What are the effects of combining a new antidepressant with Bupropion (Wellbutrin)?

From the Guidelines

Combining a new antidepressant with Bupropion (Wellbutrin) should be done with caution and under close medical supervision, as it may increase the risk of side effects, but can be beneficial for patients who have not responded to single-medication treatment. This approach, called combination therapy, may be beneficial for patients who haven't responded adequately to single-medication treatment. Wellbutrin works differently from many other antidepressants by primarily affecting dopamine and norepinephrine rather than serotonin, making it potentially complementary to SSRIs or SNRIs 1. Common combinations include Wellbutrin with medications like sertraline (Zoloft), escitalopram (Lexapro), or venlafaxine (Effexor).

Key Considerations

• Typical Wellbutrin dosing ranges from 150-450 mg daily, often starting at a lower dose and gradually increasing.
• When combining medications, the doctor will likely start one medication first, stabilize the dose, then add the second medication at a low dose before adjusting as needed.
• Potential benefits include improved depression symptoms, reduced sexual side effects from SSRIs, and increased energy.
• However, combination therapy may increase the risk of side effects, drug interactions, and rarely, seizures or elevated blood pressure.
• Regular follow-up appointments are essential to monitor effectiveness and any adverse effects, as recommended by the American College of Physicians 1.

Monitoring and Safety

• The U.S. Food and Drug Administration advises that all patients receiving antidepressants be closely monitored on a regular basis for increases in suicidal thoughts and behaviors, particularly during the first 1 to 2 months of treatment 1.
• Patients should be monitored for the emergence of agitation, irritability, or unusual changes in behavior, as these symptoms can indicate that the depression is getting worse.
• The risk of adverse effects, such as gastrointestinal bleeding, hepatotoxicity, hyponatremia, QT prolongation, and sexual effects, should be carefully evaluated and monitored 1.

From the Research

Effects of Combining a New Antidepressant with Bupropion (Wellbutrin)

• The combination of antidepressants, including Bupropion, is a strategy used to treat depression, especially in cases where monotherapy is ineffective 2.
• There is limited evidence supporting the use of combination antidepressant therapies, and safety concerns are often cited 2.
• Bupropion has been used in the treatment of bipolar disorders, but it may pose the same risks as other antidepressants in precipitating manic episodes in depressed bipolar patients 3.
• The use of antidepressant combinations, including Bupropion, can be an effective treatment option for therapy-resistant depression, but it also carries potential safety risks due to pharmacokinetic and pharmacodynamic interactions 4.
• Antidepressants, including Bupropion, are probably effective in bipolar depression and possibly not less than in major depressive disorder (MDD), but optimal treatment of depression requires further investigation 5.

Safety and Efficacy Considerations

• The combination of benzodiazepines and antidepressants has been shown to be more effective than antidepressants alone in improving depression severity, response in depression, and remission in depression in the early phase, but these effects were not maintained in the acute or continuous phase 6.
• Combined therapy resulted in fewer dropouts due to adverse events than antidepressants alone, but combined therapy was associated with a greater proportion of participants reporting at least one adverse effect 6.
• The use of Bupropion in combination with other antidepressants requires careful consideration of the potential risks and benefits, including the risk of precipitating manic episodes in bipolar patients 3, 5.

Treatment Guidelines

• Preferred antidepressants for bipolar depression include serotonin-reuptake inhibitors (SRIs) and Bupropion, given in moderate doses for limited times, and best combined with lithium, some anticonvulsants, or certain atypical antipsychotics 5.
• The distinct knowledge of available antidepressant combination strategies, including Bupropion, may help to increase response and remission rates in therapy-resistant depression, but further research is urgently needed to determine relative efficacy 4.