What non-stimulant medication is best to add to a regimen of Remeron (mirtazapine) and Cymbalta (duloxetine)?

Bupropion is the Best Non-Stimulant Addition to Remeron and Cymbalta

For patients taking Remeron (mirtazapine) and Cymbalta (duloxetine), bupropion is the optimal non-stimulant medication to add to the regimen due to its complementary mechanism of action and favorable side effect profile.

Rationale for Choosing Bupropion

Bupropion offers several advantages when added to a regimen of Remeron and Cymbalta:

1. Complementary Mechanism of Action:

   • Bupropion primarily inhibits the reuptake of norepinephrine and dopamine 1
   • This provides a different mechanism than Remeron (which affects serotonin, norepinephrine, and histamine) and Cymbalta (which inhibits serotonin and norepinephrine reuptake)
   • The combination targets all three major neurotransmitters: serotonin, norepinephrine, and dopamine

2. Favorable Side Effect Profile:

   • Bupropion tends to be activating rather than sedating 2
   • It can counterbalance the sedative effects of Remeron
   • Unlike many other antidepressants, bupropion is associated with weight loss rather than weight gain 2
   • Has very low rates of sexual dysfunction compared to other options 3

Dosing Considerations

• Start with a low dose of bupropion (100-150 mg daily) 2
• Titrate gradually to minimize side effects, typically increasing by 100 mg every 5-7 days 2
• Maximum recommended dose is 400 mg daily for SR formulation 2
• Administer bupropion in the morning to minimize risk of insomnia 1
• Consider using extended-release formulations to reduce peak concentration effects 1

Monitoring and Safety Considerations

1. Potential Side Effects to Monitor:

   • Insomnia and agitation (most common) 4
   • Increased blood pressure and heart rate 1
   • Seizure risk (though rare at therapeutic doses) 4

2. Important Precautions:

   • Regular follow-up within 1-2 weeks of initiation 1
   • Monitor vital signs, particularly blood pressure and heart rate 1
   • Watch for signs of excessive stimulation (insomnia, anxiety, agitation, tremor) 1
   • Bupropion should not be used in patients with a history of seizures 1

Alternative Options (If Bupropion Is Contraindicated)

If bupropion is contraindicated, consider:

1. Atomoxetine:

   • Non-stimulant option for ADHD 2
   • Starting dose of 40 mg daily, can be titrated up to 80-100 mg daily 2
   • Less data on combination with antidepressants

2. Anticonvulsants:

   • Divalproex sodium or sodium valproate have evidence for efficacy in mood disorders 2
   • Consider especially if there are features of bipolar disorder or migraine

Contraindications for Bupropion

Do not use bupropion in patients with:

• History of seizures
• Current or prior diagnosis of bulimia or anorexia nervosa
• Undergoing abrupt discontinuation of alcohol or sedatives
• Concurrent use of MAO inhibitors
• Uncontrolled hypertension 1

Conclusion

When adding a non-stimulant medication to a regimen of Remeron and Cymbalta, bupropion represents the best choice due to its complementary mechanism of action, activating properties that can offset Remeron's sedation, and favorable side effect profile regarding weight and sexual function. Start with a low dose, monitor closely for side effects, and adjust as needed based on response and tolerability.