What are the side effects of Venlafaxine (Effexor)

Venlafaxine Side Effects

Venlafaxine causes a distinct profile of side effects dominated by gastrointestinal symptoms (especially nausea), neurological effects, dose-dependent blood pressure elevation, and a particularly severe discontinuation syndrome that requires careful monitoring and slow tapering when stopping the medication. 1, 2

Common Side Effects

Gastrointestinal Effects

• Nausea is the most common side effect and the leading cause of treatment discontinuation, occurring in 37% of patients compared to 11% with placebo 2
• Constipation affects 15% of patients, diarrhea 8%, vomiting 6%, dry mouth 22%, and decreased appetite 11% 1, 2
• Nausea typically resolves within 1-3 weeks of therapy but can be severe enough to require discontinuation in 6% of patients 2, 3

Neurological Effects

• Dizziness (19%), headache, tremor (5%), insomnia (18%), somnolence (23%), and nervousness (13%) are frequently reported 1, 2
• These symptoms show dose-dependency, with tremor increasing from 1.1% at 75 mg/day to 10.2% at 375 mg/day 2

Autonomic Effects

• Excessive sweating (diaphoresis) occurs more frequently with venlafaxine than with most other antidepressants, affecting 12-19% of patients in a dose-dependent manner 1, 2
• Dry mouth affects 22% of patients compared to 11% with placebo 2

Sexual Dysfunction

• Abnormal ejaculation/orgasm occurs in 12% of male patients, with impotence affecting 6% 1, 2
• Sexual dysfunction affects both men and women and is a common reason for treatment discontinuation 1

Cardiovascular Side Effects

Venlafaxine causes dose-dependent increases in blood pressure that distinguish it from other antidepressants and require regular monitoring. 1, 4

• Blood pressure elevation occurs in 3-5% of patients at doses ≤200 mg/day, 7% at 201-300 mg/day, and 13% at doses >300 mg/day 2, 3
• Sustained clinical hypertension may require treatment discontinuation, particularly at doses above 300 mg/day 1, 4
• Mean pulse rate increases by approximately 2-3 beats per minute 2
• Monitor blood pressure and pulse regularly, especially when initiating treatment or adjusting dosage 1, 4
• For patients older than 40 years with cardiac risk factors, obtain a screening electrocardiogram 4
• QT interval prolongation can occur, potentially leading to torsades de pointes 5

Serious Adverse Effects

Suicidality

• Increased risk of suicidal thoughts and behavior, particularly in children, adolescents, and young adults up to age 24 years 1, 2
• Watch for new or sudden changes in mood, behavior, actions, thoughts, or feelings, especially when starting treatment or changing doses 2

Serotonin Syndrome

• This potentially life-threatening condition can occur, especially when combined with other serotonergic medications 1, 2
• Symptoms include agitation, hallucinations, coma, coordination problems, muscle twitching, racing heartbeat, blood pressure changes, sweating, fever, nausea, vomiting, diarrhea, and muscle rigidity 2
• Concomitant use with MAOIs is contraindicated 1

Discontinuation Syndrome

Venlafaxine causes one of the most severe discontinuation syndromes among antidepressants, with symptoms occurring within hours of a missed dose. 6, 7

• Symptoms include anxiety, irritability, fatigue, restlessness, insomnia, headache, sweating, dizziness, electric shock-like sensations, shaking, confusion, nightmares, vomiting, nausea, and diarrhea 2, 6
• Severe withdrawal symptoms may occur after missing even a single dose 6, 7
• Hallucinations can occur during withdrawal 6
• Motor and coordination skills may be affected to such a degree that patients should not drive during withdrawal 7
• Always use a slow tapering schedule when discontinuing venlafaxine 1, 2

Other Serious Effects

• Seizures may be triggered, though this is uncommon 1
• Hyponatremia (low sodium levels), particularly in elderly patients 2
• Abnormal bleeding risk, especially when combined with warfarin, NSAIDs, or aspirin 2
• Elevated cholesterol levels requiring monitoring 2
• Rare lung problems including pneumonia 2
• Mydriasis (enlarged pupils) and potential for narrow-angle glaucoma 2
• Manic/hypomanic episodes in patients with bipolar disorder 2

Comparative Safety Profile

• Venlafaxine has higher rates of nausea, vomiting, and treatment discontinuation due to adverse effects compared to SSRIs 1, 5
• Venlafaxine overdoses are more frequently fatal than SSRI overdoses 5
• Treatment discontinuation due to adverse effects is more common with venlafaxine than with SSRI antidepressants, based on meta-analyses of over 70 trials involving approximately 7,000 patients 5
• 19% of patients discontinued venlafaxine in clinical trials due to adverse events 2

Special Populations

Pregnancy and Breastfeeding

• Exposure during the second and third trimesters increases the risk of pre-eclampsia and eclampsia 5
• Newborns whose mothers take venlafaxine in the third trimester may have feeding and breathing problems, seizures, shaking, jitteriness, or constant crying 2
• Venlafaxine passes into breast milk 2

Pediatric Patients

• Height and weight should be monitored during treatment in children and adolescents 2

Monitoring Requirements

• Blood pressure and pulse at baseline and regularly during treatment, especially with dose adjustments 1, 4
• Weight monitoring, particularly in children and adolescents 1, 2
• Cholesterol levels 2
• Screening ECG for patients >40 years with cardiac risk factors 4
• Close monitoring for suicidality, especially in the first few months of treatment or with dose changes 2

Common Pitfalls

• Failing to warn patients about severe discontinuation symptoms and the need for strict medication adherence 6, 7
• Not monitoring blood pressure regularly, particularly at higher doses 1, 4
• Abrupt discontinuation rather than slow tapering 1, 2
• Combining with other serotonergic medications without considering serotonin syndrome risk 1, 2
• Overlooking the higher cardiovascular risk and overdose fatality compared to SSRIs 5