Mirtazapine with Dextromethorphan Interaction Details

Brand Names Associated with Mirtazapine

Brand Names Associated with Dextromethorphan

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 15, 2023

Interaction Effect

Increased risk of serotonin syndrome

Interaction Summary

Concomitant use of mirtazapine with other serotonergic agents may increase the risk of serotonin syndrome due to additive serotonergic effects. Monitor for symptoms of serotonin syndrome, especially during treatment initiation and dose increases, and if the patient shows symptoms, treatment with mirtazapine and any concomitant serotonergic agent should be discontinued. Symptoms of serotonin syndrome include neuromuscular abnormalities (including hyperreflexia, tremor, muscle rigidity, clonus, peripheral hypertonicity, and shivering), autonomic hyperactivity (including tachycardia, mydriasis, diaphoresis, the presence of bowel sounds, and diarrhea), and mental status changes (including agitation and delirium). Serotonin syndrome can be life-threatening. If serotonin syndrome develops after discontinuation of the offending agents, provide supportive care and other therapy as necessary .

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Concomitant use of mirtazapine with other serotonergic agents may increase the risk of serotonin syndrome. If concomitant use with other serotonergic drugs is clinically warranted, monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. Discontinue use of both agents if a patient shows symptoms of serotonin syndrome.

Mechanism Of Interaction

Additive serotonin effects

Literature Reports

A) Within a few hours of starting mirtazapine and shortly after stopping fluoxetine, a 75-year-old woman experienced symptoms consistent with serotonin syndrome. Current medication for depression included fluoxetine, chlorpromazine, and lorazepam. Due to lack of response, fluoxetine was discontinued and soon afterward mirtazapine 30 mg/day was started. Within a few hours of starting mirtazapine, she experience dizziness, headache, nausea, dry mouth, intense anxiety and agitation with suicidal ideas. Other symptoms were difficulty walking, marked resting tremor of the hands, and insomnia. Over the next 3 days, she progressively worsened. Mirtazapine was discontinued on day 5. Her symptoms improved the following day. Fluoxetine 20 mg/day was restarted on day 7 with subsequent resolution of dizziness, nausea, headache, and agitation resolution over the following days. Over the next 10 days, tremor, anxiety, difficulty walking, dry mouth, and insomnia improved .

B) A 26-year-old woman with anorexia nervosa receiving fluvoxamine for 4 months developed symptoms of serotonin syndrome after mirtazapine was initiated. The symptoms of twitching, tremors, agitation, restlessness, and "feeling like she could crawl out of her skin" developed over a period of 4 days after starting mirtazapine 30 mg/day. Symptoms rapidly progressed to twitching, tremors, and restlessness. She was hospitalized with further symptoms of diaphoresis, flushing, fasciculations, and nausea and treated with cyproheptadine, acetaminophen, and IV fluids. She remained afebrile throughout the event. Symptoms completely resolved within 24 hours .

Mirtazapine Overview

• Mirtazapine is used to treat depression. Mirtazapine is in a class of medications called antidepressants. It works by increasing certain types of activity in the brain to maintain mental balance.

Dextromethorphan Overview

• Dextromethorphan is used to temporarily relieve cough caused by the common cold, the flu, or other conditions. Dextromethorphan will relieve a cough but will not treat the cause of the cough or speed recovery. Dextromethorphan is in a class of medications called antitussives. It works by decreasing activity in the part of the brain that causes coughing.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.