Lamictal doesn't cause Weight Gain in Patients with Bipolar Disorder
May 5, 2004
from The Science of Mental Health

Results from an analysis presented today show that long-term treatment with Lamictal(R) (lamotrigine) is not associated with clinically relevant changes in weight when used in patients with bipolar I disorder compared to placebo. The results were presented at the 157th annual meeting of the American Psychiatric Association (APA) in New York, NY.

The data reports on the long-term impact of mood stabilizers on body weight. Weight gain is an area of concern for psychiatrists and patients in the long-term treatment of bipolar I disorder. It has previously been reported that side effects such as medication-related weight gain may have a negative impact on compliance. In fact, medication compliance is considered to be an essential component of the long-term management of bipolar disorder.

Researchers evaluated weight data retrospectively from patients with bipolar I disorder in two 18 month maintenance studies of Lamictal, lithium and placebo. The analysis showed that for patients taking Lamictal and placebo, a low proportion of patients experienced clinically important weight changes and weight-related adverse events. Furthermore, no statistically significant weight differences were seen between patients taking Lamictal and placebo over the course of the study. For patients taking lithium, the study found that body weight increased over time and that after one year of treatment, patients experienced moderate weight gain, although not statistically significantly different from placebo.

"This study shows that weight gain is not an inherent part of treatment for people with bipolar I disorder," said Gary Sachs, M.D., Associate Professor of Psychiatry, Harvard Medical School and Director, Bipolar Disorder Clinic and Research Program, Massachusetts General Hospital. "This is good news for patients concerned about weight gain who are being treated for bipolar I disorder."

Lamictal received approval from the U.S. Food and Drug Administration in June 2003 for maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy. The effectiveness of Lamictal in the acute treatment of mood episodes has not been established.

BACKGROUND ON BIPOLAR DISORDER
Bipolar I disorder is characterized by the occurrence of one or more manic or mixed episodes and often individuals also have had one or more major depressive episodes. In bipolar II disorder, a person experiences one or more major depressive episodes and hypomania (a milder form of mania with less severe symptoms). If manic and depressive symptoms overlap for a period of time, it is called a "mixed" episode. Overall, the predominant structure of bipolar disorder is depressive rather than manic.

Bipolar disorder is a lifelong condition; effective and tolerable maintenance therapy is critical to disease management. Bipolar illness is often misdiagnosed, most commonly with major depressive disorder. Inappropriate treatment due to misdiagnosis can have a harmful effect on patients potentially accelerating the natural course of the illness. When left untreated, bipolar disorder can worsen and patients can experience a greater frequency of events.

Lamictal is approved for maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy. The effectiveness of Lamictal in the acute treatment of mood episodes has not been established. A prospectively defined combined analysis revealed significant benefits for Lamictal over placebo for delaying both time to intervention for mania (P=0.034) and depression (P=0.009) - the finding in depression was more robust.

Lamictal is also indicated as adjunctive therapy for adult and pediatric (greater than or equal to 2 years of age or older) patients with epilepsy who have partial seizures and for the generalized seizures of Lennox-Gastaut syndrome in adult and pediatric patients (greater than or equal to 2 years of age or older).

Lamictal is also indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with a single enzyme- inducing AED and, more recently, in patients converting from valproate.

The safety and effectiveness of Lamictal have not been established 1) as initial monotherapy, 2) for conversion to monotherapy from non-enzyme-inducing anti epileptic drugs (except for valproate), or 3) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs. Safety and effectiveness in patients below the age of 16 other than those with partial seizures and the generalized seizures of 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 0.8% (8 per 1,000) in pediatric patients under the age of 16 years receiving Lamictal as adjunctive therapy for epilepsy, and 0.3% (3 per 1,000) in adults on adjunctive therapy for epilepsy. In mood and bipolar disorder clinical trials, the rate of serious rash was 0.08% of adult patients who received Lamictal as initial monotherapy and 0.13% of adult patients who received

Lamictal as adjunctive therapy. In a prospectively followed cohort of 1,983 pediatric patients taking adjunctive Lamictal, there was one rash-related death. In worldwide post-marketing experience, rare cases of toxic epidermal necrolysis (TEN) and/or rash-related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate.

Because the rate of serious rash is greater in pediatric patients than in adults, it bears emphasis that Lamictal is approved only for use in pediatric patients below the age of 16 years who have partial seizures or seizures associated with the Lennox-Gastaut syndrome (see Indications Section in Prescribing Information).

Other than age, there are as yet no factors identified that are known to predict the risk of occurrence or the severity of rash associated with Lamictal. There are suggestions, yet to be proven, that the risk of rash may also be increased by co-administration of Lamictal with valproate, exceeding the recommended initial dose of Lamictal, or exceeding the recommended dose escalation for Lamictal. However, cases have been reported in the absence of these factors. Lamictal should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug related.