vortioxetine (Trintellix)

the boxed warning: suicidal thoughts and behaviors, by age

the boxed warning says antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents and young adults in short-term studies, that everyone on the drug should be watched for worsening, and that trintellix is not approved for use in pediatric patients [label, boxed warning and 5.1].

the numbers come from pooled placebo-controlled trials of antidepressants covering about 77,000 adults and 4,500 children. per 1,000 people treated, the difference against placebo was: under 18, 14 additional people with suicidal thoughts or behaviors; 18 to 24, 5 additional; 25 to 64, 1 fewer; 65 and older, 6 fewer [label 5.1, table 1]. the label adds that the absolute risk was highest in people treated for depression and that whether the risk extends beyond four months is unknown. so the warning is specific: thoughts and behaviors, not deaths; the first months; and above age 24 the pooled trials showed no increase [label 5.1; age-ceiling row].

vortioxetine’s own pediatric record is in section 8.4, and it is unusual in being there at all. two randomised, placebo- and active-controlled 8-week trials, 540 children aged 7 to 11 and 616 adolescents aged 12 to 17, measured change on the children’s depression rating scale; "trintellix was not superior to placebo in either study" [label 8.4]. so the age line in the boxed warning is not only a class caution here: the drug was tested in 1,156 children and did not beat placebo in either group.

the seven other warnings, in plain words

the label’s warnings and precautions run from 5.2 to 5.8. none is boxed, and all seven appear on the ssri labels in near-identical words. the contraindications and the dose-adjustment rules in section 2 add three more facts worth knowing, listed after them.

• serotonin syndrome [5.2]: too much serotonin signalling, which can be life-threatening. the risk rises with other serotonergic drugs (the label names triptans, tricyclics, fentanyl, lithium, tramadol, tryptophan, meperidine, methadone, buspirone, amphetamines and st john’s wort) and with maois, and it can happen on vortioxetine alone. two maois that are not psychiatric drugs are named: the antibiotic linezolid and intravenous methylene blue, and the label adds that "no reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection)". signs are agitation, hallucinations or confusion, racing heart, swinging blood pressure, sweating, fever, tremor, muscle jerking, overactive reflexes, and in some cases seizures.
• bleeding [5.3]: drugs that block serotonin reuptake make platelets less effective. aspirin, nsaids and blood thinners add to the risk, and ssri or snri use in the month before delivery has been linked to a less than twofold rise in postpartum bleeding. the label’s own warfarin and aspirin studies found no change in clotting measures or platelet function [7.2], and it still tells prescribers to watch the inr when vortioxetine is started or stopped.
• activation of mania or hypomania [5.4]: in someone with bipolar disorder an antidepressant can tip a depressive episode into a manic one. symptoms were reported in fewer than 0.1% of people on vortioxetine in the premarketing studies. the label tells prescribers to screen for a personal or family history first [2.2].
• discontinuation syndrome [5.5]: the label says trintellix "can be abruptly discontinued", then reports what happened when it was. people stopping 15 or 20 mg a day abruptly had headache, muscle tension, mood swings, sudden outbursts of anger, dizziness and runny nose in the first week, measured on a discontinuation-symptoms scale in the trials [6.1]. it recommends gradual reduction whenever possible, and specifically that 15 or 20 mg be reduced to 10 mg for one week before stopping [2.3]. the general list for serotonergic antidepressants follows: nausea, sweating, low mood, irritability, agitation, dizziness, electric-shock sensations, tremor, anxiety, confusion, headache, lethargy, insomnia, hypomania, tinnitus and seizures.
• angle-closure glaucoma [5.6]: the pupil dilation many antidepressants cause can trigger an attack in an eye with narrow drainage angles that has not been treated.
• low sodium [5.7]: hyponatremia, usually from the hormone syndrome siadh; one case below 110 mmol/l was reported in a premarketing study. early signs are headache, poor concentration, confusion, weakness and unsteadiness; severe cases have included seizures, coma and death. older people, people on diuretics and anyone dehydrated may be at greater risk.
• sexual dysfunction [5.8]: delayed or absent ejaculation, erectile dysfunction and reduced desire in men; reduced desire and delayed or absent orgasm in women. the label tells prescribers to ask before starting and to ask again during treatment. the label’s own measured rates, which are higher than the volunteered ones, are in the side-effects section below.
• maois, with dates [4; 2.4]: an maoi for a psychiatric condition is contraindicated with vortioxetine, within 14 days after stopping the maoi, and for 21 days after stopping vortioxetine.
• dose by enzyme [2.5; 2.6; 7.1]: the maximum dose is 10 mg a day in known cyp2d6 poor metabolizers, and the dose is halved when a strong cyp2d6 inhibitor is added; the label’s examples are bupropion, fluoxetine, paroxetine and quinidine. with a strong inducer such as rifampin, carbamazepine or phenytoin taken for more than 14 days, the label allows up to three times the original dose.
• a false positive on a drug screen [7.3]: urine immunoassays for methadone have returned false positives in people taking vortioxetine; the label says a chromatographic method should confirm any positive result.

