For a 67‑year‑old woman with treatment‑resistant depression on sertraline and receiving transcranial magnetic stimulation, how long should I stay on lamotrigine 25 mg before increasing the dose?

Lamotrigine 25 mg Duration Before Dose Escalation

Stay on lamotrigine 25 mg for 2 weeks, then increase to 50 mg for 2 weeks, followed by 100 mg as the target therapeutic dose for treatment-resistant depression augmentation. 1

Titration Protocol for Treatment-Resistant Depression

The standard lamotrigine titration for augmentation in treatment-resistant depression follows a structured schedule to minimize risk of serious rash while achieving therapeutic benefit:

• Week 1-2: Lamotrigine 25 mg daily 1
• Week 3-4: Increase to 50 mg daily 1
• Week 5 onward: Increase to 100 mg daily (target therapeutic dose) 1
• Maximum dose if needed: 200 mg daily 1

This slow titration is critical—the 2-week interval at each dose level is mandatory to reduce the risk of Stevens-Johnson syndrome and other serious dermatologic reactions. 1

Evidence for Therapeutic Dosing

The mean effective dose in treatment-resistant depression studies is approximately 100-141 mg daily, with a range of 50-200 mg. 2, 3, 4 Research demonstrates:

• Mean dose of responders: 141 mg in treatment-resistant bipolar depression 5
• Mean dose: 112.90 mg in treatment-resistant unipolar depression 4
• Dose range in controlled trials: 50-200 mg daily 3
• Target dose in placebo-controlled trial: 100 mg daily 6

No significant difference in efficacy was found between different doses within the therapeutic range (50-200 mg), suggesting that 100 mg may be optimal for most patients. 4

Expected Timeline for Response

• Early response: Significant clinical improvement may begin within 2 weeks of reaching therapeutic dose 3
• Full assessment: Allow 6-8 weeks at therapeutic dose (100 mg) to adequately evaluate response 6, 4
• Lamotrigine shows faster onset compared to lithium augmentation, with significant improvement by week 2 versus week 4. 3

Clinical Considerations for Your Patient

Given this is a 67-year-old woman with treatment-resistant depression already on sertraline:

• Lamotrigine augmentation is particularly effective with SSRIs like sertraline—studies show greater magnitude of improvement when combined with SSRIs versus SNRIs 2
• Patients with more severe illness and longer duration respond better to lamotrigine augmentation 2
• Response rates in treatment-resistant depression: 40.5-48.4% achieve much or very much improved status 4

Safety Monitoring During Titration

Monitor weekly during the titration phase for:

• Rash (most critical): Any rash requires immediate evaluation and likely discontinuation 1
• Dizziness, headache, nausea (common but usually mild) 2, 3
• Drop-out rates due to adverse events are low (approximately 16% in studies) 4

Common Pitfalls to Avoid

• Never accelerate the titration schedule—the 2-week intervals are non-negotiable for safety 1
• Do not assume lack of response at 25 mg or 50 mg—these are sub-therapeutic doses used only for titration 2, 6
• Patients who fail fewer previous antidepressant trials respond better—this suggests earlier use of lamotrigine augmentation may be advantageous 4
• Do not discontinue prematurely—allow full 6-8 weeks at therapeutic dose before declaring treatment failure 6, 4

Concurrent TMS Therapy

Your patient is receiving transcranial magnetic stimulation, which is complementary to pharmacologic augmentation. Continue both interventions as they target treatment resistance through different mechanisms and may have additive benefits.