Is it safe to take Sertraline (Zoloft) and Bupropion (Wellbutrin) together?

From the Guidelines

Yes, Zoloft (sertraline) and Wellbutrin (bupropion) can be taken together, and this combination is sometimes prescribed by healthcare providers. These medications work differently in the brain - Zoloft is a selective serotonin reuptake inhibitor (SSRI) that increases serotonin levels, while Wellbutrin affects dopamine and norepinephrine. This combination may be particularly helpful for people who haven't responded adequately to either medication alone or who experience certain side effects from one medication that might be counteracted by the other. For example, Wellbutrin might help with the sexual side effects or fatigue sometimes caused by Zoloft.

According to the American College of Physicians, second-generation antidepressants, including Zoloft and Wellbutrin, can be effective for treating depression, and the choice of medication should be based on adverse effect profiles, cost, and patient preferences 1. The evidence suggests that Bupropion is associated with a lower rate of sexual adverse events than fluoxetine or sertraline, whereas paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 1.

Some key points to consider when taking Zoloft and Wellbutrin together include:

• The combination should only be taken under medical supervision, as there can be potential drug interactions and side effects to monitor.
• Your doctor will need to determine appropriate dosages for your specific situation and will want to monitor you for any adverse effects, particularly during the initial adjustment period.
• Always inform your healthcare provider about all medications you're taking to ensure safe and effective treatment.
• 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.
• 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 1.

It's also important to note that more recent evidence from 2015 suggests that selective serotonin reuptake inhibitors, such as Zoloft, are more likely than placebo to produce depression remission in the primary care population, and serotonin-norepinephrine reuptake inhibitors are slightly more likely than selective serotonin reuptake inhibitors to improve depression symptoms, but they are associated with higher rates of adverse effects 1.

Overall, the decision to take Zoloft and Wellbutrin together should be made on a case-by-case basis, taking into account the individual's specific needs and medical history, and under the close supervision of a healthcare provider.

From the FDA Drug Label

DRUG INTERACTIONS Drugs metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline)

• Key Interaction: Bupropion (Wellbutrin) can increase concentrations of sertraline (Zoloft) due to CYP2D6 inhibition.
• Clinical Decision: When taking Zoloft and Wellbutrin together, consider a dose reduction of Zoloft to minimize potential increased concentrations and adverse effects 2.

From the Research

Combination of Zoloft and Wellbutrin

The combination of Zoloft (sertraline) and Wellbutrin (bupropion) has been studied in various research papers.

• A study published in 2004 3 reported a case of serotonin syndrome induced by the combination of bupropion and SSRIs, including sertraline.
• However, another study published in 1995 4 found that the combination of bupropion and sertraline was effective in treating refractory depression in four patients, with no adverse effects reported.

Potential Risks and Benefits

• The 2004 study 3 highlights the potential risk of serotonin syndrome when combining bupropion with SSRIs, which can be potentially fatal.
• On the other hand, the 1995 study 4 suggests that the combination of bupropion and sertraline may be effective in treating depression due to the synergism of its two distinct antidepressant mechanisms.
• It is essential to note that the role of bupropion in serotonin syndrome is possibly related to its inhibition of the cytochrome P450 2D6 pathway, which can increase blood levels of SSRIs and tricyclic antidepressants 3.

Important Considerations

• The combination of Zoloft and Wellbutrin should be approached with caution, and patients should be closely monitored for signs of serotonin syndrome, such as myoclonic jerks, confusion, and dysautonomia 3.
• The decision to combine these medications should be made on a case-by-case basis, taking into account the individual patient's medical history and response to treatment 4.