What are the common side effects of Vortioxetine (Brintellix) for treating major depressive disorder?

Vortioxetine Side Effects for Major Depressive Disorder

The most common side effects of vortioxetine are nausea (21-32% depending on dose), constipation (3-6%), vomiting (3-6%), diarrhea (7-10%), dizziness (6-9%), and dry mouth (6-8%), with nausea being dose-related and typically mild to moderate, lasting approximately two weeks. 1

Gastrointestinal Side Effects

• Nausea is the most prevalent adverse reaction, occurring in a dose-dependent manner: 21% at 5 mg/day, 26% at 10 mg/day, 32% at 15 mg/day, and 32% at 20 mg/day (compared to 9% with placebo) 1
• Nausea typically begins within 1-2 days of treatment initiation, with 15-20% of patients experiencing it in the first week, and has a median duration of two weeks 1
• Females experience nausea more frequently than males 1
• Constipation occurs in 3-6% of patients (versus 3% with placebo), while vomiting affects 3-6% (versus 1% with placebo) 1
• Diarrhea is reported in 7-10% of patients across dosing ranges 1
• Nausea and vomiting are the most common reasons for treatment discontinuation 1

Neurological Side Effects

• Dizziness occurs in 6-9% of patients taking vortioxetine compared to 6% with placebo 1
• Headaches are commonly reported and are typically transient 2
• Dry mouth affects 6-8% of patients (versus 6% with placebo) 1

Sexual Dysfunction

• Vortioxetine has a notably lower incidence of sexual dysfunction compared to traditional SSRIs 2, 3
• In male patients with normal baseline sexual function, treatment-emergent sexual dysfunction occurred in 16-29% (versus 14% with placebo) 1
• In female patients with normal baseline sexual function, rates were 22-34% (versus 20% with placebo) 1
• Voluntarily reported sexual adverse events were 3-5% in males and <1-2% in females across dose ranges 1
• The low incidence of sexual dysfunction may be attributed to vortioxetine's unique receptor modulation profile 3

Psychiatric and Sleep-Related Effects

• Abnormal dreams occur in 2-3% of patients taking higher doses (15-20 mg/day) versus <1% with placebo 1
• Sleep disruption has a low incidence, which distinguishes vortioxetine from many SSRIs 3

Dermatological Effects

• Pruritus (itching) affects 1-3% of patients (versus 1% with placebo) 1

Discontinuation Rates

• Overall discontinuation due to adverse effects: 5% at 5 mg/day, 6% at 10 mg/day, and 8% at both 15 mg/day and 20 mg/day (compared to 4% with placebo) 1
• Approximately 63% of patients on second-generation antidepressants experience at least one adverse effect during treatment, though vortioxetine's profile is generally well-tolerated 4

Serious Adverse Events (Rare but Important)

• All second-generation antidepressants, including vortioxetine, carry FDA warnings for increased suicidal thinking and behavior, particularly in the first 1-2 months of treatment 4
• Serotonin syndrome risk exists, especially when combined with other serotonergic medications 4
• Hyponatremia, angle-closure glaucoma, and bleeding risk are potential concerns with all serotonergic antidepressants 1
• Activation of mania/hypomania is possible 1

Dose-Related Tolerability

• Rates of adverse events and treatment withdrawal do not increase during up-titration from 10 mg/day to 20 mg/day 5
• The side effect profile remains similar to SSRIs, with gastrointestinal symptoms being most common 3
• Vortioxetine has advantages over conventional antidepressants regarding low incidence of weight gain and cardiovascular alterations 6

Clinical Context

• When selecting vortioxetine, discuss the adverse effect profile with patients before initiation, as recommended by the American College of Physicians for all second-generation antidepressants 4
• Monitor patients within 1-2 weeks of starting treatment for adverse effects and therapeutic response 4
• The overall tolerability profile is comparable to existing first-line antidepressants, with the most common side effects being mild to moderate 2, 7