Risk of fall injuries with concomitant use of antidepressants and CYP2D6 inhibitors

[Speaker] Karin Soderberg-Lofdal:1,2
[Co-author] Max Vikstrom:3, Karin Leander:3, Marja-Liisa Dahl:1,2
1:Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Sweden, 2:Department of Clinical Pharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden, 3:Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Background: With an aging population, morbidity, fall injuries, polypharmacy and risk of drug-drug interactions increase. The risk of adverse drug-drug interactions (DDIs) increases with more frequent polypharmacy. Antidepressants have been associated with fall injuries in several studies. Adverse effects that could increase the risk of falls, such as syncope, postural hypotension and dizziness, are more pronounced during the first few weeks after initiation of the drug. Many antidepressants are metabolized through CYP2D6 and inhibited metabolism results in increased concentrations. This study explores if use of drugs that inhibit CYP2D6 increases the risk of fall injuries in patients with newly initiated treatment of antidepressants, such as citalopram and venlafaxine.

Methods: The material consists of all adult hospital-admitted fall injuries in Sweden from 2006 to 2013 from the National Patient Register with linked data about dispensed drugs from the Swedish Prescribed Drug Register. The study design is case-crossover design, which can be thought of as a matched case-control study where the caseves as its own control and is analyzed with conditional logistic regression. The exposure to newly initiated treatment with antidepressants (about 35 000 cases) and CYP2D6-inhibitors in the case period, the 28 days preceding the occurrence of fall injury, was compared to a previous control period of equal length.

Results: We found an increased risk of fall injury associated with CYP2D6-metabolized antidepressants with concomitant use of CYP2D6-inhibitors [odds ratio (OR) 4.03; 95% confidence interval (95% CI) 3.51-4.63]. Without concomitant use of CYP2D6-inhibitors, there was no association (OR 1.05; 95% CI 1.01-1.10).

Conclusions: The risk of fall injury was increased when CYP2D6-metabolized antidepressants and CYP2D6-inhibiting drugs were used at the same time; without concomitant use of CYP2D6-inhibitors the risk was not affected.

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