Vortioxetine: Independent Evidence on Depression, Cognition Claims, Side Effects

Table of contents

• Evidence summary
• What vortioxetine is
• How it works
• What it is prescribed for
• What works and what does not
• Benefits by claim
• Risks and all side effects
• All interactions
• Who should avoid vortioxetine
• Dosage and how to take it
• Follow the money: who makes it and who funded the evidence
• Related research
• Frequently asked questions
• Sources and funding notes

Evidence summary

Independent evidence and credibility scorecard

What vortioxetine is

Vortioxetine is an oral antidepressant. Regulators and its maker describe it as "multimodal" because, besides blocking serotonin reuptake as SSRIs do, it acts directly on several serotonin receptors. It was discovered at H. Lundbeck A/S in Copenhagen-Valby, Denmark, where it was first known by the code name Lu AA21004 (Bang-Andersen et al., J Med Chem 2011). Lundbeck developed it in a strategic alliance with Takeda that began in September 2007 (Takeda/Lundbeck 2013 release).

• US: The US application (NDA 204447) was approved on 30 September 2013 as a new molecular entity. The application holder is Takeda (Drugs@FDA). It was first sold as Brintellix. In May 2016 it was renamed Trintellix in the US "after receiving reports of name confusion" with the anti-clotting drug Brilinta (ticagrelor); the formulation, indication and doses did not change (Takeda 2016). The current US label says it is "distributed and marketed by" Takeda Pharmaceuticals America, Inc., and that Trintellix is a trademark of H. Lundbeck A/S used under licence (FDA label).
• EU and UK: Brintellix was authorised in the EU on 18 December 2013. The marketing-authorisation holder is H. Lundbeck A/S, Ottiliavej 9, Valby, Denmark (EMA EPAR). NICE confirms it has a UK marketing authorisation "for the treatment of major depressive episodes in adults" (NICE TA367 section 2). It is a prescription-only medicine in both the UK and the US. The EU product information classes it as a "medicinal product subject to medical prescription" (EMA product information).
• Forms: Film-coated tablets of 5, 10, 15 and 20 mg (EU). The US label lists 5, 10 and 20 mg tablets (EMA SmPC, FDA label).
• Generic status: When we searched Drugs@FDA we found only Takeda's original application and no approved US generic. Lundbeck reports generic competition for Brintellix in Canada, Brazil and China (Lundbeck FY2025). We did not verify whether generics are available in the UK.

How it works

The FDA label is candid: "The mechanism of the antidepressant effect of vortioxetine is not fully understood". It is thought to relate to blocking serotonin reuptake, and the label adds that "5-HT3 receptor antagonism and 5-HT1A receptor agonism" are among its other activities, whose "contribution ... to vortioxetine's antidepressant effect has not been established" (FDA label 12.1).

Lundbeck's discovery paper lists the drug's receptor targets. It is a potent serotonin-transporter blocker (K_i 1.6 nM). It blocks 5-HT3A and 5-HT7 receptors, partially stimulates 5-HT1B receptors, stimulates 5-HT1A receptors, and also binds β1 noradrenergic receptors (Bang-Andersen et al. 2011). The EMA product information says this activity is considered responsible for the "improvement of cognitive function, learning and memory observed with vortioxetine in animal studies". It warns that "caution should be applied when extrapolating animal data directly to man" (EMA SmPC 5.1).

Several properties of the drug affect how it is used:

• It has a long mean half-life of about 66 hours, and steady-state levels are usually reached within two weeks.
• Food does not affect absorption.
• It is broken down mainly by the liver enzyme CYP2D6. People who are genetically poor CYP2D6 metabolisers have about twice the blood level (FDA label 12.3).

The long half-life is one likely reason why stopping it has produced fewer withdrawal symptoms in trials than stopping short-acting antidepressants.

What it is prescribed for

Licensed use. The only licensed use is depression in adults. In the US that is "major depressive disorder (MDD) in adults"; in the EU and UK it is "major depressive episodes in adults" (FDA label, EMA). It is not licensed for anxiety disorders, for use in children, or as a treatment for cognitive impairment. The FDA refused to create a cognitive indication (see below).

