Mirtazapine - Mechanism of Action, Uses, and Side-Effects

What Is Mirtazapine?

Mirtazapine belongs to the class of medications known as antidepressants or tetracyclic antidepressants. Doctors commonly recommend it to manage depression, anxiety, and obsessive-compulsive disorder. Mirtazapine helps balance the neurotransmitter or chemical messengers in the brain that regulate a person's mood. The drug enhances the synthesis of mood-enhancing substances, including noradrenaline and serotonin. Mirtazapine can be purchased only after the doctor’s prescription and comes as a tablet that can be taken orally or as a liquid that a patient can swallow. In addition, Mirtazapine can be taken as a part of the combination therapy, meaning the drug can be taken in combination with other medications. Mirtazapine was first manufactured by Organon Inc. and approved by the Food and Drug Administration (FDA) on 17th March 1997.

What Are the Medical Uses of Mirtazapine?

Doctors primarily prescribe Mirtazapine to treat depression. Studies report that it is effective in treating the following types of depression:

1. Melancholic depression.

2. Depression with anxiety.

3. Geriatric depression.

4. Treatment-resistant depression.

5. Depression and anxiety due to alcohol dependence.

In addition to the uses listed above, Mirtazapine can also be used for the following:

• Nausea after the operation.

• Problems related to sleep.

• Low appetite.

• Management of pain.

What Is the Mechanism of Action of Mirtazapine?

Mirtazapine is a tetracyclic antidepressant that inhibits the presynaptic alpha 2-adrenergic receptors. As a result, the levels of serotonin and norepinephrine (noradrenaline) increase. Norepinephrine stimulates the sympathetic nervous system and produces a sedating and calming effect. It also antagonizes the 5-HTA and 5-HT3 receptors. As a result, the remaining serotonin interacts with the 5-HT1 receptors leading to an antidepressant effect. The drug is absorbed rapidly and demonstrates a plasma protein binding of 85 % and an oral bioavailability of 50 %.

What Warnings Are Associated With Mirtazapine?

Mirtazapine has a black box warning as it can simulate suicidal thoughts or actions in a person. The risk of suicidal tendencies is higher in children, young adults, and teenagers. Therefore, the patient must consult the doctor immediately if there are any changes in mood, behavior, feelings, or thoughts. Other warnings associated with Mirtazapine are listed below:

• Serotonin Syndrome - Mirtazapine can induce a life-threatening disease known as serotonin syndrome. The risk is usually higher in patients taking drugs with effects similar to Mirtazapine. The signs and symptoms of serotonin syndrome are listed below:

  • Confusion.

  • Coma.

  • Coordination issues.

  • Agitation.

  • Hallucinations.

  • Fever.

  • Nausea.

  • Low blood pressure.

  • Diarrhea.

  • Muscle twitching.

• Withdrawal Symptoms - The patient must not stop taking the drug before consulting the doctor because the medicine can cause withdrawal symptoms. The withdrawal symptoms include agitation, anxiety, and a tingling sensation. The doctor might taper the dosage of Mirtazapine gradually to avoid withdrawal symptoms.

• Drowsiness - Mirtazapine can affect the patient's thinking or decision-making abilities as it causes drowsiness. The patient must not drive or operate any machinery while taking Mirtazapine.

• Weight Gain - Mirtazapine can increase the hunger of a patient leading to weight gain. Patients with weight gain issues must consult the doctor to know about alternative drugs.

• Pregnant Females - Mirtazapine is a pregnancy category C drug, so females who are pregnant or planning to conceive must take the drug only with the doctor's consent. The doctor must outweigh the risk-benefit ratio in such cases.

• QT Prolongation - Patients with cardiac diseases must take the drug carefully, as Mirtazapine can increase the risk of QT prolongation. This implies that the patient might have the following:

  • An irregular or extremely fast heartbeat.

  • Fainting.

  • Nausea.

  • Dizziness.

What Should the Patient Inform the Doctor Before Taking Mirtazapine?

Before taking Mirtazapine, the patient must inform the doctor if:

• Allergic to Mirtazapine or any of its ingredients.

• Consuming prescription and nonprescription medications and other vitamins or herbal supplements.

• Had a heart attack, kidney or liver diseases, and low blood pressure.

• Has undergone or planned to undergo dental surgery.

• Addicted to alcohol.

How Should the Patient Take Mirtazapine?

Mirtazapine is available in two forms, oral tablets and dissolvable tablets. The dosages for both tablets are similar. As per the FDA reports, the starting dose of Mirtazapine is 15 milligrams a day. The patient should preferably take the drug in the evening before going to bed. The usual range of dose of Mirtazapine is between 15 to 45 mg. The patient can increase the dose gradually after one to two weeks. The tablet is available in the following doses:

• 15 mg.

• 30 mg.

• 45 mg.

Some doctors might ask the patient to split the dose and take half the dose twice daily. The patient must swallow the tablet without chewing it. The doctor might prescribe the dissolved tablet for patients having difficulty swallowing the pill. The patient must break the tablet from the blister, keep it on his tongue, and wait for the drug to dissolve. Follow the doctor's recommendation for the drug and avoid altering the dose.

What Are Some of the Severe Side Effects of Mirtazapine?

Mirtazapine can cause drowsiness and affect the patient's ability to make quick decisions. Some of the mild side effects of Mirtazapine are listed below:

• Sleepiness.

• Increased appetite.

• Constipation.

• Weight gain.

• Dryness of the mouth.

• Lightheadedness.

• Dizziness.

• Sweating.

Some of the severe side effects of Mirtazapine are listed below:

• Suicidal thoughts and actions.
• Depression.
• Anxiety or panic attacks.
• Agitation.
• Restlessness.
• Irritability.
• Mood swings.
• Behavioral changes.
• Talking faster than usual.
• Weakened immune system.
• Fever.
• Chills.
• Sore throat.
• Flu-like symptoms.
• Muscle twitching or muscle aches.
• Seizures.
• Widened pupils.
• Eye pain.
• Low sodium levels.
• Painful blisters or ulcers on the skin.
• Respiratory difficulties.
• Elevated cholesterol levels.

What Are Some of the Drugs That Can Interact With Mirtazapine?

Mirtazapine can interact with various medications, vitamins, and herbal supplements. A drug interaction is a phenomenon wherein the substances change how the drug works. To avoid drug interactions, the patient must prepare a list of all his medications and inform the doctor. For example, the following medicines can interact with Mirtazapine:

• Isocarboxazid.

• Phenelzine.

• Tranylcypromine.

• Linezolid.

• Benzodiazepines including Midazolam and Diazepam.

• Serotonergic drugs, including Tramadol and Fentanyl.

• Antipsychotics.

• Cimetidine.

• Ketoconazole.

• Phenytoin.

• Erythromycin.

Conclusion:

Mirtazapine is a commonly prescribed antidepressant with several therapeutic uses. The drug must be taken only after consultation with a doctor as it changes the mood and impacts a person's daily activities. Patients taking antidepressants tend to become addicted to them. Therefore, the patient must consume the drug as per the doctor's recommendation and seek medical attention if he experiences any side effects.