Lamotrigine Does Not Cause Vitamin B12 Deficiency
Lamotrigine is not associated with vitamin B12 deficiency based on current evidence. The most recent and comprehensive guidelines on B12 deficiency do not list lamotrigine as a causative medication.
Medications That Actually Cause B12 Deficiency
The 2024 NICE guidelines explicitly identify the following medications as risk factors for vitamin B12 deficiency 1:
- Metformin (well-established association)
- H2 receptor antagonists
- Colchicine
- Phenobarbital
- Pregabalin
- Primidone
Notably absent from this list is lamotrigine, despite the guideline's comprehensive review of drug-induced B12 deficiency 1.
Evidence Regarding Lamotrigine and B Vitamins
The available research on lamotrigine shows:
No significant association with B12 deficiency: A 2012 study examining B-vitamin deficiencies in patients switching from enzyme-inducing antiepileptic drugs to non-inducing drugs (including lamotrigine) found no folate or B12 deficiency in any patient 2.
Lamotrigine is a non-inducing antiepileptic: Unlike older anticonvulsants such as phenobarbital (which does cause B12 deficiency), lamotrigine does not induce hepatic enzymes that interfere with vitamin metabolism 2.
Limited case reports only: One 2006 case report suggested possible B6 and B12 changes in a pregnant patient on lamotrigine, but this was confounded by multiple factors including triplet pregnancy and genetic polymorphisms, making causality impossible to establish 3.
Systematic review findings: A 2018 systematic review examining anticonvulsants (valproic acid, carbamazepine, lamotrigine, and topiramate) and their effects on folate, B12, and homocysteine concluded that "we were unable to make any clear statement about lamotrigine because there have been very few publications" linking it to vitamin deficiencies 4.
Clinical Implications
Do not routinely monitor B12 in patients on lamotrigine unless other risk factors are present (vegan diet, malabsorption disorders, concurrent use of metformin or other causative medications) 1.
If B12 deficiency is found in a patient taking lamotrigine, investigate other causes rather than attributing it to the medication 1.
Contrast with metformin: Metformin requires annual B12 monitoring after 4 years of use or with doses ≥1500 mg daily, demonstrating the clear difference in evidence quality between established drug-induced deficiency and lamotrigine 5.