Mirtazapine NHS: everything you need to know

Mirtazapine is an antidepressant that belongs to the class of medicines known as noradrenergic and specific serotonergic antidepressants (NaSSAs).

It has been available in the UK since 1997 and is widely prescribed on the NHS.

How mirtazapine works:

Mirtazapine has a complex pharmacological profile:

• Alpha-2 adrenergic antagonist: blocks presynaptic alpha-2 receptors, increasing the release of noradrenaline and serotonin
• 5-HT2A, 5-HT2C and 5-HT3 antagonist: blocks specific serotonin receptors, which contributes to its antidepressant and anti-nausea effects
• H1 histamine receptor antagonist: responsible for its sedating and appetite-stimulating properties

This means mirtazapine increases both noradrenaline and serotonin signalling in the brain, but through a different mechanism from SSRIs (such as sertraline or fluoxetine) or SNRIs (such as venlafaxine).

What mirtazapine is prescribed for:

• Depression: the primary licensed indication
• Anxiety: commonly used off-label when anxiety is prominent alongside depression
• Insomnia with depression: its sedating properties make it a preferred choice when sleep disturbance is significant
• Appetite stimulation: sometimes used in elderly or medically unwell patients with poor appetite

Mirtazapine is available as standard tablets, orodispersible tablets (which dissolve on the tongue) and an oral solution. All are available on the NHS.

Dosing schedule:

• Starting dose: 15 mg once daily, taken at bedtime
• Dose increases: after 2 to 4 weeks, the dose may be increased to 30 mg if there is insufficient response
• Maximum dose: 45 mg once daily
• Elderly patients: the same doses apply, but increases should be made more cautiously under close supervision

Practical tips:

• Take mirtazapine at the same time each day, preferably 1 to 2 hours before bedtime
• It can be taken with or without food
• Swallow standard tablets whole with water
• Orodispersible tablets should be placed on the tongue and allowed to dissolve; they can be taken without water
• If you miss a dose, take it as soon as you remember unless it is nearly time for the next dose. Do not take a double dose

How long until it works:

• Sleep and appetite improvements are often noticed within the first week
• The full antidepressant effect typically takes 2 to 4 weeks to develop
• NICE recommends continuing treatment for at least 6 months after recovery to reduce the risk of relapse
• Do not stop taking mirtazapine without discussing it with your prescriber

The NHS lists the following side effects for mirtazapine. Most are manageable and tend to improve with continued treatment.

Common side effects:

• Increased appetite and weight gain
• Drowsiness or sleepiness (especially at lower doses)
• Headaches
• Dry mouth
• Constipation
• Feeling dizzy or faint
• Swelling in the feet or ankles

Less common but important side effects:

• Vivid or unusual dreams
• Joint pain or muscle aches
• Tremor
• Restless legs

Serious side effects requiring medical attention:

• Yellowing of the eyes or skin (jaundice)
• Fever with sore throat or mouth ulcers (possible blood disorder)
• Thoughts of self-harm or suicide
• Fits or seizures
• Allergic reactions (rash, swelling, difficulty breathing)

For a detailed analysis of mirtazapine side effects and management strategies, see our dedicated side effects guide.

You can report any suspected side effects through the Yellow Card Scheme at yellowcard.mhra.gov.uk.

Mirtazapine interacts with several other medicines and is not suitable for everyone.

Important drug interactions:

• MAOIs (e.g. phenelzine, tranylcypromine): must not be taken within 14 days of mirtazapine. The combination can cause serotonin syndrome
• Other serotonergic drugs (SSRIs, SNRIs, tramadol, triptans, St John's wort): increased risk of serotonin syndrome when combined with mirtazapine
• Benzodiazepines and Z-drugs: additive sedation
• Alcohol: enhanced sedating effects
• Warfarin: mirtazapine may increase the anticoagulant effect. INR monitoring is advised

Cautions:

• Epilepsy: mirtazapine may lower the seizure threshold
• Liver or kidney impairment: clearance may be reduced, requiring dose adjustment
• Diabetes: weight gain and metabolic effects may worsen blood sugar control
• Cardiac disease: use with caution in patients with cardiac conduction disorders
• Urinary retention or prostatic hypertrophy: antimuscarinic effects may worsen symptoms
• Angle-closure glaucoma: mirtazapine has weak anticholinergic effects

Pregnancy and breastfeeding:

Mirtazapine should be used in pregnancy only if the benefit outweighs the risk. It passes into breast milk.

Specialist advice should be sought, and the decision should involve the patient, prescriber and, ideally, a perinatal psychiatrist.

Mirtazapine should not be stopped suddenly. The NHS and BNF advise a gradual dose reduction to minimise withdrawal effects.

Possible withdrawal symptoms:

• Dizziness and headache
• Nausea and vomiting
• Anxiety and agitation
• Insomnia and vivid dreams
• Irritability
• Paraesthesia (tingling or "electric shock" sensations)
• Flu-like symptoms

Recommended approach:

• Reduce the dose gradually over at least 4 weeks, and longer if you have been taking mirtazapine for an extended period
• NICE suggests that some patients may need to reduce over several months using smaller dose decrements
• If withdrawal symptoms are troublesome, slow the taper or return to the previous dose temporarily
• Keep in contact with your GP throughout the withdrawal process

When to consider stopping:

• After at least 6 months of feeling well (for a first episode of depression)
• After at least 2 years of feeling well (for recurrent depression)
• The decision should be made jointly between you and your prescriber

Some patients find the withdrawal process difficult and benefit from additional support, such as counselling or cognitive behavioural therapy, during the taper.