What is the recommended starting dose and titration schedule of lamotrigine (Lamictal) for a 65‑year‑old man?

Starting Dose of Lamotrigine in a 65-Year-Old Male

Begin with 25 mg once daily for 14 days, then increase to 50 mg once daily for the next 14 days, following the standard adult titration protocol regardless of age. 1

Standard Dosing Protocol

The initial titration without valproic acid or enzyme-inducing medications involves:

• Weeks 1–2: 25 mg once daily 1
• Weeks 3–4: 50 mg once daily 1
• Subsequent titration: Increase by 25–50 mg every 1–2 weeks as tolerated, targeting a maintenance dose of 100–200 mg/day for bipolar disorder or 100–400 mg/day for epilepsy 1, 2, 3

Age alone does not mandate a lower starting dose of 12.5 mg in a 65-year-old patient. 1 The standard 25 mg starting dose applies across the adult age spectrum, with adjustments made only for specific drug interactions or organ dysfunction, not chronological age. 1

Critical Dosing Adjustments Based on Concomitant Medications

If Taking Valproic Acid

Start at 12.5 mg once daily (half the standard dose) because valproic acid prolongs lamotrigine's half-life to 48–59 hours, dramatically increasing toxicity risk. 1, 4

• Weeks 1–2: 12.5 mg once daily 1
• Weeks 3–4: 25 mg once daily 1
• Maintenance: Target 100–200 mg/day (approximately 50% of standard dose) 1

If Taking Enzyme-Inducing AEDs (Carbamazepine, Phenytoin, Phenobarbital)

Start at 50 mg once daily (double the standard dose) because these drugs reduce lamotrigine's half-life to 13.5–15 hours. 1, 4

• Weeks 1–2: 50 mg once daily 1
• Weeks 3–4: 100 mg daily in divided doses 1
• Maintenance: Target 300–500 mg/day in divided doses 1

Special Considerations for Older Adults

While the 2010 neuropathic pain guidelines recommend lower starting doses and slower titration in geriatric patients for certain medications, 5 lamotrigine-specific guidelines do not mandate age-based dose reduction. 1 However, consider:

• Renal function: Obtain baseline creatinine clearance, as lamotrigine is 43–87% renally excreted. 4 If creatinine clearance is significantly reduced, slower titration may be prudent, though specific renal dosing adjustments are not established. 4
• Polypharmacy: Review all medications for potential interactions, particularly valproic acid and enzyme inducers. 1
• Baseline laboratory tests: Complete blood count, liver function tests, and renal function tests should be obtained before initiating therapy. 1

Critical Safety Warnings

Never exceed the recommended initial dose or accelerate titration beyond 2-week intervals. 1 Exceeding the recommended initial dosage is a major risk factor for serious rash, including Stevens-Johnson syndrome, which occurs in approximately 0.1% of bipolar disorder patients. 1, 2 The risk of severe rash is minimized through strict adherence to the slow titration schedule. 2, 3

If lamotrigine has been interrupted for more than 5 days, restart the full titration schedule from 25 mg daily rather than resuming the previous maintenance dose. 1

Formulation Options

• Regular tablets: Swallow whole with water 6
• Dissolving tablets: Place on tongue to dissolve; do not chew, crush, or break 6

Dissolving tablets provide an alternative for patients with swallowing difficulties but follow the same dosing schedule. 6

Monitoring

No routine therapeutic drug monitoring is mandated, though checking lamotrigine levels may be useful to verify adherence or assess pharmacokinetic variability. 1 If monitoring is performed, obtain trough (pre-dose) levels at steady state—approximately 1 week after dose changes in patients not on valproate, or 2–3 weeks in those receiving valproate. 1