Vortioxetine: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on Sep 28, 2023.

1. How it works

• Vortioxetine may be used to treat depression.
• Experts are unsure exactly how vortioxetine works, although historically it was believed that vortioxetine’s effects were due to its ability to rebalance chemicals in the brain, such as serotonin, that were thought to be imbalanced in people with mood disorders. Studies confirm that vortioxetine is still effective for treating mood disorders, such as depression, even though the way it works is unknown.
• Vortioxetine has effects on other serotonin receptors, such as 5-HT1A (agonist effects) and 5-HT3 (antagonist effects), but experts are not sure if these actions contribute to vortioxetine’s antidepressant effect.
• Vortioxetine is different from other antidepressants currently on the market because of its direct effects on various serotonin receptors as well as inhibiting serotonin reuptake. Because it acts as an antagonist/agonist and partial agonist, this is thought to enhance its antidepressant effects and prevent desensitization of the presynaptic neuron, although the exact way it works is unknown. It aims to reduce depressive symptoms and prevent them from returning.
• Vortioxetine is classified as a miscellaneous antidepressant, although some classify it as an SSRI (selective serotonin reuptake inhibitor) and a serotonin receptor modulator.

2. Upsides

• Vortioxetine may be used to treat major depressive disorder (MDD) in adults.
• Although not FDA-approved to treat anxiety, Vortioxetine has been used off-label to treat generalized anxiety disorder (GAD). It appears to work best in those with severe GAD (HAMA of >25).
• Vortioxetine is an oral tablet that is taken once a day.
• May be taken with or without food.
• Vortioxetine is different from other antidepressants currently on the market because it directly affects serotonin receptors as well as inhibits serotonin reuptake, although how this contributes to its antidepressant effect is unknown.
• Vortioxetine is far less likely to cause weight gain than some other antidepressants, such as tricyclic antidepressants, MAOIs, or SSRIs.
• Some improvement in symptoms of depression should be noticed by most people after two weeks of treatment; however, the full effects of Vortioxetine may take four weeks or more to be seen.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Nausea is the most common side effect and is more likely at higher dosages, occurring in up to 32% of people taking vortioxetine 20 mg/day. Other gastrointestinal side effects include diarrhea, dry mouth, constipation, and vomiting.
• Dizziness, abnormal dreams, and pruritus (itchy skin), or sexual dysfunction, may also occur.
• As with other antidepressants, vortioxetine may increase the risk of suicidal thoughts or behavior; the risk is higher in children and young adults aged less than 24. Monitor for worsening mood.
• Interaction or overdosage may cause serotonin syndrome (symptoms include mental status changes [such as agitation, hallucinations, coma, delirium], fast heart rate, dizziness, flushing, muscle tremor or rigidity, and stomach symptoms [such as nausea, vomiting, or diarrhea]).
• May increase the risk of bleeding, especially if used with other drugs that also increase bleeding risk.
• May precipitate a manic episode in people with undiagnosed bipolar disorder. Screen for bipolar disorder before starting treatment.
• May cause a lowering of total body sodium (hyponatremia); elderly people or people taking diuretics or already dehydrated are more at risk.
• May cause headaches, mood swings, sudden outbursts of anger, dizziness, and a runny nose if abruptly stopped. Reduced the dose to 10 mg/day for one week before stopping.
• Seek medical advice if a rash or any other signs of an allergic reaction, such as swelling or difficulty breathing, develops while taking vortioxetine.
• May trigger angle-closure glaucoma in people with anatomically narrow angles who do not have a patent iridectomy.
• May interact with several other drugs including other antidepressants, tramadol, bupropion, diuretics, CYP2D6 inducers/inhibitors, and St John's Wort.
• Although weight gain is less likely with vortioxetine than with some other antidepressants, clinically significant weight gain may occur in 11-13% and weight loss in 7.7% of users in the long term. The average weight increase was 1.54 lbs. to 1.76 lbs. Weight gain with vortioxetine may be due to vortioxetine increasing appetite (or reversing a poor appetite that is the result of untreated major depressive disorder), or because vortioxetine has slightly altered a person’s hormones and metabolism. Weight gain may also be due to bloating, constipation, social eating, or fatigue. Some Blog posts have also reported weight loss as a side effect of vortioxetine. Weight loss with vortioxetine may be due to nausea, appetite reduction, diarrhea, or healthier food choices.
• May not be suitable for those with liver problems, a history of seizures, mania or bipolar disorder, hyponatremia, bleeding problems, or with certain other medical conditions.
• The safety and effectiveness of vortioxetine in children has not been established.
• Vortioxetine taken during the third trimester of pregnancy has been associated with withdrawal symptoms in the newborn baby and persistent pulmonary hypertension of the newborn (PPHN). Not recommended during pregnancy unless the benefits outweigh the risks. There is no information regarding vortioxetine during breastfeeding, but animal studies have shown its presence in milk.
• Vortioxetine is available under the brand (trade) name Trintellix. The former trade name for vortioxetine was Brintellix, but this was changed in 2016 because of dispensing errors associated with another medication that sounded similar, called Brilinta. Trintellix is currently the only brand of vortioxetine available in the United States.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Vortioxetine may be used to treat depression in adults. It is different from other antidepressants currently on the market because it directly affects serotonin receptors as well as inhibits serotonin reuptake, although how this contributes to its antidepressant effect is unknown. Nausea is the most commonly reported side effect and it may take up to 4 weeks before the full effects of treatment are seen. It is available under the brand (trade) name Trintellix.

