What are the potential side effects of combining trazodone and Wellbutrin (bupropion)?

Side Effects of Combining Trazodone and Wellbutrin (Bupropion)

The combination of trazodone and bupropion is generally considered safe based on clinical experience, though specific side effects from each medication can occur and there is a theoretical risk of serotonin syndrome that requires monitoring. 1

Individual Medication Side Effects

Trazodone Side Effects

The most common side effects of trazodone include 2:

• Somnolence/sedation (the predominant side effect, occurring at higher rates than other antidepressants including bupropion) 2
• Dizziness, particularly with position changes 2
• Headache 2
• Dry mouth 2
• Nausea and vomiting 2

Serious but less common side effects include 3:

• Orthostatic hypotension (especially in elderly or those with cardiovascular disease) 3
• QT interval prolongation and potential cardiac arrhythmias 3
• Priapism (occurred in approximately 7% of patients who discontinued in one study) 2

Bupropion (Wellbutrin) Side Effects

Common side effects of bupropion include 4:

• Agitation 4
• Dry mouth 4
• Insomnia 4
• Headaches and migraines 4
• Nausea, vomiting, and constipation 4
• Tremor 4

The most serious side effect is 4:

• Seizures (dose-dependent; maximum 450 mg/day immediate-release or 400 mg/day sustained-release) 4

Combination-Specific Concerns

Serotonin Syndrome Risk

While rare, serotonin syndrome is the most serious potential complication when combining these medications. 5 A case report documented serotonin syndrome in a patient taking both trazodone and bupropion (along with quetiapine) after electroconvulsive therapy 5.

Monitor for these symptoms 6, 5:

• Anxiety and restlessness 6
• Tremor and myoclonus 6
• Hyperreflexia 6
• Diaphoresis (excessive sweating) 6
• Rigidity 6
• Hyperthermia 6

Overlapping Side Effects

Both medications can cause 2, 4:

• Dry mouth (additive effect possible) 2, 4
• Headache 2, 4
• Nausea and vomiting 2, 4

Counterbalancing Effects

Interestingly, some side effects may counterbalance 2, 4:

• Trazodone causes sedation while bupropion causes insomnia/activation 2, 4
• This combination is sometimes intentionally used clinically, with trazodone at bedtime for sleep and bupropion during the day for depression 1

Clinical Practice Considerations

General Safety Profile

Clinical experience suggests this combination is generally safe and effective when used appropriately. 1 The American Academy of Sleep Medicine notes that combining benzodiazepine receptor agonists with antidepressants has "a wealth of clinical experience" supporting general safety, and this principle extends to combining different antidepressant classes 1.

Monitoring Recommendations

When prescribing this combination 1, 3:

• Monitor for daytime sedation from trazodone, especially initially 1, 2
• Watch for signs of serotonin syndrome, particularly during dose adjustments 6, 5
• Assess cardiovascular status in elderly patients or those with heart disease due to trazodone's effects 3
• Ensure bupropion doses remain within safe limits to minimize seizure risk 4

Common Pitfalls to Avoid

• Do not combine with alcohol or other CNS depressants due to additive sedation from trazodone 1
• Avoid rapid dose escalation of either medication 4
• Be cautious in elderly patients who may be more sensitive to orthostatic hypotension and sedation 1, 3
• Consider cardiovascular screening before initiating trazodone in patients with known heart disease 3

Dosing Strategy

Use lower doses of trazodone (typically 25-150 mg) when combining with other antidepressants to minimize side effects while maintaining efficacy for sleep or augmentation 1, 3. Bupropion should be titrated gradually to therapeutic doses while monitoring for activation or seizure risk 4.