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Mirtazapine side effects and how to avoid them

Although mirtazapine is considered a highly effective antidepressant, patients should learn more about the side effects and drug interactions before taking the drug

Mirtazapine side effects | Suicide | Serotonin syndrome | Angle-closure glaucoma | Weight changes | How long do side effects last? | Warnings | Interactions | How to avoid side effects

Mirtazapine (brand names: Remeron and Remeron SolTab) is a generic prescription drug used to treat major depressive disorder (MDD) in adults. Mirtazapine is classified as an atypical or tetracyclic antidepressant. The exact way in which mirtazapine works is not clear. However, it is believed to increase the production of two neurotransmitters in the brain, serotonin, and norepinephrine. These neurotransmitters activate nerve pathways involved with mood, anxiety, and other emotions. 

Although it is considered a highly effective antidepressant, mirtazapine does cause side effects. Some side effects can be mild while others can affect your daily quality of life and lead to serious complications. Before taking mirtazapine, take some time to review its side effects, drug interactions, and warnings, as well as potential ways to minimize problems when taking this drug.

RELATED: Learn more about mirtazapine

Common side effects of mirtazapine

The most common side effects of mirtazapine include:

  • Sleepiness
  • Dry mouth
  • Increased appetite
  • High cholesterol levels
  • Weight gain
  • Constipation
  • Weakness
  • Dizziness
  • High triglyceride levels
  • Abnormal dreams
  • Abnormal thoughts
  • Swelling of the hands and feet
  • Confusion
  • Tremors
  • Elevated liver enzymes
  • Muscle pain
  • Back pain
  • Frequent urination

Serious side effects of mirtazapine

Mirtazapine can cause serious side effects including:

  • Suicidal thoughts and behaviors
  • Worsening of depression
  • Serotonin syndrome
  • Low white blood cell counts
  • Mania or hypomania
  • Seizures
  • Angle-closure glaucoma
  • Low sodium levels
  • Changes in heart rhythm
  • Muscle damage
  • Low blood pressure
  • Severe skin reactions
  • Severe allergic reactions
  • Withdrawal symptoms upon discontinuation of the medicine

Mirtazapine and suicide

Mirtazapine, like other antidepressants, carries an increased risk of causing worsened depression and provoking suicidal behaviors in children, teens, and young adults. For antidepressants in general, there is an increased suicide risk of 1.4% in patients younger than 18 and 0.5% in patients aged 18 to 24. However, people older than 24 taking antidepressants are at a lower risk of suicidality than patients not taking antidepressants. All people on mirtazapine should be watched for signs of suicidality such as:

  • Suicide attempts
  • Thoughts about suicide or death
  • New or worse depression, anxiety, or irritability
  • Panic attacks
  • Mood changes
  • Aggressive behaviors
  • Unusual behaviors
  • Risk-taking behaviors

Mirtazapine and serotonin syndrome

Serotonin syndrome is a rare condition that can develop when more than one serotonergic drug is being taken at the same time, causing high levels of serotonin in the brain. In most cases, symptoms will be mild and the condition will pass in a few days after the drugs are stopped. Severe cases, however, can be life-threatening. Get medical help if you experience any signs of serotonin syndrome such as:

  • Agitation
  • Confusion
  • Rapid heartbeat
  • Dizziness
  • Loss of coordination
  • Increased sweating
  • Diarrhea
  • Skin flushing
  • Nausea or vomiting
  • High blood pressure
  • Tremors
  • Rigid muscles
  • Hallucinations
  • Seizures
  • Coma

Mirtazapine and low white blood cell counts

Mirtazapine, like other antidepressants, often causes a decrease in white blood cells. White blood cells fight off infections and cancers, so low white blood cell counts leave patients vulnerable to infections. Consult a healthcare provider immediately if you notice signs of infection such as: 

  • Flu-like symptoms
  • Fever
  • Chills
  • Sore throat
  • Mouth sores

Mirtazapine and angle-closure glaucoma

Angle-closure glaucoma is a serious condition that happens suddenly and can quickly cause serious or total vision loss. People with uncorrected “narrow angles” between the iris and the cornea, the area that drains fluid from the eye, are most vulnerable. Mirtazapine can cause this “narrow angle” to close, resulting in a rapid build-up of fluid in the eye. Immediately stop using the medication and go to an emergency room if you experience signs of angle-closure glaucoma such as:

  • Eye pain
  • Vision changes
  • Swelling or redness in or around the eye

Mirtazapine and weight changes

Two of the most common side effects of mirtazapine are increased appetite and weight gain. In clinical trials, 17% of participants experienced increased appetite and 12% gained weight. If weight gain is noticed while taking mirtazapine, get advice from your healthcare provider. Managing weight may require dietary and lifestyle changes.