what the trials measured, which of them failed, and for how long

the depression approval rested on six randomised, double-blind, placebo-controlled, fixed-dose trials of 6 to 8 weeks, five in adults aged 18 to 75 and one in people aged 64 to 88, plus a maintenance trial [label 14]. the outcome was change on a depression rating scale, the madrs in four trials and the 24-item hamilton in two. the label prints every arm in table 5, and the arithmetic splits by geography. in the three non-us trials the placebo-subtracted difference ran from 4.1 to 7.1 points: 5.9 and 5.7 points at 5 and 10 mg in study 1 (108, 100 and 105 people per arm), 4.1 and 4.9 at 5 and 10 mg in study 2 (139 per arm), 5.5 and 7.1 at 15 and 20 mg in study 3 (149, 151 and 158). in the two us trials it ran from 1.5 to 3.6 points: in study 4, 15 mg scored 1.5 points better than placebo with a confidence interval that included zero (minus 3.9 to plus 0.9) and 20 mg 2.8 points (145, 147 and 153 people); in study 5, 10 mg scored 2.2 points with an interval that included zero (minus 4.5 to plus 0.1) and 20 mg 3.6 points (154, 148 and 155). the elderly trial found 3.3 hamilton points at 5 mg (155 against 145). then one sentence the table does not show: "two studies of the 5 mg dose in the u.s. (not represented in table 5) failed to show effectiveness" [label 14]. the label also says the full effect was "generally not seen until study week 4 or later".

two longer trials followed. in a non-us maintenance study, 639 people took open-label vortioxetine for 12 weeks and the 396 in remission were randomised to continue or switch to placebo for 24 to 64 weeks; time to recurrence was longer on the drug, and the label gives no percentages. in a us study, 1,106 people took 10 mg for 16 weeks and 580 in remission were randomised to 5, 10 or 20 mg or placebo for 32 weeks; all three doses lengthened time to recurrence [label 14]. as on every antidepressant page here, a design that stops the drug in people doing well on it cannot separate relapse from withdrawal, and this label records withdrawal symptoms at the higher doses.

the trials behind the claim people hear most. two 8-week trials measured the digit symbol substitution test, a 90-second processing-speed task on which healthy 45 to 54 year olds score about 50. in study 7 (193, 204 and 194 people) vortioxetine 10 and 20 mg scored 4.2 and 4.3 more correct matches than placebo; in study 8 (175 against 167), in people who reported trouble concentrating, 1.8 more, with an interval of 0.3 to 3.2. the label’s own caveats follow: "the effects observed on dsst may reflect improvement in depression. comparative studies have not been conducted to demonstrate a therapeutic advantage over other antidepressants on the dsst", and neither trial enrolled people whose depression had remitted but whose concentration had not [label 14]. the label does not approve it for cognition, and the indication is depression only [label 1].

