RESEARCH MONOGRAPH · KDC-MN-243
Lamotrigine
Lamotrigine (Lamictal) is a clean voltage-gated sodium channel blocker from GSK, approved by the FDA in 1994 for partial seizures and now equally important as a first-line mood stabilizer for bipolar depression and bipolar maintenance. It is unusual in mood medicine because, unlike lithium and valproate, it is more effective at preventing depressive episodes than manic ones. The mechanism is state-dependent: it preferentially binds inactivated sodium channels, which selectively dampens hyperactive neurons while leaving normal firing alone. The infamous risk is Stevens-Johnson syndrome (potentially fatal skin reaction) if titrated too quickly, which is why the dose-up schedule is conservative and stretched over weeks. Otherwise it is one of the most metabolically clean drugs in psychiatry. Not stocked by Kodiac. This monograph is provided for research and educational reference.
Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.
Phenyltriazine sodium channel blocker / mood stabilizer
A phenyltriazine voltage-gated sodium channel blocker; uniquely effective for bipolar depression and a first-line maintenance mood stabilizer.
Abstract
Lamotrigine (3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine; CAS 84057-84-1; molecular formula C9H7Cl2N5; molecular weight 256.09) is a phenyltriazine voltage-gated sodium channel blocker developed at Wellcome (now GSK) and approved by the FDA in 1994 under the trade name Lamictal. Mechanism: state-dependent inhibition of voltage-gated sodium channels (preferentially binding inactivated state), reducing release of presynaptic glutamate and aspartate. Secondary inhibition of high-voltage-activated calcium channels and weak antagonism at 5-HT3 receptors contribute to the broader profile. Distinct among anticonvulsants for efficacy in bipolar depression and maintenance mood stabilization (more effective at preventing depressive than manic episodes, opposite the lithium pattern). Plasma half-life is 25 to 33 hours alone, shortened by enzyme-inducing comedications. Hepatic metabolism is primarily glucuronidation. The principal limitation is a benign rash incidence of approximately 10 percent and Stevens-Johnson syndrome at approximately 1 in 1000, both reduced by slow titration over 4 to 6 weeks. Approved for partial-onset seizures, primary generalized tonic-clonic seizures, Lennox-Gastaut syndrome, and bipolar I disorder maintenance. Used as the reference anticonvulsant mood stabilizer and as a clean voltage-gated sodium channel blocker.
Mechanism of action
State-dependent voltage-gated sodium channel inhibition; reduces presynaptic glutamate/aspartate release. Secondary calcium channel and 5-HT3 effects.
Reported research dose ranges
Clinical 100 to 400 mg per oral administration daily, with slow titration. Rodent studies 5 to 30 mg/kg/day.
References
- Goldsmith DR, et al. Lamotrigine: a review of its use in bipolar disorder. Drugs 2003.
- Calabrese JR, et al. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. J Clin Psychiatry 1999.
- Cheriyan J, et al. Lamotrigine and Stevens-Johnson syndrome. Pediatr Dermatol 2018.
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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.