Manish Jha, MD: Treatment Options for Treatment-Resistant Depression


In an interview with HCPLive, Jha said clinicians should think of interventional approaches for treatment-resistant depression “sooner rather than later.”

Patients with treatment-resistant depression may need to turn to second or third-line medication to receive any improvement benefit.

At the annual American Psychiatric Association (APA) conference in New York, Manish Jha, MD, associate professor at the department of psychiatry at UT Southwestern Medical Center, and Alan F. Schatzberg, MD, a psychiatry and behavioral sciences professor at Stanford University ran a course informing participants on the options for managing treatment-resistant depression. In an interview with HCPLive, Jha explained the diagnosis of treatment-resistant depression and the medications these patients can take to alleviate symptoms.

“The study data showed us that after 2 trials of adequate dose and duration, the likelihood of improving with a third or a fourth of commonly used antidepressant is less than 20%,” Jha said. “So less than 1 in 5 people get better with that.”

Due to this, a range of treatments are available for depression management. The first antipsychotic medication approved for treatment-resistant depression was olanzapine and fluoxetine. Second-generation antipsychotics are approved for the treatment as an augmentation strategy.

The FDA approved another treatment option—intranasal esketamine—in 2019. Beyond medication options, neuromodulation strategies exist to manage treatment-resistant depression, such as electroconvulsive therapy, transcranial magnetic stimulation, and ketamine by intravenous route. Other options include cognitive behavioral therapy or other psychotherapy options.

Jha said measurement-based care helps manage treatment-resistant depression since it considers the fact patients have gone through several trials but may not have had an adequate dose or duration. Measurement-based care examines symptom severity, adverse event adherence, and antidepression treatment history to diagnose treatment-resistant depression.

It often takes patients 5 or 7 medication trials before deciding what treatment works. Although Jha stressed the importance of using a bit of trial and error to see what medication provides benefits, a study showed after using a third or fourth antidepressant, the “benefit drops.”

“So that's why we may have to start thinking about using one of these interventional approaches earlier rather than later,” Jha said. “That's one of the key aspects I want clinicians to take away is to start thinking about treatment-resistant depression sooner rather than later.”


  1. Jha, M. Diagnosing and Managing Treatment-Resistant Depression (TRD): What’s Available and What’s on the Horizon? Session presented at: American Psychiatric Association (APA) 2024 Annual Meeting. New York, NY. May 7, 2024.
  2. Cutler, A. Management of Treatment-Resistant Depression (TRD). HCPLive. Accessed May 10, 2024.

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