the sexual-function trials. in study 11, 424 people whose depression was controlled on citalopram, sertraline or paroxetine but who had sexual dysfunction from it were switched to vortioxetine (217) or escitalopram (207) for 8 weeks; the vortioxetine group improved 2.2 points more on a 14-item sexual-function questionnaire (confidence interval 0.48 to 4.02), on a scale where the label says 2 to 3 points is clinically meaningful, and both groups kept their antidepressant response. in study 12, 348 healthy volunteers aged 18 to 40 took vortioxetine 10 or 20 mg, paroxetine 20 mg or placebo: at 10 mg vortioxetine caused significantly less sexual dysfunction than paroxetine; at 20 mg, the usual target dose, it did not [label 14]. the exposure arithmetic: 2,616 people took vortioxetine in the 6 to 8 week placebo-controlled trials, 204 and 429 in the two maintenance trials, and 885 for at least a year in open-label follow-on studies [label 6.1].

the most common side effects, with the label’s numbers

the label reports side effects by dose from the 6 to 8 week placebo-controlled trials: 1,013 people on 5 mg, 699 on 10 mg, 449 on 15 mg, 455 on 20 mg, 1,621 on placebo. the reactions at 5% or more and twice placebo were nausea, constipation and vomiting. nausea was 21%, 26%, 32% and 32% by rising dose against 9% on placebo; vomiting 3%, 5%, 6%, 6% against 1%; constipation 3%, 5%, 6%, 6% against 3%; diarrhea 7%, 7%, 10%, 7% against 6%; dizziness 6%, 6%, 8%, 9% against 6%; dry mouth 6% to 8% against 6%; abnormal dreams up to 3% against 1%; itching up to 3% against 1% [label 6.1, table 2]. nausea is the whole story of this table: it was the most common reason for stopping, 15 to 20% of people had it after one or two days, the median duration was two weeks, and about 10% of people on 10 to 20 mg still had it at the end of the trial [label 6.1]. stopping for a side effect ran 5%, 6%, 8% and 8% by dose against 4% on placebo.

sexual side effects, two ways of counting. volunteered: in men 3%, 4%, 4% and 5% by dose against 2% on placebo; in women under 1% to 2% against under 1%. measured with a questionnaire in the people who had normal sexual function at the start, about a third of each trial: in women 22%, 23%, 33% and 34% by dose against 20% on placebo; in men 16%, 20%, 19% and 29% against 14% [label 6.1, table 3]. the label states the reason for the gap, that people and physicians are reluctant to raise it, and tells prescribers to ask routinely.

what the label did not find: no significant effect on weight in the 6 to 8 week trials or in the 6-month placebo-controlled phase of the long-term study, and no clinically significant effect on blood pressure or heart rate [label 6.1]. weight gain, hyperprolactinemia, acute pancreatitis, seizure, and aggression, agitation, anger, hostility and irritability have been reported since marketing, at rates the label cannot estimate [label 6.2]. in overdose, 40 to 75 mg brought nausea, dizziness, diarrhea, itching, sleepiness and flushing; above 80 mg, one case of serotonin syndrome with another serotonergic drug and one seizure have been reported [label 10]. pregnancy: "there are limited human data on trintellix use during pregnancy", and the class warnings on newborn adaptation problems and persistent pulmonary hypertension are carried over from the ssri labels [label 8.1].

two cautions the label attaches to all of these: rates from trials cannot be compared directly with rates for other drugs, and they may not match what happens in ordinary practice.

what independent research says, in both directions

in favour. in the largest comparison of antidepressants, 522 randomised trials with 116,477 adults, vortioxetine’s odds of response against placebo were 1.66 (credible interval 1.45 to 1.92), and its odds of dropping out for any reason were 1.01 (0.86 to 1.19), which is to say no different from placebo; in head-to-head trials it was named in both of the paper’s favourable groups, among the more effective drugs (odds ratios 1.19 to 1.96) and among the more tolerable (0.43 to 0.77) [cipriani-2018; the vortioxetine figures were read from the paper’s figure 3 and abstract for this site’s comparison pages]. only escitalopram and agomelatine shared that double listing. the label’s own switch trial, in which people with ssri-induced sexual dysfunction did better after switching to vortioxetine than to escitalopram, is the one head-to-head comparison against another antidepressant that the label prints [label 14].

