What Lamictal (Lamotrigine) Is Used For
Lamictal is FDA-approved for maintenance treatment of bipolar I disorder in adults, specifically to delay time to intervention for mood episodes, with particular efficacy in preventing depressive episodes. 1
Primary Psychiatric Indication
Maintenance Therapy for Bipolar I Disorder
- Lamotrigine significantly delays time to intervention for any new mood episode (mania, hypomania, depression, and mixed episodes) compared to placebo in adults with bipolar I disorder 2, 3
- The drug is particularly effective at prolonging time to intervention for depressive episodes, which dominate the clinical picture of bipolar disorder 2, 4
- Lamotrigine shows limited efficacy in delaying manic/hypomanic episodes, with lithium demonstrating superior efficacy for preventing mania 2, 3
- The American Academy of Child and Adolescent Psychiatry recognizes lamotrigine as an approved maintenance therapy option for bipolar disorder 1
Acute Bipolar Depression (Off-Label)
- Two of four double-blind studies demonstrated lamotrigine superiority over placebo in treating patients with treatment-refractory bipolar disorder or bipolar depression 2, 3
- Lamotrigine is used off-label for acute bipolar depression treatment, though this is not its FDA-approved indication 4
Important Limitation: Lamotrigine has NOT demonstrated efficacy in treating acute mania and should not be used for this indication 2, 3
Primary Neurological Indication
Epilepsy Treatment
- Lamotrigine is a broad-spectrum antiepileptic drug approved for adjunctive treatment of partial seizures in adults 5
- It is approved for generalized seizures of Lennox-Gastaut syndrome in pediatric (>2 years old) and adult populations 5
- The drug has demonstrated particular benefit in treating women and elderly patients with epilepsy 5
Other Potential Uses (Off-Label)
- Rapid cycling bipolar affective disorder 6
- Bipolar disorder type II with rapid phase change 4
- Resistant depression 6
- Mood changes in borderline personality disorder 6
- Migraines and neuropathic pain management 5
- Schizoaffective disorder 6
Mechanism of Action
- Lamotrigine inhibits voltage-dependent sodium and calcium channels in presynaptic neurons, stabilizing the neuronal membrane 2, 4
- This mechanism results in inhibition of glutamate and aspartate neurotransmitter release into the postsynaptic neuron 4
Critical Safety Considerations
Rash Risk and Titration Requirements
- The incidence of serious rash with lamotrigine is 0.1% in bipolar disorder studies, including Stevens-Johnson syndrome 2, 3
- Avoid rapid titration—lamotrigine must be titrated over a 6-week period to 200 mg/day to minimize serious rash risk 7, 2, 3
- If lamotrigine is discontinued for more than 5 days, restart with the full titration schedule rather than resuming the previous dose 7
Drug Interactions Requiring Dose Adjustment
- Combined oral contraceptives significantly decrease lamotrigine levels, potentially precipitating breakthrough mood episodes or increased seizure activity 7
- Dose adjustments are required when coadministered with valproate or carbamazepine 2, 3
- Lamotrigine has few significant drug interactions beyond enzyme-inducing anticonvulsants and is compatible with most medication regimens, including atypical antipsychotics 7, 8
Advantages Over Other Mood Stabilizers
- Lamotrigine does not cause bodyweight gain, unlike many alternatives 2, 3
- Unlike lithium, lamotrigine generally does not require monitoring of serum levels 2, 3
- Lower incidences of diarrhea and tremor compared to lithium-treated patients 2, 3
- Preferable side-effect profile compared to standard agents like lithium or carbamazepine 6
Common Adverse Effects
- Most common adverse events include headache, nausea, infection, and insomnia 2, 3
- Rare but serious: Stevens-Johnson syndrome, hemophagocytic lymphohistiocytosis, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome 4