Can you take Pristiq (desvenlafaxine) 300 mg daily and Mirtazapine (remeron) 45 mg daily together?

Safety of Combining Pristiq 300 mg and Mirtazapine 45 mg Daily

Combining Pristiq (desvenlafaxine) 300 mg daily with Mirtazapine (Remeron) 45 mg daily is not recommended due to the significant risk of serotonin syndrome, which can be life-threatening.

Risk of Serotonin Syndrome

Combining these two antidepressants at high doses creates a dangerous situation due to their overlapping serotonergic effects:

• Pristiq (desvenlafaxine) is an SNRI (serotonin-norepinephrine reuptake inhibitor) that increases both serotonin and norepinephrine levels
• Mirtazapine, while having a unique mechanism as a NaSSA (noradrenergic and specific serotonergic antidepressant), still enhances serotonergic neurotransmission 1
• Both medications at these high doses significantly increase serotonin levels in the brain, creating a high risk for serotonin syndrome

Serotonin Syndrome Warning Signs

Serotonin syndrome can develop within 24-48 hours of combining serotonergic medications and presents with 2:

• Mental status changes (confusion, agitation, anxiety)
• Neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity)
• Autonomic hyperactivity (hypertension, tachycardia, arrhythmias, diaphoresis)
• Advanced symptoms include fever, seizures, and unconsciousness, which can be fatal

Dosing Concerns

Both medications are being used at their maximum or above-maximum recommended doses:

• Pristiq 300 mg daily exceeds the typical maximum dose of 100 mg daily
• Mirtazapine 45 mg is at the upper limit of its recommended dosage range 2

Using both medications at these high doses substantially increases the risk of adverse effects.

Alternative Approaches

If treatment for depression is needed, consider these safer options:

1. Use a single antidepressant at an optimal dose rather than combining two at high doses
2. If combination therapy is necessary:
   • Reduce doses of both medications significantly
   • Consider a different combination with lower serotonergic activity
   • Implement careful monitoring for signs of serotonin syndrome

Monitoring Requirements

If a provider still decides to use this combination (which is not recommended):

• Start with much lower doses of both medications
• Increase doses very gradually with at least 1-2 weeks between adjustments
• Monitor closely for symptoms of serotonin syndrome, especially in the first 24-48 hours after any dose change 2
• Educate the patient about warning signs that require immediate medical attention

Conclusion

The combination of Pristiq 300 mg and mirtazapine 45 mg daily poses a significant risk of serotonin syndrome and other adverse effects. A safer approach would be to use a single antidepressant at an optimal dose or, if combination therapy is necessary, use much lower doses with careful monitoring.