Lamotrigine and Weight Gain
Lamotrigine is weight-neutral and does not cause weight gain; in fact, it may be associated with modest weight loss, making it one of the preferred anticonvulsants when metabolic concerns are paramount. 1, 2
Evidence for Weight Neutrality
Lamotrigine stands out among anticonvulsants for its favorable metabolic profile:
Direct comparative trials demonstrate weight stability with lamotrigine monotherapy, with patients gaining only 1.3 ± 11.9 lb over 32 weeks compared to 12.8 ± 9.3 lb with valproate (p < 0.001). 3
Lamotrigine is classified as a weight-neutral antiepileptic drug in systematic reviews, contrasting sharply with weight-gaining agents like valproate, carbamazepine, gabapentin, and pregabalin. 1, 2
A placebo-controlled obesity trial showed lamotrigine 200 mg/day produced a statistically significant reduction in BMI (-1.5 ± 2.78 vs -0.1 ± 1.05 for placebo, p = 0.0421) and a trend toward weight loss (-6.4 lb vs -1.2 lb, p = 0.0623). 4
Clinical Context Among Mood Stabilizers
When comparing lamotrigine to other mood stabilizers and anticonvulsants:
Valproate causes significant weight gain within 10 weeks of initiation and continues throughout treatment, making it problematic for metabolic health. 3
Lithium shows more reports of severe weight gain than lamotrigine (ROR 2.1, though not statistically significant), but substantially less than olanzapine (ROR 11.5), quetiapine (ROR 3.4), or valproate (ROR 2.4). 5
Gabapentin and pregabalin are associated with weight gain, with pregabalin specifically listing weight gain as one of its most frequent side effects alongside dizziness and peripheral edema. 6
Evaluation and Management Algorithm
For Patients Currently on Lamotrigine:
Monitor weight at baseline, monthly for 3 months, then quarterly, though weight gain is unlikely with lamotrigine monotherapy. 2
If weight gain occurs on lamotrigine, investigate alternative causes including polypharmacy (especially concurrent antipsychotics, other mood stabilizers, or antidepressants), dietary changes, reduced physical activity, or endocrine disorders. 1
For Patients Requiring Mood Stabilizer Selection:
Choose lamotrigine as first-line when weight concerns exist, particularly over valproate, carbamazepine, or lithium. 1, 3, 2
Avoid switching from lamotrigine to valproate, gabapentin, or pregabalin if weight is a concern, as these consistently promote weight gain. 6, 1
Important Clinical Caveats
Lamotrigine's weight neutrality makes it advantageous for patients with metabolic syndrome, diabetes, or obesity, where weight gain from alternatives like valproate would worsen comorbidities. 1, 3
Patient satisfaction is significantly higher with lamotrigine compared to placebo in weight-related outcomes (p = 0.0065), suggesting improved adherence when metabolic concerns are addressed. 4
The most common adverse effect is mild-to-moderate headache, not metabolic disturbances, making lamotrigine well-tolerated overall. 4