What are the side effects of venlafaxine (Effexor)

Side Effects of Venlafaxine (Effexor)

Venlafaxine commonly causes numerous side effects including nausea, dizziness, sweating, sexual dysfunction, increased blood pressure, and potentially dangerous discontinuation symptoms that require careful tapering when stopping the medication. 1, 2

Common Side Effects

Venlafaxine, as a serotonin-norepinephrine reuptake inhibitor (SNRI), is associated with a range of common side effects:

• Gastrointestinal effects:

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

• Neurological effects:

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

• Other common effects:

  • Sweating/diaphoresis (common)
  • Fatigue/asthenia
  • Blurred vision (6%)
  • Sexual dysfunction (12% abnormal ejaculation/orgasm in men)
  • Impotence (6% in men)

1, 2

Cardiovascular Side Effects

Venlafaxine has notable cardiovascular effects that distinguish it from many other antidepressants:

• Increased blood pressure (dose-dependent)
• Elevated pulse rate (approximately 2-3 beats per minute)
• Sustained clinical hypertension (requires monitoring)

These cardiovascular effects are more pronounced with venlafaxine than with SSRIs, making it potentially more dangerous for patients with pre-existing cardiovascular conditions. 1, 2, 3

Serious/Severe Adverse Effects

Venlafaxine can cause several serious adverse effects that require monitoring:

• Suicidal thinking and behavior (especially in young adults under 24 years)
• Serotonin syndrome (agitation, hallucinations, coma, coordination problems, racing heartbeat, fluctuating blood pressure, fever, muscle rigidity)
• Behavioral activation/agitation
• Hypomania/mania
• Seizures (higher risk compared to some other antidepressants)
• Abnormal bleeding (especially when combined with NSAIDs, aspirin, or warfarin)
• Low sodium levels (hyponatremia, especially in elderly patients)
• Elevated cholesterol
• Severe allergic reactions (rare)

1, 2, 3

Discontinuation Syndrome

One of the most significant concerns with venlafaxine is its discontinuation syndrome:

• Symptoms include: dizziness, electric shock-like sensations, headache, nausea, vomiting, irritability, anxiety, fatigue, and insomnia
• Can occur after missing even a single dose due to venlafaxine's short half-life (3-4 hours)
• More severe than with many SSRIs
• Requires slow tapering when discontinuing (never stop abruptly)

1, 2, 4

Overdose Risk

Venlafaxine overdose carries higher risks than SSRI overdoses:

• More frequently fatal than SSRI overdoses
• Risk of QT interval prolongation leading to potential cardiac arrhythmias
• Both venlafaxine and desvenlafaxine have been associated with overdose fatalities

1, 3

Drug Interactions

Important drug interactions to consider:

• MAOIs: Contraindicated due to risk of serotonin syndrome
• CYP450 system: Venlafaxine has less effect on the CYP450 system compared to some SSRIs
• Triptans, other antidepressants, tramadol: Increased risk of serotonin syndrome
• Blood thinners: Increased bleeding risk
• NSAIDs/Aspirin: Increased bleeding risk

1, 2

Monitoring Recommendations

When prescribing venlafaxine, the following monitoring is recommended:

• Blood pressure and pulse at baseline and regularly during treatment
• Weight monitoring
• Mental status for signs of suicidality, especially early in treatment and after dose changes
• Symptoms of serotonin syndrome or behavioral activation
• Electrolytes (particularly sodium) in elderly patients

1, 2

Special Considerations

• Pregnancy: Increased risk of pre-eclampsia and eclampsia during second and third trimesters
• Immediate vs. Extended Release: Immediate release venlafaxine may require multiple daily dosing due to short half-life
• Dosing: Side effects are often dose-dependent, with higher doses (>375 mg/day) associated with more severe side effects, though discontinuation rates may not increase proportionally 5
• Comparative safety: Venlafaxine is considered more dangerous than most SSRIs due to its cardiovascular effects and higher risk of fatal overdose 3

In conclusion, while venlafaxine is effective for depression and anxiety disorders, its side effect profile requires careful consideration, especially regarding cardiovascular effects and discontinuation syndrome. For many patients, an SSRI might represent a safer first-line option with similar efficacy but fewer serious adverse effects.