From the Guidelines
Concurrent use of linezolid and mirtazapine carries a significant risk of serotonin syndrome and should generally be avoided. The risk of serotonin syndrome is a major concern when combining these two medications, as linezolid is a monoamine oxidase inhibitor (MAOI) and mirtazapine increases serotonin levels in the brain, leading to potential dangerous serotonin accumulation 1. If treatment with both medications is absolutely necessary, the mirtazapine should be discontinued at least 2 weeks before starting linezolid. In emergency situations where linezolid must be started immediately, mirtazapine should be stopped right away and the patient closely monitored for signs of serotonin syndrome for at least 2 weeks. Symptoms to watch for include:
- Agitation
- Confusion
- Rapid heart rate
- High blood pressure
- Dilated pupils
- Muscle rigidity
- Tremor
- Excessive sweating
- Diarrhea
- Hyperthermia If serotonin syndrome develops, both medications should be discontinued immediately and supportive care provided, which may include treatment of agitation, amelioration of hyperthermia, and management of autonomic instability 1. Consider psychiatric consultation to manage depression during this period, as alternative antidepressants like bupropion may have a lower risk of interaction with linezolid. It is essential to prioritize the patient's safety and take a cautious approach when considering the concurrent use of linezolid and mirtazapine, given the potential for severe adverse effects 1.
From the FDA Drug Label
Mirtazapine tablets are contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration (2.4), Contraindications (4), Warnings and Precautions (5. 3)] The concomitant use of serotonergic drugs, including Mirtazapine Tablets, and MAOIs increases the risk of serotonin syndrome The concomitant use of mirtazapine tablets with MAOIs is contraindicated. In addition, do not initiate mirtazapine tablets in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking mirtazapine tablets, discontinue mirtazapine tablets before initiating treatment with the MAOI [see Contraindications (4), Drug Interactions (7)]
The administration of Linezolid with Mirtazapine is contraindicated due to the increased risk of serotonin syndrome.
- Key points:
- Concomitant use of MAOIs (including Linezolid) and Mirtazapine increases the risk of serotonin syndrome.
- Mirtazapine should be discontinued before initiating treatment with MAOIs such as Linezolid.
- The combination of Linezolid and Mirtazapine is contraindicated due to the risk of serotonin syndrome 2, 2, 2.
From the Research
Risk of Serotonin Syndrome
The risk of serotonin syndrome when linezolid is administered with mirtazapine is a significant concern.
- Linezolid can inhibit monoamine oxidase, an enzyme that metabolizes serotonin and other biogenic amines, which can predispose patients to serotonin syndrome when concomitantly taking serotonin agonists like mirtazapine 3.
- A case report describes a patient who developed serotonin syndrome after concomitant treatment with linezolid, citalopram, and mirtazepine, highlighting the potential risk of this combination 4.
- Another study found that the incidence of serotonin toxicity with linezolid combination therapy, including with serotonergic agents like mirtazapine, was higher than with linezolid monotherapy, at 0.0134% compared to 0.0050% 5.
Clinical Implications
- Clinicians should be aware of the potential risk of serotonin syndrome when administering linezolid with mirtazapine and closely monitor patients for signs and symptoms of toxicity 3, 5.
- A multidisciplinary team is important for optimal diagnosis and management of serotonin syndrome cases, and linezolid should be discontinued if symptoms occur 6.
- The data collected reveals a low prevalence of serotonin toxicity in both linezolid monotherapy and linezolid concurrent with other serotonergic agents, but clinicians should still exercise caution when co-administering these medications 5.
Case Reports
- A case report describes a patient who developed serotonin syndrome on day 13 of linezolid therapy, despite not receiving any serotonergic agents concurrently with linezolid, and maprotiline and mirtazapine were stopped 17 days before the development of serotonin syndrome 6.
- Another case report presents the first reported case of serotonin syndrome associated with linezolid and methadone, highlighting the potential risk of co-administering linezolid with other serotonergic agents 7.