Should I discontinue Remeron (mirtazapine) with a therapeutic lithium level?

Should You Discontinue Remeron with Therapeutic Lithium?

No, you should not automatically discontinue Remeron (mirtazapine) simply because lithium is at a therapeutic level—the decision depends on the clinical indication for each medication and whether mirtazapine is still serving a necessary therapeutic purpose. 1

Clinical Decision Framework

Assess the Original Indication for Mirtazapine

If mirtazapine was prescribed for depression augmentation:

• Lithium at 0.8 mEq/L is within the therapeutic range for mood stabilization (0.6-0.8 mEq/L), but this does not automatically mean mirtazapine is redundant 2, 3
• Mirtazapine may have been added to address residual depressive symptoms, anxiety, or sleep disturbances that lithium alone does not fully control 1, 4
• The combination of lithium with antidepressants (including mirtazapine) is common and evidence-based in bipolar depression treatment 5

If mirtazapine was prescribed for specific symptoms:

• Mirtazapine is particularly effective for sleep disturbances, appetite stimulation, and anxiety symptoms associated with depression 1, 4
• These benefits may be independent of lithium's mood-stabilizing effects 6
• Evaluate whether these target symptoms have resolved or still require treatment 4

Consider Serotonin Syndrome Risk

The combination of lithium and mirtazapine carries a risk of serotonin syndrome, though this is generally manageable with monitoring:

• The FDA label explicitly warns that lithium increases serotonin syndrome risk when combined with serotonergic antidepressants like mirtazapine 7
• Monitor for mental status changes, autonomic instability, neuromuscular symptoms, and gastrointestinal symptoms 7
• If the patient has been stable on this combination without signs of serotonin syndrome, the risk-benefit ratio may favor continuation 7

Evaluate Current Clinical Status

Before discontinuing mirtazapine, assess:

• Is the patient's mood stable, or are there residual depressive or anxiety symptoms? 4
• Has the patient experienced weight gain (common with mirtazapine at 7.5-30 mg doses), and is this problematic? 1, 7
• Are sleep and appetite normalized, or does mirtazapine continue to provide benefit in these domains? 1, 6
• How long has the patient been stable on the current regimen? 1

Discontinuation Strategy If Appropriate

If you decide to discontinue mirtazapine:

• Taper over 10-14 days to minimize withdrawal symptoms, as recommended for antidepressants 1
• Monitor closely for re-emergence of depressive symptoms, anxiety, or sleep disturbances 1
• Ensure lithium levels remain stable during the transition 2

Common Pitfalls to Avoid

Do not assume lithium monotherapy is always sufficient:

• Combination therapy with lithium plus antidepressants (including mirtazapine) is frequently used in clinical practice for bipolar depression 5
• Lithium at therapeutic levels addresses mood cycling but may not fully resolve all depressive symptoms 2, 3

Do not abruptly discontinue mirtazapine:

• Gradual tapering over 10-14 days is recommended to avoid withdrawal symptoms 1

Do not ignore ongoing symptom monitoring:

• Continue to monitor for both therapeutic response and potential adverse effects of the lithium-mirtazapine combination 7