Can mirtazapine cause edema?

Mirtazapine and Edema

Yes, mirtazapine can cause peripheral edema as documented in the FDA drug label, with an incidence of approximately 2% compared to 1% with placebo. 1

Evidence for Mirtazapine-Induced Edema

FDA Drug Label Evidence

The FDA drug label for mirtazapine clearly documents peripheral edema as an adverse reaction:

• Peripheral edema occurs in 2% of patients taking mirtazapine compared to 1% in placebo groups 1
• Edema (not specified as peripheral) occurs in 1% of patients taking mirtazapine compared to 0% in placebo groups 1

Recent Research Evidence

• A 2024 pharmacovigilance study found that mirtazapine had the second highest incidence of severe edema (0.8‰) among psychotropic medications, second only to pregabalin (1.46‰) 2
• A 2025 case report documented peripheral edema occurring in a palliative care patient with oral cavity cancer just three days after starting mirtazapine 15mg daily, with complete resolution after discontinuation 3
• Edema appears to be more common in women (80% of cases) and older patients (mean age 51.8 years) 2

Mechanism of Action

Mirtazapine's mechanism for causing edema is not fully elucidated, but may relate to:

• Its action as a tetracyclic antidepressant that enhances both noradrenergic and serotonergic transmission 4
• Blockade of central α2-adrenergic auto- and heteroreceptors 4
• High affinity for serotonin 5-HT2 and 5-HT3 receptors, which may influence vascular tone 4

Clinical Considerations

Risk Factors

• Advanced age 2
• Female gender 2
• Pre-existing cardiovascular disease 5
• Concurrent use with other medications that cause fluid retention 5

Monitoring Recommendations

• Monitor for weight gain and peripheral edema, particularly during the first few months of therapy 5
• Perform periodic assessment of the lower extremities 5
• Be vigilant for edema development as early as 3 days after initiation 3

Management Options

For patients who develop edema while on mirtazapine:

1. Non-pharmacological interventions:

   • Elevate legs when sitting or lying down
   • Use compression stockings if appropriate
   • Limit sodium intake 5

2. Pharmacological interventions:

   • Consider low-dose diuretic therapy (e.g., furosemide) for persistent cases 5
   • In severe cases, discontinuation of mirtazapine may be necessary 5, 3

3. Alternative antidepressants:

   • SSRIs may be preferable among patients with cardiovascular disease, though they carry their own risks 6
   • Note that SSRIs have been associated with hyponatremia, which mirtazapine also carries a moderate risk for 7

Special Populations

Cardiovascular Disease Patients

• The American Heart Association notes that mirtazapine has been shown to be safe in cardiovascular disease patients, though its efficacy in treating depression in this population has not been fully assessed 6
• Mirtazapine offers additional benefits including appetite stimulation and may be used for sleep in these patients 6

Elderly Patients

• Older patients appear to be at higher risk for developing edema with mirtazapine 2
• Careful monitoring is especially important in this population

Rare but Serious Considerations

While peripheral edema is the most common form of edema with mirtazapine, rare cases of more serious presentations have been reported:

• A case of papilledema (optic disc swelling due to increased intracranial pressure) has been reported with mirtazapine use, which resolved after discontinuation 8
• This suggests the importance of regular fundoscopic examinations in patients on long-term mirtazapine therapy 8

In conclusion, while mirtazapine is generally well-tolerated compared to many other antidepressants, clinicians should be aware of the potential for peripheral edema and monitor accordingly, especially in high-risk populations.