What is the next step for a patient with a history (HX) of depression who is currently on lamotrigine (100mg) and still experiences depressive symptoms?

Management of Persistent Depression on Lamotrigine 100mg

The patient requires immediate dose optimization of lamotrigine to 200mg daily, as the current 100mg dose is subtherapeutic for treating depression, and if depressive symptoms persist after 6-8 weeks at this optimized dose, switch to a first-line antidepressant such as an SSRI or SNRI, or augment with one of these agents. 1

Critical Context: Lamotrigine's Role in Depression

Lamotrigine is FDA-approved for bipolar disorder maintenance, not unipolar depression. The evidence shows:

• For bipolar depression: Lamotrigine demonstrates efficacy as monotherapy at 200mg daily, with significant improvements in depressive symptoms compared to placebo 2, 3
• For unipolar depression: Lamotrigine is only supported as an augmentation strategy to standard antidepressants in treatment-resistant cases, not as monotherapy 4, 5, 6

Immediate Action Steps

1. Clarify the Diagnosis

• If this is bipolar depression: Increase lamotrigine to 200mg daily (the therapeutic dose), as 100mg is inadequate 2, 3
• If this is unipolar depression: Lamotrigine monotherapy is inappropriate; add a first-line antidepressant (SSRI or SNRI) immediately while continuing lamotrigine as augmentation 4, 5

2. Dose Optimization Protocol

• Titrate lamotrigine from 100mg to 200mg daily over 1-2 weeks to minimize rash risk 2
• Critical safety note: Check for concurrent valproate use, which requires lower lamotrigine dosing; check for enzyme-inducing medications (carbamazepine, phenytoin) which require higher dosing 2
• Monitor for serious rash (0.1% incidence), though risk is lower with proper titration 2

3. Assessment Before Modifying Treatment

Evaluate the following within the next 1-2 weeks:

• Suicidal ideation: Must be assessed at every visit, particularly critical in first 1-2 months of any treatment change 7, 1
• Treatment adherence: Confirm patient is actually taking the 100mg daily 1
• Duration at current dose: Has patient been on 100mg for at least 6-8 weeks? 7, 1
• Comorbid conditions: Rule out hypothyroidism, substance use, medical causes of depression 1
• Psychosocial stressors: Identify ongoing life stressors that may require psychotherapy 1

Treatment Algorithm Based on Diagnosis

If Bipolar Depression:

1. Increase to lamotrigine 200mg daily and reassess in 6-8 weeks 2, 3
2. If inadequate response at 200mg after 6-8 weeks, consider adding an antidepressant or switching to lithium 2
3. Continue successful treatment for 6-12 months minimum after remission 7, 1

If Unipolar Depression:

1. Add an SSRI or SNRI immediately (e.g., sertraline 50-200mg, venlafaxine XR 75-225mg) while continuing lamotrigine 100-200mg as augmentation 1, 4, 5
2. Meta-analysis shows lamotrigine augmentation significantly improves Hamilton Depression Rating Scale scores and response rates when added to standard antidepressants 5
3. Lamotrigine augmentation may accelerate onset of antidepressant action, with improvements seen as early as week 2 4
4. If no response after 6-8 weeks of optimized combination therapy, switch antidepressant (to bupropion SR, different SSRI, or SNRI) 7, 1

Monitoring Schedule

• Weeks 1-2: Weekly visits to assess suicidal ideation, medication side effects, and early response 7, 1
• Weeks 3-8: Every 2 weeks to monitor depressive symptom severity and treatment adherence 1
• After stabilization: Monthly visits once stable 1

Duration of Treatment After Remission

• First episode: Continue for 6-12 months minimum after achieving remission 7, 1
• Recurrent depression (≥2 episodes): Continue for up to 2 years or longer 7, 1

Common Pitfalls to Avoid

• Do not continue subtherapeutic dosing: 100mg lamotrigine is below the effective dose for depression; therapeutic range is 200mg daily 2, 3
• Do not use lamotrigine monotherapy for unipolar depression: Evidence only supports its use as augmentation to standard antidepressants 4, 5
• Do not forget rash monitoring: While rare (0.1%), serious rash including Stevens-Johnson syndrome can occur; proper dose titration minimizes this risk 2
• Do not neglect psychotherapy: Adding cognitive behavioral therapy or structured psychotherapy enhances outcomes beyond medication alone 1