Is it safe to combine Wellbutrin (bupropion) and duloxetine for treatment?

From the Guidelines

Combining Wellbutrin (bupropion) and duloxetine can be done safely for some patients, but should only be attempted under close medical supervision. This combination is sometimes prescribed for treatment-resistant depression or when a patient has partial response to either medication alone. Both medications affect brain neurotransmitters but work through different mechanisms - Wellbutrin primarily affects dopamine and norepinephrine, while duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI).

Key Considerations

• The main concern with this combination is an increased risk of seizures, as both medications can lower seizure threshold.
• Other potential side effects include increased blood pressure, heart rate, excessive sweating, insomnia, anxiety, and dry mouth.
• Patients with certain conditions like seizure disorders, eating disorders, or those withdrawing from alcohol or benzodiazepines face higher risks with this combination.
• Starting with lower doses of each medication and gradually increasing while monitoring for side effects is typically recommended.
• Regular follow-up appointments to check blood pressure, heart rate, and mental health symptoms are essential when taking these medications together, as recommended by the American College of Physicians 1.

Mechanism and Efficacy

• Duloxetine has shown consistent efficacy in painful diabetic peripheral neuropathy, with effectiveness sustained for 1 year in an open-label trial, as noted in the Mayo Clinic Proceedings 1.
• The most common adverse effect of duloxetine is nausea, which seems to be reduced by administering 30 mg once daily for 1 week before increasing to 60 mg once daily.
• Venlafaxine, another SNRI, has shown efficacy in painful diabetic peripheral neuropathy and painful polyneuropathies of different origins but not in postherpetic neuralgia.

Monitoring and Titration

• It is crucial to monitor patients closely for adverse effects and adjust dosages accordingly, considering the potential for drug interactions and the need for dosage reduction in patients with renal insufficiency.
• The American College of Physicians recommends that clinicians assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy 1.

From the Research

Safety of Combining Wellbutrin and Duloxetine

• The combination of Wellbutrin (bupropion) and duloxetine has been studied in various contexts, including treatment-resistant major depressive disorder (TRD) and atypical depression 2, 3.
• A retrospective chart review found that the combination of duloxetine and bupropion was effective in reducing symptoms of TRD, with a significant decrease in Clinical Global Impressions (CGI) scores 2.
• However, the combination of these two medications also carries a risk of side effects, including nausea, dry mouth, jitteriness/agitation, fatigue/drowsiness, and increased blood pressure 2.
• A double-blind, randomized, placebo-controlled trial found that the addition of bupropion to duloxetine did not significantly improve response rates in patients with treatment-resistant atypical depression, although the study was limited by its small sample size and short duration 3.

Mechanism of Action

• Duloxetine is a serotonin-norepinephrine reuptake inhibitor, which increases the levels of these neurotransmitters in the brain by blocking their reabsorption 4.
• Bupropion, on the other hand, is a norepinephrine-dopamine reuptake inhibitor, which increases the levels of these neurotransmitters in the brain by blocking their reabsorption 5.
• The combination of these two medications may increase the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive levels of serotonin in the brain 5.

Efficacy and Tolerability

• The efficacy and tolerability of duloxetine have been established in various studies, including a systematic review of 85 studies that found it to be effective and safe for the treatment of major depressive disorder, generalized anxiety disorder, neuropathic pain, fibromyalgia, and stress incontinence urinary 4.
• The combination of duloxetine and bupropion may be effective for TRD, although more studies are needed to confirm its efficacy and safety 2, 3.
• The tolerability of the combination of duloxetine and bupropion is generally good, although side effects can occur, as mentioned earlier 2, 3.