Factors associated with drug–drug interactions involving citalopram in the UK Biobank

Background Adults with mood and/or anxiety disorders have increased risks of comorbidities, chronic treatments and polypharmacy, increasing the risk of drug-drug interactions (DDIs) with antidepressants.Aims To use primary care records from the UK Biobank to assess DDIs with citalopram, the most widely prescribed antidepressant in UK primary care.Method We classified drugs with pharmacokinetic or pharmacodynamic DDIs with citalopram, then identified prescription windows for these drugs that overlapped with citalopram prescriptions in UK Biobank participants with primary care records. We tested for associations of DDI status (yes/no) with sociodemographic and clinical characteristics and with cytochrome 2C19 activity, using univariate tests, then fitted multivariable models for variables that reached Bonferroni-corrected significance.Results In UK Biobank primary care data, 25 508 participants received citalopram prescription(s), among which 11 941 (46.8%) had at least one DDI, with an average of 1.96 interacting drugs. The drugs most commonly involved were proton pump inhibitors (40% of co-prescription instances). Individuals with DDIs were more often female and older, had more severe and less treatment-responsive depression, and had higher rates of psychiatric and physical disorders. In the multivariable models, treatment resistance and markers of severity (e.g. history of suicidal and self-harm behaviours) were strongly associated with DDIs, as well as comorbidity with cardiovascular disorders. Cytochrome 2C19 activity was not associated with the occurrence of DDIs.Conclusions The high frequency of DDIs with citalopram in fragile groups confirms the need for careful consideration before prescribing and periodic re-evaluation.