Vortioxetine side effects: what 16,901 FDA adverse event reports show
Drug class
Not stated in label
Brand names
Trintellix
Who reports
16,901 reports · 48% serious · 1,001 with death outcome · 70% female
Used for
TRINTELLIX is indicated for the treatment of major depressive disorder (MDD) in adults. TRINTELLIX is indicated for the treatment of major depressive disorder (MDD) in adults ( 1 , 14 ).
What it is
TRINTELLIX is an immediate-release tablet for oral administration that contains the beta (β) polymorph of vortioxetine hydrobromide (HBr), an antidepressant. Vortioxetine HBr is known chemically as 1-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]-piperazine, hydrobromide.
Boxed warning
SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1) ] .
Causality screen of the 40 strongest signals
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 1,015 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Dystonic tremor | 30 | 654.8 420.4–1,020.0ROR 656.0 · χ² 12,330 / p <1e-300 | 335.4 EB05 246.2 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious n=30 · ♀ 0% (drug 70%) | not reported in cached trials |
| Decompression sickness | 17 | 611.2 341.5–1,093.8ROR 611.8 · χ² 6,503 / p <1e-300 | 279.6 EB05 184.9 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=17 | not reported in cached trials |
| Neuroglycopenia | 28 | 433.2 281.6–666.5ROR 433.9 · χ² 8,598 / p <1e-300 | 262.8 EB05 190.8 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious n=28 · ♀ 100% (drug 70%) · 100% clinician | not reported in cached trials |
| Amaurosis fugax | 219 | 319.8 275.8–370.8ROR 324.0 · χ² 54,919 / p <1e-300 | 248.2 EB05 221.8 · IC025 +7.1 3/3 methods agree | Not in label — unassessed | serious n=219 · 93% clinician | not reported in cached trials |
| Feeling guilty | 173 | 186.0 158.6–218.1ROR 187.9 · χ² 27,468 / p <1e-300 | 158.8 EB05 139.9 · IC025 +6.5 3/3 methods agree | Not in label — unassessed | serious n=12 · 93% consumer | not reported in cached trials |
| Peripheral circulatory failure | 33 | 108.7 76.2–155.2ROR 108.9 · χ² 3,136 / p <1e-300 | 94.6 EB05 70.5 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious n=33 · ♀ 100% (drug 70%) · 100% clinician | not reported in cached trials |
| Painful ejaculation | 12 | 68.5 38.3–122.6ROR 68.6 · χ² 694 / p 4e-153 | 59.2 EB05 36.1 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=9 | not reported in cached trials |
| Alcoholic | 10 | 65.0 34.4–122.8ROR 65.1 · χ² 539 / p 1e-119 | 55.6 EB05 32.3 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Central pain syndrome | 13 | 63.8 36.5–111.4ROR 63.9 · χ² 705 / p 1e-155 | 56.0 EB05 34.8 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Multiple drug therapy | 34 | 63.4 45.0–89.5ROR 63.6 · χ² 1,928 / p <1e-300 | 58.5 EB05 43.8 · IC025 +4.4 3/3 methods agree | Reporting / coding artifact | serious n=34 · ♀ 100% (drug 70%) · 100% clinician | not reported in cached trials |
| Urinary tract disorder | 195 | 56.1 48.7–64.8ROR 56.8 · χ² 10,048 / p <1e-300 | 53.5 EB05 47.5 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | serious n=194 · 94% clinician | not reported in cached trials |
| Hyperphagia | 168 | 54.8 47.0–63.9ROR 55.4 · χ² 8,446 / p <1e-300 | 52.2 EB05 45.9 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | 100% consumer | not reported in cached trials |
