Lamotrigine Dosing for Depression and ADHD
Lamotrigine (Lamictal) is not FDA-approved for depression or ADHD, and there is no established "standard dosage" for these indications. However, when used off-label in patients with bipolar disorder who have comorbid depression and ADHD, the evidence suggests specific dosing strategies.
Off-Label Use in Bipolar Depression with Comorbid ADHD
For bipolar depression, lamotrigine should be titrated to a target dose of 200 mg/day over 6 weeks to minimize the risk of serious rash, including Stevens-Johnson syndrome. 1, 2 This slow titration is mandatory and non-negotiable for safety.
Evidence-Based Dosing Strategy
- Target dose: 200 mg/day is the standard maintenance dose for bipolar depression, demonstrated to be effective in controlled trials 1, 2, 3
- Higher doses up to 300 mg/day may provide additional benefit in treatment-resistant bipolar depression, with one case series showing significant improvement in depression scores when lamotrigine was increased from 200 mg to 300 mg daily 4
- For ADHD comorbid with mood disorders, a retrospective chart review found a mean effective dose of 125.6 ± 47.8 mg (range 25-250 mg), with 77.5% of patients showing improvement 5
Critical Titration Schedule
The 6-week titration to 200 mg/day is essential to prevent life-threatening rash: 1, 2
- Weeks 1-2: 25 mg/day
- Weeks 3-4: 50 mg/day
- Week 5: 100 mg/day
- Week 6 onward: 200 mg/day (target maintenance dose)
Important caveat: If lamotrigine is coadministered with valproate, the dosing must be reduced by 50% due to drug interactions 1, 2. Conversely, if coadministered with carbamazepine, higher doses are required 1, 2.
Clinical Context and Limitations
- Lamotrigine has NOT demonstrated efficacy for acute mania and should not be used as monotherapy during manic episodes 1, 2
- For ADHD symptoms specifically, lamotrigine should be combined with traditional ADHD medications (stimulants or non-stimulants) once mood symptoms are adequately controlled 6
- Lamotrigine is primarily effective for the depressive pole of bipolar disorder, significantly delaying time to intervention for depressive episodes compared to placebo 1, 2
Common Pitfalls to Avoid
- Never rapid-load lamotrigine - this dramatically increases the risk of Stevens-Johnson syndrome, which can be fatal 6
- If lamotrigine is discontinued for more than 5 days, restart with the full titration schedule rather than resuming the previous dose 6
- Do not use lamotrigine as monotherapy for ADHD - the evidence only supports its use as adjunctive treatment in patients with comorbid mood disorders 5
Monitoring Requirements
- Weekly monitoring for rash is essential during the first 8 weeks of titration 6
- Unlike lithium, lamotrigine generally does not require routine serum level monitoring 1, 2
- Assess mood symptoms, suicidal ideation, and medication adherence at each visit 6