Predictors of Selective Serotonin Reuptake Inhibitor Treatment Failure in Persons With Cystic Fibrosis

Introduction: Depression and anxiety are common in persons with cystic fibrosis (PwCF). Genetic polymorphisms in CYP2C19 and CYP2D6 are well-established predictors of selective serotonin reuptake inhibitors (SSRIs) treatment failure yet have not been studied specifically in PwCF. The purpose of this study was to determine the rate of SSRI failure in PwCF and to identify factors that predict treatment failure.

Methods: A retrospective cohort study was conducted of PwCF prescribed an SSRI for depression or anxiety. Potential predictors of SSRI failure were compared between PwCF for SSRI treatment success and failure. When CYP2D6 and CYP2C19 pharmacogenetic (PGx) test results were available, SSRI selection was compared to appropriateness per Clinical PGx Implementation Consortium (CPIC) guideline. PGx results were not available at the time of prescribing.

Results: The study included 184 PwCF and 45% experienced SSRI treatment failure. Demographics, concomitant drug-drug interactions, concomitant antidepressant medications, liver disease, and pulmonary function tests were not different between success and failure groups. Only 44 PwCF had PGx results and of these, only nine had actionable genotypes and prescribed an affected SSRI. This cohort had a failure rate of 78% (7 of 9) which was significantly higher compared to 40% (14 of 35) and 45% (83 of 184) in our PGx cohort and total cohort, respectively (p = 0.04; p = 0.04).

Conclusion: SSRI failure rate in PwCF is high and consistent with rates of the general population. Greater depression severity and number of SSRIs trialed were seen in the failure group. Pre-emptive PGx testing may improve SSRI success rates in PwCF.