Can sertraline and bupropion (Wellbutrin) be administered together for the treatment of depression and Attention Deficit Hyperactivity Disorder (ADHD)?

From the Guidelines

Yes, sertraline and bupropion can be prescribed together for patients with both depression and ADHD, as this combination is commonly used in clinical practice and works through different mechanisms to address both conditions. Sertraline is an SSRI that primarily addresses depression and anxiety by increasing serotonin levels, while bupropion works on dopamine and norepinephrine systems, which can help with both depression and ADHD symptoms, particularly with focus, concentration, and energy 1. Typical starting doses are sertraline 25-50mg daily, gradually increasing to 50-200mg daily as needed, and bupropion 150mg daily, potentially increasing to 150mg twice daily or 300mg XL once daily.

When initiating this combination, it's essential to start one medication first, stabilize the dose, then add the second medication to better monitor for side effects, as recommended by the American College of Physicians 1. Patients should be monitored for potential side effects, including increased anxiety, insomnia, dry mouth, headache, and rarely, increased risk of seizures with bupropion. This combination may be particularly helpful for patients who have partial response to either medication alone or who experience sexual side effects from sertraline, as bupropion may help counteract these effects 1.

Some key points to consider when prescribing this combination include:

• Monitoring 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
• Being aware of the potential for increased risk of suicidal thoughts and behaviors, particularly during the first 1 to 2 months of treatment 1
• Considering the use of bupropion as an alternative to other antidepressants, due to its lower rate of sexual adverse events 1
• Evaluating the effectiveness of combination therapy and adjusting treatment as needed to achieve optimal outcomes for patients with depression and ADHD 1

From the FDA Drug Label

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

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

From the Research

Combination Therapy for Depression and ADHD

• The combination of sertraline and bupropion (Wellbutrin) has been studied as a potential treatment for depression, with some evidence suggesting its effectiveness in patients with refractory depression 3.
• A double-blind comparison of bupropion sustained release and sertraline found that both treatments were similarly effective for the treatment of depression, with bupropion having a more favorable side effect profile 4.
• The use of bupropion in combination with serotonin reuptake inhibitors, such as sertraline, has been reviewed in the literature, with evidence suggesting that this combination can be effective for the treatment of major depressive disorder (MDD) and can help to reverse antidepressant-associated sexual dysfunction 5.

Treatment of Comorbid ADHD and Depression

• A study examining treatment outcome with antidepressants and/or stimulants in adults with comorbid attention-deficit disorder (ADD) and major depressive disorder (MDD) found that venlafaxine monotherapy may have similar efficacy to a treatment with a combination of stimulant plus antidepressant therapy, and superior to stimulant therapy alone 6.
• Another study found that bupropion SR augmentation of partial and non-responders to serotonergic antidepressants, such as sertraline, can be an effective strategy in the treatment of resistant depression 7.

Potential Benefits and Risks

• The combination of sertraline and bupropion may offer a synergistic effect, with bupropion's dopaminergic and noradrenergic mechanisms complementing sertraline's serotonergic effects 3.
• However, the safety and efficacy of this combination in patients with comorbid ADHD and depression require further study, and patients should be closely monitored for potential side effects and interactions 4, 5.