Vigabatrin and lamotrigine in refractory epilepsy.

Abstract

Epilepsy arises from an imbalance of inhibitory and excitatory influences in the brain. Vigabatrin (VIG) decreases the breakdown of the inhibitory neurotransmitter y-aminobutyric acid, whereas lamotrigine (LTG) reduces presynaptic excitatory amino acid release. 22 patients with refractory epilepsy, treated with an anticonvulsant regimen containing VIG, entered a balanced, double blind, placebo controlled, crossover trial of additional LTG. Treatment periods of 12 weeks (25 mg, 50 mg, 100 mg LTG twice daily for four weeks at each dose, and matched placebo) were followed by wash out intervals of four weeks. 14 of the 20 patients completing the study improved, resulting in a significant fall in seizure days and numbers. Analysis of seizure type confirmed a beneficial effect on partial and secondary generalised tonic-clonic seizures. At the highest LTG dose (200 mg daily) there was a median fall of 37% in seizure count with nine (45%) patients reporting >50% reduction. Three of these patients were seizure free during this month of treatment. Side effects were minimal throughout the study. Concentrations of other antiepileptic drugs, including those of carbamazepine 10,11-epoxide, were not modified by LTG. This study suggests a substantial efficacy for a regimen containing VIG and LTG. Combinations of drugs with complementary modes of action may provide a rational pharmacological approach to the management of refractory epilepsy. (7 Neurol Neurosurg Psychiatry 1994;57:921-924)

Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation

“…Twelve crossover trials 40,55,82,89,91,134,136,[158][159][160][161][162] and two parallel trials 137,142 compared adjunctive LTG with placebo in patients with refractory epilepsy. One trial included only patients with partial seizures 162 and another only patients with generalised seizures.…”

“…One trial included only patients with partial seizures 162 and another only patients with generalised seizures. 134 The remainder of the trials included patients with either partial or generalised seizures.…”

“…Two crossover studies did not report first-phase data 40,82 and the third did not report first-phase data for the placebo group. 162 One of these studies reported that 52.7% (19/36) of participants receiving LTG responded to treatment, 82 another reported that 37.5% of participants receiving LTG responded to treatment 40 and the final study reported that four out of 22 participants responded to treatment with LTG. 162 The unpooled data showed a trend in favour of LTG compared with placebo, but only two trials showed significant differences in favour of LTG (500 142 and 100-300 mg/day 160 ).…”

Low-Dose Gabapentin Combined with either Lamotrigine or Carbamazepine Can Be Useful Therapies for Trigeminal Neuralgia in Multiple Sclerosis

“…Although no study has compared the efficacy of these medications separately, we found that in both groups, when treated with CBZ or LMT alone, patients experienced adverse effects and/or insufficient pain control. A number of authors have reported the use of combination antiepileptic drugs with similar or different pharmacodynamic profiles for the treatment of nonrespondent seizures [9, 10, 11, 12]. We evaluated whether combination therapy of medications with different mechanisms of action could produce clinical benefit while reducing adverse effects, since many MS patients are sensitive to drugs with CNS effects, even in small doses.…”

The New Antiepileptic Drugs Pharmacological and Clinical Aspects

“…Randomized placebo-controlled trials have clearly shown that oxcarbazepine [53,[81][82][83][84][85], Lamotrigine-vigabatrin Partial seizures Anecdotical [162] Tiagabine-vigabatrin Partial seizures Anecdotical [163] Lamotrigine-gabapentin Partial seizures Anecdotical [164] Lamotrigine-topiramate Partial seizures Anecdotical [165] tiagabine [8,9,86,87], gabapentin [30,88] and vigabatrin [7,[89][90][91][92] are effective against partial seizures (with or without secondary generalization) and, possibly, also against primarily generalized tonic-clonic seizures. In addition, vigabatrin shows remarkable value in the treatment of infantile spasms, especially those associated with tuberous sclerosis [93][94][95][96].…”