Mirtazapine

What Does Mirtazapine Do?

Mirtazapine is an antidepressant, generally prescribed for the treatment of major depressive disorder. Its off-label uses include treatment for anxiety disorders, PTSD, OCD, and insomnia. The medication's effects include improvement in mood, appetite, and sleep patterns, as well as reduced anxiety and agitation.

How Does Mirtazapine Work? (the complicated stuff)

Mirtazapine functions by blocking the presynaptic alpha-2 adrenergic receptors resulting in an increase in norepinephrine and serotonin release in the brain. It concurrently acts as an antagonist at serotonin receptors, helping to balance serotonin levels thereby reducing symptoms of anxiety and depression.

Drug Type and Category of Mirtazapine

Mirtazapine is a tetracyclic antidepressant prescription medicine.

What dosage of Mirtazapine should you be taking?

NICE Guidelines ¹

The dosing guidelines for mirtazapine are as follows:

Initial Dosage

The usual initial dose is 15 mg to 30 mg taken once daily, preferably at bedtime due to its sedative effects.

Maintenance Dosage

After 2 to 4 weeks, the dose can be adjusted based on the patient's response, with a maximum dose of 45 mg per day.

Mirtazapine can be taken with or without food and should be swallowed whole with water. For orally disintegrating tablets, place the tablet on the tongue and allow it to dissolve before swallowing.

Special Considerations

Liver and Kidney Impairment: Dosage adjustments may be necessary for patients with liver or kidney issues, and lower doses may be prescribed in such cases.

Duration of Treatment

It is generally recommended to continue treatment for 6 months to a year after symptoms improve to prevent relapse.

What are the side-effects of Mirtazapine?

Common Side Effects:

• Drowsiness/Sedation: Mirtazapine is known for its sedative effects, which can be pronounced, especially when starting the medication. This is why it's often prescribed to be taken at night.
• Increased Appetite and Weight Gain: Many people taking mirtazapine experience an increase in appetite, leading to weight gain. This is one of the more notable side effects.
• Dry Mouth: A dry mouth is a common side effect and can be managed by staying hydrated and using sugar-free gum or lozenges.
• Dizziness: Some people may feel lightheaded or dizzy, particularly when standing up quickly.
• Constipation: Mirtazapine can slow down the digestive system, leading to constipation. Increasing fiber intake and staying hydrated can help.
• Fatigue: Even though mirtazapine can improve sleep in those with insomnia, it may also cause feelings of fatigue or grogginess during the day.

Less Common Side Effects

• Restless Legs Syndrome (RLS): Some patients report the development or worsening of RLS while on mirtazapine. RLS is a neurological disorder characterised by an uncontrollable urge to move the legs, usually due to uncomfortable sensations.
• Orthostatic Hypotension: This is a drop in blood pressure upon standing, which can cause dizziness or fainting.
• Agranulocytosis: Though rare, mirtazapine has been associated with a potentially serious condition called agranulocytosis, where the white blood cell count drops significantly. Monitoring is usually advised in the early stages of treatment.
• Mania/Hypomania: In people with bipolar disorder, mirtazapine can sometimes trigger manic or hypomanic episodes.
• Increased Cholesterol and Triglycerides: Mirtazapine has been linked to elevated levels of cholesterol and triglycerides in some individuals.
• Sexual Dysfunction: While less common compared to other antidepressants, mirtazapine can still cause sexual side effects, including decreased libido, erectile dysfunction, or difficulty achieving orgasm.
• Serotonin Syndrome: This is a rare but serious condition that can occur when mirtazapine is taken with other medications that increase serotonin levels. Symptoms include confusion, rapid heart rate, high blood pressure, dilated pupils, and muscle rigidity.

Drug Interactions

Combining mirtazapine with Monoamine Oxidase Inhibitors (MAOIs e.g., phenelzine, tranylcypromine) or within 14 days of stopping an MAOI can lead to serious interactions, including the risk of serotonin syndrome, a potentially life-threatening condition.

