REVIEW OF: Kim TT et al, J Affect Disord 2025;376:47–51
STUDY TYPE: Retrospective cohort (chart review)

Older antidepressants like monoamine oxidase inhibitors (MAOIs) and tricyclics (TCAs) can work when newer agents fail, but their potential side effects may scare clinicians away. By bypassing first-pass metabolism, the selegiline transdermal system (STS, or selegiline patch, brand name Emsam) eliminates the need for dietary restrictions required with other MAOIs when it is given at the 6 mg/24 hours dose.

This study took a retrospective look at 117 patients with treatment-resistant depression (TRD) treated at a university mood clinic to see how STS compared with flexibly dosed oral MAOIs and TCAs in both effectiveness and tolerability. The primary outcome was change in depression severity, rated retrospectively using the seven-point CGI-S scale.

STS was less effective for reducing severity than oral MAOIs (by 0.62 points on the CGI-S, p=0.035) but more effective than TCAs (by 0.81 points, p=0.016). However, researchers acknowledged that longer treatment durations with oral MAOIs may have contributed to their greater effectiveness. STS was associated with fewer total side effect categories than either comparator. Compared with oral MAOIs, STS led to fewer cardiovascular side effects but (unsurprisingly) more patch-site reactions; compared with TCAs, it produced fewer gastrointestinal complaints. No serious adverse events such as hypertensive crises or serotonin syndrome were reported.

CARLAT TAKE
While limited by its retrospective, non-randomized design, this “real-world” analysis supports giving Emsam another look in difficult-to-treat depression. Although the patch wasn’t as effective as oral MAOIs, it outperformed TCAs and was better tolerated overall. That said, interpret the findings with caution—the study was small and observational, so treatment durations and dosages of comparators were not standardized, and outcomes were rated retrospectively by a single treating clinician who was also a study author. Also, while Emsam’s 6 mg/24 hours dose does not require dietary restrictions, drug interaction risks are similar to oral MAOIs: Serotonergic medications can cause serotonin syndrome, and sympathomimetic medications can trigger hypertensive crises.