REVIEW OF: Dalhuisen I et al, Am J Psychiatry 2024;181(9):806–814

STUDY TYPE: Unblinded RCT

After two failed antidepressants, the odds of responding to a third aren’t good; remission rates fall below 15%, while side effects accumulate. So, what’s the right next move? This Dutch multicenter RCT is the first to put repetitive transcranial magnetic stimulation (rTMS) head-to-head against pharmacologic next steps in moderately treatment-resistant depression.

Eighty-nine adults with unipolar, nonpsychotic major depressive disorder who hadn’t responded to 2 or more adequate antidepressant trials were randomized to either rTMS (25 high-frequency sessions to the left dorsolateral prefrontal cortex over 8 weeks) or a medication switch—typically to a tricyclic antidepressant or augmentation with lithium or an antipsychotic, per Dutch guidelines. Both groups also received weekly psychotherapy. The trial was unblinded, and the primary outcome was change on the Hamilton Depression Rating Scale (HAM-D).

rTMS produced a larger drop in HAM-D scores than medication switching (mean reduction 10.0 vs 4.2 points). Response rates were 38% with rTMS versus 15% with medication, and remission rates were 27% versus 5%. rTMS also outperformed medication on anxiety and anhedonia, though both treatments had similar effects on rumination, sleep, and cognitive reactivity. Patients assigned to the rTMS arm had higher expectations, and greater baseline expectations correlated with better outcomes in both groups.

CARLAT TAKE

This pragmatic trial mirrors real-world conditions, and dropout due to intolerability was lower in the rTMS group, which is a clinically meaningful finding. For patients who haven’t responded to two antidepressants, don’t just reach for a third. If rTMS is available, consider it earlier. Patients with prominent anxiety or anhedonia may be especially good candidates, since those were the symptom dimensions where rTMS pulled ahead most clearly.