What is the recommended approach for titrating down Lamotrigine (lamotrigine) in a patient with bipolar 2 disorder who is currently on 300mg?

Tapering Lamotrigine in Bipolar 2 Disorder

For a patient with bipolar 2 disorder on 300mg of lamotrigine, taper the dose by 50-100mg every 1-2 weeks in the outpatient setting, monitoring closely for depressive relapse, which is the primary risk when discontinuing this medication. 1, 2

Rationale for Tapering Strategy

Lamotrigine is particularly effective at preventing depressive episodes in bipolar disorder, which are the predominant mood episodes in bipolar 2. 1, 2 Discontinuing this medication carries significant risk of depressive relapse, as maintenance therapy should typically continue for at least 2 years after the last episode. 2

• Withdrawal of maintenance mood stabilizer therapy is associated with dramatically increased relapse risk, with studies showing >90% relapse rates in noncompliant patients versus 37.5% in compliant patients. 1
• The risk of relapse is particularly high within the first 6 months following discontinuation. 1

Specific Tapering Protocol

Reduce the dose by 50-100mg every 1-2 weeks, which allows for gradual discontinuation while monitoring for mood destabilization. 1

• Week 1-2: Reduce from 300mg to 200mg daily 1
• Week 3-4: Reduce from 200mg to 100mg daily 1
• Week 5-6: Reduce from 100mg to 50mg daily 1
• Week 7-8: Discontinue completely 1

This schedule can be slowed if any depressive symptoms emerge during the taper. 1

Critical Monitoring Requirements

Assess for depressive symptoms at each dose reduction using standardized rating scales. 1

• Monitor specifically for: low mood, anhedonia, sleep disturbance, appetite changes, energy level, and suicidal ideation. 1
• Schedule follow-up visits every 2-4 weeks during the taper to catch early signs of relapse. 1
• If depressive symptoms emerge at any point, hold the taper and consider returning to the previous effective dose. 1

Important Clinical Caveats

Unlike some medications, lamotrigine does not require ultra-slow tapering to prevent withdrawal symptoms—the primary concern is mood relapse, not discontinuation syndrome. 3, 4

• Lamotrigine does not cause physical dependence or withdrawal symptoms like benzodiazepines or antidepressants. 3
• The slow taper is designed to detect mood destabilization early, not to prevent physiological withdrawal. 3

If lamotrigine is restarted after being discontinued for more than 5 days, you must restart with the full titration schedule (starting at 25mg) rather than resuming the previous dose to minimize risk of serious rash. 1

Common Pitfalls to Avoid

• Inadequate duration of maintenance therapy: Many patients discontinue too early, leading to high relapse rates. 1 Ensure the patient has been stable for at least 12-24 months before considering discontinuation. 1
• Failure to monitor for depressive relapse: Depression is the most common presentation in bipolar 2 disorder, and lamotrigine is specifically effective at preventing depressive episodes. 2, 5 Missing early signs of relapse can lead to full depressive episodes requiring hospitalization. 1
• Abrupt discontinuation: While lamotrigine doesn't cause withdrawal syndrome, abrupt stops prevent early detection of mood destabilization. 1
• Not having a backup plan: Discuss with the patient what to do if depressive symptoms emerge (e.g., holding the taper, returning to previous dose, scheduling urgent follow-up). 1

When to Reconsider Discontinuation

Stop the taper and return to the previous effective dose if any of the following occur:

• Emergence of depressive symptoms (low mood, anhedonia, sleep disturbance) 1, 2
• Development of hypomanic symptoms (though less common with lamotrigine discontinuation) 1
• Patient reports subjective sense of mood instability 1
• Functional impairment begins to develop 1