| Activation syndrome | 12 | 44.0 24.8–78.3ROR 44.1 · χ² 447 / p 2e-99 | 40.1 EB05 24.4 · IC025 +3.0 3/3 methods agree | Labeled (related wording) related wording | serious n=10 | not reported in cached trials |
| Myoglobinuria | 16 | 39.1 23.8–64.3ROR 39.2 · χ² 539 / p 1e-119 | 36.4 EB05 23.8 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=16 | not reported in cached trials |
| Haemorrhagic stroke | 239 | 38.9 34.2–44.2ROR 39.4 · χ² 8,509 / p <1e-300 | 37.6 EB05 33.8 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious PRR 45.4 · 92% clinician | not reported in cached trials |
| Abulia | 22 | 30.7 20.1–46.8ROR 30.7 · χ² 587 / p 5e-130 | 29.3 EB05 20.4 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=17 | not reported in cached trials |
| Ocular discomfort | 244 | 28.5 25.1–32.3ROR 28.9 · χ² 6,298 / p <1e-300 | 27.8 EB05 25.0 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=237 | not reported in cached trials |
| Dissociative disorder | 15 | 26.5 15.9–44.2ROR 26.5 · χ² 336 / p 3e-75 | 25.2 EB05 16.1 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Apathy | 287 | 25.0 22.2–28.0ROR 25.4 · χ² 6,452 / p <1e-300 | 24.5 EB05 22.2 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious PRR 3.3 · 96% consumer | not reported in cached trials |
| Cardiospasm | 10 | 22.6 12.1–42.2ROR 22.6 · χ² 182 / p 9e-42 | 21.0 EB05 11.6 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Generalised oedema | 203 | 20.8 18.1–23.8ROR 21.0 · χ² 3,738 / p <1e-300 | 20.4 EB05 18.2 · IC025 +4.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 26.8 · 94% clinician | not reported in cached trials |
| Libido decreased (lower sex drive) | 203 | 20.6 18.0–23.7ROR 20.9 · χ² 3,712 / p <1e-300 | 20.3 EB05 18.0 · IC025 +4.0 3/3 methods agree | Labeled (related wording) related wording | serious PRR 5.1 · 92% consumer | not reported in cached trials |
| Blood cholesterol decreased | 30 | 20.3 14.1–29.1ROR 20.3 · χ² 522 / p 7e-116 | 19.7 EB05 14.4 · IC025 +3.3 3/3 methods agree | Lab value / disease marker | serious n=30 · ♀ 100% (drug 70%) · 100% clinician | not reported in cached trials |
| Perineal pain | 11 | 19.9 11.0–36.1ROR 19.9 · χ² 176 / p 2e-40 | 18.5 EB05 10.3 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Feelings of worthlessness | 20 | 19.1 12.3–29.7ROR 19.1 · χ² 320 / p 7e-72 | 18.4 EB05 12.4 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=17 | not reported in cached trials |
| Product ineffective | 10 | 18.2 9.7–33.9ROR 18.2 · χ² 143 / p 2e-33 | 16.6 EB05 8.5 · IC025 +2.2 3/3 methods agree | Reporting / coding artifact | serious n=10 | not reported in cached trials |
| Labelled drug-drug interaction issue | 20 | 17.9 11.5–27.8ROR 17.9 · χ² 298 / p 4e-67 | 17.2 EB05 11.5 · IC025 +2.9 3/3 methods agree | Reporting / coding artifact | serious n=17 | not reported in cached trials |
| Drug-disease interaction | 10 | 17.7 9.5–33.0ROR 17.7 · χ² 139 / p 2e-32 | 16.0 EB05 8.2 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Reduced facial expression | 14 | 17.6 10.4–29.7ROR 17.6 · χ² 199 / p 1e-45 | 16.5 EB05 9.9 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious n=13 | not reported in cached trials |
| Palmoplantar keratoderma | 10 | 17.4 9.3–32.5ROR 17.4 · χ² 137 / p 6e-32 | 15.8 EB05 8.0 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Gastric polyps | 31 | 17.2 12.1–24.5ROR 17.2 · χ² 451 / p 3e-100 | 16.7 EB05 12.2 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=31 · ♀ 100% (drug 70%) · 100% clinician | not reported in cached trials |