Where guidelines place it:

• NICE (England): TA367 (November 2015, reviewed in 2018 with no change) recommends vortioxetine "as an option for treating major depressive episodes in adults whose condition has responded inadequately to 2 antidepressants within the current episode". In practice that makes it a third-line option (NICE TA367, overview). The 2022 depression guideline repeats this position (rec 1.9.7). It also says SSRIs should usually be the first choice, and that antidepressants should not routinely be the first-line treatment for less severe depression (NICE NG222).
• CANMAT (Canada, 2023): CANMAT lists vortioxetine among 8 antidepressants with "evidence for superior response", adding that such differences "are in the range of 5 to 10 percentage points". It places vortioxetine among the drugs with lower rates of sexual side effects and "low or minimal" discontinuation risk. It says that vortioxetine, bupropion and SNRIs "may have superior efficacy for cognitive dysfunction compared to SSRIs" (Lam et al., CANMAT 2023). Note that CANMAT took no industry money as an organisation, but many of its authors declare fees from Lundbeck and Takeda.
• Germany (IQWiG, 2015): IQWiG concluded that "no added benefit can be derived" versus the comparator set by Germany's G-BA (an SSRI such as citalopram). The manufacturer had identified 14 vortioxetine and 10 citalopram trials but used only 3 and 4 of them in its indirect comparison, which IQWiG called "not convincingly justified and inadequate" (IQWiG 2015).
• WHO: WHO's mhGAP depression recommendation names SSRIs and amitriptyline, not vortioxetine (WHO mhGAP 2023).

What works and what does not

Benefits by claim

1. Depression in adults: a real but small effect

The most independent summary is the 2017 Cochrane review by Koesters and colleagues. It covered 15 randomised trials with 7,746 participants: seven were placebo-controlled and eight compared vortioxetine with SNRIs (duloxetine or venlafaxine). Against placebo, vortioxetine gave:

• a response RR of 1.35 (95% CI 1.22 to 1.49; 14 studies, 6,220 participants);
• a remission RR of 1.32 (95% CI 1.15 to 1.53);
• a mean MADRS difference of −2.94 points (95% CI −4.07 to −1.80).

In its summary-of-findings table, that means about 480 responders per 1,000 on vortioxetine against 356 per 1,000 on placebo. The quality of evidence was "low for response and remission and very low for depressive symptoms". More people stopped vortioxetine because of side effects (RR 1.41, 95% CI 1.09 to 1.81), and fewer stopped because it was not working (RR 0.56) (Koesters et al. 2017). The authors' judgement is that "the clinical relevance of these effects is uncertain, because of the small magnitude of effect, the poor quality of evidence and the highly selected participants enrolled" (full text).

The manufacturers' own pooled analysis points the same way, with somewhat more favourable numbers. Across 11 trials, MADRS reductions over placebo were −2.27, −3.57 and −4.57 points at 5, 10 and 20 mg, while 15 mg (−2.60) did not separate from placebo (Thase et al. 2016; co-authors include Takeda staff). The EMA summary gives the same pattern. It reports responder rates of 46–49% on vortioxetine versus 34% on placebo, and says efficacy was shown "across 9 of the 12 studies" (EMA SmPC 5.1). An independent Chinese dose-response meta-analysis of 16 studies estimated the 50% effective dose at 4.37 mg a day. It found that acceptability, tolerability and safety declined as the dose went up (Yang et al. 2024; funded by China's National Key R&D Program).

How big is a 3-point MADRS difference? The MADRS runs from 0 to 60 points, and trial participants typically start around 30–34 points. The 2–3 point average gap between drug and placebo is similar to what independent analyses find for antidepressants in general. The FDA's own pooled data put the average difference at about 1.75 points on the older HAM-D scale (Stone et al., BMJ 2022). In the vortioxetine trials, people on placebo improved by 10–15 MADRS points on average, which shows how much of the improvement seen in trials happens without the drug (FDA label Table 5). Averages hide variation between people: some benefit substantially and others not at all.

The US trials were weaker than the non-US trials. The FDA label's efficacy table is worth reading closely:

• In the three non-US studies, differences from placebo ranged from −4.1 to −7.1 points.
• In the two US studies, 15 mg (−1.5, CI −3.9 to 0.9) and 10 mg (−2.2, CI −4.5 to 0.1) did not reach significance, and only 20 mg did (−2.8 and −3.6).
• The label also states that "two studies of the 5 mg dose in the U.S. ... failed to show effectiveness" (FDA label, section 14).

Differences between regions in placebo response are common in antidepressant trials. The pattern is a reminder that the headline figures depend on which trials are pooled.

