In the July 9 New York Times, Dr. Peter Kramer wrote a piece titled, "In Defense of Antidepressants". It seems ironic that such an article is needed, given the substantial evidence that antidepressants have helped millions of people. However, there continues to be a confusing, academic argument about some of the studies of antidepressants.

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Dr. Kramer is a gifted psychiatrist. He achieved national recognition 18 years ago when he wrote the book "Listening to Prozac". He made his patients come to life for the reader. I read the book and was impressed by how many people he had helped to find their way forward by combining sensitive psychotherapy and appropriate use of one of the earliest serotonin reuptake inhibitors, Prozac.

While his recent article takes on a difficult topic, I was pleased that the paper published it. While some of the details are too esoteric for most readers to follow, the balance of evidence clearly demonstrates that antidepressants work. That's also the conclusion of the FDA and is the experience of many people who have recovered from a serious depression.

Of course, as has been discussed at great lengths on this blog, not all antidepressants work for everyone. Additionally, for some of you, the side effects can be intolerable. Despite millions of dollars of research, the process of finding the right antidepressant is still a difficult one.

While some new tools, such as pharmacogenomic testing, make this process somewhat more rational, it's clear that the search for a better antidepressant must continue and that research designed to identify which people will respond to which medication should have a high funding priority from the National Institute of Health.

One type of study that Dr. Kramer discusses is particularly interesting and rarely considered. These are "maintenance studies". In his article, Dr. Kramer refers to a large study of 4,410 patients who initially had a good response to an antidepressant. The study was designed to focus on the question of how long to continue treatment. The study also wanted to examine the possibility that some patients may respond to treatment as a consequence of other factors besides their medication.

In this study, after successful treatment, half of the patients were switched to a placebo and the remainder continued to receive their active antidepressant. The participants didn't know if they were still getting their antidepressant or had been switched to a sugar pill. In many ways, this is a tough study to volunteer to be in. However, the results were clear. About 70 percent of those who were switched to the placebo relapsed, while most who remained on their medication didn't relapse.

This finding strongly suggests that simply believing that you're taking your antidepressant is not sufficient to maintain a good response. This result makes good sense and supports the importance of staying on a medication that's working.

A link to Dr. Kramer's article can be found in the Resources tab above.

Please share your thoughts.

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In reading your comments, I'm struck by a number of observations:

Many of you have suffered for a long time with depression but haven't given up. Most impressively, many are trying to help others.It's common to find an antidepressant medication that works for awhile and then after some months or years, it stops working. This is extremely frustrating for you and your doctor. The truth is that we don't really understand why this happens. There are probably different reasons for different medications. Fortunately for some of you, it doesn't happen.National Suicide Prevention Lifeline
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When you're doing well on an antidepressant, it's reasonable to ask how long you should keep taking it. Unfortunately, there's no absolutely correct answer. However, most clinicians feel that as long as the medication is having a beneficial effect, it's probably wise to keep using it. This is particularly true because some of you do well on the same medication for many years.

One of the current theories for why antidepressants stop working is that over time the genes that produce enzymes that regulate the metabolism of medications become upregulated and consequently produce more enzymes. If this is the case, it may lead to a decrease in the blood level and it may be necessary to increase the dose in order to get the same effect.

Some of you decide to stop taking antidepressants when you feel better, and then find that symptoms return. At that point, you want to begin taking the medication again. For some, the medicine once again helps, but for others it doesn't seem to have the same positive effect that it initially had.

It would be helpful if you'd share your own stories related to a particular medication losing effectiveness. The personal stories might provide some clues that could help others to better understand why a particular antidepressant medication stops working. It would be important to know the name of the medication that initially worked and what events were associated with it losing its effectiveness. While it's frustrating to have a medication lose its effectiveness, usually a replacement can be found that will once again lead to some relief of depressive symptoms.

One of you asked about being an ultrarapid metabolizer. This means that for some antidepressants it would be difficult for you to achieve an adequate blood level and therefore it would be unlikely you'd have a good clinical response at a safe dose.  However, it's important to understand that even though someone is an ultrarapid metabolizer for one type of antidepressant, it's quite possible that they could be a normal metabolizer of other antidepressants. This is a critical concept for both patients and their doctors to understand.Another question was how pharmacogenomic testing can be obtained in Canada.  It's my understanding that it's available at the major academic medical centers in Canada as they have good access to major reference laboratories which all offer pharmacogenomic testing. However, I don't believe that it's routinely paid for by the Canada's national health system. Hopefully, this will change as the benefits of testing become more widely understood.blog index

Some of you have been interested in the recent discussion of pharmacogenetic testing and have asked if it's available. Yes, it's available, but many psychiatrists aren't yet comfortable with interpreting the results.

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The Mayo Medical Laboratory began testing in 2003 to determine whether people could tolerate certain antidepressants. In a relatively short time, other large medical laboratories also began offering these tests.

Two things have happened to improve access to testing:

First, a company called AssureRx Health was created to provide the results of these tests to psychiatrists using a more "physician friendly" report. A psychiatrist can now collect just a simple cheek swab sample of DNA, send it overnight to AssureRx and receive the results electronically within 36 to 48 hours.Second, more than 2,000 psychiatrists have taken a Mayo Clinic course designed to help them use this testing more efficiently.

By incorporating new research results from ongoing scientific studies, the testing is getting increasingly more accurate. While the results still can't provide a certain prediction of which antidepressant will be most effective, the tests do increase the chances of identifying an effective medication and can definitely identify medications that you're unlikely to be able to tolerate.

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