How long do side effects last?

Most common side effects of mirtazapine are temporary. They usually go away as your body adjusts to the medication after a few days to a couple of weeks. Severe side effects can take weeks to resolve and should be managed by a healthcare provider. Left untreated, severe side effects like angle-closure glaucoma could have lifelong consequences. 

Mirtazapine contraindications & warnings

Although mirtazapine is considered a highly effective antidepressant, not everyone should take it. Mirtazapine may worsen pre-existing medical conditions. Tell your doctor if you have a history of medical conditions like bipolar disorder, glaucoma, heart problems, seizures, high cholesterol levels, kidney or liver problems, or low blood pressure before starting treatment with mirtazapine.

Abuse and dependence

The U.S. Food and Drug Administration (FDA) does not classify mirtazapine as a controlled substance, meaning that it does not carry a high risk of abuse. Doctors are not advised to monitor patients for signs of mirtazapine abuse or diversion.

People who suddenly stop taking mirtazapine may experience withdrawal symptoms such as anxiety, agitation, dizziness, confusion, weird or prickling skin sensations, bizarre dreams, headache, sweating, nausea, and vomiting. When it’s time to stop taking mirtazapine, a healthcare provider will prescribe a gradually tapering dose to prevent withdrawal.

Overdose

An overdose of mirtazapine can cause symptoms such as:

  • Drowsiness
  • Disorientation
  • Impaired memory
  • Fast heartbeat

Seek emergency medical treatment if a mirtazapine overdose is suspected.

Restrictions

Because of the risk of severe allergic reactions, anyone with allergies to mirtazapine should not take the medication. Other people may experience side effects or other problems when taking mirtazapine, so the drug will be prescribed under the guidance of a healthcare provider.

  • Because of the risk of suicidal thoughts and behaviors, people younger than the age of 25 taking mirtazapine should be monitored by healthcare providers and caretakers for signs of worsening depression or suicidality.
  • Mirtazapine can provoke manic or hypomanic episodes in people with bipolar disorder, so people with a history of mania will need to be watched for signs of mania or hypomania.
  • Mirtazapine will require careful dosing and monitoring in people with liver, renal, or heart problems. People with a history of unusual heart rhythms, congestive heart failure, or heart attack may require regular ECGs to keep track of mirtazapine’s effects on the heart. In some cases, dosages may be modified.
  • Mirtazapine may cause low sodium levels, especially in the elderly, people taking diuretics, and those who have low blood volume. Electrolyte levels may need to be monitored to prevent adverse effects. 
  • Mirtazapine makes people more vulnerable to seizures, so people with a history of seizures may require monitoring. 
  • People with uncorrected narrow angles are at a higher risk of narrow-angle glaucoma, so they should closely monitor any eye problems when taking mirtazapine.

Pregnancy and nursing

There is no evidence that mirtazapine increases the risk of birth defects, miscarriage, or other problems when taken during pregnancy. However, mirtazapine should only be taken while pregnant if the potential benefits outweigh the potential risks. 

Although mirtazapine is present in breast milk in very small amounts, there is no evidence of any harm to a breastfeeding infant when the mother is taking mirtazapine. Consult a healthcare provider before taking mirtazapine while pregnant or breastfeeding. 

Children

The Food and Drug Administration (FDA) has not approved mirtazapine as safe and effective for children. Mirtazapine may, however, be prescribed off-label to children if deemed appropriate by a healthcare provider. Antidepressants, however, are associated with a high risk of worsening depression and suicidality when given to children.

