Mirtazapine interactions to avoid

Drug interactions | Other interactions | Alcohol interactions | Avoiding interactions | When to see a doctor

Mirtazapine is a member of a drug class called tetracyclic antidepressants. Mirtazapine is approved by the U.S. Food and Drug Administration (FDA) to treat depression, also known as major depressive disorder or major depression, in adults. It works by increasing levels of serotonin and norepinephrine in the brain. Serotonin and norepinephrine are neurotransmitters (chemical messengers). They regulate various functions, like mood, sleep, memory, and others. 

Mirtazapine is a generic medication and is commonly known by the brand name Remeron. It is available in several formulations, including oral tablets (Remeron) and orally disintegrating tablets (Remeron Soltab).

Some of the most common side effects of mirtazapine include:

• Stomach problems like nausea, vomiting, and constipation
• Dizziness and drowsiness
• Anxiety
• Confusion
• Increased appetite
• Weight gain
• Dry mouth
• Increased cholesterol and triglycerides

Mirtazapine interacts with various drugs, including monoamine oxidase inhibitors (MAOIs) and other drugs that increase serotonin levels, benzodiazepines, and others. For those who take mirtazapine, it’s important to be aware of possible interactions that can affect the effectiveness of this medication or cause other potential complications.

Mirtazapine drug interactions

Mirtazapine interacts with various drugs and classes of drugs, which can result in different complications.

Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) are a class of drugs used to treat depression and other neurologic conditions such as Parkinson’s disease and Alzheimer’s disease. 

An MAOI drug should never be taken with mirtazapine or within 14 days of taking mirtazapine. Combining an MAOI with mirtazapine could result in a life-threatening condition called serotonin syndrome, which occurs due to the buildup of too much serotonin.  

Serotonin syndrome symptoms can range from mild to life-threatening and can even cause death if untreated. Symptoms of serotonin syndrome may include:

• Changes in mental status, such as agitation, delirium, and hallucinations
• Fast heartbeat
• Changes in blood pressure
• Dizziness
• Sweating, flushing, high fever
• Shaking
• Stiff muscles
• Incoordination
• Seizures
• Stomach symptoms like nausea, vomiting, and diarrhea

If you take an MAOI, your healthcare provider will not prescribe mirtazapine. Examples of MAOIs include:

• Azilect (rasagiline)
• Marplan (isocarboxazid)
• Methylene blue
• Nardil (phenelzine)
• Parnate (tranylcypromine)
• Selegiline
• Zyvox (linezolid)

Serotonin syndrome does not always involve a drug interaction. It can occur with just one drug, including mirtazapine alone. If you take mirtazapine, your healthcare provider will monitor you for serotonin syndrome. 

Other drugs that increase the risk of serotonin syndrome

In addition to MAOIs, other drugs may increase the risk of serotonin syndrome when used in combination with mirtazapine. However, the difference is that, with these other medications, a two-week period is not required between using mirtazapine and using another medication that affects serotonin levels (called serotonergic drugs).

Healthcare providers try to avoid combining two drugs that increase serotonin levels. However, in some cases, another alternative is not available, and two serotonergic drugs are prescribed together. In these cases, the patient will be closely monitored for symptoms of serotonin syndrome. People with symptoms of serotonin syndrome should get emergency medical help. 

Examples of drugs that increase the risk of serotonin syndrome include:

• SSRI antidepressants such as Celexa (citalopram), Paxil (paroxetine), Prozac (fluoxetine), or Lexapro (escitalopram)
• SNRI antidepressants such as Cymbalta (duloxetine) or Effexor (venlafaxine)
• Tricyclic antidepressants such as Elavil (amitriptyline)
• Triptans for migraine such as Imitrex (sumatriptan)
• Lithium
• Amphetamines such as Adderall (mixed amphetamine salts)
• Opioid pain medications such as fentanyl or Ultram (tramadol)
• Buspirone 
• Dietary supplements such as St. John’s wort, tryptophan, and SAMe

Drugs that affect an enzyme called CYP3A4

Cytochrome P450 3A4 is an enzyme involved in the processing of many medications. Certain drugs can affect this enzyme. 

For example, strong CYP3A inducers speed up the processing of mirtazapine in the body. This means your body eliminates it faster, so a regular dose may not be as effective. If you take mirtazapine with a strong CYP3A inducer, you may need a higher dose of mirtazapine. Examples of strong CYP3A inducers include Dilantin (phenytoin), Tegretol (carbamazepine), and rifampin. 

On the other hand, strong CYP3A inhibitors slow down the processing of mirtazapine in the body. This could lead to higher levels of mirtazapine in the body and worsening of adverse effects. If you take mirtazapine with a strong CYP3A inhibitor, you may need a lower dose of mirtazapine. Examples of strong CYP3A inhibitors include itraconazole, ketoconazole, and ritonavir. 