against, or smaller than the badge suggests. the same comparison’s authors wrote that "positive results need to be taken with great caution, because the trials in this network meta-analysis were of short duration", and graded the certainty of the evidence moderate to very low [cipriani-2018]. the fda’s own files tell a flatter story than the journals: a 2022 study of 30 placebo-controlled trials of four antidepressants approved from 2008 to 2013, vortioxetine among them, 13,747 patients in all, found an effect size of 0.24 (0.18 to 0.30) in the fda’s records against 0.29 in the published papers, and that only 7 of the 15 negative trials were published transparently against 15 of 15 positive ones [turner-2022]. the label fits that: its two failed us trials of 5 mg are a sentence, not a table, and the us trials that did succeed showed roughly half the margin the non-us trials showed [label 14]. the cognition claim rests on a processing-speed test and the label says the gain "may reflect improvement in depression" [label 14]. and in 1,156 children and adolescents it did not beat placebo [label 8.4].

on stopping and on sex, where the record is thinner than the label reads. in may 2019 the european regulator’s safety committee ordered a warning on ten ssris and snris that sexual dysfunction can continue after the drug is stopped; vortioxetine was part of the same signal assessment, and the committee’s document says it is "not concerned by the recommendation to update the product information", which is not a finding that it does not happen, and the us label carries no such wording either way [prac-2019]. the label’s "can be abruptly discontinued" sits beside its own discontinuation-scale findings at 15 and 20 mg [label 2.3, 6.1]; the uk guideline nice ng215 says coming off antidepressants can take months and that tapers should get smaller as the dose gets lower [nice-2022], and the royal college of psychiatrists conceded in 2019 that for some people withdrawal is severe and long-lasting [rcpsych-2019]; neither document is specific to vortioxetine. serotonin toxicity, which the label asks people to watch for, has a seven-sign definition built from 2,222 overdoses: inducible muscle jerking, agitation, sweating, tremor, overactive reflexes, and in severe cases rigidity and fever [hunter-2003].

questions people ask

does vortioxetine (Trintellix) have a black box warning?

yes. the fda label carries one boxed warning, on suicidal thoughts and behaviors in children, adolescents and young adults in short-term studies, and states that trintellix is not approved for use in pediatric patients. per 1,000 people treated, the pooled numbers are 14 additional cases under 18, 5 additional at 18 to 24, 1 fewer at 25 to 64 and 6 fewer at 65 and over. vortioxetine’s own two pediatric trials, in 540 children and 616 adolescents, did not beat placebo.

is vortioxetine an ssri?

not exactly. the label describes it as a serotonin reuptake inhibitor, which is what an ssri is, plus two receptor actions, 5-ht3 blockade and 5-ht1a stimulation, and says the contribution of those actions to its antidepressant effect "has not been established". its warnings are the same seven an ssri carries. the two places its label differs from an ssri label are a prospective sexual-function comparison, which it won against escitalopram in people switched for ssri-induced sexual dysfunction and against paroxetine at 10 mg but not 20 mg, and two trials of a processing-speed test, which the label says "may reflect improvement in depression".

what are the most common vortioxetine side effects?

nausea, by a distance: 21%, 26%, 32% and 32% at 5, 10, 15 and 20 mg against 9% on placebo in the 6 to 8 week trials, most often starting in the first day or two, lasting a median of two weeks, and still present at the end of the trial in about 10% of people on 10 to 20 mg. then vomiting (3% to 6% vs 1%), constipation (3% to 6% vs 3%), diarrhea (up to 10% vs 6%) and dizziness (up to 9% vs 6%). the label found no significant effect on weight, blood pressure or heart rate in the trials; weight gain has been reported since marketing at a rate the label cannot estimate.

does vortioxetine cause sexual side effects?

yes, and how many depends on how you count. volunteered reports were 3% to 5% of men and under 1% to 2% of women by dose. measured with a questionnaire in people who started with normal sexual function, 22% to 34% of women and 16% to 29% of men developed sexual dysfunction, against 20% and 14% on placebo. the label’s switch trial found people with ssri-induced sexual dysfunction improved more after switching to vortioxetine than to escitalopram, by 2.2 points on a scale where 2 to 3 points is meaningful. the european regulator’s 2019 persistent-sexual-dysfunction warning covered ten ssris and snris and did not extend to vortioxetine, which its document frames as a scope decision, not a finding.

