Mirtazapine

Is mirtazapine safe?

For most adults with depression it is a reasonable choice, especially when poor sleep, poor appetite or sexual side effects on an SSRI are the problem. Mirtazapine, sold as Remeron in the US and mostly as a generic in the UK, works differently from SSRIs: it blocks certain receptors rather than serotonin reuptake. It is not addictive and is taken once a day, usually at bedtime.

Its trade-offs are the reverse of the SSRIs'. Instead of nausea and sexual problems, expect sleepiness and a bigger appetite. And while overdoses of mirtazapine alone are usually mild, it is more often involved in fatal mixed overdoses than SSRIs are. We score it 65, just below trazodone (67) and below sertraline (72), but well above amitriptyline (52).

Sleepiness and weight gain

These two side effects dominate the label:

Sleepiness made 10.4% of people stop in those trials, and the label says it is unclear whether tolerance develops. The UK label adds that cutting the dose does not usually reduce sleepiness. Do not drive or use machinery until you know how it affects you the next morning. In longer studies 8% stopped because of weight gain, so it is worth weighing yourself in the first months if weight matters for your health, for example with diabetes.

Overall, 16% stopped for side effects in the six-week US trials, against 7% on placebo. On the plus side, nausea and sexual problems are less common than with SSRIs.

Rare but serious risks

• Low white blood cells. Two of 2,796 trial patients developed agranulocytosis and a third severe neutropenia; all recovered after stopping. Fever, sore throat or mouth ulcers need a call to the doctor.
• Skin reactions. DRESS, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported and can be fatal.
• Heart rhythm. QT prolongationQT prolongationA delay in the heart's electrical recovery between beats, seen on an ECG. Some medicines cause it, and in rare cases it leads to a serious heart rhythm problem.More in the glossary and torsade de pointes have been reported, mostly in overdose or with other QT-prolonging drugs.
• Liver and sodium. ALT rose to three times normal in 2.0% of trial patients against 0.3% on placebo, and low sodium can occur, mainly in older people.

Like every US antidepressant, mirtazapine carries a boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary on suicidal thoughts and behaviour in people under 25. It is not approved for children; in a trial in children 49% gained at least 7% of their weight.

Overdose and mixed drugs

Mirtazapine alone is less toxic than older antidepressants: the UK label says overdoses usually cause disorientation, prolonged sedation and a fast heart rate. But in a study of England and Wales from 2000 to 2006, its case fatality ratio was 1.9, nearly four times the SSRI figure of 0.5, although far below tricyclics (13.8).

In 2024 mirtazapine was mentioned on 175 drug-poisoning death certificates in England and Wales, up from 90 in 2014 and more than any other single antidepressant the ONS reports. Only 13 involved no other drug, and 53 involved alcohol. The pattern points to its sedation adding to opioids, benzodiazepines, pregabalin and alcohol. If you take any of these, make sure every prescriber knows.

In the US call Poison Help on 1-800-222-1222; in the UK call 111, or 999 if someone is very drowsy, hard to wake or breathing slowly.

Who should be careful

Talk to your doctor or pharmacist before starting mirtazapine, or adding anything to it, if you:

• drink regularly or take opioids, benzodiazepines, gabapentin or pregabalin
• are older, have dementia or a history of falls
• have diabetes, high cholesterol or are worried about weight
• have heart disease, a long QT intervalQT prolongationA delay in the heart's electrical recovery between beats, seen on an ECG. Some medicines cause it, and in rare cases it leads to a serious heart rhythm problem.More in the glossary, or take QT-prolonging drugs
• have liver or kidney disease, epilepsy or bipolar disorder
• take warfarin, as the label advises checking INR
• have phenylketonuria (the orally disintegrating tablets contain aspartame)

In people with dementia, the SYMBAD trial in 2021 found that mirtazapine did not reduce agitation, and 7 people on it died by week 16 against 1 on placebo. Stopping suddenly after long use can cause dizziness, anxiety and nausea, so changes should be planned with your prescriber.

How we scored it

Dependence (80) and track record (88) are strong. Serious side effects (60) reflect the high rates of sedation and weight gain plus rare blood and skin reactions. The overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (64) sits between SSRIs and tricyclics, below citalopram and above venlafaxine, in line with their case fatality ratios. A lower score is not a reason to stop a medicine that is working.