2. Compared with other antidepressants: no proven advantage

• Versus SNRIs (Cochrane): very low-quality evidence showed "no clinically significant difference" for response (RR 0.91, 95% CI 0.82 to 1.00). There was a small MADRS difference favouring SNRIs (MD 1.52, 95% CI 0.50 to 2.53). Vortioxetine "may be less effective than duloxetine" for response (RR 0.86, 95% CI 0.79 to 0.94), but fewer people reported adverse effects on it than on duloxetine (RR 0.89) (Koesters et al. 2017).
• Versus SSRIs: The Cochrane authors "were unable to identify any study" comparing vortioxetine with antidepressants from other classes, such as SSRIs, for acute depression. It called this "a major limitation", because SSRIs are the usual first-line treatment (Cochrane).
• Network meta-analyses: The 2018 Cipriani analysis, which is publicly funded, grouped vortioxetine with the drugs that were more effective in head-to-head studies (ORs 1.19–1.96 for that group) and more tolerable (ORs 0.43–0.77). However, the certainty of evidence was "low to very low for most comparisons involving vortioxetine" (Cipriani et al. 2018). An Austrian network meta-analysis concluded that the evidence "does not indicate greater benefits or fewer harms" for vortioxetine than for other second-generation antidepressants (Wagner et al. 2018).
• Versus agomelatine (REVIVE): In people who had not responded well to an SSRI or SNRI, vortioxetine beat agomelatine by 2.2 MADRS points at week 8 (Montgomery et al. 2014; Lundbeck-sponsored, with Lundbeck employees as co-authors). NICE judged REVIVE to be "of good quality". However, because agomelatine is little used in the NHS, it considered the comparison "of limited relevance to clinical practice in England" (NICE TA367 4.5).

NICE noted that one academic meta-analysis (Pae et al., which NICE said was "not sponsored by the company") concluded vortioxetine was "more effective than placebo but the difference was of doubtful clinical significance". A company-sponsored analysis (Llorca et al.) called its efficacy "comparable or favourable". NICE's overall conclusion was that "no convincing evidence existed to show that vortioxetine was more or less effective than other antidepressants" (NICE TA367 4.10; Pae et al. 2015). NICE still recommended it as a third-line option. When equal effectiveness was assumed, the cost-effectiveness ratios were "£9,000 per QALY gained or below" against other third-line antidepressants, and the evidence suggested people tolerate vortioxetine better in the short term (NICE 4.11 and 4.19).

3. The cognitive claim: what the evidence actually shows

Much of vortioxetine's marketing rests on "cognitive symptoms": slowed thinking, poor concentration and forgetfulness, which are common in depression. The core evidence comes from two 8-week, manufacturer-run trials that used the Digit Symbol Substitution Test (DSST). The DSST measures processing speed: how many symbol–number pairs a person can match correctly in 90 seconds.

• FOCUS (US label "Study 7"): 602 adults with recurrent depression (McIntyre et al. 2014). The DSST improvement over placebo was 4.2 symbols at 10 mg and 4.3 at 20 mg. Lundbeck sponsored the study and "was involved in the study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication". Two of the three authors were Lundbeck employees.
• CONNECT (US label "Study 8"): adults with depression who reported cognitive problems (Mahableshwarkar et al. 2015). The DSST improvement over placebo was 1.8 symbols (95% CI 0.3 to 3.2). The lead author and two co-authors were Takeda employees.

To put these numbers in context, the label notes that healthy 45- to 54-year-olds score about 50 on the DSST, with a standard deviation of 15 (FDA label, Table 6). A 1.8–4.3 symbol gain is therefore roughly an eighth to a quarter of one standard deviation among healthy adults. Regulators and independent critics have raised four limits on this evidence:

1. It may just be the depression improving. The FDA label states: "The effects observed on DSST may reflect improvement in depression." Neither study included people whose depression had lifted but who still had concentration problems (FDA label). The company's own meta-analysis tried to separate the effects statistically. After adjusting for mood improvement, the standardised effect size fell from 0.35 to 0.24 (EMA SmPC; McIntyre et al. 2016, with Lundbeck and Takeda employees as co-authors).
2. There is no comparison with other antidepressants. The label states: "Comparative studies have not been conducted to demonstrate a therapeutic advantage over other antidepressants on the DSST." Duloxetine was included as a reference arm in some trials, but only for internal validation.
3. The results on how people rated their own thinking were mixed. In one study vortioxetine beat placebo on the Perceived Deficits Questionnaire (−14.6 vs −10.5), but it "did not separate from placebo" on the Cognitive and Physical Functioning Questionnaire (−8.1 vs −6.9, p=0.086) (EMA SmPC 5.1).
4. Independent critics say the trials were short and narrow. At the 2016 FDA advisory meeting, the National Center for Health Research raised several concerns: whether the DSST is a meaningful measure of cognition, the 8-week duration, the exclusion of people over 65, and a trial population that was more than 85% white. It concluded there was "insufficient data to claim that vortioxetine is effective in providing a meaningful improvement in cognitive dysfunction" (NCHR testimony).

