Medical Editor: John P. Cunha, DO, FACOEP
What Is Trintellix?
Trintellix (vortioxetine) tablets are an antidepressant indicated for the treatment of major depressive disorder (MDD).
What Are Side Effects of Trintellix?
Common side effects of Trintellix include:
- nausea
- diarrhea
- dry mouth
- constipation
- vomiting
- gas
- dizziness
- abnormal dreams
- itching, and
- decreased sexual desire
Antidepressants such as Trintellix increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. Tell your doctor if you experience any thoughts of suicide while taking Trintellix.
Dosage for Trintellix
The recommended starting dose of Trintellix is 10 mg administered orally once daily without regard to meals. Dosage should then be increased to 20 mg/day, as tolerated.
What Drugs, Substances, or Supplements Interact with Trintellix?
Trintellix may interact with monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, buspirone, tramadol, tryptophan products, NSAIDs, aspirin, warfarin, bupropion, fluoxetine, paroxetine, quinidine, rifampicin, carbamazepine, and phenytoin. Tell your doctor all medications and supplements you use.
Trintellix During Pregnancy and Breastfeeding
During pregnancy, Trintellix should be used only if prescribed. It is unknown if it would affect a fetus. It is unknown if Trintellix passes into breast milk. Breastfeeding while using Trintellix is not recommended.
Additional Information
Our Trintellix (vortioxetine) tablets Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
QUESTION
Depression is a(n) __________ . See Answer
SIDE EFFECTS
The following adverse reactions are discussed in greater detail in other sections of the label.
- Hypersensitivity [see CONTRAINDICATIONS]
- Clinical Worsening and Suicide Risk [see WARNINGS AND PRECAUTIONS]
- Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]
- Abnormal Bleeding [see WARNINGS AND PRECAUTIONS]
- Activation of Mania/Hypomania [see WARNINGS AND PRECAUTIONS]
- Angle Closure Glaucoma [see WARNINGS AND PRECAUTIONS]
- Hyponatremia [see WARNINGS AND PRECAUTIONS]
Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.
Patient Exposure
TRINTELLIX was evaluated for safety in 4746 patients (18 years to 88 years of age) diagnosed with MDD who participated in premarketing clinical studies; 2616 of those patients were exposed to TRINTELLIX in 6 to 8 week, placebo-controlled studies at doses ranging from 5 mg to 20mg once daily and 204 patients were exposed to TRINTELLIX in a 24 to 64 week placebo-controlled maintenance study at doses of 5 mg to 10 mg once daily. Patients from the 6 to 8 week studies continued into 12 month open-label studies. A total of 2586 patients were exposed to at least one dose of TRINTELLIX in open-label studies, 1727 were exposed to TRINTELLIX for six months and 885 were exposed for at least one year.
Adverse Reactions Reported As Reasons For Discontinuation Of Treatment
In pooled 6 to 8 week placebo-controlled studies the incidence of patients who received TRINTELLIX 5 mg/day, 10 mg/day, 15 mg/day and 20 mg/day and discontinued treatment because of an adverse reaction was 5%, 6%, 8% and 8%, respectively, compared to 4% of placebo-treated patients. Nausea was the most common adverse reaction reported as a reason for discontinuation.
Common Adverse Reactions In Placebo-Controlled Mdd Studies
The most commonly observed adverse reactions in MDD patients treated with TRINTELLIX in 6 to 8 week placebo-controlled studies (incidence ≥5% and at least twice the rate of placebo) were nausea, constipation and vomiting.
Table 2 shows the incidence of common adverse reactions that occurred in ≥2% of MDD patients treated with any TRINTELLIX dose and at least 2% more frequently than in placebo-treated patients in the 6 to 8 week placebo-controlled studies.
Table 2. Common Adverse Reactions Occurring in ≥2% of Patients Treated with any TRINTELLIX Dose and at Least 2% Greater than the Incidence in Placebo-treated Patients
| System Organ Class Preferred Term | TRINTELLIX 5 mg/day |
TRINTELLIX 10 mg/day |
TRINTELLIX 15 mg/day |
TRINTELLIX 20 mg/day |
Placebo |
| N=1013 % |
N=699 % |
N=449 % |
N=455 % |
N=1621 % |
|
| Gastrointestinal disorders | |||||
| Nausea | 21 | 26 | 32 | 32 | 9 |
| Diarrhea | 7 | 7 | 10 | 7 | 6 |
| Dry mouth | 7 | 7 | 6 | 8 | 6 |
| Constipation | 3 | 5 | 6 | 6 | 3 |
| Vomiting | 3 | 5 | 6 | 6 | 1 |
| Flatulence | 1 | 3 | 2 | 1 | 1 |
| Nervous system disorders | |||||
| Dizziness | 6 | 6 | 8 | 9 | 6 |
| Psychiatric disorders | |||||
| Abnormal dreams | <1 | <1 | 2 | 3 | 1 |
| Skin and subcutaneous tissue disorders | |||||
| Pruritus* | 1 | 2 | 3 | 3 | 1 |
| * includes pruritus generalized | |||||
Nausea
Nausea was the most common adverse reaction and its frequency was dose-related (Table 2). It was usually considered mild or moderate in intensity and the median duration was two weeks. Nausea was more common in females than males. Nausea most commonly occurred in the first week of TRINTELLIX treatment with 15 to 20% of patients experiencing nausea after one to two days of treatment. Approximately 10% of patients taking TRINTELLIX 10 mg/day to 20 mg/day had nausea at the end of the 6 to 8 week placebo-controlled studies.
