Finding Solutions When Depression Resists Treatment

Updated Oct. 10, 2023

Taking an antidepressant or going to psychotherapy, or a combination of both, eases depression for most people. But for individuals who experience a form known as treatment-resistant depression, or TRD, standard treatments provide little or no relief.

Individuals are considered to have resistant depression if they haven’t responded to an adequate trial of two different antidepressants.

Studies indicate that 29% to 46% of patients with major depressive disorder show partial or no response to treatments.

“By the time patients are referred to us, they’ve often tried multiple therapies, pharmacological and nonpharmacological,” said Adrian Jacques H Ambrose, MD, MPH, who with Joshua Berman, MD, PhD, directs the Interventional Neurotherapeutic Psychiatry Program (INP) at Columbia Psychiatry’s Faculty Practice. 

“I’ve heard countless patients say that they feel completely hopeless,” Dr. Ambrose added. “They have suffered for months and sometimes years, and since medications and therapy have not worked, they feel like it’s their fault—like they’re broken.”

A suite of services

The Columbia program provides a range of evidence-based services to address refractory depression, starting with a comprehensive evaluation to create an individualized plan for each patient. The clinical team is trained in interventional neurotherapeutic psychiatry, which refers to a collection of nervous system stimulation therapies focused on modulating dysfunctional brain circuitry.

Interventional neurotherapeutic services available to patients include transcranial magnetic stimulation (TMS), electro-convulsive therapy (ECT), esketamine, and ketamine. 

“With these treatments, we do see people get better and experience real change,” Dr. Berman said. “Often times, patients will say things like, they’ve gotten their lives back. As a doctor, you really can’t beat that feeling.”

Future directions

Future directions for the INP program include expanding access to interventional treatments for psychotic disorders, OCD, and post-traumatic stress disorder.  The team is also working to introduce new treatment modalities such as intensive and intermittent theta-burst TMS, psychedelics (e.g. psilocybin)  and entactogen-assisted (e.g. MDMA) psychotherapy (pending FDA approval).

“Entactogen-assisted psychotherapy works (in theory) through the interactions between the medication/entactogens and the psychotherapy for a variety of treatment-refractory psychiatric conditions,” Dr. Ambrose said.

Dr. Berman said the team is also collaborating in a study of parcellation, a brain mapping technique that processes images that patients can easily obtain from radiologists in the community to improve TMS efficacy, guiding treatment to the right brain targets to a degree that has only been possible using research techniques impossible for most patients to access.

Additionally, the group is also a partner in a study on treatment of depression in patients with trauma that combines TMS with intersectional Transcranial Electric Stimulation (iTES), a novel brain stimulation method, and functional near infrared spectroscopy (fNIRS), a novel portable imaging technique. The idea is to expand the range of TMS while allowing assessment of treatment effects on the brain in real time.