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Abstract & Commentary
Source: Eisenberg E, et al. Lamotrigine for intractable sciatica: Correlation between dose, plasma concentration and analgesia. Eur J Pain. 2003;7:485-491.
Fourteen consecutive patients with sciatica were enrolled in this open-label trial of lamotrigine (LTG) to determine its efficacy in pain control and its dose response curve. Patients ranged in age from 18 to 75 and suffered from painful lumbar radiculopathy, documented by CT or MRI evidence of disc herniation, for 1-3 years. Exclusionary criteria included epilepsy and cardiac, renal, or liver dysfunction. Washout of previous analgesics for 1 week preceded a 6-week titration period, beginning at 25 mg q.d. and doubling weekly to 400 mg daily, given in divided dosage. A dose of 400 mg q.d. was then maintained for 4 weeks and subsequently discontinued. End points included a daily numerical pain scale (NPS), with the average weekly NPS serving as the primary end point. Other measurements included a visual analog pain scale (VAS) and the short form McGill pain questionnaire (SFMPQ), both performed 9 times over the 11-week study. Range of lumbar motion and the straight leg raise test using a manual goniometer, the neurological examination, and LTG blood concentrations were also performed. Statistical analysis included repeated measures ANOVA and Tukey-Kramer HSD tests, with a P value of .05 considered significant.
Of 14 enrolled patients, 13 received at least 1 week of drug, but only 7 completed the entire trial. One declined the final phase due to lack of efficacy, and 6 did not complete the titration phase due to dizziness, diarrhea (n = 1 each), or personal/nonspecific reasons. All outcome measures improved but significantly so only at the maximum dose of 400 mg, with a linear relationship seen between mean dose, plasma concentration, weekly pain score, lumbar movement, and straight leg raise. LTG may be safe and effective for intractable sciatica in patients who tolerate the medication, but double-blinded confirmation of these findings in a larger trial will be needed first.
Approved as an anti-epileptic medication, LTG has broad-spectrum efficacy against partial, generalized tonic-clonic, and absence seizures, comparable to phenytoin and carbamazepine.1 Low protein binding (approximately 55%) allows for few drug-drug interactions and good patient tolerance, including no interaction with oral contraceptives, make LTG an attractive alternative, save for a 0.3% risk of serious rash. Serving to stabilize neuronal membranes by acting on voltage-sensitive sodium channels, it inhibits the release of excitatory neurotransmitters, including glutamate and aspartate, and has also been shown to inhibit calcium currents in cortical neurons. Doses between 300 mg and 500 mg are recommended but may go up to 700 mg/d. About 10% of patients discontinue therapy due to adverse effects, but most commonly only rash (3%), dizziness (2.8%), and headache (2.5%) are experienced.
Attention, however, should be drawn to recently reported unusual side effects of LTG therapy in children.2 An 8-year-old boy with myoclonic jerks developed tremor, unsteadiness, chorea, and eye movement abnormalities while starting LTG, and a 7-year-old boy with suspected absence seizures developed eye movement abnormalities and cognitive decline. In both instances, symptoms and signs resolved on stopping LTG. — Michael Rubin
Dr. Rubin, Professor of Clinical Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.
1. Choi H, Morrell MJ. Expert Opin Pharmacother. 2003;4:243-251.
2. Das KB, et al. J Child Neurol. 2003;18:479-480.