Vortioxetine

Is vortioxetine safe?

For most adults with depression it is, and on several points it is easier to live with than the older antidepressants. Vortioxetine, sold as Trintellix in the US and Brintellix in the UK and Europe, blocks serotonin reuptake like an SSRI and also acts directly on several serotonin receptors. It is licensed only for major depression in adults. The US name changed from Brintellix in 2016 after mix-ups with the blood thinner Brilinta (ticagrelor).

The main catch is nausea, which affects about a quarter to a third of people at the usual doses, mostly in the first two weeks. Against that, it has less effect on sex drive at 10 mg than many SSRIs, no measurable effect on the heart rhythm, and a very long half-life that makes withdrawal milder. We score it 71, level with escitalopram (71) and above venlafaxine (59). What holds it back is age: it has been on the market for 13 years, not the 30 that SSRIs have.

Nausea and other side effects

The US label pools 6 to 8 week trials in more than 2,600 people on vortioxetine. Nausea rose with dose:

It was usually mild, started in the first days and lasted a median of two weeks. Constipation, diarrhoea, dizziness and itching were the other effects seen more often than on placebo. Rates of stopping for side effects were low for an antidepressant; for comparison, about 12% stopped venlafaxine in its trials.

The serious risks are the ones shared by serotonin antidepressants: serotonin syndromeSerotonin syndromeA reaction caused by too much serotonin in the body, usually from combining medicines that raise it. Symptoms range from shivering to high fever.More in the glossary (mostly when combined with other serotonin drugs), bleeding, low sodium in older people, triggering mania in bipolar disorder, and angle-closure glaucoma in people with narrow eye angles. Like all antidepressants in the US, it 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 about suicidal thoughts in people under 25. Watch closely in the first months and after any dose change.

Sexual side effects and weight

Sexual problems are a common reason people stop SSRIs, and this is where vortioxetine looks better, though not free of them. The label used a structured questionnaire in people with normal sexual function at the start. New problems appeared in 23% of women and 20% of men at 10 mg, against 20% and 14% on placebo. At 20 mg the figures rose to 34% and 29%. In a dedicated trial in people with sexual problems from an SSRI, switching to vortioxetine improved sexual function more than switching to escitalopram.

Weight gain is not listed among its common side effects, and a thorough heart study found no 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 even at 40 mg, twice the maximum dose. That makes it one option to discuss for people with heart rhythm concerns or those worried about weight.

Stopping vortioxetine and overdose

Vortioxetine has a half-life of about 66 hours, against about 30 for escitalopram and 5 for venlafaxine. Levels fall slowly when it is stopped. The US label is unusual in saying it can be stopped abruptly, though people on 15 or 20 mg had headache, muscle tension, mood swings, anger outbursts, dizziness and runny nose in the first week after a sudden stop. It advises a week at 10 mg first. The UK label says a gradual reduction may be considered. Either way, plan it with your prescriber.

Overdose data are limited because the drug is newer. Post-marketing reports of up to 80 mg (four times the top dose) mostly involved nausea and vomiting. Above that, a seizure and a case of serotonin syndromeSerotonin syndromeA reaction caused by too much serotonin in the body, usually from combining medicines that raise it. Symptoms range from shivering to high fever.More in the glossary with another serotonin drug have been reported. A 2024 London case report described a man who took 1,260 mg, 63 times the maximum dose, together with diazepam, and developed no significant toxicity. There is no antidote. In the US call Poison Help on 1-800-222-1222; in the UK call 111, or 999 if someone is drowsy, fitting or very agitated.

Interactions that matter

The liver breaks vortioxetine down mainly through the CYP2D6CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary enzyme. Strong blockers of that enzyme, including bupropion, fluoxetine, paroxetine and quinidine, roughly double its levels, and the label says to halve the dose. Rifampicin, carbamazepine and phenytoin lower its levels. People who are genetically poor CYP2D6 metabolisers should take no more than 10 mg.

As with all serotonin antidepressants, MAOIs are contraindicatedContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary, and the gap after stopping vortioxetine is long: 21 days before an MAOI can start. Tramadol, triptans, lithium, fentanyl and St John's wort raise serotonin syndromeSerotonin syndromeA reaction caused by too much serotonin in the body, usually from combining medicines that raise it. Symptoms range from shivering to high fever.More in the glossary risk. Aspirin, NSAIDs and anticoagulants raise bleeding risk, although a label study found no change in warfarin's INR. Vortioxetine itself does not block liver enzymes, so it rarely raises the levels of other medicines.

Who should be careful

Talk to your doctor or pharmacist before starting vortioxetine if you have bipolar disorder or a family history of it, epilepsy, narrow-angle glaucoma, a bleeding disorder, or low sodium, or if you take a blood thinner, another antidepressant, bupropion or a migraine triptan. People over 65 start at 5 mg in the UK. Its safety in pregnancy is less well studied than for sertraline. A lower score elsewhere is no reason to stop a medicine that works; changes should be planned with your prescriber.

How we scored it

Dependence (85) is a strength, thanks to the long half-life. Serious side effects (72) reflect frequent but mostly mild nausea and no heart rhythm signal. Track record (72) is the weakest factor: 13 years and a smaller evidence base than the SSRIs. 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 (76) looks wide in the reports so far, but there are few of them, which is why our confidence is medium.