What are the most common adverse effects of Effexor (venlafaxine)?

Most Common Adverse Effects of Effexor (Venlafaxine)

The most common adverse effects of venlafaxine are nausea (37%), dry mouth (22%), somnolence (23%), dizziness (19%), insomnia (18%), constipation (15%), nervousness (13%), and sweating, with nausea being the single most frequent reason for treatment discontinuation. 1

Gastrointestinal Effects

Nausea is the predominant adverse effect and the leading cause of discontinuation:

• Nausea occurs in 37% of patients versus 11% on placebo, with 6% discontinuing treatment specifically due to nausea 1
• The American Academy of Child and Adolescent Psychiatry confirms nausea as the most common gastrointestinal side effect and primary discontinuation cause in clinical trials 2, 3
• Nausea typically resolves within the first 1-3 weeks of therapy 4
• To minimize nausea, start with 37.5 mg/day and increase to 75 mg after one week if needed 2
• Other gastrointestinal effects include constipation (15%), anorexia (11%), vomiting (6%), diarrhea (8%), and dyspepsia (5%) 1

Neurological and Psychiatric Effects

• Somnolence affects 23% of patients (versus 9% on placebo), with 3% discontinuing due to this effect 1
• Dizziness occurs in 19% (versus 7% on placebo), leading to 3% discontinuation 1
• Insomnia affects 18% (versus 10% on placebo), with 3% discontinuing 1
• Nervousness occurs in 13% (versus 6% on placebo), with 2% discontinuing 1
• Additional neurological effects include headache, tremor (5%), anxiety (6%), and abnormal dreams (4%) 3, 1

Autonomic Effects

• Dry mouth occurs in 22% of patients versus 11% on placebo 1
• Sweating (diaphoresis) is notably more frequent with venlafaxine than with many other antidepressants, affecting enough patients to cause 2% to discontinue 3, 1

Sexual Dysfunction

• Abnormal ejaculation/orgasm occurs in 12% of male patients (versus 2% on placebo), with 3% discontinuing 1
• Impotence affects 6% of male patients (versus 2% on placebo) 1
• Sexual dysfunction occurs in both men and women 3

Cardiovascular Effects

A critical dose-dependent adverse effect that requires monitoring:

• Venlafaxine causes dose-dependent increases in blood pressure, with higher risk at doses above 300 mg/day 3
• Sustained hypertension occurred in 3-5% of patients receiving ≤200 mg/day, 7% receiving 201-300 mg/day, and 13% receiving >300 mg/day (versus 2% on placebo) 4
• Regular blood pressure monitoring is essential, especially when initiating treatment or adjusting dosage 3
• Cardiovascular adverse events limit venlafaxine's use in diabetes 5

Weight and Appetite Changes

• Decreased appetite (anorexia) occurs in 11% versus 2% on placebo 1
• Dose-dependent weight loss is common, with 6% of patients losing ≥5% of body weight (versus 1% on placebo) 1
• Weight loss is not limited to patients with treatment-emergent anorexia 1
• Venlafaxine has a more favorable weight profile than mirtazapine or paroxetine 6

Discontinuation Syndrome

A serious consideration requiring specific management:

• Abrupt discontinuation causes withdrawal symptoms including dizziness, sensory disturbances (shock-like electrical sensations), nausea, anxiety, confusion, headache, insomnia, and sweating 1
• Always taper gradually rather than stopping abruptly; if intolerable symptoms occur, resume the previous dose and taper more slowly 1
• The frequency of discontinuation symptoms increases with higher doses and longer treatment duration 1

Comparative Safety Profile

• Venlafaxine has a significantly higher incidence of nausea compared to other SSRIs 2, 3
• The overall tolerability profile is comparable to SSRIs but superior to tricyclic antidepressants 7, 8
• Venlafaxine lacks notable muscarinic-cholinergic or alpha-adrenergic effects, resulting in fewer anticholinergic side effects than tricyclics 4, 8
• The frequency of anticholinergic events with tricyclic comparators is approximately twice that of venlafaxine 8

Common Pitfalls to Avoid

• Do not start at high doses—begin at 37.5 mg/day to minimize nausea 2
• Never discontinue abruptly—always use gradual tapering to prevent discontinuation syndrome 1
• Monitor blood pressure regularly, particularly at doses >300 mg/day where hypertension risk increases substantially 3, 4
• Inform patients that nausea typically resolves within 1-3 weeks to improve adherence during the initial period 4