What regulators did:

• February 2016: the FDA's Psychopharmacologic Drugs Advisory Committee voted 8 to 2 that the companies had presented substantial evidence for "certain aspects of cognitive dysfunction".
• March 2016: the FDA nonetheless issued a complete response letter, meaning it did not approve the application (Lundbeck/Takeda 2016).
• June 2017: the FDA issued a second complete response letter on a revised application (Lundbeck/Takeda 2017).
• May 2018: the DSST data were added to the "clinical studies" section of the US label, together with the caveats above. This is data in the label, not an approved indication for cognitive dysfunction (Lundbeck/Takeda 2018; Drugs@FDA).

The companies' public statements did not give the FDA's reasons for either rejection, so we do not state them.

What NICE and the independent reviews concluded:

• Lundbeck argued to NICE that vortioxetine "reduces cognitive dysfunction independent of its effect on MADRS". NICE accepted that it "may be a valuable treatment option" for people with cognitive dysfunction, but noted that the quality-of-life (EQ-5D) data from REVIVE "did not suggest" a notable difference between treatments. It concluded that all benefits were already captured in the model (NICE TA367 4.21).
• An independent Taiwanese meta-analysis of 6 trials (1,782 patients) found improvements in DSST and in how patients rated their own thinking. It called for "further studies with longer follow-up" (Huang et al. 2022; no conflicts declared). Every trial it pooled came from the same manufacturer-sponsored programme.

Our reading: vortioxetine does speed up performance on a timed test in depressed adults over 8 weeks, and the effect is consistent across company trials. What is unproven is whether this is a meaningful, lasting benefit to thinking that goes beyond mood improvement, and whether any other antidepressant would do the same. We grade the cognitive claim Weak.

4. Relapse prevention

In the EU relapse-prevention study, people in remission after 12 weeks of open-label vortioxetine were randomised to stay on it or switch to placebo. The risk of relapse was twice as high on placebo (HR 2.0, p=0.004) (EMA SmPC). A US maintenance study randomised 580 remitted patients and found a longer time to recurrence at 5, 10 and 20 mg (FDA label). This randomised withdrawal design is standard, and it has a known weakness: part of the "relapse" in the placebo group may be discontinuation effects after the drug is stopped abruptly.

Risks and all side effects

In the 6–8 week US trials, people stopped vortioxetine because of side effects at rates of 5%, 6%, 8% and 8% at 5, 10, 15 and 20 mg, against 4% on placebo. Nausea was the most common reason (FDA label 6.1). The table below combines the FDA and EU labels.

Weight. In the 6–8 week trials and the 6-month maintenance phase, vortioxetine "had no significant effect on body weight" compared with placebo. Weight gain has nonetheless been reported after marketing (FDA label).

Sleep. The EU label states that vortioxetine "did not increase the incidence of insomnia or somnolence relative to placebo" in trials, although insomnia appears among the post-marketing reports (EMA SmPC).

Discontinuation (withdrawal) symptoms: the labels differ.

• US label: after abrupt stopping of 15–20 mg, "some patients experienced discontinuation symptoms such as headache, muscle tension, mood swings, sudden outbursts of anger, dizziness, and runny nose in the first week". It recommends dropping to 10 mg for a week first (FDA label).
• EU label: in trials there was "no clinically relevant difference to placebo" in discontinuation symptoms. It does, however, list post-marketing cases of dizziness, headache, electric-shock sensations, sleep disturbance, nausea, anxiety, irritability and tremor (EMA SmPC 4.8).
• CANMAT: classes vortioxetine as "low or minimal" discontinuation risk (CANMAT 2023).

