Can a patient taking lamotrigine (mood stabilizer) stop and start with sertraline (selective serotonin reuptake inhibitor)?

Switching from Lamotrigine to Sertraline: Clinical Recommendation

Do not abruptly stop lamotrigine to start sertraline—this is a dangerous approach that risks mood destabilization, seizures (if used for epilepsy), and potentially life-threatening withdrawal effects. These medications serve fundamentally different therapeutic purposes and the decision to switch requires careful consideration of the underlying diagnosis and clinical context.

Critical Diagnostic Considerations

The appropriateness of this switch depends entirely on the correct underlying diagnosis:

• If lamotrigine is being used for bipolar disorder maintenance: Switching to sertraline monotherapy is contraindicated and dangerous. Lamotrigine is FDA-approved for bipolar maintenance therapy and has demonstrated efficacy in preventing mood episodes, particularly depressive episodes 1, 2. Sertraline (an SSRI) can precipitate manic episodes or rapid cycling when used without mood stabilization 1.

• If the patient has unipolar depression misdiagnosed as bipolar: Then transitioning to sertraline may be appropriate, but this requires psychiatric consultation to confirm the diagnosis before making any medication changes.

Why Abrupt Discontinuation is Dangerous

Lamotrigine must be tapered gradually when discontinued:

• Abrupt cessation can cause withdrawal symptoms including dizziness, sensory disturbances, anxiety, irritability, and mood destabilization 1.
• If used for seizure disorder, sudden discontinuation significantly increases seizure risk 1.
• The medication has a half-life requiring careful down-titration over weeks, not days 2.

Safe Approach to Medication Management

If a switch is clinically indicated after diagnostic confirmation, follow this algorithm:

Step 1: Psychiatric Consultation

• Confirm the diagnosis with a psychiatrist before any medication changes
• Review family history of bipolar disorder (present in many patients on lamotrigine) 3
• Assess for history of antidepressant-induced mania or hypomania 1, 3

Step 2: If Switch is Appropriate (Confirmed Unipolar Depression)

• Begin sertraline at low dose (25 mg daily) while maintaining full lamotrigine dose 1
• Monitor closely for 2-4 weeks for behavioral activation, agitation, or mood destabilization 1
• Only after sertraline reaches therapeutic dose (50-200 mg) and patient is stable, begin lamotrigine taper 1

Step 3: Lamotrigine Taper Protocol

• Reduce lamotrigine by 25-50 mg every 1-2 weeks 2
• Monitor for withdrawal symptoms and mood changes throughout taper
• Complete taper typically takes 4-8 weeks depending on dose

Important Drug Interaction Considerations

There is a documented case report of delirium occurring when sertraline was added to lamotrigine plus valproic acid, suggesting potential metabolic interactions 4. While sertraline and lamotrigine can be co-administered safely in most cases 5, close monitoring is essential during any transition period, particularly in the first 24-48 hours after dosage changes 1.

Monitor for these specific concerns during co-administration:

• Mental status changes or confusion (potential lamotrigine toxicity even at therapeutic levels) 4
• Behavioral activation or agitation from sertraline 1
• Discontinuation syndrome symptoms if lamotrigine is tapered too quickly 1

Alternative: Combination Therapy May Be Superior

Consider maintaining lamotrigine and adding sertraline rather than switching:

• If the patient has treatment-resistant depression or bipolar depression, combination therapy may be more effective than monotherapy 3, 2
• Lamotrigine has demonstrated efficacy specifically for bipolar depression 2
• One case series showed robust response when sertraline was added to failed lamotrigine trials 3
• This avoids the risks of lamotrigine discontinuation while addressing depressive symptoms

Common Pitfalls to Avoid

• Never assume lamotrigine can be stopped abruptly like some other psychiatric medications
• Never start an SSRI in a patient with bipolar disorder without mood stabilizer coverage 1
• Never interpret "mood stabilizer" as interchangeable with "antidepressant"—these are distinct medication classes with different mechanisms and indications
• Do not rely solely on lamotrigine levels to rule out toxicity during transitions—clinical correlation is essential 4