what happens if you stop vortioxetine suddenly?

the label says trintellix "can be abruptly discontinued" and then reports that people who stopped 15 or 20 mg abruptly had headache, muscle tension, mood swings, sudden outbursts of anger, dizziness and runny nose in the first week. it recommends gradual reduction whenever possible, specifically a step down to 10 mg for one week before stopping 15 or 20 mg. a taper plan is a conversation with a prescriber, not something to decide from a web page.

does vortioxetine help with concentration or brain fog?

two 8-week trials in people with depression found 4.2 to 4.3 more correct answers on a 90-second symbol-matching test at 10 and 20 mg, and 1.8 more in people who reported trouble concentrating. the label attaches its own caveat: the effect "may reflect improvement in depression", no trial compared it with another antidepressant on that test, and neither trial enrolled people whose depression had lifted but whose concentration had not. the approved use is depression in adults, not cognition.

how does vortioxetine compare with escitalopram or sertraline?

in the 2018 comparison of 21 antidepressants, vortioxetine and escitalopram were the two drugs named in both favourable groups, more effective and more tolerable than other antidepressants in head-to-head trials, with vortioxetine’s dropout rate no different from placebo. the same authors cautioned that the trials were short and the certainty moderate to very low, and an fda-file analysis of the newest antidepressants, vortioxetine among them, found a smaller effect in the regulator’s records than in the journals. the escitalopram comparison page on this site lays the two labels side by side.

sources for this section

the library rows link to our one-page summary of each study, with the original paper, its funding and our evidence grade on that page.

1. trintellix (vortioxetine) tablets prescribing information, fda label on dailymed (set id 239215eb-be32-4286-9677-1e5556c6cccf, version 4, effective april 23, 2026; repackaged copy of the takeda label, nda 204447): boxed warning; sections 1, 2.1 to 2.6, 4, 5.1 to 5.8, 6.1 tables 2 and 3, 6.2, 7.1 to 7.3, 8.1, 8.4, 8.5, 10, 12.1, 14 tables 5 and 6
2. drugs@fda, nda 204447 (trintellix, originally brintellix), approved september 30, 2013; the approval record the dossier above cites
3. ahrq medical expenditure panel survey, prescribed medicines public-use files 2014 (hc-168a) to 2024 (hc-254a): vortioxetine has no reportable year (name masked in the public file for 2014, 2015 and 2021 to 2024; fewer than 60 respondents in 2016 to 2020); method on the usage section of this page
4. the antidepressant suicidality warning has an age ceiling most people never hear about (fda boxed warning, read off the label) (library row)
5. cipriani a, et al. comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder. lancet 2018 (the library row is written up for venlafaxine; vortioxetine’s odds ratios were read from the paper’s figure 3 and abstract on 2026-10-11 for this site’s comparison pages) (library row)
6. turner eh, et al. selective publication of antidepressant trials and its influence on apparent efficacy: updated comparisons and meta-analyses of newer versus older trials. plos medicine 2022 (library row)
7. european medicines agency, pharmacovigilance risk assessment committee. recommendations on signals, 13 to 16 may 2019, section 1.3: ssris and snris, persistent sexual dysfunction after drug withdrawal (footnote 6: "clomipramine and vortioxetine were part of the signal assessment but are not concerned by the recommendation to update the product information") (library row)
8. fda, medication errors related to cder-regulated drug products (the brintellix to trintellix name change, recorded to avoid confusion with brilinta), as read for the library (library row)
9. dunkley ej, et al. the hunter serotonin toxicity criteria. qjm 2003 (library row)
10. national institute for health and care excellence. medicines associated with dependence or withdrawal symptoms (ng215), 2022 (library row)
11. royal college of psychiatrists. position statement on antidepressants and depression (ps04/19), 2019 (library row)
12. escitalopram vs vortioxetine: the two labels side by side, on this site

Most-reported reactions

• Nausea2,259
• Fatigue1,212
• Drug ineffective1,130
• Headache1,066
• Anxiety1,039
• Vomiting1,020
• Suicidal ideation942
• Off label use936
• Insomnia925
• Dizziness890