REVIEW OF: Kessing LV et al, Acta Psychiatr Scand 2024;149(5):378–388

STUDY TYPE: Retrospective cohort

Choosing an antidepressant for major depressive disorder often requires our best educated guesses. While we have short-term data, longer-term outcomes are less clear. 

Kessing et al addressed this by analyzing antidepressant prescriptions for over 100,000 Danish adults with a first diagnosis of depression from 1995 to 2018. They tracked nonresponse, defined as switching, augmenting, or hospitalization. Patients on multiple first-line meds were excluded. The researchers used a “target trial” design to mimic RCTs, comparing drugs within the same class and adjusting for variables like age, sex, employment, and some comorbidities. In the results below, note that relative risk (RR) refers to how much more (or less) likely a certain outcome is with one treatment compared to another. An RR of 1.13, for instance, means there’s a 13% greater chance of nonresponse compared to the reference medication. 

Results
Among selective serotonin reuptake inhibitors (SSRIs), sertraline marginally outperformed escitalopram (RR: 1.22), fluoxetine (RR: 1.13), and paroxetine (RR: 1.06), but was similar to citalopram.

Among serotonin/norepinephrine reuptake inhibitors (SNRIs), ­venlafaxine slightly outperformed duloxetine (RR: 1.04).

Among tricyclic antidepressants (TCAs), amitriptyline did better than clomipramine (RR: 1.20) and nortriptyline (RR: 1.15).

In the “other” category, sertraline outperformed vortioxetine (RR: 1.15).

CARLAT TAKE
This study was observational, involved a Danish cohort, and relied solely on prescription data. It did not examine side effects, response rates, symptom severity, or the reasons for changing or augmenting medications. The differences between antidepressants were also not very pronounced. That said, when all other things are equal, these findings support sertraline and citalopram among SSRIs, venlafaxine among SNRIs, and amitriptyline among TCAs for long-term treatment of depression.