For context, an independent meta-analysis across antidepressants estimated placebo-adjusted discontinuation symptoms at about 15%, and severe symptoms at 2.8% versus 0.6% on placebo (Henssler et al., Lancet Psychiatry 2024; no funding and no competing interests).

Overdose. Experience is limited. Doses of 40–75 mg caused more nausea, dizziness, diarrhoea, itching, sleepiness and flushing. A case of serotonin syndrome has been reported with overdoses above 80 mg (FDA label 10).

Heart and blood pressure. The FDA label reports no clinically significant effects on blood pressure or heart rate in placebo-controlled studies (FDA label).

All interactions

Who should avoid vortioxetine

• Contraindicated: people who are allergic to vortioxetine or any ingredient (anaphylaxis, angioedema and urticaria have been reported), and anyone taking or recently taking an MAOI, linezolid or intravenous methylene blue (FDA label 4, EMA SmPC 4.3).
• Children and adolescents: not approved. Both paediatric trials failed, and the EU label says it "should not be used" under 18 (EMA SmPC).
• Bipolar disorder or a history of mania: needs screening and caution, because vortioxetine may trigger a mixed or manic episode (FDA label 5.4).
• Epilepsy or a history of seizures, bleeding disorders, narrow-angle glaucoma or raised eye pressure, and cirrhosis: use only with caution (EMA SmPC 4.4).
• Pregnancy: human data are limited. As with SSRIs and SNRIs, exposure late in pregnancy can cause complications in the newborn (breathing difficulty, feeding problems, jitteriness) and may raise the risk of persistent pulmonary hypertension of the newborn (PPHN). Use in the month before delivery may raise the risk of postpartum haemorrhage. In animal studies, rats and rabbits showed developmental delay at doses 10–15 times the maximum human dose, but no malformations (FDA label 8.1). Stopping an antidepressant during pregnancy also carries a risk of relapse, so decisions belong with the prescriber.
• Breastfeeding: the EU label says that limited data show vortioxetine passes into breast milk in small amounts, with an estimated relative infant dose below 2%, and that no harmful effects were seen in infants. It adds that "a risk to the breastfeeding child cannot be excluded" (EMA SmPC 4.6).
• Older adults: the EU label says to start at 5 mg in people aged 65 and over, and to take care above 10 mg because data are limited. At 20 mg, nausea and constipation were more common in this age group, and older people are at greater risk of hyponatraemia (EMA SmPC). We did not verify whether vortioxetine is named specifically in the American Geriatrics Society Beers Criteria.
• Liver or kidney impairment: the US label found no effect on clearance, and the EU label says no dose adjustment is needed. The EU label still advises caution because data are limited (FDA label 12.3, EMA SmPC 4.4).
• CYP2D6 poor metabolisers: the US label caps the dose at 10 mg a day (FDA label 2.5).

Dosage and how to take it

Sources: EMA SmPC 4.2, FDA label section 2. NICE lists the same UK dosing (NICE TA367 section 2).

How long before it works. In the trials, an effect "was generally observed starting at Week 2 and increased in subsequent weeks", with the full effect "generally not seen until Study Week 4 or later" (FDA label 14). NICE's depression guideline says people starting an antidepressant should be reviewed within 2 weeks, or within 1 week if they are aged 18–25 or at risk of suicide (NICE NG222).

How to stop. Only stop under supervision.

• US label: vortioxetine "can be discontinued abruptly", but at 15–20 mg it recommends reducing to 10 mg a day for one week before stopping completely.
• EU label: a gradual reduction "may be considered", but "there is insufficient data to provide specific recommendations for a tapering schedule" (FDA label 2.3, EMA SmPC 4.2).
• NICE's general approach for all antidepressants: reduce the dose step by step, "at each step prescribing a proportion of the previous dose (for example, 50% of previous dose)", with smaller reductions as the dose gets lower. The pace should take account of the drug's half-life (NICE NG222 1.4.16). Vortioxetine's half-life of about 66 hours is long.

Missed doses. We did not find official missed-dose wording in the documents we reviewed. Ask the pharmacist or check the patient information leaflet.

