From the FDA Drug Label
The development of a potentially life-threatening serotonin syndrome have been reported with SNRIs and SSRIs, including venlafaxine HCl, alone but particularly with concomitant use of serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone and St John's Wort) with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). If concomitant use of venlafaxine HCl with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan and St. John’s Wort is clinically warranted, patients should be made aware of a potential increased risk of serotonin syndrome, particularly during treatment initiation and dose increases
Serotonin Syndrome Risk: Taking Wellbutrin (Bupropion) XL 300mg daily and Venlafaxine (Effexor) XR 150mg daily may increase the risk of serotonin syndrome, a potentially life-threatening condition.
- Key Factors:
- Concomitant use of serotonergic drugs
- Increased risk during treatment initiation and dose increases
- Patients should be monitored for the emergence of serotonin syndrome
- Recommendation: Patients should be made aware of the potential increased risk of serotonin syndrome, and treatment with venlafaxine HCl and any concomitant serotonergic agents should be discontinued immediately if symptoms occur 1.
From the Research
Taking Wellbutrin (Bupropion) XL 300mg daily and Venlafaxine (Effexor) XR 150mg daily can potentially cause serotonin syndrome, though the risk is relatively low compared to other antidepressant combinations. This combination requires caution because Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that significantly increases serotonin levels, while Bupropion, though primarily affecting dopamine and norepinephrine, may have some minor effects on serotonin 2. When monitoring this combination, watch for symptoms of serotonin syndrome including:
- Confusion
- Rapid heart rate
- Dilated pupils
- Muscle rigidity
- High blood pressure
- Hyperthermia
- Agitation
- Tremors These symptoms typically develop within hours to days after starting or increasing the dose of either medication. If you experience these symptoms, seek immediate medical attention. While this combination is sometimes prescribed intentionally for treatment-resistant depression, it should only be done under close medical supervision with regular follow-up appointments to monitor for adverse effects, as noted in cases where serotonin syndrome occurred with the use of venlafaxine alone or in combination with other serotonergic agents 3, 4. Your doctor may start with lower doses and gradually increase them to minimize risks. It's also important to consider the potential for serotonin syndrome when combining these medications with other treatments, such as electroconvulsive therapy (ECT), as seen in a case report where a patient developed serotonin syndrome after ECT while on bupropion, trazodone, and quetiapine 5.