What are the side effects of combining Mirtazapine (Remeron) with Venlafaxine (Effexor)?

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Last updated: April 29, 2025View editorial policy

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From the Research

Taking mirtazapine with Effexor (venlafaxine) can cause significant side effects, including increased risk of serotonin syndrome, and should only be done under close medical supervision, with careful consideration of the patient's blood pressure status and cardiovascular comorbidities, as suggested by the most recent study 1.

Side Effects of Mirtazapine with Effexor

The combination of mirtazapine and venlafaxine has been used to treat depression, particularly in cases where single medications have been ineffective. However, this combination can lead to several side effects due to their combined action on brain chemicals.

  • Common side effects include:
    • Increased drowsiness
    • Dizziness
    • Dry mouth
    • Constipation
    • Weight gain
    • Increased appetite
  • More serious concerns include:
    • Serotonin syndrome, which can cause confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures or loss of consciousness, as reported in a case study 2
    • Increased risk of suicidal thoughts, especially when starting treatment or changing doses
    • Blood pressure changes, as discussed in a review of antidepressant effects on blood pressure 1
    • Sexual dysfunction
    • Abnormal bleeding

Dosage and Supervision

This combination is sometimes prescribed intentionally as "California rocket fuel" to treat depression resistant to single medications.

  • Dosages typically start low (such as 7.5-15mg mirtazapine and 37.5-75mg venlafaxine) and are adjusted based on response and side effects.
  • It is essential to inform your doctor about all medications you're taking to avoid dangerous interactions.

Clinical Evidence

Studies have shown that the combination of venlafaxine and mirtazapine can be effective in treating depression, with response rates of 81.8% and remission rates of 27.3% in one prospective case series 3. However, nearly half of the patients in this study experienced significant side effects during treatment.

  • A systematic review and dose-response meta-analysis found that the lower range of the licensed dose of antidepressants, including venlafaxine and mirtazapine, achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression 4.
  • Another study found that 44% of patients experienced some adverse effects with sedation (19%) and weight gain (19%) being the most frequent, and five patients discontinued treatment due to these effects 5.

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.

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