Lamotrigine Augmentation for Treatment-Resistant Depression on Sertraline with TMS
Yes, you can start lamotrigine 25 mg as augmentation for this 67-year-old woman with treatment-resistant depression who is on sertraline and undergoing TMS. Lamotrigine is a reasonable augmentation strategy in this clinical scenario, and the TMS recommendation does not contraindicate its use.
Rationale for Lamotrigine Augmentation
Lamotrigine is supported as an augmentation option in treatment-resistant depression, though it is generally considered a second-line strategy after atypical antipsychotics. 1, 2 The evidence base shows:
A 2019 meta-analysis of 8 randomized controlled trials (677 patients) demonstrated significant improvements in depression severity and response rates with lamotrigine augmentation compared to placebo. 3 This represents the highest quality and most recent comprehensive evidence.
Patients with more severe illness and longer duration of illness responded more effectively to lamotrigine augmentation. 3 This is particularly relevant for treatment-resistant cases.
Lamotrigine augmentation is well-tolerated with acceptable discontinuation rates and adverse event profiles. 3
Compatibility with TMS
Patients undergoing non-invasive brain stimulation interventions like TMS should not be excluded from pharmacological augmentation trials. 4 The 2022 Molecular Psychiatry consensus guidelines explicitly state with 88% consensus that individuals in whom TMS failed should not be excluded from treatment studies, and conversely, ongoing TMS does not preclude medication augmentation. 4
Dosing Protocol
Start lamotrigine at 25 mg daily as recommended by the TMS consultant. This is the standard initial dose used in clinical trials. 5, 6
Titrate slowly upward from 25 mg/day to target doses of 100-200 mg/day over several weeks. 5, 6 The slow titration is critical to minimize risk of serious rash.
Most studies used flexible dosing regimens ranging from 50-200 mg/day or up to 400 mg/day. 5, 7
Clinical improvement may be seen within 2 weeks, though full evaluation requires 6-8 weeks of treatment. 5
Important Caveats
Monitor closely for rash, particularly during the first 8 weeks of treatment. Lamotrigine carries a risk of serious dermatologic reactions including Stevens-Johnson syndrome, which is minimized by slow dose titration. 3
Ensure sertraline has been at adequate dose (typically ≥50 mg daily) for at least 4 weeks before declaring it a treatment failure requiring augmentation. 4, 1 This confirms true treatment resistance rather than inadequate trial.
Document that this patient has failed at least one (preferably two) adequate antidepressant trials with different mechanisms of action to confirm treatment-resistant depression diagnosis. 1, 2, 8 This justifies the augmentation strategy.
Evidence Limitations
The largest placebo-controlled trial (183 patients) failed to show statistically significant separation from placebo on primary outcomes, though post-hoc analyses suggested benefit in more severely ill patients. 7 This creates some uncertainty about lamotrigine's efficacy.
However, the 2019 meta-analysis pooling multiple trials showed overall positive effects, particularly in patients treated with SSRIs like sertraline. 3 The magnitude of depression improvement was higher when lamotrigine was combined with SSRIs versus SNRIs. 3
Note that atypical antipsychotics (particularly aripiprazole) remain the primary first-line augmentation strategy with stronger evidence. 1, 2 If lamotrigine fails or is not tolerated, consider switching to aripiprazole augmentation.