5. Tips

• Vortioxetine only needs to be taken once a day. You can choose whether you take vortioxetine in the morning or at night; however, if you find vortioxetine interferes with your sleep or makes you restless or energized, try taking it in the morning.
• Vortioxetine is usually started at 10mg once daily which may be increased to 20mg once a day if needed or decreased down to 5 mg/day in those who do not tolerate 10 mg/day.
• Vortioxetine may be taken with or without food.
• Take vortioxetine exactly as directed by your doctor. Do not stop suddenly without your doctor's advice. Vortioxetine is best tapered down slowly on discontinuation.
• Be alert for worsening mood and suicide-related thoughts or behaviors. Seek medical advice if changes are apparent.
• Seek urgent medical advice if symptoms consistent with serotonin syndrome (such as agitation, hallucinations, fast heart rate, dizziness, flushing, nausea, diarrhea) develop.
• Talk to your doctor immediately if you develop a rash or seek urgent medical advice with severe allergy-type symptoms such as swelling of the face or throat, or shortness of breath.
• Do not take any other medicines, including those bought over-the-counter, without first consulting a doctor or pharmacist and asking if the medicine is safe to take with vortioxetine.
• Talk with your doctor if you experience any:

• Unusual bruising or increased bleeding while taking vortioxetine
• Persistent headaches, confusion, weakness, or unsteadiness resulting in falls
• An increase, irregularity, or slowing of your heart rate or shortness of breath
• Eye pain, swelling, or visual disturbances
• Seizures
• Manic behavior such as recklessness, racing thoughts, increased energy, and severe difficulty sleeping.

• Vortioxetine is not recommended during pregnancy because it may cause withdrawal symptoms in the newborn baby or persistent pulmonary hypertension of the newborn (PPHN). If you inadvertently become pregnant while taking vortioxetine, tell your doctor straight away.

6. Response and effectiveness

• Vortioxetine has a long half-life (approximately 66 hours) and is given once a day. It takes seven to eleven hours to reach maximum vortioxetine concentrations in the blood after a single dose, but once regular dosing is established, blood levels remain relatively constant. It takes approximately two weeks for levels to stabilize in the body.
• Some reduction in depressive symptoms may occur within two weeks of vortioxetine treatment; however, the full effects may not be seen until week 4 or later.
• In one study, 61% experienced a remission of depressive symptoms after 4 weeks of treatment, but for another 15%, it took eight weeks for remission to occur. After eight weeks of treatment, the effects begin to level off but they persist.
• At least five trials of 6 to 8 weeks duration have established the effectiveness of vortioxetine.
• People taking vortioxetine also experienced a statistically significantly longer time before a recurrence of depressive episodes than those who were taking a placebo (an inactive pill).
• Although vortioxetine is only approved for treating depression, it may be used off-label to treat anxiety. Off-label means the drug is being used for a different purpose than that which it has been approved for. An analysis of four trials showed patients with severe GAD (Hamilton Anxiety Rating Scale [HAMA] total score of at least 25 had a significantly greater effect from vortioxetine than those without; people were more likely to experience response (Odds ratio: 1.2) and remission (Odds ratio: 1.05) with vortioxetine than they were taking a placebo (pretend) pill. The authors concluded that because of the limited number of trials, more trials are needed before vortioxetine is given routinely for GAD.

7. Interactions

Medicines that interact with vortioxetine may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with vortioxetine. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with vortioxetine include:

• anticoagulants (blood thinners), such as warfarin, or other drugs that have blood-thinning effects such as aspirin or NSAIDs
• anticonvulsants, such as phenytoin, phenobarbital, or primidone
• antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
• any medication that may cause drowsiness, such as benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine, morphine)
• diuretics, such as furosemide
• linezolid
• lithium
• medications that may affect the heartbeat by prolonging the QT interval, such as amiodarone, encainide, or flecainide
• methylene blue
• migraine medications, such as sumatriptan or rizatriptan)
• pimozide
• other antidepressants, such as tricyclic antidepressants (eg, amitriptyline), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), and SSRIs (eg, paroxetine, sertraline)
• other medications that affect serotonin, such as amphetamines, fentanyl, lithium, tramadol, triptans (eg, almotriptan, eletriptan, or sumatriptan), or St. John's Wort
• other medications that are metabolized by the same enzymes (CYP2D6) such as tricyclic antidepressants, most antipsychotics, flecainide, propafenone, or vinblastine
• others, such as HIV medications (fosamprenavir, ritonavir), procyclidine, or theophylline.

Serious, sometimes fatal reactions may occur in vortioxetine is taken with an MAOI, such as isocarboxazid, phenelzine, or tranylcypromine. Do not take vortioxetine with an MAOI and within 14 days of stopping an MAOI. Do not start an MAOI within 21 days of stopping vortioxetine.

Reduce the dosage of vortioxetine when it is given with strong CYP2D6 inhibitors, such as bupropion, fluoxetine, paroxetine, or quinidine. Consider increasing the dosage of vortioxetine up to a maximum of 3 times the usual dosage when taking with a strong CYP2D6 inducer, such as rifampin, carbamazepine, or phenytoin.

Note that this list is not all-inclusive and includes only common medications that may interact with vortioxetine. You should refer to the prescribing information for vortioxetine for a complete list of interactions.

References

• Vortioxetine. Updated Oct 31, 2022. ASHP monograph. https://www.drugs.com/monograph/vortioxetine.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use vortioxetine only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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