Sexual Dysfunction
Difficulties in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of psychiatric disorders, but they may also be consequences of pharmacologic treatment. In addition to the data from the MDD studies mentioned below, TRINTELLIX has been prospectively assessed for its effects in MDD patients with existing TESD induced by prior SSRI treatment and in healthy adults with normal sexual function at baseline [see Clinical Studies].
Voluntarily Reported Adverse Reactions of Sexual Dysfunction
In the MDD 6 to 8 week controlled trials of TRINTELLIX, voluntarily reported adverse reactions related to sexual dysfunction were captured as individual event terms. These event terms have been aggregated and the overall incidence was as follows. In male patients the overall incidence was 3%, 4%, 4%, 5% in TRINTELLIX 5 mg/day, 10 mg/day, 15 mg/day, 20 mg/day, respectively, compared to 2% in placebo. In female patients, the overall incidence was <1%, 1%, <1%, 2% in TRINTELLIX 5 mg/day, 10 mg/day, 15 mg/day, 20 mg/day, respectively, compared to <1% in placebo.
Adverse Reactions of Sexual Dysfunction in Patients with Normal Sexual Functioning at Baseline
Because voluntarily reported adverse sexual reactions are known to be underreported, in part because patients and physicians may be reluctant to discuss them, the Arizona Sexual Experiences Scale (ASEX), a validated measure designed to identify sexual side effects, was used prospectively in seven placebo-controlled trials. The ASEX scale includes five questions that pertain to the following aspects of sexual function: 1) sex drive, 2) ease of arousal, 3) ability to achieve erection (men) or lubrication (women), 4) ease of reaching orgasm, and 5) orgasm satisfaction.
The presence or absence of sexual dysfunction among patients entering clinical studies was based on their self-reported ASEX scores. For patients without sexual dysfunction at baseline (approximately 1/3 of the population across all treatment groups in each study), Table 3 shows the incidence of patients that developed TESD when treated with TRINTELLIX or placebo in any fixed dose group. Physicians should routinely inquire about possible sexual side effects.
Table 3. ASEX Incidence of Treatment Emergent Sexual Dysfunction*
| TRINTELLIX 5 mg/day N=65:67† |
TRINTELLIX 10 mg/day N=94:86† |
TRINTELLIX 15 mg/day N=57:67† |
TRINTELLIX 20 mg/day N=67:59† |
Placebo N=135:162† |
|
| Females | 22% | 23% | 33% | 34% | 20% |
| Males | 16% | 20% | 19% | 29% | 14% |
| * Incidence based on number of subjects with sexual dysfunction during the study/number of subjects without sexual dysfunction at baseline. Sexual dysfunction was defined as a subject scoring any of the following on the ASEX scale at two consecutive visits during the study: 1) total score ≥19; 2) any single item ≥5; 3) three or more items each with a score ≥4 † Sample size for each dose group is the number of patients (females:males) without sexual dysfunction at baseline |
|||||
Adverse Reactions Following Abrupt Discontinuation Of Trintellix Treatment
Discontinuation symptoms have been prospectively evaluated in patients taking TRINTELLIX 10 mg/day, 15 mg/day, and 20 mg/day using the Discontinuation-Emergent Signs and Symptoms (DESS) scale in clinical trials. Some patients experienced discontinuation symptoms such as headache, muscle tension, mood swings, sudden outbursts of anger, dizziness, and runny nose in the first week of abrupt discontinuation of TRINTELLIX 15 mg/day and 20 mg/day.
Laboratory Tests
TRINTELLIX has not been associated with any clinically important changes in laboratory test parameters in serum chemistry (except sodium), hematology and urinalysis as measured in the 6 to 8 week placebo-controlled studies. Hyponatremia has been reported with the treatment of TRINTELLIX [see WARNINGS AND PRECAUTIONS]. In the six month, double-blind, placebo-controlled phase of a long-term study in patients who had responded to TRINTELLIX during the initial 12 week, open-label phase, there were no clinically important changes in lab test parameters between TRINTELLIX and placebo-treated patients.
Weight
TRINTELLIX had no significant effect on body weight as measured by the mean change from baseline in the 6 to 8 week placebo-controlled studies. In the six month, double-blind, placebo-controlled phase of a long-term study in patients who had responded to TRINTELLIX during the initial 12 week, open-label phase, there was no significant effect on body weight between TRINTELLIX and placebo-treated patients.
Vital Signs
TRINTELLIX has not been associated with any clinically significant effects on vital signs, including systolic and diastolic blood pressure and heart rate, as measured in placebo-controlled studies.
Other Adverse Reactions Observed In Clinical Studies
The following listing does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo.
Ear and labyrinth disorders - vertigo
Gastrointestinal disorders - dyspepsia
Nervous system disorders - dysgeusia
Vascular disorders - flushing
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of TRINTELLIX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Metabolic disorders - weight gain
Nervous system disorders - seizure
Skin and subcutaneous tissue disorders - rash, generalized rash
Gastrointestinal System - acute pancreatitis
Read the entire FDA prescribing information for Trintellix (Vortioxetine Tablets)
