When treatment hasn't worked

Many people don't feel better enough with the first or second medicine they try. That's common, and it doesn't mean nothing will work. There are more options, and many people find one that helps.

Doctors sometimes call this "treatment-resistant depression". It usually means depression that hasn't improved enough after at least two antidepressants, each taken long enough (often 6 weeks or more) at a full dose.

First, review the basics

Before moving on, it helps to check a few things with a clinician:

• Was each medicine taken long enough, at a full dose?
• Could something else be affecting mood, like a thyroid problem, another medicine, sleep problems, or alcohol or drug use?
• Is bipolar disorder possible? It's treated differently.
• Has therapy been part of the plan? Adding therapy to medicine often helps.

A psychiatrist is the right person for this review. Ask your primary care doctor for a referral, or find one in our directory.

Medicine changes

A prescriber may suggest switching to a different medicine, raising the dose, or adding a second medicine to boost the first. These are often the next steps, and they help many people.

Specialist treatments

TMS (transcranial magnetic stimulation)

Uses magnetic pulses, from a device held against the head, to stimulate areas of the brain involved in mood. No anesthesia; you're awake and can drive home. Usually sessions on most weekdays for several weeks. FDA-cleared since 2008 for depression that hasn't responded to medicine.

Esketamine (Spravato)

A nasal spray approved by the FDA for treatment-resistant depression in adults, on its own or with an antidepressant. You use it at a certified treatment center and stay to be monitored for at least 2 hours each time, so you'll need a ride home.

ECT (electroconvulsive therapy)

Done under general anesthesia, so you're asleep and don't feel it. A small electric current causes a brief seizure in the brain. It's one of the most effective treatments for severe depression. Memory problems around the time of treatment are the main side effect, and they usually improve. Newer methods lower that risk.

Insurers often need prior approval (prior authorization) for TMS and esketamine. Your prescriber's office usually handles the paperwork. See paying for care.

Clinical trials

Research studies test new treatments. Taking part is free, and some studies pay for your time. A study team explains the risks before you decide, and you can leave at any time. See studies recruiting in Pennsylvania on our research page.

How to ask for a referral

It's OK to bring this up yourself. You could say:

• "I've tried [number] medicines and I'm still not feeling better enough. Could I see a psychiatrist to review my treatment?"
• "Would TMS, esketamine or ECT be worth considering for me?"

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