Treatment-Resistant Depression Care

Medically Reviewed by Smitha Bhandari, MD on September 29, 2022
3 min read


There is no universally agreed upon approach to controlling treatment-resistant depression, also referred to as TRD. Your treatment will depend on your doctor's expertise as well as your own needs, concerns, and medical history.

But while the details may vary, most doctors follow the same basic pattern. Here is a rough outline of how your doctor might treat your depression. If you have treatment-resistant depression, your depression has already typically failed to respond to two or more treatments, usually one or more antidepressants and/or psychotherapy. At that point, your doctor may suggest other options.

  • Other antidepressants. If one type of antidepressant hasn't worked -- or has caused unpleasant side effects -- your doctor may suggest that you try another. This might be a new depression medicine in the same class of drugs or one in a different class. Again, you may need to stay on this medicine up to eight weeks to see its full effects. You'll then need to stay on it for at least several months, depending on your doctor's recommendations. If this second one doesn't work, your doctor may try a combination of depression medicines. Your doctor may also recommend older drugs for depression, such as MAOIs or tricyclics.
  • Augmentation with other drugs. If standard treatments aren't working, your doctor may add other medicines to your antidepressants. The combination can work in cases where antidepressants on their own did not. Types of drugs might include anti-anxiety drugs, anticonvulsants, antipsychotics, lithium, thyroid hormones, intranasal ketamine, and others. Your doctor may want to try a number of different drugs in different combinations. One drawback is that the more medications you take, the greater potential for side effects.
  • ECT (electroconvulsive therapy). Although sometimes used as an initial treatment for people with severe, life-threatening depression, ECT is usually reserved for people with serious depression that can't be controlled with other treatments. It uses an electrical impulse to trigger a brief controlled seizure in the brain while the patient is asleep under general anesthesia. This treatment can rapidly relieve depression, although its effects often fade unless "maintenance" ECT treatments are continued or an effective medicine is used to prevent relapse.
  • TMS (transcranial magnetic stimulation). In 2008, the FDA approved a TMS device for treating severely depressed adults for whom one antidepressant has failed to work. TMS creates a magnetic field to induce a much smaller electric current in a specific part of the brain without causing a seizure or loss of consciousness. An electromagnetic coil is held above the head to induce the magnetic field.
  • VNS (vagus nerve stimulation). VNS is a surgical procedure used in people with serious depression that hasn't responded to other treatments. Through a pacemaker-like device implanted under the collarbone, VNS delivers regular electrical impulses to the vagus nerve in the neck, one of the nerves that relays information to and from the brain.
  • Other techniques. Researchers are working on therapies to tackle treatment-resistant depression, such as MST (magnetic seizure therapy) and DBS (deep brain stimulation), and ketamine (a novel drug often infused intravenously).