Do Lisdexamfetamine (Vyvanse) and Bupropion (Wellbutrin), Escitalopram (Lexapro) interact?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Article Review Status
Submitted
Under Review
Approved

Last updated: April 27, 2025 • View editorial policy

From the Guidelines

Vyvanse and Wellbutrin, when combined with Lexapro, can interact and increase the risk of adverse effects, and therefore, their concurrent use should be approached with caution and close monitoring. The combination of Vyvanse (lisdexamfetamine) and Wellbutrin (bupropion) may increase the risk of seizures, as both medications can lower the seizure threshold 1. Additionally, both Vyvanse and Wellbutrin can cause increased blood pressure and heart rate, potentially amplifying these effects when used together. When combining Lexapro (escitalopram) with these medications, there's a risk of serotonin syndrome, particularly with Vyvanse, as both can increase serotonin levels. Some key points to consider when prescribing these medications together include:

  • Monitoring for symptoms of serotonin syndrome, such as agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and hyperthermia
  • Closely observing blood pressure and heart rate due to the potential for these medications to cause increases in these parameters
  • Being aware of the potential for increased risk of seizures, although there are no case reports of side effects when these agents were combined, as noted in the practice parameter for the use of stimulant medications 1
  • Ensuring patients are informed about the potential risks and the importance of reporting any unusual symptoms immediately. It's crucial for healthcare providers to weigh the benefits against the potential risks when prescribing these medications together and to adjust treatment plans accordingly, based on the most recent and highest quality evidence available.

From the Research

Interaction between Vyvanse, Wellbutrin, and Lexapro

  • The combination of bupropion (Wellbutrin) and selective serotonin reuptake inhibitors (SSRIs) like escitalopram (Lexapro) can increase the risk of serotonin syndrome, a potentially fatal complication 2.
  • Bupropion inhibits the reuptake of noradrenaline and dopamine, and has mild effects on serotonergic activity, which can contribute to the development of serotonin syndrome when combined with SSRIs 2.
  • A study reported a case of serotonin syndrome in a patient treated with bupropion and sertraline, highlighting the potential for misinterpretation of early symptoms as signs of aggravation of the underlying condition 2.
  • The use of bupropion in combination with SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs) is generally well-tolerated and can be effective in treating major depressive disorder (MDD) and reversing antidepressant-associated sexual dysfunction 3.
  • Lisdexamfetamine (Vyvanse) is a long-acting amfetamine prodrug that has been approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults, and has a safety profile consistent with long-acting stimulants 4, 5.
  • There is no direct evidence on the interaction between Vyvanse, Wellbutrin, and Lexapro, but the combination of bupropion and SSRIs can increase the risk of serotonin syndrome, and the use of lisdexamfetamine with other medications should be monitored closely to minimize potential adverse effects 2, 4, 5, 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.