What are the possible side effects of Lamotrigine (lamotrigine)?

Possible Side Effects of Lamotrigine

Lamotrigine is generally well tolerated, but skin rash—occurring in approximately 5-10% of patients—is the most significant adverse effect and the most common reason for treatment discontinuation. 1, 2

Most Common Side Effects

Central Nervous System Effects

• Dizziness, somnolence (drowsiness), and headache are the most frequently reported CNS side effects 3, 4
• Ataxia (loss of coordination) occurs significantly more often than with placebo but rarely requires discontinuation 2
• These neurological effects are generally mild to moderate and dose-related 1

Gastrointestinal Effects

• Mild to moderate transient nausea is one of the most frequently reported side effects 3
• Diarrhea may occur, though less commonly than with lithium 5

Dermatological Effects (Most Critical)

• Maculopapular or erythematous skin rash occurs in approximately 5-10% of patients and is the most common cause of treatment withdrawal 1, 2
• The incidence of serious rash is 0.1% in bipolar disorder studies, including rare cases of Stevens-Johnson syndrome 5
• Risk of rash can be minimized through low, slow dosage titration when initiating therapy 1
• Patients with a history of allergies are more likely to discontinue treatment early due to adverse effects 6

Other Notable Side Effects

General Tolerability

• Infection and insomnia are commonly reported 5
• Headache occurs frequently 5
• Lamotrigine does not appear to cause weight gain, unlike many other mood stabilizers 5

Psychiatric Side Effects (Less Common)

• Affective switches, acute psychotic episodes, and hallucinations have been reported in patients using lamotrigine for mental disorders or epilepsy 7
• In pediatric populations, insomnia and hyperactivity have been specifically associated with lamotrigine use 4

Important Clinical Considerations

Timing of Adverse Effects

• Most adverse effects occur early during the titration phase 6
• Of patients who continue treatment for 6 months or longer, only 2% later discontinue due to adverse effects 6
• Long-term use is very well tolerated, even at high maintenance doses (>200 mg/day) 6

Comparative Tolerability

• Lamotrigine produces less drowsiness than carbamazepine or phenytoin 1
• Less asthenia and ataxia than phenytoin in monotherapy 1
• Lower incidences of diarrhea and tremor compared to lithium 5
• Does not cause clinically significant impairment of alertness, unlike other antiepileptics 4

Drug Interactions Affecting Side Effects

• Combined oral contraceptives can significantly decrease lamotrigine levels, potentially increasing seizure activity 8
• Enzyme-inducing anticonvulsants may decrease lamotrigine efficacy 3
• Valproate increases lamotrigine levels and requires dosage adjustment to minimize rash risk 5

Key Safety Points

The risk-benefit profile of lamotrigine is favorable compared to traditional antiepileptic drugs 2. However, clinicians must be vigilant during the initial titration period, particularly for rash development. Patients with a history of allergic reactions require closer monitoring 6. The drug's excellent long-term tolerability profile and lack of weight gain make it particularly advantageous for maintenance therapy 5, 6.