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Johns Hopkins Health Alert

What To Do When Your Antidepressant Doesn’t Work

If you’re on an antidepressant and it’s not working, don’t give up on it: You may need a higher dose, a longer duration of therapy, a different antidepressant altogether, or a combination of medications. That’s the important lesson to learn from a large, six-year, four-step government study called the Sequenced Treatment Alternatives to Relieve Depression trial, or STAR*D. In fact, the researchers found that systematically trying these treatment options can lead to a remission in symptoms in up to half of severely depressed, treatment-resistant patients.

The STAR*D study, which looked at the use of popular antidepressants in people with chronic depression (lasting, in some cases, 15–16 years), is the first to provide "real world" scientific data on what to do when someone doesn't respond to a particular antidepressant, has severe depression, or suffers from multiple mental and physical ailments. These types of treatment-resistant patients are not typically included in antidepressant drug trials sponsored by pharmaceutical companies.

Here are nine important take-home messages from the STAR*D study:

  • One antidepressant treatment does not fit all. You may need to try several medications to find a drug regimen that works for you. What fits one person may not fit your particular biology.
  • Persevering through several different treatment attempts, as arduous as that may be, can improve results for many people.
  • At standard doses of the most commonly used class of antidepressants -- selective serotonin reuptake inhibitors (SSRIs) -- 30% of patients with severe depression achieve remission with the first medication prescribed.
  • It often takes 12 weeks to achieve an adequate response to an antidepressant, not the standard four to eight weeks that most doctors and mental health specialists were previously using to guide decisions.
  • If the first choice of antidepressant does not provide adequate symptom relief, switching to a new drug is effective about 25% of the time.
  • Switching from one SSRI to another is almost as effective as switching to a drug from another class.
  • If the first choice of an antidepressant does not provide adequate symptom relief, adding a new drug while continuing to take the first medication is effective in about one-third of people.
  • For people who don’t respond to first-line therapy with an SSRI, adding a second drug to the SSRI drug regimen appears to be slightly better than completely switching medications.
  • For those who don’t respond to switching to a new antidepressant or adding a second drug, trying a third medication can still help about one in five people.

Posted in Depression and Anxiety on June 25, 2008
Reviewed July 2009

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Health Alerts registered users may post comments and share experiences here at their own discretion. We regret that questions on individual health concerns to the Johns Hopkins editors cannot be answered in this space.

The views expressed here do not constitute medical advice, and do not represent the position of Johns Hopkins Medicine or MediZine LLC, which has no responsibility for any comments posted on this site.


I was treated for 16 months from a sudden onset of depression/bipolar and suicide at age 46. Naturally being sensitive to medications in general,all of the SSRI's gave me severe side effects and with no relief from depression and feeling constantly suicidal, I was in and out of the hospital 7 times and I stayed for 4-6 weeks ech time during those 16 months. Finally my Dr tried an MAOI inhibitor,the newly released Emsam Patch(Segeline). For the first time I felt like the "fog of death" had lifted and my whole world was coming back to me, but most of all I had no side effects to the Emsam Patch. I have a little itching around the patch site during the day but believe me I will gladly take that as a side effect as long as I have my life back...

Posted by: Linda Mom o f 7 | June 28, 2008

used cymbalta which worked for my depression however i had to go off it because of the side effect. i would break out in profuse sweats which soaked my hair. no physical activity was involved. two monyhs after stopping i relapsed into depression. started a new medication prestiq however after 10 dys usage profuse sweating returned. called the company and they said drug was similr to cymbalta and thus sweating was a listed side effect. any advice.

Posted by: mrriz1ootball1 | October 14, 2008

Posted by: mrriz1ootball1 | October 14, 2008



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