Criscuolo S, Auletta C, Lippi S, Brogi F, Brogi A. Oxcarbazepine monotherapy in postherpetic neuralgia unresponsive to carbamazepine and gabapentin. Acta Neurol Scand 2005 DOI: 10.1111/j.1600-0404.2005.00300.x (c) Blackwell Munksgaard 2005.Objectives -We present the results of a preliminary, open-label trial to evaluate the efficacy and tolerability of oxcarbazepine in postherpetic neuralgia (PHN) unresponsive to treatment with antiepileptic drugs (carbamazepine and gabapentin) and local anesthetic blocks. Materials and methods -Twenty-four patients were treated with oxcarbazepine monotherapy for 8 weeks. Starting dose was 150 mg/day, subsequently increased by 150 mg/day every 2 days until a maintenance dose of 900 mg/day. Pain was assessed using a visual analog scale (VAS). Results -There was a significant decrease in the mean VAS score following 8 weeks of treatment (Delta = 5.33; pairedt-test: P < 0.0001) compared with baseline. Oxcarbazepine was effective from the first week of treatment. There was a significant reduction in allodynia, leading to improvements in patients' functioning and quality of life. Oxcarbazepine was generally well tolerated. Conclusion -Oxcarbazepine appears to be a promising alternative monotherapeutic approach for patients affected by PHN.

Clinical studies evaluating a calcium channel modulator, gabapentin, for the treatment of vasomotor symptoms have been reported. The present studies evaluated three calcium channel modulators in ovariectomized (OVX) rodent models of temperature regulation. Gabapentin, reported to interact with the alpha(2)delta subunit of voltage-sensitive calcium channels and the L-type voltage-gated calcium channel blockers, verapamil and nifedipine, were examined. These series of experiments demonstrated that orally administered gabapentin, verapamil and nifedipine all acutely and dose-dependently lower tail skin temperature in both models of OVX-induced thermoregulatory dysfunction. These compounds all had a rapid onset of action, however, the efficacy of all three calcium channel modulators is less than that observed following chronic estrogen treatment. Additionally, these compounds were also tested in a telemetric rat model measuring core body temperature to evaluate any temperature effects on internal core temperature. The present data suggests that gabapentin, verapamil and nifedipine all act to globally alter temperature regulation in steroid-dependent models of thermoregulatory function.

Treatment options for epilepsy have increased in the last decade with the introduction of several new antiepileptic drugs (AEDs). As drug selection becomes more challenging, the use of evidence-based guidelines to aid in treatment decisions has become increasingly valued. The American Academy of Neurology's (AAN) guidelines for the use of new AEDs in refractory epilepsy offers many benefits, including expert panel recommendations based on clinically relevant questions with evidence-based responses. However, lack of evidence from randomized-controlled trials, particularly as they relate to monotherapy, limits the recommendations and their use in practice. The studies of new AEDs as monotherapy in treatment-refractory epilepsy are difficult to incorporate into clinical use because they are driven by Food and Drug Administration requirements to show superiority over placebo or pseudoplacebo (ie, low dose of active drug) rather than by clinical questions. However, based on Class I evidence, the AAN guidelines have granted Level A recommendations (established effectiveness) for oxcarbazepine and topiramate monotherapy, and a Level B recommendation (probable effectiveness) for lamotrigine monotherapy in the use of refractory partial epilepsy. There is insufficient evidence to recommend gabapentin, levetiracetam, tiagabine, or zonisamide monotherapy. No monotherapy AED trials have been conducted in refractory generalized epilepsy. Because no differences in efficacy have been reported for AEDs as initial therapy of partial seizures, differences in adverse events, such as weight gain, tremor, and hair loss, are key in drug selection. More comparative studies between the AEDs are necessary for both monotherapy and add-on therapy for treatment-refactory epilepsy.

The effect of gabapentin at a dose of 10 mg/kg (single administration) and at 3 mg/kg/day (administered for 10 days) on the analgesic action of morphine (10 mg/kg), metamizol (500 mg/kg) and indomethacin (10 mg/kg and 1.4 mg/kg) in mice was assessed on the basis of hot-plate and tail-flick tests. All the drugs were administered intraperitoneally (i.p.). Gabapentin was administered to mice 30 min before the administration of analgesics. The animals reactions to noxious stimuli were measured 60, 90 and 120 min after gabapentin administration. Gabapentin administered in a single dose, as well as in multiple ones, was found to cause antinociception, especially evident in the hot-plate test. The single dose of gabapentin enhances the analgesic effect of morphine in the hot-plate test, whereas in the tail-flick test it demonstrates an opposite effect. Gabapentin in a single dose does not affect significantly the effects of metamizol and indomethacin, whereas multiple doses decrease the action of these drugs. Gabapentin abolishes the tolerance of antinociceptive effect of morphine.

OBJECTIVE: To evaluate the cognitive effects of topiramate (TPM) and gabapentin (GBP). METHODS: Forty healthy volunteers were randomized to a 12-week course of TPM, GBP, or placebo. Doses were gradually escalated over 10 weeks to a maximum of 400 mg/day of TPM or 3,600 mg/day of GBP or to the highest tolerated dose. Subjects were interviewed and examined biweekly. Cognitive testing was performed prior to initiating the drug and again 12 weeks later, at least 2 weeks after achieving plateau dosing. For each subject and cognitive measure, test-retest Z scores were calculated based on regression equations derived from 73 healthy volunteers. Group comparisons utilized the Wilcoxon test. RESULTS: There were significant TPM vs GBP and TPM vs placebo differences in test-retest Z scores for four of six target cognitive measures (Digit Symbol, Story Recall, Selective Reminding, Controlled Oral Word Association), always indicating worse retest performance for subjects receiving TPM. Overall, 12 of 24 cognitive measures were similarly affected. TPM effects were large, and several target measures averaged >2 SD of negative change. One measure was significantly affected by GBP. CONCLUSIONS: Topiramate (TPM) impaired cognitive test performance, whereas gabapentin had minimal effects. The effects of TPM were of sufficient magnitude potentially to affect daily and occupational function.