Antidepressant Research: Which Depression Medications Work Best?

Merely Me Health Guide
  • In a previous post we explored the possible reasons for the dramatic increase in antidepressant use over the past two decades. One theory is that antidepressants are being overprescribed to people who are not clinically diagnosed with depression or a mood disorder. But for the many individuals who do suffer from clinical depression, medication can be an effective and sometimes life-saving treatment option. The decision to take medication to treat your depression can be a difficult choice. Many of our members on MyDepressionConnection ask about which antidepressants are the “best.” This is an impossible question to answer because so much depends upon the individual’s diagnosis, body chemistry, ability or willingness to tolerate side effects, and many other factors. The more precise question is, “Which antidepressant is right for me?” In making such a decision a review of the medical literature and research can be helpful. In this post we are going to take a look at the latest research on which antidepressants are rated as the most effective.

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    Note: The decision to take medication to treat your depression is a personal choice. Nobody can make this choice for you. Take the time to research any drugs you may use including possible side effects or interactions with other medications. If you do decide you want to try medication discuss your options with your doctor to find the antidepressant right for you.


    Do the newer antidepressants (Effexor and Cymbalta) work better than older medications such as Prozac or Celexa?


    There appears to be some evidence that the newer and more costly SNRI’s (serotonin and norepinephrin reuptake inhibitors) do not work any better than the generic and less expensive older class of antidepressants called SSRIs (selective serotonin reuptake inhibitors). Here is some of the research on this topic:


    • A 2009 Consumer Reports survey found that SSRI’s such as Lexapro, Celexa, Prozac and Zoloft are just as effective and with fewer side effects than some of the newer SNRI’s like Cymbalta and Effexor. According to Nancy Metcalf, the senior program editor for Consumer Reports Health, their survey showed “…that a combination of therapy and medication works best, and that despite the intense marketing push consumers are subjected to, there is no evidence that newer drugs like Pristiq and Cymbalta work any better than older medications in their class.”


    • A 2008 study by Gartlehner et. al. shows similar results as the Consumer Reports survey. The study authors concluded that: “Current evidence does not warrant the choice of one second-generation antidepressant over another on the basis of differences in efficacy and effectiveness. Other differences with respect to onset of action and adverse events may be relevant for the choice of a medication.”


    Which antidepressants have been found to be the most effective?


    The answer to this question greatly depends upon which study you are looking at. In addition, a 2008 study published in the New England Journal of Medicine found that research studies showing positive results were more likely to be published in journals than those studies with inconclusive or negative results. In fact, a drug’s efficacy in published reports was found to be 32% more positive, on average, than unpublished company reports. The moral of the story is to look at any medication research studies with a skeptical eye. The other thing to keep in mind is that different medications will work better for different types of depression. There are some antidepressants found to work better for those with moderate to severe depression, for example. With these factors in mind, here are some of the latest research findings on the most effective antidepressants.


    Montgomery (2007) found that three antidepressants were superior in treating moderate to severe depression. These antidepressants included: Anafranil (clomipramine), Effexor (venlafaxine), and Lexapro (escitalopram).


    Consumer Reports Best Buy Drugs for Treating Depression  list five medications as the best antidepressants to try first in treating your depression. They considered effectiveness, safety, side effects, and cost into their ranking. Their top five medications are all generic versions of bupropion (Wellbutrin), citalopram (Celexa), fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft). 

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    Cipriani et. al (2009) assessed the effects of 12 new-generation antidepressants on major depression. The study authors defined effectiveness as a 50% reduction in clinical ratings of depression after eight weeks on a drug. They also took into account, drug acceptability, which means that the drug is well tolerated. Lexapro and Zoloft were found to be the best in terms of efficacy and tolerability. Their conclusion is that Zoloft may be the best antidepressant to begin medication therapy: “Sertraline might be the best choice when starting treatment for moderate to severe major depression in adults because it has the most favourable balance between benefits, acceptability, and acquisition cost.”


    Confused yet? It is clear that different studies will yield different results depending on which types of methodology and statistical analysis are used. Despite all the research it seems more probable that many doctors and patients will base their decision of choosing an antidepressant on other factors. As we discussed in my previous article, pharmaceutical advertising may have the biggest impact upon our medication choices. Dr. Lon Schneider, a professor of psychiatry at USC's Keck School of Medicine, was quoted in a 2009 Los Angeles Times article on antidepressants as saying, “What mainly determines what antidepressant physicians prescribe is, unfortunately, the marketing."


    We are going to continue our exploration of medication treatment for depression by taking a look at which antidepressants are least likely to cause certain side effects. We are also going to provide the latest research on combination treatments (adding a supplement or other medication to your antidepressant).  Lastly, we are going to look at the research on the overall effectiveness of antidepressant treatment for depression.  


    You are the true experts here. We would love to hear your take on this research. What is your personal opinion about the “best” antidepressants for treating depression? Which antidepressants have been the most effective for you? Which have been the worst as far as cost, effectiveness, and adverse side effects? Tell us your story. We are listening!


    Here are some additional Health Central articles on the topic of choosing an antidepressant:


    Finding the Most Effective Antidepressant to Treat Your Depression 


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    Member Medication Review


    Antidepressant Studies-Getting the Whole Picture 

Published On: July 25, 2011