Pharmacotherapy, drug-drug interactions and potentially inappropriate medication in depressive disorders

Abstract

Introduction: The aim of this study was to analyse prescription patterns and the determinants of drug-drug interactions (DDI) and potentially inappropriate medication (PIM) in pharmacotherapy of depressive disorders. Methods: Our study was part of a larger pharmacovigilance project funded by the German Innovation Funds. It included all inpatients with a main diagnosis in the group of depressive episodes (F32, ICD-10) or recurrent depressive disorders (F33) discharged from eight psychiatric hospitals in Germany between 1 October 2017 and 30 September 2018 or between 1 January and 31 December 2019. Results: The study included 14,418 inpatient cases. The mean number of drugs per day was 3.7 (psychotropic drugs = 1.7; others = 2.0). Thirty-one percent of cases received at least five drugs simultaneously (polypharmacy). Almost one half of all cases received a combination of multiple antidepressant drugs (24.8%, 95% CI 24.1% - 25.5%) or a treatment with antidepressant drugs augmented by antipsychotic drugs (21.9%, 95% CI 21.3% - 22.6%). The most frequently used antidepressants were selective serotonin reuptake inhibitors, followed by serotonin and norepinephrine reuptake inhibitors and tetracyclic antidepressants. In multivariate analyses, cases with recurrent depressive disorders and cases with severe depression were more likely to receive a combination of multiple antidepressant drugs (Odds ratio recurrent depressive disorder: 1.56, 95% CI 1.41 - 1.70, severe depression 1.33, 95% CI 1.18 - 1.48). The risk of any DDI and PIM in elderly patients increased substantially with each additional drug (Odds Ratio: DDI 1.32, 95% CI: 1.27 - 1.38, PIM 1.18, 95% CI: 1.14 - 1.22) and severity of disease (Odds Ratio per point on CGI-Scale: DDI 1.29, 95% CI: 1.11 - 1.46, PIM 1.27, 95% CI: 1.11 - 1.44), respectively. Conclusion: This study identified potential sources and determinants of safety risks in pharmacotherapy of depressive disorders and provided additional data which were previously unavailable. Most inpatients with depressive disorders receive multiple psychotropic and non-psychotropic drugs and DDI and PIM are relatively frequent. Patients with a high number of different drugs must be intensively monitored in the management of their individual drug-related risk-benefit profiles.

Polypharmacy and the risk of drug–drug interactions and potentially inappropriate medications in hospital psychiatry

“…In accordance with the ethics approval, our retrospective study did not require individual patient consent. Previous publications from this research project that have used the same or similar datasets can be found in the reference list 24,26,29,36,38–40 …”

Deprescribing as a strategy for improving safety of medicines in older people: Clinical and regulatory perspective

“…Regarding DDIs, polypharmacy is one of the most relevant risk factors (Johnell and Klarin, 2007;Wolff et al, 2021). The prevalence of clinically relevant DDIs among home-dwelling older adults reported in the scientific literature widely ranges from 35% to 77% (Novaes et al, 2017;Santos et al, 2017;Hermann et al, 2021;Sheikh-Taha and Asmar, 2021), and the most commonly reported are myopathy due to the increased levels of statins when used with calcium channel blockers and postural hypotension caused by the interaction between thiazide diuretics and ACE inhibitors (Sheikh-Taha and Asmar, 2021).…”

Reduced prevalence of drug-related problems in psychiatric inpatients after implementation of a pharmacist-supported computerized physician order entry system - a retrospective cohort study

“…Prescription data from public health insurance providers in Germany show that outpatients were prescribed more than two billion daily defined doses (DDD) of psychotropic drugs in 2021, most of which were antidepressants (1.7 billion DDD, 79% of psychotropic drug prescriptions including tranquillizers, antipsychotics and antidepressants) (1). In a big retrospective study conducted in eight psychiatric hospitals in Germany including 14,418 inpatient cases, 31% of cases received at least five drugs simultaneously (polypharmacy) with a mean of 3.7 drugs daily (1.7 psychotropic drugs, 2.0 others) (2). In addition, due to the widespread anticholinergic properties of psychotropic drugs, especially antipsychotics (3)(4)(5), researchers have pointed out the need for interventions to reduce the prescription frequency of anticholinergic drugs and their assessment regarding their impact on clinical risks, especially in patients older than 65 years (6,7).…”