Follow the money: who makes it and who funded the evidence

Who owns and sells it:

• Originator: H. Lundbeck A/S, Valby (Copenhagen), Denmark. Lundbeck scientists discovered the molecule (Bang-Andersen et al. 2011), and Lundbeck holds the EU marketing authorisation (EMA).
• Lundbeck's owner: the Lundbeck Foundation, which "owns about 69% of the share capital and controls approximately 77% of the total voting rights" (Lundbeck shareholders page). The Foundation says it gives out more than DKK 500 million a year for Danish health research, mostly on the brain (Lundbeck Foundation). Profits from vortioxetine therefore help fund a large Danish brain-research charity.
• US partner: Takeda (Japan) has been Lundbeck's alliance partner since September 2007. It holds the US application (NDA 204447), and the US clinical programme "was conducted jointly by Lundbeck and Takeda" (Takeda/Lundbeck 2013, 2018 release). Lundbeck transferred its US sales operations for Trintellix to Takeda on 1 January 2025 (Lundbeck FY2025). The current US label names Takeda Pharmaceuticals America, Inc. (Cambridge, Massachusetts) as distributor and marketer (FDA label).
• Generics: none approved in the US when we checked Drugs@FDA. Lundbeck reports generic competition in Canada, Brazil and China.

Revenue. Lundbeck's audited 2025 release reports Brintellix/Trintellix revenue of DKK 4,554 million, down 4% at constant exchange rates. That is roughly 18% of Lundbeck's total revenue of DKK 24,630 million, making it the company's second-largest product after Rexulti (DKK 6,205 million). By region (Lundbeck FY2025 release):

• US: DKK 1,293 million, down 15%. The fall reflects the handover to Takeda and changes to Medicare Part D.
• Europe: DKK 2,008 million, up 15%. Lundbeck cites market shares of 6.4% in Spain, 5.7% in Italy and 4.5% in France.
• International Operations: DKK 1,253 million, down 12%, hit by generic competition.

List price (UK, 2015). NICE recorded £27.72 for 28 tablets at any strength (company submission, excluding VAT). Actual NHS prices may differ (NICE TA367). We did not verify a current UK price.

Who funded the evidence:

• Efficacy trials: the Cochrane authors state that "all studies were sponsored by the pharmaceutical companies that manufactures vortioxetine (Lundbeck, Takeda)", and two of the included trials were unpublished (Koesters et al. 2017). In the trials we checked, Lundbeck generated the randomisation lists (FOCUS, REVIVE), and company employees were co-authors.
• Cognition trials: Lundbeck sponsored FOCUS "as part of a joint clinical development program with the Takeda Pharmaceutical Company" and was involved in its design, analysis, writing and the decision to publish. The lead author of CONNECT and two co-authors were Takeda employees. The pooled cognitive meta-analysis was written with Lundbeck and Takeda employees (FOCUS, CONNECT, McIntyre 2016).
• Independent reviews: the Cochrane review had no funding and no declared interests. NICE and IQWiG are public bodies. Cipriani 2018 was publicly funded, but some co-authors declared fees from antidepressant makers, including Lundbeck. At least one recent positive review (Berardelli et al. 2025, which concluded vortioxetine "should be considered efficacious as a first- and second-line therapy") has authors declaring fees from Lundbeck, Takeda and other makers (Berardelli et al. 2025).

What this means. Almost all the primary data on vortioxetine come from its makers. That is normal for a patented drug, and it does not make the results false. The randomised, double-blind design and the regulator review of raw data are real safeguards. But in our reading, the independent reviewers (Cochrane, NICE, IQWiG and the Austrian network meta-analysis) consistently reached more cautious conclusions than company-authored analyses and several commercially conflicted academic reviews. The field-wide problem of publication bias in antidepressant trials is well documented (Turner et al., NEJM 2008). Vortioxetine is also one of the drugs for which Cipriani's team obtained unpublished data (Cipriani 2018).

Documented regulatory events (factual record only):

• May 2016: after reports of name confusion with the anti-clotting drug Brilinta, the US brand was renamed Trintellix (Takeda 2016).
• 2016–2017: the FDA twice declined applications to add cognitive data to the label before accepting a version in 2018.

We found no sourced evidence of misconduct relating to vortioxetine, and we make no such claim.