Seniors

Mirtazapine should be used with caution in the elderly, and the lowest effective dose should be started if treatment with mirtazapine is recommended. Mirtazapine levels may be higher in the elderly than in other people, which can lead to an increased risk of drowsiness, confusion, and low sodium levels, among other side effects.

Mirtazapine interactions

Most mirtazapine drug interactions are minor. Some, however, can cause serious problems. For instance, there is an increased risk of severe or even life-threatening heart rhythm problems when mirtazapine is taken at the same time as the antipsychotic drugs pimozide or thioridazine.
Mirtazapine should never be taken with monoamine oxidase inhibitors (MAOIs), a small family of drugs that includes the antidepressants isocarboxazid, phenelzine, tranylcypromine, and selegiline. Other MAOIs include the cancer drug procarbazine, the antibiotic linezolid, and methylene blue. Combining mirtazapine with MAOIs can cause severe serotonin syndrome.

Other drugs, when combined with mirtazapine, can also cause serotonin syndrome. These drugs include:

Sedation is a very common side effect of mirtazapine. Combining mirtazapine with other drugs that slow down the central nervous system (CNS) can worsen side effects such as sleepiness and cognitive impairment. Drugs that can act as CNS depressants include: 

This is not a complete list of drugs that can interact with mirtazapine. Medications that act as CYP3A4 inhibitors, like ketoconazole or clarithromycin, should also be avoided in combination with mirtazapine. Consult a healthcare provider for a complete list of possible drug interactions with mirtazapine. 

How to avoid mirtazapine side effects

A few tips can help minimize possible side effects:

1. Take Mirtazapine as directed

Take mirtazapine tablets or orally-disintegrating tablets exactly as instructed. The typical dose is 15 to 45 mg taken once at bedtime with or without food. Don’t take extra medicine or skip a dose. Don’t take extra medicine to make up for a missed dose.

2. Tell the healthcare provider about all medical conditions

Before taking mirtazapine, you should inform your healthcare provider about any medical conditions you have, especially:

  • Any history of suicide or depression
  • Any history of mania, hypomania, or bipolar disorder
  • Heart problems or irregular heartbeat, particularly QT prolongation
  • Liver problems
  • Kidney problems
  • Low sodium levels
  • Seizure disorders
  • Any history of stroke
  • Low blood pressure (hypotension)
  • High cholesterol levels
  • High triglyceride levels
  • Pregnancy or pregnancy plans
  • Breastfeeding or plans to breastfeed

3. Tell the healthcare provider about all medications

Drug interactions can be a major cause of adverse effects, so any healthcare provider needs to know about all medications being taken. View the contraindications and interactions sections above to learn about some medications to avoid while using mirtazapine, then talk to your healthcare professional about steps to avoid any drug interactions. 

4. Take mirtazapine at bedtime

For maximum benefits, mirtazapine should be taken at the same time every day. Unless instructed otherwise, it’s best to take mirtazapine at bedtime. Most people taking mirtazapine will experience sleepiness, so taking it at bedtime will help minimize interruptions in daily activities.

5. Do not drink alcohol

Combining alcohol with mirtazapine can worsen sleepiness and mental impairment caused by the drug. Avoid drinking if possible. It’s also a good idea to stay away from medications that also cause sleepiness such as benzodiazepines.

6. Be careful about driving and other risky activities

Most people taking mirtazapine will experience some level of sedation or impairment. Driving while sedated is very risky, as is operating machinery or engaging in potentially hazardous activities that require focus, such as skiing. Take this medication for a week or two to see how this medication affects you. Then approach driving or other activities with care.

7. Eat a healthy diet

To avoid weight gain, eat a healthy diet when taking mirtazapine. Lean protein can satisfy an increased appetite caused by mirtazapine without leading to weight gain. If you need help, it’s a good idea to consult with a dietitian or nutritionist if appetite and weight changes become a problem while taking this medication.

8. Do not stop taking mirtazapine

Suddenly stopping mirtazapine may cause withdrawal side effects. If you’re thinking about discontinuing the use of mirtazapine, get medical advice before doing so. A healthcare professional will recommend a plan to wean you off the drug in order to prevent withdrawal.

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