What side effects should an adult patient with a history of depression or anxiety look for when stopping bupropion (Wellbutrin) and starting venlafaxine (Effexor)?

Side Effects When Switching from Wellbutrin to Effexor

When stopping bupropion (Wellbutrin) and starting venlafaxine (Effexor), the patient should primarily watch for gastrointestinal symptoms—especially severe nausea and vomiting from the new venlafaxine—along with cardiovascular changes including increased blood pressure and heart rate. 1

Primary Side Effects from Starting Venlafaxine (Effexor)

Gastrointestinal Effects (Most Common)

• Nausea and vomiting are the predominant side effects and the most common reasons patients discontinue venlafaxine 1
• Venlafaxine has a significantly higher incidence of nausea and vomiting compared to other SSRIs and antidepressants 1
• Diarrhea, constipation, and abdominal discomfort can occur 1

Cardiovascular Effects (Critical to Monitor)

• Sustained increases in blood pressure and heart rate are specific concerns with venlafaxine 1
• Venlafaxine may be associated with increased cardiovascular events compared to other second-generation antidepressants 1
• Monitor blood pressure and pulse regularly after starting 1

Neuropsychiatric Effects

• Headache, dizziness, and insomnia are common 1
• Somnolence may occur 1
• Monitor for worsening depression or emergence of suicidal thoughts, particularly in younger adults 1
• Anxiety and agitation can develop 1

Other Notable Effects

• Diaphoresis (excessive sweating) 1
• Dry mouth 1
• Decreased appetite and weight loss 1
• Sexual dysfunction (though less than with some SSRIs) 1
• Tremor 1

Side Effects from Stopping Bupropion (Wellbutrin)

Withdrawal/Discontinuation Effects

• Bupropion generally has fewer discontinuation symptoms compared to venlafaxine 1
• The patient may experience temporary worsening of mood or energy as bupropion's dopaminergic and noradrenergic effects wear off 2, 3
• Some patients report fatigue or concentration difficulties during the transition 3

Loss of Bupropion's Beneficial Effects

• Sexual function may worsen when switching from bupropion to venlafaxine, as bupropion has the lowest rate of sexual side effects among antidepressants 1
• Patients who benefited from bupropion's activating properties may experience increased sedation with venlafaxine 2, 3

Serious Adverse Events to Monitor

Serotonin Syndrome Risk

• If any overlap occurs between stopping bupropion and starting venlafaxine, watch for serotonin syndrome 1, 4
• Symptoms include tremor, diarrhea, delirium, neuromuscular rigidity, hyperthermia, and confusion 1
• Although bupropion has minimal serotonergic activity, it can inhibit cytochrome P450 2D6, potentially increasing venlafaxine levels if taken concurrently 4

Hyponatremia

• Venlafaxine can cause hyponatremia, particularly in patients taking diuretics 1, 5
• Monitor electrolytes if the patient has risk factors 5

Seizure Risk Changes

• Bupropion lowers seizure threshold; stopping it reduces this risk 1
• Venlafaxine has minimal seizure risk 1

Suicidality

• All second-generation antidepressants carry risk of increased suicidal thinking in young adults, particularly in the first few months 1
• Monitor closely for behavioral changes, agitation, or worsening depression 1

Critical Discontinuation Syndrome from Venlafaxine (Future Consideration)

Important for Long-Term Planning

• Venlafaxine has one of the most severe discontinuation syndromes among antidepressants 6
• Symptoms include headache, nausea, fatigue, dizziness, dysphoria, and can occur even after missing a single dose 6
• When eventually discontinuing venlafaxine, it must be tapered very slowly to avoid severe withdrawal symptoms 5, 6

Practical Monitoring Algorithm

Week 1-2

• Monitor for nausea/vomiting daily (most likely to cause discontinuation) 1
• Check blood pressure and heart rate at baseline and weekly 1
• Assess for headache, dizziness, insomnia 1

Week 2-4

• Continue cardiovascular monitoring 1
• Evaluate mood changes, suicidal ideation, or behavioral activation 1
• Assess sexual function changes 1

Ongoing

• Monthly blood pressure checks once stabilized 1
• Monitor for sustained hypertension requiring intervention 1
• Assess electrolytes if risk factors present 5

Common Pitfalls to Avoid

• Do not abruptly stop bupropion if the patient has been on high doses or extended-release formulations 1
• Do not overlook cardiovascular monitoring—venlafaxine's blood pressure effects are clinically significant 1
• Do not dismiss early nausea as minor—it is the leading cause of venlafaxine discontinuation and should be proactively managed 1
• Do not assume sexual side effects will be similar—expect potential worsening when switching from bupropion 1
• Do not forget to counsel about future discontinuation challenges with venlafaxine, as patients may experience severe withdrawal even from missed doses 6