What are the side effects of vilazodone (Selective Serotonin Reuptake Inhibitor - SSRI)?

Side Effects of Vilazodone

Vilazodone's most common side effects are diarrhea (26-29%), nausea (22-24%), vomiting (4-5%), and insomnia (6-7%), with gastrointestinal symptoms being the predominant tolerability concern. 1

Most Common Side Effects (≥5% and twice placebo rate)

Gastrointestinal Effects

• Diarrhea occurs in 26-29% of patients (compared to 10% with placebo), making it the single most frequent adverse effect 1
• Nausea affects 22-24% of patients (versus 7% placebo) and is the most common reason for treatment discontinuation at 1.4% 1
• Vomiting occurs in 4-5% of patients taking the 40 mg dose (versus 2% placebo) 1
• Dry mouth develops in 7-8% of patients 1
• Abdominal pain affects 4-7% of patients 1

Neuropsychiatric Effects

• Insomnia occurs in 6-7% of patients (versus 2% placebo) 1
• Dizziness affects 6-8% of patients 1
• Headache occurs in 14-15% of patients 1
• Somnolence develops in 4-5% of patients 1
• Abnormal dreams occur in 2-3% of patients 1

Other Common Effects

• Fatigue affects 3-4% of patients 1
• Palpitations occur in 1-2% of patients 1
• Weight gain develops in 1-2% of patients 1

Sexual Dysfunction

Male Sexual Side Effects

• Erectile dysfunction occurs in 3% of men taking vilazodone 40 mg (versus 1% placebo) 1
• Decreased libido affects 3-4% of men (versus <1% placebo) 1
• Ejaculation disorders occur in 1-2% of men 1
• Abnormal orgasm/anorgasmia affects 2% of men 1

Female Sexual Side Effects

• Decreased libido occurs in 2% of women (versus <1% placebo) 1
• Abnormal orgasm/anorgasmia affects 1% of women 1

Vilazodone demonstrates lower rates of sexual dysfunction compared to other SSRIs, as it combines SSRI properties with 5-HT1A partial agonist activity 2, 3

Serious Adverse Effects (Rare but Potentially Life-Threatening)

Serotonin Syndrome

• Potentially life-threatening condition requiring immediate emergency care with symptoms including agitation, hallucinations, confusion, coma, tachycardia, blood pressure changes, hyperthermia, tremors, muscle rigidity, seizures, and gastrointestinal distress 1
• Risk increases with concomitant use of other serotonergic agents 1

Suicidality

• Black box warning for increased suicidal thinking and behavior in patients up to age 24 years 1
• As an SSRI-class medication, vilazodone carries the class risk of increased nonfatal suicide attempts (odds ratio 1.57-2.25 versus placebo) 4
• Close monitoring is mandatory, especially during the first months of treatment and following dose adjustments 4, 1

Bleeding Risk

• Increased risk of abnormal bleeding when combined with aspirin, NSAIDs, warfarin, or other anticoagulants 1
• Patients should be monitored for unusual bleeding or bruising 1

Mania/Hypomania Activation

• Risk of manic episodes in patients with bipolar disorder history, presenting with greatly increased energy, severe insomnia, racing thoughts, reckless behavior, unusually grand ideas, excessive happiness or irritability, and pressured speech 1
• More common in younger children than adolescents when SSRIs are used in pediatric populations 4

Hyponatremia

• Serum sodium can drop below 110 mmol/L, presenting with headache, difficulty concentrating, memory impairment, confusion, weakness, unsteadiness leading to falls, and in severe cases: hallucinations, syncope, seizures, coma, respiratory arrest, and death 1
• Elderly patients, those taking diuretics, and volume-depleted patients are at highest risk 1
• Often results from syndrome of inappropriate antidiuretic hormone secretion (SIADH) 1

Angle-Closure Glaucoma

• Vilazodone may precipitate angle-closure glaucoma requiring immediate ophthalmologic evaluation for vision changes or eye pain 1

Seizures

• Seizures are a recognized but uncommon adverse effect of vilazodone 1

Discontinuation Syndrome

Abrupt cessation of vilazodone can cause withdrawal symptoms including:

• Nausea, sweating, mood changes, headache, irritability, agitation, fatigue, dizziness, insomnia, electric shock sensations (paresthesias), hypomania, anxiety, tinnitus, confusion, and seizures 1
• Slow taper is mandatory when discontinuing vilazodone 1

Less Common Adverse Effects (1-2% incidence)

• Paresthesia (1-2%) 1
• Restlessness (2-3%) 1
• Increased appetite (1-3%) 1
• Arthralgia (1-2%) 1
• Sedation and tremor (frequent: ≥1/100 patients) 1
• Migraine (infrequent: 1/100 to 1/1,000 patients) 1
• Panic attack (infrequent) 1
• Hyperhidrosis and night sweats (infrequent) 1
• Dry eye and blurred vision (infrequent) 1
• Ventricular extrasystoles (infrequent) 1

Discontinuation Rates

• 7.3% of patients discontinued vilazodone due to adverse effects in 8-week trials (versus 3.5% placebo) 1, 5
• 20.7% discontinued in 52-week long-term studies 5
• Nausea was the most common reason for discontinuation at 1.4% 1, 5

Key Clinical Considerations

Most adverse effects emerge within the first few weeks of treatment and are generally mild to moderate in severity, with the majority being self-limited and resolving within 4-5 days 4, 2

Vilazodone must be taken with food to optimize absorption and tolerability, as all clinical trials administered the medication with food 1

Vilazodone demonstrates a more favorable tolerability profile compared to many SSRIs, particularly regarding sexual dysfunction and weight gain 2, 3, 6