Venlafaxine Side Effects
Venlafaxine has numerous significant side effects including dose-dependent blood pressure elevation, serious discontinuation syndrome, and increased risk of serious adverse events compared to other antidepressants, requiring careful monitoring and slow tapering when discontinuing. 1, 2, 3
Common Side Effects
- Gastrointestinal effects are frequently reported, with nausea being the most common reason for discontinuation in clinical trials, along with vomiting, diarrhea, constipation, abdominal discomfort, and dry mouth 1
- Neurological effects include dizziness, headache, tremor, insomnia, somnolence, and nervousness 1, 2
- Autonomic effects, particularly diaphoresis (excessive sweating), occur more frequently with venlafaxine than with many other antidepressants 1, 2
- Sexual dysfunction, including abnormal ejaculation/orgasm in men and sexual dysfunction in both women and men 1, 4
- Decreased appetite and weight loss can occur during treatment, with 6% of patients experiencing a loss of 5% or more of body weight 1, 2
Cardiovascular Side Effects
- Dose-dependent increases in blood pressure, with higher risk at doses above 300 mg/day 1, 5
- Sustained clinical hypertension requiring monitoring, especially at higher doses 1, 6
- Both systolic and diastolic blood pressure elevations have been reported 2, 5
- Regular monitoring of blood pressure and pulse is recommended, especially when initiating treatment or adjusting dosage 6, 2
Serious Adverse Effects
- Increased risk of suicidal thoughts and behavior, particularly in children, adolescents, and young adults up to age 24 years 2, 1
- Serotonin syndrome, a potentially life-threatening condition characterized by agitation, hallucinations, coma, coordination problems, racing heartbeat, fluctuating blood pressure, fever, nausea, vomiting, diarrhea, and muscle rigidity 2, 1
- Discontinuation syndrome, characterized by withdrawal symptoms when stopping venlafaxine abruptly, requiring slow tapering when discontinuing 1, 7
- Withdrawal symptoms include anxiety, irritability, sleep disturbances, headache, dizziness, electric shock-like sensations, tremor, and nausea, which can begin within hours of missed doses 2, 7
- Seizures, though uncommon, may be triggered by venlafaxine 1, 2
- Low sodium levels in the blood (hyponatremia), particularly in elderly patients 2
Special Populations and Considerations
- Overdose risk is higher with venlafaxine compared to SSRIs, with more frequent fatal outcomes 8, 1
- Concomitant use with MAOIs is contraindicated due to risk of serotonin syndrome 1, 2
- Pediatric patients may experience weight loss and reduced growth during treatment 2
- Pregnant women exposed to venlafaxine during the second and third trimesters have increased risk of pre-eclampsia and eclampsia 8
- QT interval prolongation has been reported, which can lead to torsades de pointes, a potentially fatal type of ventricular tachycardia 8
Monitoring Recommendations
- Regular monitoring of blood pressure and pulse is essential, especially when initiating treatment or adjusting dosage 6, 1
- Screening electrocardiogram for patients older than 40 years with cardiac risk factors 6
- Monitor weight regularly, particularly in pediatric patients 2
- Careful observation for signs of suicidal thinking or behavior, especially early in treatment or with dose changes 2
Discontinuation Considerations
- A slow, gradual discontinuation taper is essential to minimize withdrawal symptoms 1, 2
- Abrupt discontinuation can lead to severe withdrawal symptoms affecting motor and coordination skills to such a degree that patients should be warned not to drive 7
- If intolerable symptoms occur following a decrease in dose, resuming the previously prescribed dose may be considered before attempting a more gradual taper 2