Can I use Mirtazapine (Remeron) and Venlafaxine (Effexor) together?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: April 29, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Combining mirtazapine and venlafaxine (Effexor) is possible, but it should only be done under close medical supervision, as this combination may increase the risk of side effects, including serotonin syndrome, increased blood pressure, sedation, and weight gain, as noted in studies such as 1. When considering this combination, it's essential to weigh the potential benefits against the risks. Mirtazapine and venlafaxine have complementary mechanisms of action, which may make them more effective for treatment-resistant depression than either medication alone. However, the increased risk of adverse events, including serotonin syndrome, a potentially dangerous condition, must be carefully monitored by a healthcare provider, as highlighted in 1 and 1. Some key points to consider when combining these medications include:

  • Increased risk of serotonin syndrome, which can be life-threatening if not recognized and treated promptly, as mentioned in 1
  • Potential for increased blood pressure, sedation, and weight gain, as noted in 1 and 1
  • Importance of close medical supervision to monitor for adverse events and adjust dosages as needed, as recommended in 1
  • Need for careful consideration of potential interactions with other medications, as highlighted in 1 and 1 If you're considering combining mirtazapine and venlafaxine due to inadequate response to your current treatment, it's crucial to schedule an appointment with your doctor to discuss your options and determine the best course of action for your specific situation, taking into account the guidelines and recommendations outlined in 1, 1, and 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Combination of Mirtazapine and Effexor

  • The combination of mirtazapine and venlafaxine (Effexor) has been reported to increase the risk of serotonin syndrome, a potentially life-threatening condition 2, 3.
  • Serotonin syndrome is characterized by symptoms such as agitation, confusion, severe shivering, diaphoresis, myoclonus, hyperreflexia, mydriasis, tachycardia, and fever 2.
  • The development of serotonin syndrome is likely due to the activation of 5-HT(1A) receptors by mirtazapine, the combined serotonin reuptake inhibition by venlafaxine, and possible serotonin release by other medications 2.

Risk of Serotonin Syndrome

  • The combination of selective serotonin reuptake inhibitors (SSRIs) with other medications, including venlafaxine and mirtazapine, increases the risk of serotonin syndrome 4.
  • The risk of serotonin syndrome is higher when SSRIs are combined with other medications that exhibit serotonergic properties, such as opioids and other antidepressants 4.
  • Close monitoring for symptoms of serotonin syndrome is recommended when combining antidepressants, including mirtazapine and venlafaxine 4.

Optimal Dosing of Antidepressants

  • The optimal dose of mirtazapine and venlafaxine for the treatment of major depression is not well established, but lower doses may achieve the optimal balance between efficacy, tolerability, and acceptability 5.
  • The dose-efficacy curve for SSRIs shows a gradual increase up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses 5.
  • Venlafaxine and mirtazapine show optimal acceptability in the lower range of their licensed dose 5.

Efficacy and Tolerability of Antidepressants

  • SSRIs are generally regarded as effective and better tolerated alternatives to tricyclic antidepressants (TCAs) for the treatment of depression 6.
  • Mirtazapine and venlafaxine are as well tolerated as SSRIs and show comparable efficacy 6.
  • Minor differences have been observed between some SSRIs and some of the newer antidepressants, but these findings are far from conclusive 6.

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.