Can you take Remeron (mirtazapine) and trazodone together?

Combining Mirtazapine and Trazodone: Safety and Efficacy

Yes, mirtazapine (Remeron) and trazodone can be safely taken together, but this combination should be monitored for excessive sedation and potential serotonin syndrome. 1, 2

Pharmacological Rationale

Mirtazapine and trazodone work through different mechanisms:

• Mirtazapine: Acts as a noradrenergic and specific serotonergic antidepressant (NaSSA) by:

  • Blocking α2-adrenergic autoreceptors
  • Antagonizing 5-HT2 and 5-HT3 receptors
  • Promoting sleep, appetite, and weight gain 3

• Trazodone: Functions as a:

  • 5-HT2A and 5-HT2C receptor antagonist
  • Selective serotonin reuptake inhibitor
  • Potent sedative at lower doses 4

Clinical Evidence for Combination Use

The American Academy of Sleep Medicine clinical guideline acknowledges that combinations of medications from different classes may improve efficacy by targeting multiple sleep-wake mechanisms while minimizing the toxicity that could occur with higher doses of a single agent 1. While no specific studies have examined the mirtazapine-trazodone combination, clinical experience suggests the general safety of combining antidepressants with different mechanisms.

Dosing Considerations

When using this combination:

• Start with lower doses of each medication
• Mirtazapine: Begin with 7.5-15 mg at bedtime 1
• Trazodone: Begin with a low dose, typically 25-50 mg at bedtime for sleep
• Timing: Administer both medications at bedtime to capitalize on their sedative effects and minimize daytime drowsiness

Monitoring and Precautions

1. Watch for excessive sedation:

   • Both medications are sedating and effects may be additive
   • Monitor for daytime drowsiness, cognitive impairment, and psychomotor effects

2. Monitor for serotonin syndrome:

   • Although the risk is lower than with other combinations, be alert for:
   • Mental status changes (agitation, hallucinations)
   • Autonomic instability (tachycardia, hyperthermia)
   • Neuromuscular symptoms (tremor, hyperreflexia) 5

3. QTc prolongation:

   • Mirtazapine has been associated with QT prolongation
   • Use caution in patients with cardiovascular disease 5

4. Blood dyscrasias:

   • Mirtazapine has rare but serious risk of agranulocytosis
   • Monitor for signs of infection, fever, or sore throat 5

Advantages of the Combination

1. Enhanced sleep benefits:

   • Both medications promote sleep through different mechanisms
   • May be particularly helpful for patients with treatment-resistant insomnia

2. Complementary antidepressant effects:

   • Different mechanisms may provide broader antidepressant coverage
   • Mirtazapine promotes appetite while trazodone has minimal effect on weight

3. Low risk of mania induction:

   • Both medications have relatively low risk for inducing mania, especially at lower doses used for sleep 6

Potential Drug Interactions

A prospective study investigating potential interactions between trazodone and SSRIs (citalopram and fluoxetine) found no significant pharmacokinetic interactions, suggesting a wide safety margin when combining trazodone with other serotonergic medications 7.

Clinical Recommendation

For patients with depression and insomnia who have not responded adequately to monotherapy, the combination of mirtazapine and trazodone at lower doses may be beneficial. Start with low doses of each medication, administer at bedtime, and monitor closely for excessive sedation and signs of serotonin syndrome.

Important Caveats

• This combination may not be appropriate for elderly patients or those with hepatic/renal impairment due to increased risk of side effects
• Avoid combining with other CNS depressants including alcohol
• Discontinuation should be gradual to prevent withdrawal symptoms