| Head discomfort | 241 | 17.2 15.1–19.5ROR 17.4 · χ² 3,609 / p <1e-300 | 16.9 EB05 15.2 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious PRR 34.2 | not reported in cached trials |
| Sexual dysfunction | 159 | 17.1 14.6–20.0ROR 17.3 · χ² 2,363 / p <1e-300 | 16.8 EB05 14.8 · IC025 +3.7 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 11.8 · ♀ 39% (drug 70%) | not reported in cached trials |
| Anorgasmia | 37 | 17.1 12.4–23.6ROR 17.1 · χ² 537 / p 5e-119 | 16.7 EB05 12.5 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=19 · 73% consumer | not reported in cached trials |
| Serotonin syndrome | 248 | 16.3 14.4–18.4ROR 16.5 · χ² 3,496 / p <1e-300 | 16.0 EB05 14.4 · IC025 +3.8 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 19.4 | not reported in cached trials |
| Alcohol use | 46 | 15.5 11.6–20.7ROR 15.5 · χ² 602 / p 4e-133 | 15.1 EB05 11.7 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | 100% consumer | not reported in cached trials |
| Anger | 393 | 14.5 13.1–16.0ROR 14.8 · χ² 4,877 / p <1e-300 | 14.3 EB05 13.2 · IC025 +3.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.4 · 85% consumer | not reported in cached trials |
| Intrusive thoughts | 13 | 14.4 8.4–24.9ROR 14.4 · χ² 148 / p 3e-34 | 13.1 EB05 7.3 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious n=8 | not reported in cached trials |
| Binge eating | 12 | 14.0 7.9–24.7ROR 14.0 · χ² 131 / p 2e-30 | 12.4 EB05 6.7 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious n=5 | not reported in cached trials |
| Altered state of consciousness | 240 | 14.0 12.3–15.8ROR 14.1 · χ² 2,843 / p <1e-300 | 13.8 EB05 12.4 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 16.8 · ♀ 39% (drug 70%) · 92% clinician | not reported in cached trials |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Vortioxetine as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (0 of 40 signal terms matched).
- NCT02371980 — Vortioxetine, 5, 10, and 20 mg, Relapse Prevention Study in Adults With Major Depressive Disorder (MDD) (N=1106, PHASE4; 23 AE terms posted; arms: Open-label: Vortioxetine 10 mg; Double-blind: Placebo; Double-blind: Vortioxetine 5 mg; Double-blind: Vortioxetine 10 mg)
- NCT01152996 — Safety and Tolerability of Vortioxetine (LuAA21004) - Open Label Extension Study (N=1075, PHASE3; 40 AE terms posted; arms: Vortioxetine)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Nausea | 2,259 | 3.6 3.4–3.7ROR 4.0 · χ² 4,300 / p <1e-300 | 3.5 EB05 3.4 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.1 | NCT02371980: 13/144 (9.0%) on Vortioxetine; 2/151 (1.3%) control |
| Fatigue (tiredness) | 1,212 | 1.9 1.8–2.0ROR 2.0 · χ² 567 / p 1e-125 | 1.9 EB05 1.8 · IC025 +0.9 | Not in label — unassessed | serious PRR 2.1 | not reported in cached trials |
| Drug ineffective (drug did not work) | 1,130 | 1.1 1.0–1.1ROR 1.1 · χ² 5 / p 0.016 | 1.1 EB05 1.0 · IC025 -0.0 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 2.0 | not reported in cached trials |
| Headache | 1,066 | 2.1 2.0–2.2ROR 2.2 · χ² 642 / p 8e-142 | 2.1 EB05 2.0 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.8 | NCT02371980: 91/1,106 (8.2%) on Vortioxetine |
