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Changing Treatments For Depression May Improve Outcomes - If First Medicine Does Not Work Try or Add Another Medication - Study Says

March 25th 2006

Changing Treatments For Depression May Improve Outcomes - If First Medicine Does Not Work Try or Add Another Medication - Study Says

Dr. Rush

Successfully treating depression may require trying different drugs, according to research from the UT (University of Texas) Southwestern Medical Center.  They found that one in three to four people who do not achieve a full remission of symptoms from an initial antidepressant became symptom-free after changing to or adding a second antidepressant.

Dr. A. John Rush said “The message to the patient is: 'Hang in there. If the first treatment does not relieve your symptoms, consider changing or adding another medication. Follow instructions from your doctor, and don't give up.”  Rush is the vice chairman of clinical sciences and professor of psychiatry at UT Southwestern Medical Center.

The $35 million six year study involved nearly 3,000 patients. The researchers wanted to assess the effectiveness of various treatments for depression in "real-world" settings for people who also have other medical and psychiatric conditions.  The study, designated STAR*D (Sequenced Treatment Alternatives to Relieve Depression), was broken down into four phases. 


In the first phase the participants were treated with the antidepressant citalopram hydrobromide (Celexa) for up to 14 weeks. A "measurement-based care" approach was used to assess progress.  The patients were evaluated for symptoms and medication side effects at each visit based on certain guidelines, with dosages modified as needed. The researchers found that at the end of phase one, about one-third of the participants were symptom-free. 

In the second phase the patients were given a choice whether to add another drug to Celexa or switch drugs.  Of those, 1,429 continued in the study. Those who chose to switch medications were randomized into three groups receiving one of three popular antidepressants: bupropion hydrochloride-SR (Wellbutrin-SR), sertraline hydrochloride (Zoloft) or venlafaxine hydrochloride-XR (Effexor-XR). Of those, approximately 25 percent achieved remission of symptoms within 14 weeks. There was no significant differences in efficacy, safety or tolerability between the three drugs.


Participants who chose to add a medication were given either bupropion hydrochloride-SR or buspirone hydrochloride, along with citalopram.  Of this group, 30 percent of these patients became symptom-free within 14 weeks. Interestingly, neither medication combination was statistically different in its effectiveness on primary outcomes.

Dr. Madhukar Trivedi said "These results show that augmenting a first antidepressant with a second one may be worthwhile for some patients and might be considered even earlier for some people."  Trivedi is professor of psychiatry at UT Southwestern and lead author of one of the studies. "If you add together the people who achieved remission in both phase one and phase two of STAR*D, you see that more than 50 percent of participants become symptom-free after one or two treatments.  That is exciting. If you compare this to the vast majority of other chronic medical diseases, getting to remission in this large percentage is good news."


Dr. Rush said "The bottom line is, 'If you can hang in there for at least two different treatments, you have better than a 50 percent chance of not just getting better, but getting well'.”  He added “The bad news is that we still have a way to go with the 40 percent of people who've had two different drug treatments and still haven't achieved remission – which means that we need better treatments. For a person walking into a doctor's office with depression, that could mean that your first treatment may not be your last. But it does suggest that it's worthwhile to keep on trying." 

There are about 19 million adults struggling with depression each year.  That accounts for 9.5 percent of the total population.  The episodes frequently return and usually last two years.  The researchers said depression, the fourth-most disabling illness worldwide, cost the United States an estimated $83 billion in the year 2000. 

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