Can you take mirtazapine (Remeron) and venlafaxine (Effexor) together?

Combining Mirtazapine and Venlafaxine for Depression Treatment

Yes, mirtazapine (Remeron) and venlafaxine (Effexor) can be taken together and this combination is sometimes used in clinical practice for treatment-resistant depression. 1, 2

Evidence for Combination Therapy

• The combination of mirtazapine and venlafaxine has shown effectiveness in patients with persistent depressive illness who have failed previous antidepressant trials, with response rates of approximately 50% at 8 weeks and 56% at 6 months 2
• In a prospective case series, the combination produced a response rate of 81.8% and a remission rate of 27.3% after approximately 8 weeks of treatment in patients who had failed at least one previous antidepressant trial 1
• The STAR*D study examined this combination as a treatment option for highly treatment-resistant depression, finding modest remission rates (13.7%) in patients who had failed three previous medication trials 3

Pharmacological Rationale

• Mirtazapine works primarily by blocking presynaptic alpha-2 adrenoreceptors and has a different mechanism of action than many other antidepressants 4
• Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that inhibits serotonin reuptake at lower doses and both serotonin and norepinephrine reuptake at higher doses 4
• The combination provides complementary mechanisms of action that may produce synergistic effects in treating depression 1

Dosing Considerations

• Clinical response to the combination typically occurs at moderate to high doses of both medications 2
• In studies, the mean daily doses at endpoint were approximately:
  • Venlafaxine: 210 mg (range varies based on individual response) 3
  • Mirtazapine: 35-36 mg (range varies based on individual response) 3

Side Effects and Monitoring

• Common side effects of the combination include:
  • Sedation (19% of patients) 2
  • Weight gain (19% of patients) 2
  • Dry mouth, decreased appetite, nausea, and constipation (particularly with venlafaxine) 5
• Approximately 44% of patients may experience some adverse effects, with about 16% discontinuing treatment due to these effects 2
• Both medications should be stopped gradually to prevent discontinuation symptoms, which are particularly common with venlafaxine 5

Special Considerations

• Mirtazapine has a faster onset of action compared to many other antidepressants, which may provide earlier symptom relief 5
• Mirtazapine may help with insomnia and anxiety symptoms that often accompany depression 5
• This combination is more commonly used after failure of first-line treatments rather than as initial therapy 3

Cautions

• The combination should be used with caution in elderly patients due to increased risk of side effects like sedation, falls, and cognitive impairment 5
• In patients with cardiovascular disease, careful monitoring is needed as SNRIs like venlafaxine may cause hypertension at higher doses 5
• Regular monitoring for serotonin syndrome is recommended, although serious adverse effects specifically linked to this combination appear to be rare in clinical studies 2