What is the starting dose of Lamotrigine (Lamictal) in an adult?

Starting Dose of Lamotrigine in Adults

The starting dose of lamotrigine in adults is 25 mg once daily for the first 2 weeks, followed by an increase to 50 mg daily, with subsequent titration based on concomitant medications and clinical response. 1, 2

Standard Dosing Protocol

Initial Titration (Without Valproic Acid or Enzyme Inducers)

• Start with 25 mg once daily for 14 days 1
• Increase to 50 mg once daily for the next 14 days 1
• Further dose escalation depends on the indication and patient response, with typical maintenance doses ranging from 100-400 mg/day 3, 4

Critical Dosing Adjustments Based on Drug Interactions

When co-administered with valproic acid:

• The starting dose must be reduced due to significant pharmacokinetic interaction that increases lamotrigine half-life to 48.3-59 hours 2, 4
• This interaction substantially increases the risk of serious rash if standard dosing is used 2

When co-administered with enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, phenobarbital):

• Higher doses may be needed as these medications reduce lamotrigine half-life to 13.5-15 hours 4
• More rapid titration may be appropriate, though the initial 25 mg starting dose remains standard 1

Rationale for Low Starting Dose

The 25 mg starting dose is specifically designed to minimize the risk of serious rash, which occurs in approximately 10% of patients and is the most common cause of treatment discontinuation. 3

• Exceeding the recommended initial dosage is a documented risk factor for serious rash 2
• The incidence of serious rash in bipolar disorder studies was 0.1% when proper titration was followed, including one case of mild Stevens-Johnson syndrome 5
• Slow titration over 6 weeks to reach 200 mg/day has been the traditional approach to minimize rash risk 5

Special Population Considerations

Elderly Patients

• The same 25 mg/day starting dose is appropriate for elderly patients (>65 years) 6
• After 15 days, increase to 50 mg/day, which may be maintained as the therapeutic dose in many elderly patients 6
• In one study of 222 elderly patients, 52% achieved seizure control on just 50 mg/day, with a mean final dose of only 72 mg/day 6

Monitoring Requirements

Before initiating lamotrigine, obtain baseline laboratory tests including complete blood count, liver function tests, and renal function tests. 2

• No routine therapeutic drug monitoring is required during maintenance therapy 2
• Check lamotrigine levels when patients are on combined hormonal contraceptives, which may reduce lamotrigine effectiveness 2
• A putative therapeutic range of 1-4 mg/L has been proposed, though some patients benefit from concentrations >10 mg/L without toxicity 4

Common Pitfalls to Avoid

• Never start at doses higher than 25 mg/day to avoid dramatically increasing rash risk 2, 3
• Do not accelerate the titration schedule beyond the recommended 2-week intervals without considering drug interactions 1
• Always adjust dosing when valproic acid is co-administered due to the profound pharmacokinetic interaction 2, 4
• Be aware that lamotrigine formulations (regular tablets, extended-release, dissolving tablets) have different administration requirements—regular tablets must be swallowed whole with water, while dissolving tablets should be placed on the tongue without chewing 7