A combined cross-sectional and cohort study to describe and quantify polypharmacy among people prescribed antidepressants, including quantifying frequent drug combinations and adverse events

Date of Approval: 
2020-11-11 00:00:00
Lay Summary: 
People are often prescribed more than one medicine at a time. This is called ‘polypharmacy’. Polypharmacy is often necessary but can cause problems. For example, taking certain medicines together can cause more side effects than either medicine on its own. Polypharmacy places a burden on patients, who must remember to take each medicine at the right time. Patients also express concerns about whether it is safe to take lots of medicines at the same time, or to add a new one. We will study polypharmacy among patients prescribed antidepressants. These patients are often prescribed other medicines, and often have other health problems. We want to explore the numbers and types of medicines these patients are prescribed. This will provide new information about patient experience in UK general practices and will help in planning future studies. We will answer the following questions, for patients prescribed antidepressants: 1. How many other medicines are patients prescribed at any one time? 2. Has this changed over time? 3. Do patients have medicine reviews, and do these change how many medicines are prescribed? 4. How often are patients prescribed more than one type of antidepressant? How many of these could be diagnosed as having “treatment resistant depression”? 5. How many patients have ‘risky’ combinations of medicines that could lead to serious side effects? 6. What groups of medicines are most often prescribed with antidepressants? 7. What are the common side effects of certain combinations of medicines? How often do they happen?
Technical Summary: 
Objectives: to describe polypharmacy among patients who are prescribed antidepressants. Study population: for the main descriptive analyses patients aged 18+ years prescribed an antidepressant in 2019 will be included. To study trends over time, patients prescribed antidepressants in 2009, 2011, 2013, 2015 and 2017 will also be included. To quantify rates of adverse events associated with polypharmacy, patients prescribed antidepressants in 2015 will be followed-up until March 2020. Polypharmacy: the number of active prescriptions at any one time. The maximum number of medicines prescribed at the same time as an antidepressant in the study years will be determined. Specific combinations of medicines will be defined, including multiple antidepressants, opioids and other central nervous system agents, and ‘risky’ combinations. Patient characteristics: a range of characteristics including demographics, lifestyle characteristics and comorbidities will be defined using primary care data. Adverse events: serotonin syndrome, gastrointestinal bleeds, cerebrovascular bleeds, falls and fractures, overdose, and death. Other common adverse events will be identified during the study. Linked primary care, Hospital Episode Statistics, and Office for National Statistics mortality data will be used to define these outcomes. Analyses: summary statistics (median and interquartile range) will be presented for maximum polypharmacy count per patient in each study year. Patient characteristics according to polypharmacy count in 2019 will be tabulated, and exploratory analyses using appropriate regression models (e.g. Poisson regression) will be used to test whether polypharmacy count differs according to patient characteristics. Numbers of patients with medication reviews in 2019 will be counted, and maximum polypharmacy count before and after reviews summarised. The numbers of patients with the specified medicine combinations will be counted. The most common combinations of antidepressants with 2+ other medicines will be found and summarised. Age-sex standardised rates of adverse events occurring while exposed to specified combinations of medicines will be estimated.
Health Outcomes to be Measured: 
Polypharmacy; all-cause mortality; serotonin syndrome; gastrointestinal bleeding; cerebrovascular bleeding; falls and fractures; overdose; medication reviews As detailed in "Study Background", serotonin syndrome, gastrointestinal bleeds, and cerebrovascular bleeds are key adverse outcomes associated with antidepressant interactions according to the British National Formulary, and combinations of central nervous system agents including opioids are associated with outcomes such as falls and overdose. These serious outcomes are often fatal, thus mortality is also of interest. Medication reviews were of interest to the patient representatives consulted, as marking the opportunity for patients and prescribers to address polypharmacy.
Application Number: 

Carol Coupland - Chief Investigator - University of Nottingham
Rebecca Joseph - Corresponding Applicant - University of Nottingham
Chris Hollis - Collaborator - University of Nottingham
Daniel Lea - Collaborator - University of Nottingham
Debbie Butler - Collaborator - University of Nottingham
Julia Hippisley-Cox - Collaborator - University of Oxford
Richard Morriss - Collaborator - University of Nottingham
Roberto Santos - Collaborator - University of Nottingham
Roger Knaggs - Collaborator - University of Nottingham
Ruth Jack - Collaborator - University of Nottingham

HES Admitted Patient Care;ONS Death Registration Data;Patient Level Townsend Score