What are the potential side effects of Venlafaxine (Effexor)

Venlafaxine Side Effects

Venlafaxine is associated with numerous significant side effects, including dose-dependent blood pressure elevation, severe discontinuation syndrome, gastrointestinal distress, sexual dysfunction, and increased risk of suicidal thoughts, particularly in young adults under 24 years of age. 1, 2

Common Side Effects

Venlafaxine commonly causes several side effects that patients should be aware of:

Gastrointestinal Effects

• Nausea (up to 37%)
• Vomiting (6%)
• Constipation (15%)
• Diarrhea (8%)
• Dry mouth (22%)
• Decreased appetite/anorexia (11%)
• Weight loss (1%) 1

Neurological Effects

• Dizziness (19%)
• Headache
• Somnolence/drowsiness (23%)
• Insomnia (18%)
• Tremor (5%)
• Nervousness (13%)
• Anxiety (6%) 1

Other Common Effects

• Sweating/diaphoresis (up to 19.3% at higher doses)
• Fatigue/asthenia
• Blurred vision (6%)
• Sexual dysfunction (12% abnormal ejaculation/orgasm in men)
• Impotence (6% in men) 1, 2

Serious Adverse Effects

Cardiovascular Effects

• Dose-dependent blood pressure elevation (more pronounced than with SSRIs)
• Increased pulse rate (approximately 2-3 beats per minute)
• Sustained clinical hypertension requiring monitoring 1

Psychiatric Effects

• Suicidal thinking and behavior (especially in young adults under 24 years)
• Behavioral activation/agitation
• Hypomania/mania 1, 2

Other Serious Effects

• Serotonin syndrome (potentially life-threatening)
• Seizures
• Abnormal bleeding (especially when combined with blood thinners)
• Low sodium levels (hyponatremia, especially in elderly patients)
• Elevated cholesterol
• Severe allergic reactions (rare) 1, 2

Discontinuation Syndrome

Venlafaxine has a particularly severe discontinuation syndrome due to its short half-life (3-4 hours), which can occur even after missing a single dose 1, 3. Symptoms include:

• Dizziness
• Electric shock-like sensations
• Headache
• Nausea and vomiting
• Irritability
• Anxiety
• Fatigue
• Insomnia 1, 2

Slow tapering is essential when discontinuing venlafaxine to minimize these effects. 1

Overdose Risks

Venlafaxine overdose carries higher risks than SSRI overdoses:

• Higher risk of fatal outcomes
• QT interval prolongation leading to potential cardiac arrhythmias
• Both venlafaxine and desvenlafaxine have been associated with overdose fatalities 1, 4

Special Populations

Pregnancy

• Increased risk of pre-eclampsia and eclampsia during second and third trimesters 1, 4

Elderly

• Higher risk of hyponatremia
• Greater sensitivity to blood pressure effects 1

Drug Interactions

Important interactions to consider:

• MAOIs (contraindicated due to risk of serotonin syndrome)
• Triptans, other antidepressants, tramadol (increased risk of serotonin syndrome)
• Blood thinners, NSAIDs/Aspirin (increased bleeding risk)
• CYP450 system interactions (though less than some SSRIs) 1, 2

Monitoring Recommendations

When taking venlafaxine, the following should be monitored:

• Blood pressure and pulse at baseline and regularly during treatment
• Weight
• Mental status for signs of suicidality
• Symptoms of serotonin syndrome or behavioral activation
• Electrolytes (particularly sodium) in elderly patients 1

Dose-Dependent Effects

Many side effects of venlafaxine are dose-dependent, with higher doses (particularly above 225 mg/day) associated with:

• Greater risk of blood pressure elevation
• Increased sweating
• More pronounced tremor
• Higher rates of sexual dysfunction 1, 2

Recent systematic reviews have highlighted that venlafaxine increases the risk of serious adverse events compared to placebo, particularly sexual dysfunction and anorexia, and that long-term effects remain poorly studied despite many patients taking the medication for years 5.