Is mirtazapine (Remeron) safe to use in patients with Chronic Obstructive Pulmonary Disease (COPD)?

Safety of Mirtazapine in COPD

Mirtazapine is not recommended for patients with COPD as it does not improve severe breathlessness and may cause adverse reactions. 1

Evidence on Mirtazapine in COPD

Recent high-quality evidence demonstrates that mirtazapine does not provide benefit for breathlessness in COPD patients:

• A 2024 international, multicentre, double-blind, randomized, placebo-controlled phase 3 trial found no evidence of difference in worst breathlessness scores between mirtazapine and placebo in patients with COPD or interstitial lung diseases 1
• The same study reported 215 adverse reactions in 64% of participants in the mirtazapine group versus 116 adverse reactions in 40% of participants in the placebo group 1
• Based on these findings, researchers explicitly do not recommend mirtazapine as a treatment to alleviate severe breathlessness in COPD 1

Previous Research on Mirtazapine for Breathlessness

Earlier studies had shown some promise but were limited:

• A 2018 case series reported subjective improvements in breathlessness with mirtazapine in patients with advanced lung disease 2
• A 2020 feasibility trial suggested mirtazapine might be beneficial for breathlessness, leading to the recommendation for a phase III trial 3
• However, the definitive 2024 phase III trial subsequently showed no benefit 1

Recommended Pharmacological Management for COPD

Guidelines recommend the following evidence-based treatments for COPD:

• For symptomatic patients with FEV1 between 60% and 80% predicted, inhaled bronchodilators may be used 4
• For symptomatic patients with FEV1 <60% predicted, inhaled bronchodilators are strongly recommended 4
• Long-acting inhaled anticholinergics or long-acting inhaled β-agonists are recommended as monotherapy for symptomatic patients with FEV1 <60% predicted 4
• Combination inhaled therapies may be considered for symptomatic patients with FEV1 <60% predicted 4
• Pulmonary rehabilitation is strongly recommended for symptomatic patients with FEV1 <50% predicted 4

Non-Pharmacological Approaches

Important non-pharmacological interventions include:

• Smoking cessation is essential at all stages of COPD 4
• Exercise should be encouraged within the limitations of airways obstruction 4
• Nutritional support should be considered, especially for malnourished patients with severe COPD 4
• Influenza vaccination is recommended, especially for moderate to severe disease 4

Common Pitfalls to Avoid

When managing COPD patients:

• Avoid beta-blocking agents (including eyedrop formulations) as they can worsen bronchospasm 4
• Do not use medications without proven benefit, such as antihistamines or mucolytics 4
• Be cautious with medications that may cause respiratory depression in patients with severe COPD 1
• Remember that while some antidepressants have been repurposed for symptom management in palliative care, the evidence does not support mirtazapine for breathlessness in COPD 1

Algorithm for Medication Selection in COPD

1. Assess COPD severity based on symptoms and FEV1
2. For mild disease with symptoms: short-acting bronchodilators as needed 4
3. For moderate disease: regular inhaled bronchodilators 4
4. For severe disease: combination therapy with regular β2 agonist and anticholinergic 4
5. Consider adding inhaled corticosteroids for patients with exacerbations 4
6. For severe hypoxemia (PaO2 ≤55 mm Hg or SpO2 ≤88%): prescribe continuous oxygen therapy 4
7. Do not use mirtazapine for breathlessness management in COPD 1