Combining Buspirone with Amitriptyline
Buspirone can be safely added to amitriptyline without significant pharmacokinetic interactions or increased adverse effects, making this a reasonable combination for patients with comorbid depression and anxiety. 1
Pharmacokinetic Safety Profile
The FDA label for buspirone specifically addresses this combination and provides reassuring data:
No clinically significant drug interactions exist between buspirone and amitriptyline. After adding buspirone to amitriptyline, no statistically significant differences were observed in steady-state pharmacokinetic parameters (Cmax, AUC, and Cmin) of amitriptyline or its metabolite nortriptyline. 1
This lack of interaction means dose adjustments of either medication are typically unnecessary when combining them. 1
Clinical Context for Combination Therapy
When to Consider This Combination
For patients with comorbid depression and anxiety (present in 50-60% of depressive disorders), the usual practice is to treat depression first. 2
However, augmentation strategies become appropriate when:
- Initial antidepressant treatment (amitriptyline in this case) provides inadequate response after 8 weeks despite good adherence 2
- Significant anxiety symptoms persist despite treatment of depression 2
- The patient requires anxiolytic therapy but you want to avoid benzodiazepines 3, 4
Evidence for Buspirone as Augmentation
The STAR*D trial demonstrated that augmenting an SSRI with buspirone showed similar efficacy to augmentation with bupropion or cognitive therapy for treatment-resistant depression. 2
Key findings from augmentation studies:
- Buspirone augmentation showed no difference in response or remission rates compared to other augmentation strategies 2
- Discontinuation due to adverse events was significantly higher with buspirone (20.6%) compared to bupropion (12.5%, P < 0.001) 2
- This higher discontinuation rate suggests tolerability concerns that warrant careful monitoring 2
Practical Implementation
Dosing Considerations
- Start buspirone at low doses (e.g., 7.5 mg twice daily) and titrate to 15-30 mg/day in divided doses 3, 4
- Buspirone should be taken consistently either always with or always without food 1
- Expect a 1-2 week lag time before anxiolytic effects become apparent—patient education about this delay is critical for compliance 3, 4
Monitoring Requirements
Assess treatment response regularly using standardized instruments at 4 weeks, 8 weeks, and end of treatment. 2
Monitor for:
- Dizziness, headache, and nausea (most common adverse effects) 5
- Restlessness or akathisia-like syndrome (may occur shortly after initiation) 1
- Palpitations (more common with twice-daily dosing) 5
Important Caveats
Buspirone is NOT appropriate for panic disorder—studies have been inconclusive, and it should not be used for this indication. 3
Avoid large amounts of grapefruit juice, which can increase buspirone concentrations 9-fold (AUC) and 4-fold (Cmax). 1
Buspirone lacks the immediate anxiolytic effect of benzodiazepines—it is most appropriate for patients who do not require immediate symptom relief and can tolerate gradual improvement over 1-2 weeks. 3
Alternative Considerations
If augmentation is needed after 8 weeks of inadequate response to amitriptyline:
- Switching to a different antidepressant may be equally effective as augmentation strategies 2
- Cognitive behavioral therapy shows similar efficacy to medication augmentation with potentially lower discontinuation rates (9.2% vs 18.8% for medications) 2
- Bupropion augmentation has better tolerability than buspirone based on discontinuation rates 2
Special Populations
- Elderly patients: No dose adjustment needed based on age alone; buspirone pharmacokinetics are unchanged in older adults 1
- Hepatic or renal impairment: Avoid buspirone in severe hepatic or renal dysfunction due to increased plasma levels and prolonged half-life 1
- Pregnancy: Category B—use only if clearly needed 1