Anxiety Augmentation Alternative to Gabapentin
For a patient on 90mg duloxetine with depression and anxiety, buspirone is the most appropriate alternative to gabapentin for anxiety augmentation, based on evidence from the STAR*D trial showing similar efficacy to bupropion with acceptable tolerability when augmenting antidepressants. 1
Primary Recommendation: Buspirone
Buspirone augmentation of existing antidepressant therapy (duloxetine in this case) demonstrated efficacy in the landmark STAR*D trial for patients with depression and anxiety who did not achieve remission on initial SSRI/SNRI monotherapy. 1
The STAR*D data showed that buspirone augmentation of citalopram achieved similar remission rates compared to bupropion augmentation, though buspirone had a higher discontinuation rate due to adverse events (20.6% vs. 12.5%). 1
Buspirone is specifically designed as an anxiolytic agent and does not carry risks of dependence, making it suitable for long-term anxiety management. 1
Typical dosing starts at 7.5mg twice daily and can be titrated up to 30mg twice daily (60mg total daily dose) based on response and tolerability. 2
Alternative Option: Bupropion SR
Bupropion SR augmentation showed similar efficacy to buspirone in STAR*D but with significantly better tolerability (12.5% discontinuation due to adverse events vs. 20.6% for buspirone). 1
Bupropion provides the additional benefit of addressing low energy and motivation that often accompany depression. 1
This option is particularly valuable if the patient has residual depressive symptoms alongside anxiety. 1
Standard augmentation dosing is 150mg daily, increased to 150mg twice daily (300mg total) as tolerated. 1
Important Clinical Considerations
Why Not Other Options
SSRIs (escitalopram, sertraline) are not appropriate here because the patient is already on maximum-dose duloxetine (90mg), an SNRI with similar mechanism of action. 3 Adding an SSRI would increase serotonin syndrome risk without addressing treatment resistance through a different mechanism.
Benzodiazepines should be avoided for chronic anxiety augmentation due to dependence risk and potential to mask underlying symptoms. 3
Pregabalin, while effective for GAD, is essentially a more potent gabapentinoid and doesn't represent a true alternative if you're moving away from gabapentin. 4
Monitoring Parameters
For buspirone: Monitor for nausea, dizziness, and headache, which are the most common side effects. 2 These typically improve after 2-3 weeks of consistent dosing.
For bupropion: Monitor for activation, insomnia, and increased anxiety initially (which may seem paradoxical but typically resolves). 1 Screen for seizure risk factors as bupropion lowers seizure threshold.
Both options require 4-6 weeks at therapeutic doses to assess full anxiolytic efficacy. 1
Evidence Quality Note
The STAR*D trial provides moderate-certainty evidence for these augmentation strategies in patients with depression and comorbid anxiety who did not respond to initial SNRI/SSRI monotherapy. 1 Importantly, the presence of comorbid anxiety did not affect the comparative efficacy of these augmentation strategies. 1