What are alternative antidepressants to Selective Serotonin Reuptake Inhibitors (SSRIs) for patients on rasagiline (Monoamine Oxidase B (MAO-B) inhibitor)?

Alternative Antidepressants for Patients on Rasagiline

For patients on rasagiline (an MAO-B inhibitor), tricyclic antidepressants and certain selective serotonin reuptake inhibitors (SSRIs) at lower doses, particularly citalopram and sertraline, are the preferred alternative antidepressants due to lower risk of serotonin syndrome compared to other antidepressants.

Understanding the Risks

Rasagiline is a selective MAO-B inhibitor used in Parkinson's disease treatment. The FDA label for rasagiline contains important warnings about potential interactions with antidepressants:

• Serotonin syndrome has been reported with concomitant use of antidepressants (SSRIs, SNRIs, tricyclic, tetracyclic, and triazolopyridine antidepressants) and MAO inhibitors, including selective MAO-B inhibitors like rasagiline 1
• The FDA label states that concomitant use of rasagiline with antidepressants is "not recommended" 1

Preferred Antidepressant Options

Despite these warnings, clinical evidence suggests certain antidepressants can be used with careful monitoring:

First-Line Options:

1. Tricyclic Antidepressants (TCAs)

   • Clomipramine has shown efficacy for depression when prescribed at doses of 25-50 mg/day 2
   • Lower risk of serotonin syndrome compared to SSRIs when combined with MAO-B inhibitors

2. Selected SSRIs at Lower Doses

   • Citalopram and Sertraline may be preferred among SSRIs when combined with MAO-B inhibitors 3
   • Keep SSRI doses at the lower end of the therapeutic range 3
   • Start with the lowest possible dose and titrate slowly

Clinical Evidence Supporting These Recommendations

A retrospective cohort study of 1,504 patients with Parkinson's disease found no cases of serotonin syndrome with coadministration of rasagiline and an SSRI 3. The ADAGIO study, which included 191 patients on antidepressants and rasagiline, reported no serious adverse events suggestive of serotonin syndrome 4.

The combination of rasagiline and antidepressants was actually associated with reduced worsening of non-motor symptoms including depression and cognitive impairment in patients with early Parkinson's disease 4.

Precautions and Monitoring

When prescribing antidepressants to patients on rasagiline:

• Start with the lowest possible dose of the antidepressant
• Monitor closely for signs of serotonin syndrome, especially during the first few weeks of treatment
• Symptoms of serotonin syndrome include:
  • Behavioral/cognitive changes (confusion, agitation, hallucinations)
  • Autonomic effects (shivering, sweating, hyperthermia, hypertension)
  • Somatic effects (muscular rigidity, myoclonus, hyperreflexia) 1
• Avoid exceeding recommended doses of either medication
• Consider discontinuing one or both medications if signs of serotonin syndrome develop

Antidepressants to Avoid

• Fluoxetine and fluvoxamine - These SSRIs have stronger CYP450 inhibition and higher risk of interactions 1
• SNRIs like venlafaxine and duloxetine carry higher risk of serotonin syndrome
• MAO-A inhibitors are absolutely contraindicated with rasagiline 1
• Meperidine, tramadol, methadone, and propoxyphene are contraindicated with rasagiline 1

Timing Considerations

If transitioning between antidepressants and rasagiline:

• Allow at least 14 days between discontinuation of rasagiline and initiation of an SSRI/SNRI 1
• For fluoxetine specifically, allow at least 5 weeks between discontinuation and starting rasagiline due to its long half-life 1

Conclusion

While the FDA label advises against combining rasagiline with antidepressants, clinical evidence suggests that certain antidepressants, particularly tricyclic antidepressants and selected SSRIs (citalopram and sertraline) at lower doses, can be used with careful monitoring in patients who require both medications. The risk of serotonin syndrome appears to be low when recommended doses are not exceeded and appropriate precautions are taken.