"This supports preliminary research showing that Lamictal may be effective for this serious pain syndrome," said Elon Eisenberg, MD, Director, Pain Relief Unit at Rambam Medical Center in Israel, and lead investigator of this study. "Additional controlled studies are needed to establish the most effective dose of Lamictal for this disorder."
According to the American Diabetes Association (ADA), neuropathy is a painful and sometimes debilitating condition resulting in nerve damage. It affects more than half of all people with diabetes. Distal symmetric polyneuropathy (DSP) is the most common among four types of neuropathy, and affects the legs, feet and occasionally the hands. Symptoms range from the feeling of "pins and needles" or tingling to more severe pain, and sometimes a lack of sensation altogether. The latter symptom, if untreated, can lead to limb amputation. All patients in this study had an established diagnosis of diabetes with stable medications to treat it, medical evidence of peripheral neuropathy, and pain from peripheral neuropathy for at least six months.
The primary findings from this double-blind, placebo-controlled, randomized, parallel-group, single-center study are based on data from 53 patients (27 receiving Lamictal, 26 on placebo) who had similar characteristics including type and severity of diabetes at baseline. However, the Lamictal group had a significantly longer duration of diabetes than the placebo group (13.9 years vs. 9.6 years, on average, respectively).
Primary and secondary measures used to evaluate patients' responses included daily patient diaries recording pain ratings based on a 0-10 scale; the use of "rescue" pain medication; completion of questionnaires on pain, depression and disability administered before and at the end of the eight-week treatment phase; and a global assessment of efficacy and tolerability on a 0-10 scale. Patients were seen at four office visits during the treatment phase and at the end of the post-treatment phase.
Lamictal was administered over the course of eight weeks at a starting daily dose of 25 mg for the first two weeks, then adjusted to twice-daily dosing as follows: 50 mg for the next two weeks, 100 mg for the fifth week, and an additional 100 mg added each week for the remaining three weeks of the study, up to 400 mg/day. Patient-rated pain intensity scores were significantly reduced from baseline to end of treatment at week eight with Lamictal 200 to 400 mg/day versus placebo (p<0.001). Additionally, almost half of the patients receiving the study drug achieved a 50% reduction in pain. Most patients receiving Lamictal who needed "rescue" pain medication at the start of the study were able to reduce the use of the additional pain medication by end of treatment, while those receiving the placebo continued to need the pain medication throughout the treatment period.
The process of slowly increasing the dose meant that patients received doses of 200 mg/day starting at week six, and the statistically significant differences between Lamictal and placebo were seen from weeks six through eight.
The researchers found that the incidence of side effects was similar in both groups. Thirteen patients did not complete the study due to adverse effects or lack of compliance (five from the Lamictal group, eight from the placebo group). Two patients receiving Lamictal discontinued use of the medication due to the development of rash, which resolved shortly after treatment discontinuation.
This study was sponsored by GlaxoSmithKline.
Lamictal is indicated as adjunctive therapy in adults with partial seizures and as adjunctive therapy in the generalized seizures of Lennox-Gastaut syndrome in pediatric and adult patients. Lamictal is indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with an enzyme-inducing antiepileptic drug.
Safety and effectiveness of Lamictal have not been established as initial monotherapy; for conversion to monotherapy from non-enzyme-inducing AEDs (e.g., valproate); or for simultaneous conversion to monotherapy from two or more concomitant AEDs. Safety and effectiveness in patients below the age of 16 other than those with Lennox-Gastaut syndrome have not been established.
Serious rashes requiring hospitalization and discontinuation of treatment have been reported in association with the use of Lamictal. The incidence of these rashes, which have included Stevens-Johnson Syndrome, is approximately one percent (1/100) in pediatric patients less than 16 years old and 0.3 percent (3/1,000) in adults. In worldwide post-marketing experience, rare cases of toxic epidermal necrolysis (TEN) and/or rash-related death have been reported, but their numbers are too few to permit a precise estimate of the rate. Lamictal ordinarily should be discontinued at the first sign of rash, unless the rash is clearly not drug-related.
The risk of nonserious rash is increased when the recommended initial dose and/or the rate of dose escalation of Lamictal is exceeded. There are suggestions, yet to be proven, that the risk of severe, potentially life threatening rash may be increased by: 1) coadministration of Lamictal with valproic acid; 2) exceeding the recommended initial dose of Lamictal; or 3) exceeding the recommended dose escalation for Lamictal. However, cases have been reported in the absence of these factors. Therefore, it is important that the dosing recommendations be followed closely.
GlaxoSmithKline, one of the world's leading research-based pharmaceutical and healthcare companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer.