Abstract by Reeha Sharon

There is an increased disease burden due to psychiatric disorders which affects approximately 970 million people. A large proportion of these patients are treated with antidepressants or antipsychotics, which are known to be associated with serious adverse drug reactions, especially in those who are more than 65 years of age. A complex interplay of polypharmacy and comorbid conditions further complicates the risks in the treatment. Our studies in this thesis are focussed on understanding risks in first time users of antidepressants or antipsychotics without any medical history of chronic psychiatric disorders.

We conducted three studies to identify and characterise the risks of acute kidney injury (AKI) or venous thromboembolism (VTE) in older population using antipsychotics and type 2 diabetes in all age-groups (young, middle aged and older) using antidepressants.

In all three studies, we used new-user study design and compared individuals who were exposed to the drug with unexposed population controls. In study I, titled “Incidence of hospital contacts with acute kidney injury after initiation of second-generation antipsychotics in older adults: a Danish population-based cohort study”, we found that patients with olanzapine use were associated with a significantly increased 90-day AKI risk. For quetiapine, the risk was elevated but not significant, and risperidone had no association [66]. Recent hospitalization was identified as a risk factor for AKI. AKI in older adults was infrequent, and limitations in this study included residual confounding and inadequate diagnosis records. Our finding recommend that clinicians should be aware that AKI can occur following short-term olanzapine and quetiapine therapy in older persons. In study II, titled “Use of olanzapine, quetiapine or risperidone and the risk of venous thromboembolism in older adults”, we found that olanzapine, quetiapine, or risperidone may increase the risk of VTE by 18-24% in older persons when compared to unexposed population in 3 months of follow-up. In the active comparator analysis with quetiapine as a comparator (head-to head comparison), we found no higher risk with olanzapine or risperidone. Long-term olanzapine use however increased VTE risk compared to quetiapine. Our results cannot say if risperidone is associated with a reduced VTE risk than olanzapine or quetiapine because risperidone may be recommended only for short-term use and the others for longer duration of use. More studies on dose- and time-dependent effects are needed to compare the safety of antipsychotics and VTE in older persons. In study III titled, “Risk of new-onset type 2 diabetes in antidepressant users: A population-based cohort study in Denmark”, we found that antidepressants were associated with an elevated incidence of type 2 diabetes in young and middle-aged people (18-64 years) but not in older adults (65 years). Current and recent users have a higher risk of type 2 diabetes than past users. SSRIs, TCAs, and SNRIs increased type 2 diabetes risk, but not in other antidepressants.

In conclusion, clinicians must be aware that among older adults using olanzapine or quetiapine are at a higher risk of developing AKI in short-term use or at a higher risk of developing VTE with long-term use. However, antidepressant use among older adults have no increased risk of developing type 2 diabetes. Though, young-middle aged population using antidepressants are at a higher risk for developing type 2 diabetes.