Does lamotrigine cause significant weight gain in adults being treated for epilepsy or bipolar disorder?

Lamotrigine and Weight Gain

Lamotrigine does not cause significant weight gain and is associated with stable body weight during treatment for both epilepsy and bipolar disorder. 1, 2, 3

Weight Profile of Lamotrigine

Lamotrigine demonstrates weight neutrality across multiple clinical contexts:

• In epilepsy monotherapy, lamotrigine-treated patients showed mean weight gain of only 1.3 ± 11.9 lb after 32 weeks, which was not statistically significant and represented stable weight. 1

• In bipolar disorder maintenance treatment, mean weight remained stable with lamotrigine over 18 months, with a mean change of -1.2 kg at week 52 (essentially weight neutral). 2

• Across 32 clinical trials involving 463 adult epilepsy patients treated for approximately 318 days at mean doses of 259 mg/day, the mean change in body weight was only 0.5 ± 5 kg, confirming weight stability. 3

Comparative Context: Lamotrigine vs. Other Mood Stabilizers

Understanding lamotrigine's weight profile requires comparison with alternative agents:

Valproate (Avoid for Weight-Concerned Patients)

• Valproate causes significant weight gain in up to 50% of users, detectable within 2-3 months of initiation. 4
• In head-to-head comparison, valproate monotherapy produced mean weight gain of 12.8 ± 9.3 lb after 32 weeks versus 1.3 ± 11.9 lb with lamotrigine (statistically significant difference). 1

Lithium (Moderate Weight Gain Risk)

• Lithium produced mean weight gain of +2.2 kg at week 52 compared to -1.2 kg with lamotrigine (statistically significant difference, p < 0.001). 2
• The percentage of patients with ≥7% weight loss was significantly higher with lamotrigine (12.1%) than lithium (5.1%). 2

Carbamazepine (Low Weight Gain Risk)

• Carbamazepine has been proven to have a low risk of weight gain, similar to lamotrigine. 4

Topiramate (Weight Loss Agent)

• Topiramate is associated with weight loss rather than gain, though it carries higher discontinuation rates due to adverse events. 5, 4

Clinical Significance: Lamotrigine May Promote Modest Weight Loss

Emerging evidence suggests lamotrigine may actually facilitate weight loss in some contexts:

• In obese adults without psychiatric illness, lamotrigine 200 mg/day for 26 weeks produced mean weight loss of -6.4 ± 10.26 lb versus -1.2 ± 7.09 lb with placebo (trend toward significance, p=0.0623), with statistically significant BMI reduction (-1.5 ± 2.78 vs. -0.1 ± 1.05, p=0.0421). 6

• In bipolar disorder maintenance, 12.1% of lamotrigine-treated patients experienced ≥7% weight loss compared to 11.5% with placebo and only 5.1% with lithium. 2

Practical Clinical Algorithm

For patients with epilepsy or bipolar disorder where weight is a concern:

1. First-line choice: Lamotrigine is an excellent option given its weight-neutral to modest weight-loss profile. 1, 2, 3

2. Avoid: Valproate (50% risk of significant weight gain within 2-3 months). 4, 1

3. Alternative considerations:

   • Carbamazepine has low weight gain risk for epilepsy. 4
   • Topiramate causes weight loss but has higher discontinuation rates. 5, 4

4. Monitoring: The incidence of ≥7% weight gain with lamotrigine (10.9%) is comparable to placebo (7.6%), so routine weight monitoring is reasonable but weight gain should not be anticipated. 2

Important Caveats

• While lamotrigine shows weight neutrality, individual responses vary—approximately 10-12% of patients may experience either ≥7% weight gain or ≥7% weight loss. 2

• The weight-neutral profile of lamotrigine represents a significant advantage over many other mood stabilizers and antiepileptic drugs, making it particularly suitable for patients with metabolic concerns or pre-existing obesity. 4, 1, 2

• Lamotrigine's efficacy is comparable to valproate for seizure control while avoiding the substantial weight gain associated with valproate. 1