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WebMD Guide: Treatment-Resistant Depression

If you're coping with long-term depression, you may wonder why you can't feel better. Other people you know may have recovered from their depression more easily -- a few months of therapy or antidepressants, and they were back to normal. But it hasn't been like that for you, no matter what treatment you've tried.

There is no one reason for treatment-resistant depression. For most people, it's probably a mix of different factors. Some of them are beyond your control, such as the genes you were born with. The good news is, some factors you can control.

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Here are the reasons why depression can sometimes be hard to treat:

  • Not staying on a medicine long enough. Antidepressants can take as long as 6 to 8 weeks before they fully take effect. Unfortunately, many people -- and sometimes even doctors -- give up on a drug too early, before it's had a chance to help.
  • Skipping doses. You'll never know if a drug is working unless you take it exactly as prescribed.
  • Unpleasant side effects. Many people who have side effects stop taking their antidepressants. That isn't a good idea. Instead, talk to your doctor and get some help. You might be able to get rid of or ease the side effects, or switch to a different drug or combo of drugs. Also, keep in mind that side effects tend to decrease over time.
  • Drug interactions. Some other medications don't mix well with antidepressants. When taken at the same time, neither one may work normally. In some cases, interactions could be dangerous.
  • The wrong medicine or the wrong dose. Antidepressant drugs work differently in different people. Unfortunately, there's no way to predict how well a depression medicine will work without trying it. So finding the right medicine, at the right dose, takes trial and error -- and occasionally, some time. Many people give up before they find the right one.
  • Your genes. Researchers have begun to examine genes that may be linked with harder-to-treat forms of depression in some people.  But genetic tests can't, as yet, pinpoint which medicines are the most effective for a given person with depression.
  • Other medical or psychiatric conditions. Some medical conditions -- like heart disease, cancer, or thyroid problems -- can contribute to depression. Other conditions, like anorexia, can too. It's important that you get appropriate treatment for any underlying conditions in addition to depression.
  • Alcohol or drug abuse. Substance abuse often goes hand-in-hand with depression. It can trigger depression or make it worse, and interfere with the effects of antidepressant medicines. If you have a substance abuse problem, you need to get help.
  • The wrong diagnosis. Some people are simply misdiagnosed with treatment-resistant depression. They might actually have another condition, like bipolar disorder or an anxiety disorder. This is why it's so important to work with an expert.

WebMD Medical Reference

Reviewed by Joseph Goldberg, MD on July 02, 2014

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