Benzodiazepines

Benzodiazepines are a class of medications used for anxiety. Some benzodiazepines have other uses as well, such as to treat muscle spasms or seizures. Mirtazapine causes central nervous system (CNS) depression, which means a slowing down of the nervous system. Benzodiazepines have the same effect, so combining mirtazapine with a benzodiazepine could result in additive effects. In severe cases, excess CNS depression can cause slowed breathing, loss of consciousness, coma, and death. Also, both mirtazapine and benzodiazepines cause sedation, so combining them can increase this sedative effect. The prescribing information states that mirtazapine and benzodiazepines should not be combined.

Examples of benzodiazepines include:

• Ativan (lorazepam)
• Klonopin (clonazepam)
• Valium (diazepam)
• Xanax (alprazolam)

Drugs that prolong the QT interval

When you get an electrocardiogram (EKG), there is a measurement called the QT interval. A prolonged QT interval could result in an arrhythmia (irregular heart rhythm), which could be dangerous or cause death. In rare cases, mirtazapine can cause a QT prolongation. Mirtazapine should be used with caution in individuals who have (or are at risk for) a prolonged QT interval. Mirtazapine should not be used with certain drugs due to an increased risk of causing a prolonged QT interval. Examples of interacting drugs include:

• Amiodarone
• Antipsychotics such as Geodon (ziprasidone) or haloperidol
• Dronedarone 
• Macrolide antibiotics such as erythromycin, Biaxin (clarithromycin), or Zithromax (azithromycin)
• Procainamide 
• Quinidine
• Sotalol

Warfarin

People who take the blood thinner warfarin with mirtazapine will require close monitoring. The combination could potentially increase the INR, which means that the blood takes longer to clot—leading to a higher risk of bleeding. Be sure to tell your doctor if you take warfarin before taking mirtazapine so that you can be appropriately monitored. This interaction does not apply to newer blood thinners such as Xarelto or Eliquis. 

Tagamet (cimetidine)

Tagamet (cimetidine) is a medication used to treat conditions such as heartburn and ulcers. Combining Tagamet with mirtazapine can lead to an interaction that causes increased levels of mirtazapine in the body. This can lead to more serious mirtazapine side effects. If you take Tagamet, your healthcare professional may recommend switching to a different stomach medication while taking mirtazapine. Or, if that is not possible, your healthcare provider may recommend that you take a lower dose of mirtazapine while you are also taking Tagamet.

Other mirtazapine contraindications and interactions

Mirtazapine has some contraindications to be aware of, and it also has interactions with alcohol, CBD, and marijuana.

Mirtazapine contraindications

Mirtazapine is not safe for everyone to take. Contraindications of mirtazapine (situations where you should not take this medication) include people who:

• Are allergic to mirtazapine or any ingredient in the medication
• Take an MAOI medication, or have taken an MAOI in the past 14 days. This includes the antibiotic Zyvox (linezolid) and intravenous methylene blue (used to treat a condition called methemoglobinemia). Both of these medications are also classified as MAOIs. 

Mirtazapine and alcohol 

While taking mirtazapine, you should avoid alcohol. This interaction is similar to the benzodiazepine interaction described above. Both mirtazapine and alcohol cause CNS depression, so combining the two could result in additive effects. In severe cases, slowed breathing, loss of consciousness, coma, and death could even occur. Also, both mirtazapine and alcohol cause sedation, so combining the two can increase the sedative effect.

Mirtazapine and CBD/marijuana

If you use CBD or marijuana, check with your healthcare provider before using it with mirtazapine. CBD and marijuana both cause CNS depression and impairment, so combining either of these with mirtazapine can result in additive effects. 

Mirtazapine and certain dietary supplements

Mirtazapine should not be combined with certain dietary supplements because of an interaction that can increase the risk for serotonin syndrome. These include:

• St. John’s wort (a dietary supplement used for mild depression)
• Tryptophan (a dietary supplement used for various conditions, including insomnia and depression)
• SAMe (a dietary supplement used for various conditions, such as depression or osteoarthritis)

How to minimize mirtazapine interactions

Although mirtazapine has some potential interactions, in many cases, it can still be taken safely with some precautions. 

Always consult your healthcare provider for medical advice before beginning a new medicine. Before you start taking mirtazapine, make your provider aware of all of your medical conditions, especially if you: 

• Are pregnant or trying to become pregnant
• Are breastfeeding 
• Have bipolar disorder
• Have glaucoma
• Have kidney disease
• Have liver disease
• Have (or have had) suicidal thoughts
• Have ever had a reaction to mirtazapine or any other allergies

Before you take mirtazapine, tell your physician about all of the medicines you take, including prescription and OTC drugs, vitamins, supplements, or herbal products. While taking mirtazapine, do not start any new medicines unless approved by your healthcare provider.

Your healthcare provider may need to change your medicine or adjust the dose of mirtazapine—or another medicine—in the event of a potential drug interaction. 

Always take your medication as directed by your healthcare provider. Do not take more medication than prescribed. If you have any questions or concerns, consult your healthcare provider.

When to talk to a healthcare provider about mirtazapine interactions

This article outlines some common mirtazapine interactions but is not a complete list of every potential interaction. Tell your healthcare provider about all the medical conditions you have—as well as all of the medicines you take, including prescription and OTC medicines, vitamins, and supplements. Doing so helps ensure proper management and monitoring of your medical condition.