Other Antidepressants

Mirtazapine taken with other serotonergic drugs (e.g., SSRIs, SNRIs, tricyclic antidepressants, or St. John's Wort) can increase the risk of serotonin syndrome.

Mirtazapine has sedative effects, which can be enhanced when combined with other central nervous system depressants like benzodiazepines (e.g., lorazepam, diazepam), alcohol, or other sedative medications. This combination can lead to increased drowsiness, dizziness, and risk of overdose.

Mirtazapine is metabolised by cytochrome P450 enzymes (particularly CYP1A2, CYP2D6, and CYP3A4). Drugs that inhibit these enzymes (e.g., cimetidine, ketoconazole) can increase mirtazapine levels, leading to enhanced effects and side effects. Conversely, drugs that induce these enzymes (e.g., carbamazepine, phenytoin, rifampin) can reduce mirtazapine levels, potentially decreasing its efficacy.

Mirtazapine may enhance the anticoagulant effects of warfarin, increasing the risk of bleeding as well as antagonise the effects of clonidine, a medication used to treat high blood pressure and certain psychiatric conditions. Some antiepileptic drugs like phenytoin and carbamazepine can lower mirtazapine levels, possibly reducing its antidepressant effects.

Natural Alternatives to Mirtazapine ²

St. John's Wort: This herb has been used traditionally to treat mild to moderate depression. However, it can interact with many medications, so it's important to consult a doctor before using it.

Chamomile: Chamomile has been used as a mild tranquilizer and sleep inducer. It may be helpful for anxiety and insomnia.

Valerian: Valerian root has been used as a sedative and sleep aid. It may help with insomnia and anxiety.

SAM-e (S-adenosylmethionine): SAM-e is a compound that occurs naturally in the body. Some studies suggest it may be helpful for depression.

Omega-3 fatty acids: Omega-3s found in fish oil may help with depression. However, more research is needed.

Melatonin: Melatonin is a natural hormone that regulates sleep-wake cycles. It may help with insomnia. Caution needs to be taken with any hormone replacement. 

Regular physical activity is beneficial for both physical and mental health, helping to improve mood and enhance sleep quality. Incorporating relaxation techniques such as yoga, meditation, and deep breathing into your routine can also be effective in reducing stress and promoting overall relaxation. 

Ultimately, addressing the underlying issues in your life are key. Look at personal or family conflicts, address financial issues, enjoy life, have fun, work in a rewarding job and spend plenty of time in nature. Get outside regularly to increase sun exposure to boost vitamin D, and practice gratitude. Addressing you and improving you is really the first step to being drug-free.

In addition to these practices, Cognitive Behavioral Therapy (CBT) is a well-established form of psychotherapy that can help individuals identify and change negative thought patterns and behaviors that contribute to depression. By addressing these underlying cognitive and behavioral issues, CBT can play a crucial role in managing and alleviating depressive symptoms.

Interesting facts about Mirtazapine

Mirtazapine was developed and first approved in the Netherlands in 1994 before gaining wider approval globally. Its distinct mechanism of action distinguished it from other antidepressants available at the time. Mirtazapine can cause some unusual side effects, such as vivid dreams or nightmares, and in some cases, Restless Legs Syndrome (RLS). Having said that, it can often be prescribed for insomnia due to its sedative effects.

Lower doses (e.g., 15 mg) are more sedating because they strongly block histamine receptors.

At higher doses (e.g., 30–45 mg), the sedative effect diminishes as the noradrenergic stimulation becomes more prominent.

Disclaimer

This article is generated for informational purposes only. It was created in August 2024. Medications and medical guidance can change over time. Therefore, it is essential to consult with your general practitioner or healthcare provider before making any decisions regarding medications or treatment plans. Your GP can provide personalised advice based on your specific health needs and conditions.

References 

1. https://bnf.nice.org.uk/drugs/mirtazapine/
2. https://www.alternativetomeds.com/blog/mirtazapine-alternatives/