What are the side effects of Trintellix (vortioxetine)?

Side Effects of Trintellix (Vortioxetine)

The most common side effects of Trintellix are nausea, constipation, and vomiting, with nausea being dose-related and typically occurring within the first week of treatment before decreasing in frequency. 1

Most Common Side Effects

• Nausea is the predominant side effect and is dose-dependent, commonly appearing within the first week of treatment, then decreasing in frequency but potentially persisting in some patients 1, 2
• Constipation and vomiting are the other most frequently reported gastrointestinal effects 1
• Additional common side effects include diarrhea, dry mouth, dizziness, and headache 3
• These gastrointestinal and general side effects are consistent with the broader class of second-generation antidepressants 4

Sexual Dysfunction

• Vortioxetine can cause sexual problems in both males and females 1
• In males: delayed ejaculation or inability to ejaculate, problems achieving or maintaining erection, and decreased sex drive 1
• In females: decreased sex drive and delayed or absent orgasm 1
• Patients should be counseled to discuss any changes in sexual function with their provider, as management strategies may be available 1
• Notably, vortioxetine may actually be beneficial for patients who experienced sexual dysfunction on other antidepressants, particularly SSRIs like paroxetine 5

Serious Side Effects Requiring Immediate Attention

Serotonin Syndrome

• A potentially life-threatening condition that requires emergency care 1
• Symptoms include: agitation, hallucinations, confusion, coma, rapid heart rate, blood pressure changes, dizziness, sweating, flushing, hyperthermia, tremors, muscle stiffness or twitching, loss of coordination, seizures, and gastrointestinal symptoms (nausea, vomiting, diarrhea) 1
• Risk increases when combined with other serotonergic medications including triptans, SSRIs, SNRIs, tricyclic antidepressants, lithium, tramadol, fentanyl, other opioids, tryptophan, buspirone, and St. John's Wort 1

Bleeding Risk

• Increased bleeding risk, particularly when combined with aspirin, NSAIDs, warfarin, or other blood thinners 1
• Patients should report any unusual bleeding or bruising immediately 1

Hyponatremia

• Low sodium levels can occur and may be serious or fatal 1
• Elderly patients and those taking diuretics are at higher risk 1
• Symptoms include: headache, difficulty concentrating, memory changes, confusion, weakness, and unsteadiness leading to falls 1
• Severe cases may present with hallucinations, fainting, seizures, coma, or respiratory arrest 1

Angle-Closure Glaucoma

• Vortioxetine can cause mild pupillary dilation, which may trigger angle-closure glaucoma in susceptible individuals 1
• Patients with pre-existing risk factors should consider prophylactic eye examination and treatment (e.g., iridectomy) 1
• Seek immediate care for eye pain, vision changes, or swelling/redness around the eye 1

Psychiatric Side Effects

Activation of Mania/Hypomania

• Manic episodes can occur in patients with bipolar disorder 1
• Warning signs include: greatly increased energy, racing thoughts, grandiose ideas, rapid or excessive talking, severe insomnia, reckless behavior, and excessive happiness or irritability 1

Suicidality

• Increased risk of suicidal thoughts and actions in patients under age 24, especially during the first few months of treatment or with dose changes 1
• Close monitoring is essential for new or sudden changes in mood, behavior, thoughts, or feelings 1
• This risk is consistent with the broader class of SSRIs, which are associated with increased nonfatal suicide attempts (odds ratio 2.25,95% CI 3.3-4.6) 4

Discontinuation Syndrome

• Abruptly stopping Trintellix can cause serious withdrawal symptoms 1
• The dose should be tapered gradually under physician supervision 1
• Discontinuation symptoms include: nausea, sweating, mood changes, irritability, agitation, dizziness, paresthesias (electric shock sensations), tremor, anxiety, confusion, headache, fatigue, insomnia, hypomania, tinnitus, and seizures 1

Pregnancy and Breastfeeding Considerations

• Trintellix may cause neonatal withdrawal symptoms or persistent pulmonary hypertension of the newborn (PPHN) when taken during the third trimester 1
• Pregnant women or those planning pregnancy should discuss risks versus benefits with their provider 1
• A pregnancy registry exists for monitoring outcomes (National Pregnancy Registry for Antidepressants: 1-844-405-6185) 1
• It is unknown whether vortioxetine passes into breast milk 1

Clinical Tolerability Profile

• Vortioxetine is generally well tolerated with side effects typically mild to moderate in severity 5, 2
• In direct comparison to duloxetine, vortioxetine demonstrated lower risk of common antidepressant-induced adverse effects, though with slightly smaller efficacy 3
• The overall safety profile is comparable to existing first-line antidepressants 2
• Nausea and vomiting are the most common reasons for treatment discontinuation in clinical trials 4, 6

Drug Interactions Requiring Caution

• Contraindicated with MAOIs (including linezolid and IV methylene blue) - do not use within 14 days of stopping an MAOI, and wait 21 days after stopping Trintellix before starting an MAOI 1
• Medications requiring careful monitoring include those affecting serotonin, bleeding risk, or metabolized by CYP2D6 1
• Strong CYP2D6 inhibitors (like bupropion) may require dose adjustment 7