and painful neuropathy were included into the study. The duration of pain symptoms ranged from 1 to 3.5 years (mean 1.9 +/- 0.6 year). Pain intensity was assessed using Short-Form McGill Pain Questionnaire (SFMPQ), visual analogue scale (VAS), and Present Pain Intensity Scale (PPI) before the study and after 6-week treatment with gabapentin. The sensory and motor conduction studies, electromyography from tibial anterior muscle and skin sympathetic response were recorded in the patients and compared with the results obtained from the control group. RESULTS: The neurophysiological examinations carried out in the patients with sensory neuropathy demonstrated a significant conduction impairment in sensory and motor nerves as well as in sympathetic sweat-secreting nerves. After six weeks of gabapentin treatment in 2400 mg daily dose a significant pain reduction was observed, assessed by means of SF-MPQ, VAS and PPI questionnaires. The authors have demonstrated a significant analgesic effect of gabapentin in patients with diabetic neuropathy and the suggest administration of this preparation in chronic diabetic neuropathy in order to improve the quality of patients' life.

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PubMed2004

A study of gabapentin in the treatment of tonic-clonic seizures of alcohol withdrawal syndrome.

In this study for thirty (30) patients with alcohol withdrawal syndrome, the response to anticolvusant gabapentin was assessed. Thirty (30) patients with median age of 57.0 years and median body weight of 79.1 kg were treated with gabapentin 3 x 300 mg daily for up 30 days. The preliminary findings of this study suggest that gabapentin is very effective against tonic-clonic seizures in alcohol withdrawal syndrome. Gabapentin was safe and well tolerated. For twenty (20) patients no side effect were observed.

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