Can You Take Mirtazapine with Clonazepam?

Severity assessment

Moderate. Concomitant use significantly increases the risk of central nervous system (CNS) depression, leading to enhanced sedation, dizziness, and impaired psychomotor function.

Mechanism (plain English)

Both clonazepam and mirtazapine affect the brain's chemical messengers, leading to a calming effect. Clonazepam, a benzodiazepine, works by enhancing the activity of gamma-aminobutyric acid (GABA), a neurotransmitter that reduces brain activity. Mirtazapine, an antidepressant, works by increasing the levels of certain neurotransmitters like noradrenaline and serotonin in the brain, but also has strong antihistaminic properties. When taken together, their combined sedative effects on the central nervous system are additive, meaning they can intensify each other, leading to increased drowsiness, slowed thinking, and reduced coordination.

Evidence level

Regulator-flagged. Both the FDA label for clonazepam and the MHRA Summary of Product Characteristics for mirtazapine explicitly warn about additive CNS depressant effects when co-administered with other CNS depressants, including benzodiazepines.

Top regulator advisories (cite verbatim or close paraphrase)

• TGA (Australia): No pair-specific public advisory found. Applicable product information for mirtazapine (e.g., MIRTAZAPINE SANDOZ) would generally advise caution with other CNS depressants due to additive effects. Similarly, clonazepam product information would advise caution with other CNS depressants.
• MHRA / NICE (UK): The MHRA Summary of Product Characteristics for mirtazapine states: "Mirtazapine may increase the sedating properties of benzodiazepines and other sedatives (notably most antipsychotics, antihistamine H1 antagonists, opioids). Caution should be exercised when these medicinal products are prescribed together with Mirtazapine." [1]
• FDA / CDC (US): The FDA label for clonazepam advises: "Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking clonazepam until you talk to your healthcare provider. When taken with alcohol or drugs that cause sleepiness or dizziness, clonazepam tablets may make your sleepiness or dizziness worse." [2] The FDA also issues a Boxed Warning for benzodiazepines regarding concomitant use with opioids due to additive CNS depression, which highlights the general concern with combining CNS depressants.
• EMA (Europe): The European Medicines Agency (EMA) would typically align with the MHRA SPC regarding the additive sedative effects of mirtazapine with benzodiazepines.

Clinical risk factors that elevate the danger

• Elderly patients: More susceptible to CNS depressant effects, increasing risk of falls, confusion, and cognitive impairment.
• Patients with respiratory compromise: Increased risk of respiratory depression.
• Patients with hepatic or renal impairment: May have reduced clearance of one or both drugs, leading to higher drug levels and increased side effects.
• Concomitant use of other CNS depressants: Including alcohol, opioids, antihistamines, or other sedatives, further exacerbating sedation.
• High doses of either medication: Increases the likelihood and severity of CNS depression.
• Rapid dose escalation: Does not allow the body to adjust to the sedative effects.

What a patient should be told

• You may experience increased drowsiness, dizziness, and difficulty concentrating when taking clonazepam and mirtazapine together. This can affect your ability to drive or operate machinery safely.
• Do not stop taking either medication suddenly without talking to your doctor or pharmacist, as this can lead to serious withdrawal symptoms or worsening of your condition.
• Be aware of warning signs such as extreme sleepiness, confusion, slow or shallow breathing, or difficulty waking up. If these occur, seek immediate medical attention.
• Discuss all other medications, supplements, and alcohol consumption with your prescriber or pharmacist to ensure safe use.
• If you experience severe dizziness, extreme sedation, or trouble breathing, seek urgent medical care immediately.

Top 3 sources (with full citation)

1. MHRA Products. MIRTAZAPINE 45 MG FILM-COATED TABLETS Summary of Product Characteristics. Medicines and Healthcare products Regulatory Agency. https://mhraproducts4853.blob.core.windows.net/docs/49a19d0d939172415a261fd37bb3dffedac19385 (Accessed June 1, 2026).
2. DailyMed. CLONAZEPAM tablet. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31a7ed52-48a6-1c87-e054-00144ff88e88 (Accessed June 1, 2026).
3. Drugs.com. Clonazepam + Mirtazapine: Can You Take Them Together?. https://www.drugs.com/drug-interactions/clonazepam-with-mirtazapine-703-0-1640-0.html (Accessed June 1, 2026).

Notes for the reviewing pharmacist

The interaction between clonazepam and mirtazapine is primarily pharmacodynamic, resulting in additive CNS depression. While not typically considered a contraindication, the combination necessitates careful patient monitoring, especially during initiation or dose adjustments. The risk of serotonin syndrome is low with this specific combination as clonazepam is not a serotonergic agent. However, vigilance for signs of excessive sedation and respiratory depression is crucial. Consider patient-specific factors such as age, comorbidities (e.g., respiratory disease, hepatic/renal impairment), and concomitant medications that also cause CNS depression. Patient education should emphasize the importance of avoiding alcohol and other sedatives, recognizing symptoms of excessive sedation, and adhering strictly to prescribed dosages. Gradual tapering is essential if discontinuation of either agent is planned.

Source metadata JSON

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  "severity": "Moderate",
  "evidence_level": "Regulator-flagged",
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