Associations between chronic kidney disease and mental health disorders and psychoactive drugs in the UK general population

This thesis examined the association between chronic kidney disease (CKD) and both mental health disorders and psychoactive drugs, using a large contemporary UK database of routine medical record data (Clinical Practice Research Datalink [CPRD]). To fill the gap between what is known and what is unknown in this field, I focused on two main topics: (i) severe mental illness (SMI), with and without a history of lithium use, and CKD, and (ii) CKD and antidepressants (mainly prescribed for common mental health disorders such as depression and anxiety) and associated serious adverse outcomes. I first conducted a population-level validation study comparing prevalence estimates of decreased kidney function (defined as estimated glomerular filtration rate of <60 ml/min/1.73 m2) and renal replacement therapy (RRT) in the CPRD population with nationally representative statistics (Health Survey for England and UK Renal Registry). Findings suggested that most patients with decreased kidney function and RRT are probably captured in the CPRD. Secondly, I conducted a cross-sectional study on the association between SMI, including schizophrenia and bipolar disorder, and CKD (defined as two measurements of estimated glomerular filtration rate of <60 ml/min/1.73 m2 over ≥3 months in the past five years). Patients with SMI, especially lithium users, had a significantly higher prevalence of both CKD and RRT than the general population. Thirdly, I conducted a matched cohort study comparing the prevalence and incidence of antidepressant prescription between patients with and without CKD (matched for age, sex, general practice, and calendar time). Patients with CKD were approximately one and a half times more likely to receive antidepressants for mental health conditions such as depression and anxiety. Finally, I examined the gastrointestinal (GI) bleeding risk of selective serotonin reuptake inhibitors (SSRIs) by level of kidney function. While the relative risk for GI bleeding associated with SSRIs (i.e. the fully-adjusted rate ratio between periods with and without SSRI prescription) was constant regardless of baseline kidney function, the excess risk for GI bleeding associated with SSRIs (i.e. the fully-adjusted rate difference between periods with and without SSRI exposure) increased markedly as baseline kidney function deteriorated. In conclusion, a close association between CKD and mental health disorders was suggested in the UK general population. It is evident that patients with CKD are more likely to be prescribed antidepressants, and this may cause serious adverse outcomes such as GI bleeding associated with SSRIs. The risk-benefit balance of antidepressants for patients with CKD may need to be reconsidered in light of this new evidence.