Can bupropion be given with escitalopram (Lexapro) as an adjunct?

From the Guidelines

Yes, bupropion can be given with Lexapro (escitalopram) as an adjunct treatment. This combination is sometimes prescribed for patients with depression who have not achieved adequate response with Lexapro alone or who experience certain side effects like sexual dysfunction or fatigue. Typically, a patient might continue their established Lexapro dose (usually 10-20 mg daily) while adding bupropion (often starting at 150 mg daily of the XL formulation, potentially increasing to 300 mg daily if needed) 1. This combination works well mechanistically because the medications affect different neurotransmitter systems - Lexapro primarily increases serotonin levels while bupropion affects dopamine and norepinephrine.

When initiating this combination, patients should be monitored for potential side effects including increased anxiety, insomnia, or elevated blood pressure. The combination may actually help counterbalance some side effects, as bupropion can reduce Lexapro-induced sexual dysfunction and fatigue. Patients with seizure disorders, eating disorders, or certain other conditions should use this combination with caution or avoid it altogether, as bupropion can lower the seizure threshold. According to the American College of Physicians, bupropion is associated with a lower rate of sexual adverse events than fluoxetine or sertraline 1.

Some key points to consider when using this combination include:

• Monitoring for increased anxiety, insomnia, or elevated blood pressure
• Starting with a low dose of bupropion (150 mg daily) and potentially increasing to 300 mg daily if needed
• Being cautious in patients with seizure disorders, eating disorders, or certain other conditions
• Considering the potential benefits of reduced sexual dysfunction and fatigue with the addition of bupropion. It's essential to weigh the potential benefits and risks of this combination and to closely monitor patients for any adverse effects, as recommended by the American College of Physicians 1.

From the Research

Combination of Bupropion and Lexapro

• The combination of bupropion and selective serotonin reuptake inhibitors (SSRIs) like Lexapro can increase the risk of serotonin syndrome, a potentially fatal complication 2.
• Bupropion inhibits noradrenaline and dopamine reuptake with milder effects on serotonergic activity, but its specific inhibition of the cytochrome P450 2D6 pathway can increase blood levels of SSRIs and tricyclic antidepressants, potentially leading to serotonin syndrome 2.
• A study found that the combination of escitalopram (another SSRI) and bupropion-SR was effective and well-tolerated in treating patients with major depressive disorder, with response and remission rates higher than typical for SSRI monotherapy 3.
• Another study reviewed the literature on combining bupropion with SSRIs or SNRIs and found that controlled and open-label studies support the effectiveness of bupropion in reversing antidepressant-associated sexual dysfunction, and open trials suggest that combination treatment is effective for treating MDD in patients refractory to SSRI or SNRI alone 4.

Safety and Tolerability

• The combination of bupropion and SSRIs can be generally well-tolerated, but clinicians should monitor for serotonergic toxicity when evaluating patients after bupropion overdose 5.
• A study found that the incidence of serotonin toxicity was 33% in patients who ingested bupropion in the absence of other serotonergic drugs, and serotonin toxicity was more likely after a suicide attempt than those with an accidental ingestion or after recreational drug use 5.
• The level of treatment-emergent adverse events was low in a study combining escitalopram and bupropion-SR, and only 3 participants (6%) discontinued treatment due to side effects 3.

Clinical Considerations

• Clinicians should be aware of the potential risks and benefits of combining bupropion with Lexapro, and carefully monitor patients for signs of serotonin syndrome or other adverse effects 2, 5, 3, 4.
• The combination of bupropion and Lexapro may be effective for treating patients with major depressive disorder who have had an inadequate response to antidepressant monotherapy, but further controlled trials are needed to confirm this 3, 4.