Which is more likely to cause psychosis: buspirone or sertraline?

Comparison of Psychosis Risk: Sertraline vs. Buspirone

Sertraline is more likely to cause psychosis than buspirone based on available evidence, though both medications have documented cases of psychosis induction or exacerbation.

Sertraline and Psychosis Risk

Evidence for Sertraline-Induced Psychosis

• Multiple case reports document the emergence of psychotic symptoms during sertraline treatment 1
• Psychotic symptoms can emerge within 3 days to 7 weeks of starting sertraline 1
• Sertraline-induced psychosis appears particularly concerning in:
  • Patients with a history of psychotic illness
  • Patients already taking antipsychotic medications 1
• A 2022 case report described psychotic symptoms (visual/auditory hallucinations and paranoid delusions) emerging in an adolescent girl shortly after starting sertraline for depression and anxiety 2

Mechanism of Sertraline-Induced Psychosis

• The FDA label for sertraline specifically mentions the risk of serotonin syndrome when combined with other serotonergic drugs (including buspirone) 3
• Serotonin syndrome symptoms can include mental status changes such as agitation, hallucinations, delirium, and coma 3
• Research shows that patients with psychotic depression respond more poorly to sertraline monotherapy than those with non-psychotic depression 4

Buspirone and Psychosis Risk

Evidence for Buspirone-Induced Psychosis

• Case reports of buspirone-induced psychosis exist but appear less common 5, 6
• One case report showed dose-dependent psychotic exacerbation in a patient with schizophrenia 6
• Another case showed worsening psychosis in a patient with schizoaffective disorder when buspirone was administered 5

Mechanism of Buspirone-Induced Psychosis

• Buspirone has a high affinity for serotonin (5-HT1A) receptors and moderate affinity for brain D2-dopamine receptors 7
• Despite acting as an antagonist at dopamine receptors, buspirone has been observed to increase dopaminergic metabolites, which might explain its potential to worsen psychosis in vulnerable individuals 5
• The FDA label for buspirone does not specifically list psychosis as a common adverse effect 7

Clinical Implications and Considerations

Patient Selection

• For patients with a history of psychosis or at risk for psychotic disorders:
  • Buspirone may be preferable to sertraline
  • Close monitoring is essential with either medication
  • Lower starting doses should be considered

Monitoring

• When prescribing either medication, monitor for:
  • Emergence of hallucinations
  • Paranoid ideation
  • Thought disorganization
  • Agitation or unusual behavior changes

Risk Mitigation

• For patients requiring both anxiolytic and antidepressant effects:
  • Consider alternative medications if there's a history of psychosis
  • Ensure appropriate antipsychotic coverage if sertraline is needed in patients with psychotic disorders
  • Be aware of the potential for serotonin syndrome when combining sertraline with buspirone 3

Conclusion

While both medications have documented cases of psychosis induction or exacerbation, sertraline appears to have more robust evidence for causing psychotic symptoms, particularly in vulnerable populations. The mechanism likely involves serotonergic effects, which are more potent with sertraline than buspirone. However, clinicians should remain vigilant for psychotic symptoms when prescribing either medication, especially in patients with pre-existing psychotic disorders or risk factors.