A comparison of four methods to quantify the cumulative effect of taking multiple drugs with sedative properties

Older people (ie, those aged >65 years) often use multiple drugs with sedative properties. These include drugs for intentional sedation and drugs that have sedation as an adverse reaction. Recent pharmacoepidemiologic studies have investigated the risks of multiple or combined sedative drug use.

The purpose of this commentary was to describe, compare, and discuss 4 previously published pharmacoepidemiologic methods used to quantify the cumulative effect of taking multiple drugs with sedative properties.

A MEDLINE literature search was conducted in January 2010 using Medical Subject Headings and the following search terms: hypnotics, sedatives, benzodiazepines, GAGA-A receptors, model, load, measurement, index, burden, system, and aged. The search was limited to English language, humans, and the year 2000 until present. Reports of methods that involved simply counting the number of sedative or psychotropic drugs, or described sedative drug use in anesthesia, were excluded. The search identified 4 methods. Research articles that have cited the descriptions of the 4 methods were retrieved using MEDLINE, Google Scholar, Scopus, and the Web of Science.

The literature search identified 14 studies describing the use of 4 different methods to quantify the cumulative effect of taking multiple drugs with sedative properties. The 4 methods are the sedative load model, the Sloane model, the Drug Burden Index, and the central nervous system drug model. The methods differed with respect to the specific drugs or drug classes considered, the sedative ratings assigned to each drug, the inclusion or exclusion of drug dose in the model, and each model's likely ease of use in clinical practice. Adverse outcomes associated with taking multiple drugs with sedative properties included impaired physical and cognitive function, and an increased risk of falls.

Evidence is accumulating in relation to a range of adverse outcomes associated with using multiple drugs with sedative properties. However, no studies have been conducted using>1 method to quantify the cumulative effect of taking multiple drugs with sedative properties. Each method has likely advantages and disadvantages. The usefulness of each method in clinical practice remains to be determined. The models must be validated in different populations of older people and may subsequently need to be refined.