Lamotrigine in Borderline Personality Disorder
Lamotrigine is NOT recommended for borderline personality disorder based on the highest quality evidence—a large 2018 randomized controlled trial showed no clinical benefit over placebo for any BPD symptoms at 52 weeks. 1
Evidence Against Lamotrigine Use
The most definitive study on this question is the 2018 multicenter, double-blind, placebo-controlled trial of 276 patients with BPD. At 52 weeks, there was no difference between lamotrigine (up to 400 mg/day) and placebo on the primary outcome (ZAN-BPD scores: 11.3 vs 11.5, adjusted difference 0.1). There were also no differences in any secondary outcomes including depressive symptoms, deliberate self-harm, social functioning, or quality of life. The study concluded lamotrigine is neither clinically effective nor cost-effective for BPD 1.
A 2020 meta-analysis of randomized controlled trials confirmed these findings, showing:
- No statistically significant difference at 12 weeks (SMD: -0.04, p=0.87)
- No benefit at study endpoints (SMD: 0.18, p=0.74)
- No improvement in impulsivity/aggression (SMD: -1.84, p=0.08)
The authors concluded there is "no consistent evidence of lamotrigine's efficacy for the core symptom domains of BPD" 2.
Contradictory Earlier Evidence
One small 2009 study (n=28) suggested lamotrigine reduced affective instability and impulsivity in BPD 3. However, this finding was not replicated in the larger, more rigorous 2018 trial, which should take precedence given its superior methodology, larger sample size, and more recent publication date.
What Actually Works for BPD
The evidence-based treatment for BPD is dialectical behavior therapy (DBT), which has been shown in randomized controlled trials to reduce suicidal and self-directed violence in patients with BPD 4, 5. DBT focuses on:
- Emotion regulation skills
- Distress tolerance
- Interpersonal effectiveness
- Mindfulness techniques
DBT typically involves individual and group sessions and has demonstrated efficacy specifically for the BPD population 5.
Clinical Bottom Line
Do not prescribe lamotrigine for BPD. The medication lacks efficacy for core BPD symptoms and represents an ineffective use of resources. Instead, refer patients for evidence-based psychotherapy (DBT) as first-line treatment. If pharmacotherapy is needed for comorbid conditions (such as bipolar disorder or major depression), treat those conditions according to their respective guidelines, but do not expect lamotrigine to improve BPD symptoms themselves.
Important Caveat
The one exception where lamotrigine might be considered: if family history reveals strong genetic loading for bipolar disorder (extending to grandparents, aunts, uncles, cousins), suggesting the patient's emotional dysregulation may have a bipolar diathesis rather than pure BPD 6. In such cases, a mood stabilizer like lamotrigine or lithium may address the underlying mood disorder component—but this is treating comorbid bipolar disorder, not BPD itself.