Clinical outcomes of common antidepressants may vary among older adults

Key takeaways:

• Risks and benefits of common antidepressants varied among older adults in a real-world study conducted in Denmark.
• Mirtazapine, venlafaxine and escitalopram had the most adverse clinical outcomes.

Clinical outcomes of commonly used antidepressants varied among older adults compared with sertraline, according to real-world study results conducted in Denmark and published in The American Journal of Psychiatry.

“Antidepressants are the first-line pharmacological treatment for depression in adults,” Kazi Ishtiak-Ahmed, PhD, of the departments of clinical medicine and affective disorders at Aarhus University in Denmark, and colleagues wrote.

“However, the efficacy of various antidepressant medications may be different in older adults than in the younger adult population, as a result of high rates of medical comorbidity, polypharmacy and age-related changes in pharmacokinetics and pharmacodynamics,” they added.

With limited real-world evidence on clinical outcomes, safety and benefits of antidepressants among older adults, Ishtiak-Ahmed and colleagues conducted a cohort study of 93,883 older adults (mean age, 78 years; standard deviation, 7.5 years; 56% women) who filled a first-time (since 1995) antidepressant prescription indicated for treatment of depression between 2006 and 2017.

Outcomes assessed during the 1-year follow-up included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events and all-cause mortality.

Researchers focused on the 10 most frequently prescribed antidepressants, which included selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%) and atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%).

Because sertraline is recommended as the first choice for treatment of depression in current Danish guidelines, researchers compared it with the other antidepressant medications using Poisson regression to estimate incidence rate ratios (IRRs) controlled for potential confounders such as age, sex, educational attainment, marital status and place of residence, among others.

During follow-up, 43.5% of users discontinued their antidepressant, 4.9% switched to another antidepressant, 20.4% had an augmentation, 3.7% had a psychiatric emergency contact, 8.7% had a psychiatric outpatient contact, 3.4% had a psychiatric inpatient contact, 0.1% had a record of suicide attempt or self-harm, 7.5% had a hospital record of fall-related injury, 3.2% had a cardiovascular event and 15.7% died, according to the researchers.

Compared with sertraline, most of the other nine antidepressants were associated with a significantly higher risk for discontinuation (eg, mirtazapine: IRR = 1.55; 95% CI, 1.5-1.61; venlafaxine: IRR = 1.22; 95% CI, 1.12-1.32), switching (amitriptyline: IRR = 1.45; 95% CI, 1.15-1.81; venlafaxine: IRR = 1.47; 95% CI = 1.2-1.8), augmentation (escitalopram: IRR = 1.19; 95% CI, 1.12-1.27), cardiovascular events (venlafaxine: IRR = 1.41; 95% CI, 1.05-1.88) and mortality (citalopram: IRR = 1.1; 95% CI, 1.03-1.16).

Researchers noted that overall, users of escitalopram, venlafaxine and mirtazapine had significantly greater risks for most of the outcomes compared with sertraline users, whereas users of citalopram had reduced risks for augmentation and psychiatric emergency and inpatient contacts, and amitriptyline users had reduced risks for all types of psychiatric contacts, emergency contacts and fall-related injuries.

“Overall, our results align with the existing Danish guidelines recommending sertraline as the first choice for the pharmacological treatment of depression in older adults and highlight the importance of careful selection of antidepressant treatment in the initial pharmacological treatment of depression in older patients,” Ishtiak-Ahmed and colleagues added.