In community interventional psychiatry practices, the typical referral looks the same week after week. The patient is in the fifth or sixth year of a major depressive episode and carries a list of four, five, sometimes seven antidepressants they have “failed.” They are finally sent for transcranial magnetic stimulation (TMS) or esketamine (Spravato) long after the point when those treatments would have done the most good. By the time the prior authorization paperwork arrives, many have lost jobs, relationships, and years of their lives.

Insurance rules and referral habits mean that depressed patients fail too many times before anyone raises these options. Primary care physicians write most antidepressant prescriptions in the United States, so primary care is where this pattern can change.

What STAR*D already showed

The largest real-world antidepressant study ever conducted should have ended the “just try one more” reflex two decades ago. In STAR*D, remission rates fell with each successive treatment step: roughly 37 percent at the first step, 31 percent at the second, and only 14 percent and 13 percent at the third and fourth.

Researchers have since argued that the turning point comes after two adequate trials, when the odds of both getting well and staying well drop sharply. That threshold now anchors the working definition of treatment-resistant depression. A 2023 reanalysis of the STAR*D patient data was even more sobering. It put the true cumulative remission rate after up to four trials at about 35 percent, roughly half of what was originally reported, although the original investigators dispute that reanalysis.

The lesson is not that antidepressants fail to work. It is that a third or fourth trial of another standard antidepressant has a low chance of success, and continuing to cycle through them is itself a clinical decision with a cost.

“Fail first” rules add delay without clear benefit

Insurance “fail first” rules add to that cost rather than justify it. The 2022 VA/DoD guideline for major depressive disorder suggests considering ketamine or esketamine for patients who have not responded to several adequate medication trials, alongside TMS and electroconvulsive therapy (ECT). Commercial coverage often demands far more:

• Requirements vary widely: An analysis of eighteen large commercial health plans found wide variation in what patients must try before esketamine is approved. Plans required different lists of failed drugs and different severity thresholds, which delays what is often urgent treatment.
• Initial denials are common: Real-world claims data show that only about a third of first esketamine pharmacy claims were approved on the first submission. Coverage denials and prior authorization requirements were among the leading reasons for rejection.
• The extra steps add little: By the time they started esketamine, patients had averaged nearly four antidepressant courses regardless of how strict their plan’s criteria were. That calls into question whether the added hurdles change anything clinically.
• Waiting itself causes harm: In routine care, longer waits between assessment and the start of treatment were associated with worse depression outcomes.
• Protocols often exceed the guidelines: Across specialty drugs, only about a third of step-therapy protocols matched clinical guidelines, a gap that health policy experts have called out.

Three changes primary care can make now

• Treat two adequate trials as a decision point, not a way station: Once a patient has failed two antidepressants at an adequate dose and duration, TMS, esketamine, and ECT should be named out loud as real options. That is the moment to start the referral conversation rather than reach for a third drug by reflex.
• Start the paperwork early and document with prior authorization in mind: Record each medication with its dose, duration, and reason for stopping, in a format that anticipates what an insurer will ask. That record is what turns an eventual denial into an approval and shortens the wait.
• Lean on collaborative and measurement-based care: Collaborative care, which pairs regular PHQ-9 tracking with an embedded or consulting psychiatrist, consistently outperforms usual care for depression in primary care. It also gives clinicians an objective trigger for escalation instead of relying on gut feel.

None of this asks primary care physicians to deliver interventional treatment. It asks only that patients stop accumulating the failures the evidence predicts, failures that a timely referral so often reverses.

Ravi Singareddy is the founder and medical director of Empower Psychiatry & Sleep in north metro Atlanta, where he leads an interventional psychiatry practice offering transcranial magnetic stimulation (TMS) and Spravato (esketamine) for treatment-resistant depression. Double board-certified in psychiatry and sleep medicine, he brings more than two decades of clinical and academic experience to patients who haven’t found relief with medications alone. He is affiliated with Emory Healthcare.

His interest in neuromodulation dates back to his years as associate professor of psychiatry at Penn State College of Medicine. There, he taught annually on vagus nerve stimulation and novel depression therapies, and he published on long-term combined electroconvulsive therapy and vagus nerve stimulation in the American Journal of Psychiatry. He has authored numerous peer-reviewed papers on sleep disorders, insomnia, anxiety, and depression, with work appearing in Sleep, the Journal of Clinical Sleep Medicine, and Psychiatry Research.

Singareddy is a Fellow of the American Psychiatric Association and the American Academy of Sleep Medicine and practices measurement-based care, tracking outcomes to guide every treatment decision. He shares updates on Instagram.