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Potential risks of antidepressants

Researchers investigated the safety of antidepressants by analyzing the adverse effects of their use in adults aged 20 to 65 years.

Antidepressants are commonly prescribed drugs worldwide for the treatment of depression. They are one of the most common types of medication prescribed for young and middle-aged adults in Canada, the United States, and the United Kingdom.

There are a number of different antidepressant drug classes available, with relatively equal efficacy, thus making the choice of an antidepressant largely dependent on the risk of adverse effects.

Limited information on antidepressant safety

Despite the widespread use of these drugs, there is relatively limited information regarding their safety, particularly in young and middle-aged adult populations.

Researchers in the UK assessed the risk of various potential adverse outcomes from antidepressant use in young to middle-aged adults and published their findings in BMC Medicine.

The researchers performed a cohort study using a UK primary care database that contained the health records of millions of patients to obtain their study population.

The patients included in the study were those who had a first diagnosis of depression and were between 20 and 64 years of age.

The researchers assessed the association between different antidepressant drug classes with several adverse outcomes that included falls, fractures, gastrointestinal bleed, adverse drug reactions, traffic accidents, and all-cause mortality.

The different antidepressant drug classes defined in the study analysis included: selective serotonin reuptake inhibitors (e.g. citalopram), tricyclic and related antidepressants (e.g. amitriptyline), monoamine oxidase inhibitors, and other antidepressants.

The final study analysis included 238,963 patients and a median follow-up period of 5.2 years.

Increased risk of falls

The analysis found a significantly increased risk of falls in all antidepressant drug classes, with an association between fall rates and antidepressant dose, when compared to periods without any antidepressant use.

There was also a significant increase in fracture risk with selective serotonin reuptake inhibitors and other antidepressants, but not with tricyclic and related antidepressants.

Tricyclic antidepressants had a significantly lower rate of fractures when directly compared to selective serotonin reuptake inhibitors.

Tricyclic antidepressants were associated with a higher rate of gastrointestinal bleed versus no antidepressant use, but this was not significantly increased when directly compared to selective serotonin reuptake inhibitors.

Increased adverse drug reactions and all-cause mortality rates

Compared to no use of antidepressants, adverse drug reaction and all-cause mortality rates were increased in all antidepressant classes, with higher rates observed in tricyclic antidepressants and other antidepressants than in selective serotonin reuptake inhibitors.

Of note, the antidepressant, mirtazapine, was found to be associated with the highest mortality rate over the five-year follow-up, including a significantly increased risk within the first year of follow-up.

Observational study method is a limitation

The results of the study are strengthened by the large representative sample size and minimization of selection and indication biases.

However, despite the researchers’ best efforts to account for potential confounders in the analysis, the nature of an observational study means there is still a risk of residual confounding.

It is also likely there is some misclassification bias, as most data on traffic road accidents didn’t indicate whether the patient was the driver or a passenger, or if they were responsible for the accident.

Authors highlight the importance of considering the risks and benefits when prescribing antidepressants

Overall, this study provides a comprehensive assessment of the potential risks and adverse outcomes of using antidepressant drugs to treat depression in young and middle-aged adults.

The study notes the increased risk of fractures but the decreased risk of mortality with selective serotonin reuptake inhibitors. The study results also highlight a need for further research confirming the safety of mirtazapine.

The study results highlight the importance of considering risks versus benefits when deciding on an antidepressant in young and middle-aged adults.

Written by Maggie Leung, PharmD

Reference: Coupland, C., Hill, T., Morriss, R., Moore, M., Arthur, A., & Hippisley-Cox, J. (2018). Antidepressant use and risk of adverse outcomes in people aged 20–64 years: Cohort study using a primary care database. BMC Medicine, 16(1). doi:10.1186/s12916-018-1022-x

Maggie Leung PharmD
Maggie Leung PharmD
Maggie is a registered pharmacist and has a PharmD from the University of Toronto. She currently works in the pharmacy informatics field as a clinician applications consultant. In her role, she supports the integration and optimization of technology in healthcare. She enjoys learning about the latest in scientific research and sharing that knowledge through her writing for Medical News Bulletin. Maggie is a big dog lover and enjoys traveling and spending time with her friends and family.


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