Can Cymbalta (duloxetine) and Buspar (buspirone) be used together in treatment?

Duloxetine (Cymbalta) and Buspirone (Buspar) Combination Therapy

Yes, duloxetine (Cymbalta) and buspirone (Buspar) can be safely used together in treatment, but caution should be exercised due to potential serotonergic effects when combining these medications. 1, 2

Mechanism of Action and Rationale

• Duloxetine: A serotonin and noradrenaline reuptake inhibitor (SNRI) that inhibits the reuptake of both serotonin and norepinephrine in the CNS 3
• Buspirone: An azaspirodecanedione anxiolytic that primarily works through 5-HT1A receptors, with a different mechanism than benzodiazepines 4

The combination can be beneficial because:

• Duloxetine addresses both depression and anxiety through dual neurotransmitter action
• Buspirone provides additional anxiolytic effects through a different mechanism
• The 2023 American College of Physicians guideline notes that various augmentation strategies can provide similar symptom relief in treatment of depression 1

Clinical Evidence Supporting Combination

The Annals of Internal Medicine systematic review (2023) found that:

• Various augmentation strategies involving different pharmacologic agents rendered similar efficacy for treating depression 1
• Augmentation strategies can be effective as second-step treatments when initial treatment with antidepressants is insufficient 1

Potential Concerns and Monitoring

Serotonin Syndrome Risk

• The FDA label for buspirone specifically warns about potential serotonin syndrome when combined with other serotonergic drugs 2
• Monitor for signs of serotonin syndrome including:
  • Mental status changes (agitation, hallucinations, delirium)
  • Autonomic instability (tachycardia, labile blood pressure, dizziness)
  • Neuromuscular changes (tremor, rigidity, myoclonus)
  • Gastrointestinal symptoms (nausea, vomiting, diarrhea) 2

Contraindications

• Do not use this combination with MAOIs due to risk of elevated blood pressure 2
• Avoid in patients with seizure disorders (particularly relevant for duloxetine)

Dosing Considerations

• Buspirone: Initial dosage of 5 mg twice daily, with maximum of 20 mg three times daily 1
• Duloxetine: Typically 60-120 mg once daily for anxiety disorders 3
• Start with lower doses when initiating combination therapy and titrate gradually

Common Side Effects to Monitor

• Duloxetine: Nausea, dry mouth, headache, constipation, dizziness, and fatigue 3
• Buspirone: Headaches, dizziness, nervousness, and lightheadedness 4

Clinical Pearls

• Unlike benzodiazepines, buspirone does not cause significant sedation, has no muscle relaxant or anticonvulsant properties, and has low abuse potential 4, 5
• Buspirone may take 2-4 weeks to become effective, so patience is required when initiating therapy 1
• Duloxetine can be administered without regard to food or time of day 3
• This combination may be particularly useful for patients with both depression and anxiety symptoms 6

Alternative Approaches

If this combination is not effective or poorly tolerated, consider:

• Switching to a different antidepressant class
• Augmentation with bupropion instead of buspirone (shown to have better outcomes in some cases) 7
• Adding cognitive behavioral therapy, which has similar effectiveness to antidepressants with fewer adverse effects 7

Remember that while this combination is generally safe, careful monitoring for serotonin syndrome and other adverse effects is essential, particularly during the initial weeks of treatment.