| Anxiety | 1,039 | 4.5 4.3–4.8ROR 4.8 · χ² 2,881 / p <1e-300 | 4.5 EB05 4.3 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.6 | NCT01152996: 1/1,073 (0.1%) on Vortioxetine (serious AE) |
| Vomiting | 1,020 | 2.7 2.5–2.9ROR 2.8 · χ² 1,113 / p 2e-244 | 2.7 EB05 2.6 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.5 | NCT01152996: 68/1,073 (6.3%) on Vortioxetine |
| Suicidal ideation (thoughts of suicide) | 942 | 12.9 12.1–13.7ROR 13.6 · χ² 10,233 / p <1e-300 | 12.7 EB05 12.1 · IC025 +3.6 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 15.7 | NCT02371980: 2/1,106 (0.2%) on Vortioxetine (serious AE) |
| Off label use (used outside approved label) | 936 | 1.3 1.3–1.4ROR 1.4 · χ² 83 / p 5e-20 | 1.3 EB05 1.3 · IC025 +0.3 | Reporting / coding artifact | serious PRR 1.7 | not reported in cached trials |
| Insomnia (trouble sleeping) | 925 | 4.3 4.0–4.6ROR 4.5 · χ² 2,370 / p <1e-300 | 4.3 EB05 4.1 · IC025 +2.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.9 | NCT01152996: 56/1,073 (5.2%) on Vortioxetine |
| Dizziness | 890 | 2.2 2.1–2.4ROR 2.3 · χ² 608 / p 2e-134 | 2.2 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.8 | not reported in cached trials |
| Diarrhoea (diarrhea) | 837 | 1.6 1.5–1.7ROR 1.6 · χ² 201 / p 7e-46 | 1.6 EB05 1.5 · IC025 +0.6 | Labeled adverse reaction exact term | serious PRR 1.9 | NCT01152996: 80/1,073 (7.5%) on Vortioxetine |
| Pruritus (itching) | 785 | 2.6 2.4–2.8ROR 2.7 · χ² 769 / p 1e-169 | 2.6 EB05 2.4 · IC025 +1.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.5 | not reported in cached trials |
| Asthenia (weakness) | 781 | 2.6 2.4–2.8ROR 2.7 · χ² 765 / p 1e-168 | 2.6 EB05 2.4 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 2.0 | not reported in cached trials |
| Depression | 769 | 4.2 3.9–4.5ROR 4.3 · χ² 1,873 / p <1e-300 | 4.2 EB05 3.9 · IC025 +1.9 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 4.9 | not reported in cached trials |
| Feeling abnormal | 681 | 3.5 3.3–3.8ROR 3.6 · χ² 1,235 / p 9e-271 | 3.5 EB05 3.3 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 2.9 · 74% consumer | not reported in cached trials |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Dystonic tremor — n=30, PRR 654.8
- Neuroglycopenia — n=28, PRR 433.2
- Amaurosis fugax — n=219, PRR 319.8
- Feeling guilty — n=173, PRR 186.0
- Peripheral circulatory failure — n=33, PRR 108.7
- Urinary tract disorder — n=195, PRR 56.1
- Hyperphagia — n=168, PRR 54.8
- Haemorrhagic stroke — n=239, PRR 38.9
- Abulia — n=22, PRR 30.7
- Ocular discomfort — n=244, PRR 28.5
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Vortioxetine?
In FDA FAERS, the most frequently co-reported reaction terms for Vortioxetine are nausea, fatigue, headache, anxiety, vomiting, suicidal ideation. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Vortioxetine have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1) ] .
Do FAERS signals prove that Vortioxetine causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID cb1e9df4-dd74-4073-9d78-bb55593dd000, effective 20260217; matched on
openfda.generic_name.exact:"VORTIOXETINE") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 1,055 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath - ClinicalTrials.gov API v2 (query
VORTIOXETINE, results-bearing studies sorted by enrollment)
Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.