Related research

• Stress, anxiety and depression: the evidence-based prevention guide
• Supplements for stress, anxiety and depression: what the evidence shows
• St John's wort: never combine it with vortioxetine without medical advice
• Saffron for depression
• Ashwagandha: evidence and safety
• Magnesium · L-theanine
• Sleep prevention guide · Sleep supplements evidence · Melatonin
• Other antidepressants: Sertraline · Escitalopram · Duloxetine · Venlafaxine · Agomelatine · Bupropion · Mirtazapine

Frequently asked questions

Sources and funding notes

• FDA Trintellix prescribing information (DailyMed setid 1a5b68e2…; version dated 5 March 2025, read via openFDA): US regulator-approved label. Takeda is the label holder; the FDA's review work is part-funded by industry user fees.
• Drugs@FDA, NDA 204447: US government record of approval and supplements.
• EMA Brintellix EPAR and product information (SmPC): EU regulator. About 91.5% of the EMA budget comes from fees (EMA funding). Lundbeck (Denmark) is the marketing-authorisation holder.
• NICE TA367 (2015): recommendations, technology, committee considerations. UK government-funded body; evidence submitted by Lundbeck and reviewed by an independent evidence review group.
• NICE NG222, Depression in adults (2022): UK government-funded guideline. We did not check individual committee declarations.
• IQWiG press release, 3 August 2015: German statutory health-technology assessment institute; assessed the manufacturer's dossier.
• Koesters M et al., Vortioxetine for depression in adults, Cochrane Database Syst Rev 2017 (PubMed): Academic authors led from Ulm University, Germany. Sources of support: none. All declared no interests. All included trials were sponsored by Lundbeck or Takeda.
• Cipriani A et al., Lancet 2018: funded by UK NIHR Oxford Health BRC and the Japan Society for the Promotion of Science. Some co-authors declared fees from antidepressant makers, including Lundbeck. 78% of included trials were industry-funded.
• Wagner G et al., J Affect Disord 2018: Danube University Krems (Austria) and UNC (US). No conflicts in the PubMed record; funding not listed there.
• Pae CU et al., J Psychiatry Neurosci 2015: Catholic University of Korea / Duke University. NICE described it as not company-sponsored; PubMed COI field "None".
• Yang X et al., Psychiatry Clin Neurosci 2024: West China Hospital, Sichuan University. Funded by the National Key R&D Program of China; no conflicts listed.
• Huang IC et al., Int J Neuropsychopharmacol 2022: Taipei Medical University (Taiwan). No conflicts declared; pooled trials were manufacturer-sponsored.
• Thase ME et al., Eur Neuropsychopharmacol 2016: company-authored pooled analysis (co-authors include Takeda Development Center Americas staff).
• McIntyre RS et al., Int J Neuropsychopharmacol 2016: cognitive meta-analysis. Two authors are Lundbeck employees and one a Takeda employee; the lead author declared consulting and speaker fees from Takeda and Lundbeck.
• McIntyre RS et al., FOCUS trial, Int J Neuropsychopharmacol 2014: sponsored by Lundbeck in a joint programme with Takeda; the sponsor was involved in design, analysis and writing.
• Mahableshwarkar AR et al., CONNECT trial, Neuropsychopharmacology 2015: lead and two co-authors are Takeda employees.
• Montgomery SA et al., REVIVE trial, Hum Psychopharmacol 2014: Lundbeck-run (randomisation by Lundbeck; two authors are Lundbeck employees).
• Berardelli I et al., J Psychopharmacol 2025: academic (Sapienza, Rome). Authors declare fees from Lundbeck, Takeda and others.
• Lam RW et al., CANMAT 2023 update: no industry funding to the organisation; many authors declare Lundbeck, Takeda and other industry ties.
• Bang-Andersen B et al., J Med Chem 2011: Lundbeck discovery paper (authors at H. Lundbeck A/S).
• Stone MB et al., BMJ 2022: FDA staff plus academic authors; "no support from any organization".
• Henssler J et al., Lancet Psychiatry 2024: Germany; no funding; no competing interests.
• Turner EH et al., NEJM 2008: publication bias in antidepressant trials (US academic/VA); funding not verified.
• WHO mhGAP guideline, 2023: multilateral public-health body, with written declarations of interest.
• National Center for Health Research, FDA testimony, 3 February 2016: US non-profit that says it does not accept industry funding.
• Takeda/Lundbeck FDA approval release, 2013; Takeda name-change release, 2016; complete response letter release, 2016; complete response letter release, 2017; label update release, 2018: company press releases (tier 4), used only for dates and corporate facts.
• Lundbeck corporate release FY2025: company financial disclosure (Denmark), used for revenue figures.
• Lundbeck shareholders page and Lundbeck Foundation, About us: company and foundation self-descriptions.

Last reviewed: 26 September 2026. Educational information from Pure City Research, not medical advice. Medicine decisions belong with a qualified prescriber.