Review of: Strawn J et al, J Psychiatric Res 2023;159:266–273

Study Type: “Mega-analysis” of three randomized-controlled trials

The trial-and-error approach of matching antidepressants with likely responders leaves many prescribers and patients frustrated. This new ­“mega-analysis” sheds light on which age groups benefit most from antidepressants, as well as which sex. 

A mega-analysis is like a meta-analysis, but it goes one step further. Instead of looking at aggregated study results, it combines and analyzes the data of individual participants to uncover results that may have been missed by other methods. This study combined data from three major randomized controlled trials sponsored by the National Institute of Mental Health. The final sample included 907 participants who had been randomly assigned to antidepressant monotherapy (bupropion, citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, or venlafaxine). Two-thirds were female, three-quarters were non-White, and the median age was 30. More than half of patients had comorbid anxiety disorders. Participants’ depression scores were measured and standardized using the Clinical Global Impression Severity (CGI-S) scale, in which a higher score corresponds to more severe illness. Participants’ scores were measured at baseline and throughout treatment. 

The results of this study confirm what previous studies and clinicians have long suspected: Age and sex matter when it comes to antidepressant response. After controlling for anxiety disorders, the researchers found the most robust response to antidepressants occurred at 12 weeks in people ages 21–35 years (coefficient -0.668 +/- 0.060, p<0.001), followed by ages 36–55 years (-0.391 +/- 0.055, p<0.001), and those over 55 years old (-0.161 +/- 0.067, p=0.014). Across all age groups, females showed greater improvement than males (-0.284 +/- 0.039, p<0.001).

There are some limitations of this mega-analysis. The three original studies used different types of antidepressants. One study required conversion of the Quick Inventory of Depressive Symptomatology to the CGI-S to standardize the measurement tool. One of the studies with youths may have had more individuals with treatment-resistant depression. 

CARLAT TAKE 

These findings suggest the savvy prescriber can anticipate a less robust response to antidepressants in patients who are younger than 21 or older than 55, as well as in males to some extent. Although this study does not tell us where to go with these patients, other research points to the benefits of psychotherapy for pediatric and geriatric populations.