What are the potential side effects of lamotrigine?

Lamotrigine Side Effects

Lamotrigine commonly causes dizziness, somnolence, headache, and nausea, but the most critical concern is skin rash, which occurs in approximately 10% of patients and can rarely progress to severe reactions like Stevens-Johnson syndrome. 1, 2

Most Common Side Effects

Central Nervous System Effects

• Dizziness, somnolence, and headache are the most frequently reported CNS adverse effects 1
• Ataxia and other CNS-related symptoms occur commonly, particularly when used as add-on therapy 3
• Lamotrigine causes less drowsiness than carbamazepine or phenytoin when used as monotherapy 2

Gastrointestinal Effects

• Nausea is one of the most frequently reported side effects, typically mild to moderate and transient 1
• Gastrointestinal symptoms are common but generally well-tolerated 2

Sleep-Related Effects

• Insomnia has been reported as a common adverse effect 4
• In pediatric populations with autism spectrum disorder, lamotrigine has been specifically associated with insomnia and hyperactivity 5

Critical Safety Concern: Skin Rash

Incidence and Severity

• Maculopapular or erythematous skin rash occurs in approximately 10% of patients and is the most common cause of treatment discontinuation 2
• The incidence of serious rash is 0.1% in bipolar disorder studies, including cases of Stevens-Johnson syndrome 4
• Exceeding recommended initial dosage is a major risk factor for serious rash 6

Risk Mitigation

• The risk of rash can be minimized through adoption of a low, slow dosage titration schedule over 6 weeks to reach 200 mg/day 4
• Patients with a history of allergy are at higher risk for early discontinuation due to adverse effects 7
• Dosage adjustments are essential when coadministered with valproic acid (which increases lamotrigine half-life to 48.3-59 hours) or enzyme-inducing antiepileptics 6, 3

Psychiatric Side Effects

Mood and Behavioral Changes

• Affective switches, acute psychotic episodes, and hallucinations have been reported in patients using lamotrigine for mental disorders or epilepsy 8
• Clinicians must be aware that lamotrigine can induce psychiatric symptoms or acute episodes, despite its efficacy in treating mood disorders 8

Drug Interactions Affecting Side Effect Profile

Contraceptive Interactions

• Combined hormonal contraceptives may reduce lamotrigine effectiveness, necessitating level monitoring 6
• Conversely, COCs decrease the effectiveness of lamotrigine, requiring dosage adjustments 9

Metabolic Interactions

• Lamotrigine is metabolized by cytochrome P450, and strong inducers may decrease its efficacy 1
• Lamotrigine may increase plasma concentrations of carbamazepine's active metabolite during concomitant administration 3

Long-Term Tolerability

Duration-Dependent Safety Profile

• Most adverse effects occur early during the titration phase; long-term use beyond 6 months is very well tolerated, even at high maintenance doses 7
• Only 2 of 54 patients who continued treatment for 6 months or longer subsequently discontinued due to adverse effects 7
• Seizure control improvements are sustained on long-term therapy (up to 3 years) and are accompanied by improvements in psychological well-being 2

Advantages Over Other Agents

• Lamotrigine does not appear to cause weight gain, unlike many other mood stabilizers 4
• Lower incidences of diarrhea and tremor compared to lithium-treated patients 4
• Less asthenia and ataxia than phenytoin when used as monotherapy 2

Monitoring Requirements

Baseline Assessment

• Complete blood count, liver function tests, and renal function tests should be obtained before initiating therapy 6
• No specific routine laboratory monitoring is mandated after baseline, except when drug interactions are suspected 6