Trintellix: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Dec 28, 2022.

1. How it works

• Trintellix is a brand (trade) name for vortioxetine which may be used to treat depression.
• Experts aren’t sure exactly how Trintellix (vortioxetine) works but it is thought to increase levels of a neurotransmitter, called serotonin in the brain. It also has effects on other serotonin receptors, such as 5-HT1A (agonist effects) and 5-HT3 (antagonist effects), although experts are not sure if these actions also contribute to vortioxetine’s antidepressant effect.
• Trintellix is different from other antidepressants currently on the market because of its direct effects on various serotonin receptors as well as inhibits 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. It aims to reduce depressive symptoms and prevent them from returning.
• Trintellix is classified as a miscellaneous antidepressant, although some classify it as an SSRI (selective serotonin reuptake inhibitor) and a serotonin receptor modulator.

2. Upsides

• Trintellix may be used to treat major depressive disorder (MDD) in adults.
• Although not FDA-approved to treat anxiety, Trintellix has been used off-label to treat generalized anxiety disorder (GAD). It appears to work best in those with severe GAD (HAMA of >25).
• Trintellix is an oral tablet that is taken once a day.
• May be taken with or without food.
• Trintellix is different from other antidepressants currently on the market because it directly affects serotonin receptors as well as inhibits serotonin reuptake.
• Trintellix 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 Trintellix may take four weeks or more to be seen.
• Available as a generic under the name vortioxetine.

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 Trintellix 20 mg/day. Other gastrointestinal side effects include diarrhea, dry mouth, constipation, and vomiting.
• Dizziness, abnormal dreams, and pruritus (itchy skin), sexual dysfunction, may also occur.
• As with other antidepressants, Trintellix 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 Trintellix.
• 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 Trintellix 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 Trintellix may be due to Trintellix increasing appetite (or reversing a poor appetite that is the result of untreated major depressive disorder), or because Trintellix 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 Trintellix. Weight loss with Trintellix 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 Trintellix in children has not been established.
• Trintellix 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 Trintellix during breastfeeding, but animal studies have shown its presence in milk.

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

Trintellix 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. Nausea is the most commonly reported side effect and it may take up to 4 weeks before the full effects of treatment are seen.

5. Tips

• Trintellix only needs to be taken once a day. You can choose whether you take Trintellix in the morning or at night; however, if you find Trintellix interferes with your sleep or makes you restless or energized, try taking it in the morning.
• Trintellix 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.
• Trintellix may be taken with or without food.
• Take Trintellix exactly as directed by your doctor. Do not stop suddenly without your doctor's advice. Trintellix 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, and 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 Trintellix.
• Talk with your doctor if you experience any:

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

• Trintellix 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 Trintellix, tell your doctor straight away.
• Trintellix was previously called Brintellix but the name was changed in 2016 after confusion in the marketplace between Brintellix and another medicine. Brintellix is no longer available.

6. Response and effectiveness

• Trintellix 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 Trintellix 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 Trintellix (vortioxetine).
• People taking Trintellix also experienced a statistically significantly longer time before a recurrence of depressive episodes than those that were taking a placebo (an inactive pill).
• Although Trintellix 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 Trintellix than those without; people were more likely to experience response (Odds ratio: 1.2) and remission (Odds ratio: 1.05) with Trintellix than they were taking a placebo (pretend) pill. The authors concluded that because of the limited number of trials, more trials are needed before Trintellix is given routinely for GAD.

7. Interactions

Medicines that interact with Trintellix may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Trintellix. 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 Trintellix 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 if Trintellix is taken with an MAOI, such as isocarboxazid, phenelzine, or tranylcypromine. Do not take Trintellix with an MAOI and within 14 days of stopping an MAOI. Do not start an MAOI within 21 days of stopping Trintellix.

Reduce the dosage of Trintellix when it is given with strong CYP2D6 inhibitors, such as bupropion, fluoxetine, paroxetine, or quinidine. Consider increasing the dosage of Trintellix up to a maximum of 3 times the usual dosage when taking it 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 Trintellix. You should refer to the prescribing information for Trintellix for a complete list of interactions.

References

• Trintellix (vortioxetine). Updated 08/2022. Cardinal Health 107, LLC https://www.drugs.com/pro/trintellix.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Trintellix 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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