Wednesday, June 23, 2004

New Antidepressant Medication
Cymbalta (duloxetine) to be Released Next Month

Eli Lily, the original makers of Prozac, have a new antidepressant medication.  It is called duloxetine; the brand name in the USA and UK will be Cymbalta.  I was told that they expect to be able to release it for sale on July 8, 2004.  I expect that there will be a considerable media blitz and we all we be subjected to a bunch of hype.  Eli Lilly had a brilliant marketing campaign when Prozac was introduced in 1987.  Cymbalta is not as much of a revolutionary product the way Prozac was.  There is almost nothing in the Blogosphere about this (except for this post, on Corente), so I decided to make a few comments. 

Among the hype will be messages about Cymbalta being effective for pain control, there is some evidence that it might work faster than other antidepressants, and it has a side effect that renders it effective for treatment of urinary stress incontinence.  It will be touted as being weight-neutral, and I expect they will say it is less likely to cause sexual dysfunction than many antidepressants.  Some of these claims may be true, but the fact is, you never really know until a drug has been on the market for at least a year. 

Notes: doctors have been using antidepressants for years to treat chronic pain and stress incontinence.  I would be skeptical of these claims until the studies have been replicated by independent research centers.  Weight gain is notoriously difficult to study.  Some antidepressants, such as Prozac, tend to cause a bit of weight loss early on, but this can be followed by slow, steady weight gain.  It may take years to get the full picture on this.  Studies on sexual functioning are notoriously unreliable, because it is hard to get people to tell the truth about it.  As to the onset of action, the time seen in a study is highly dependent upon the study sample and the methodology used.  I would want to see large head-to-head comparison trials before reaching any conclusion.  Also, as much as people with depression want to get over it quickly, what is much more important is the relapse rate.  Again, it will be a while before we have firm, reliable data on that. 

Much hay will be made over the drug's mechanism of action.  It inhibits reuptake of both serotonin and norepinepherine, much like some of the tricyclic antidepressants, and venlafaxine at higher doses.  You will hear that this "dual mechanism" is better than selective serotonin reuptake inhibition.  Although it is tempting to believe this, there is not a lot of evidence to support the hypothesis.  we still are not very good at inferring the clinical effect of a drug based upon the in-vitro  pharmacology. 

Some of the initial claims may be true.  I am just pointing out that one must be cautious with the initial claims about any new product.   I expect that Cymbalta will turn out to be a useful drug for many people.   I also expect that, when the dust settles, it will turn out to have exactly the same effectiveness, on average, as all existing antidepressants.  To the individual patient, though, the average effectiveness is not important.  What is important to the individual, is how effective the drug is for him or her. 

Advice?  The Corpus Callosum is reluctant to give advice.  But there are a few things I would like to mention:
  • Unless there is a specific reason to do otherwise, it is best to wait until a new drug has been on the market for about six months before considering it for routine use.
  • For patients who have failed multiple adequate medication trials, a new drug might be worth trying.  To count as an adequate trial, you have to have been on a drug at the maximum dose for at least six weeks.  And you have to take it reliably, be adequately nourished, and not poison yourself with alcohol while taking the drug, for the trial to count as an adequate trial.
  • Similarly, if you are going to try a new drug, it is very important to give it a fair trial.  This means taking it exactly as prescribed, at an adequate dose, for an adequate duration, in the absence of factors that would be expected to diminish its effectiveness. 
  • Patients with depression who are already taking a drug for stress incontinence might be able to treat both conditions with one drug, using duloxetine. 
  • Remember that little will be known about drug interactions with any new drug.  There are theoretical reasons to think that Cymbalta will have few significant interactions, but remember that we are not very good about inferring the clinical effect of a drug based upon the in-vitro  pharmacology.  Therefore, if you take several different medications, be extremely cautious about any new drug. 
  • Initially, there will be no data about the use of the drug in women who are pregnant or breast feeding.  Women of childbearing age should keep this in mind, regardless of how many times they have said "it won't happen to me."
I expect to have more to say about this soon.