Sunday, November 8, 2015

Escitalopam vs. Citalopram (Cipralex or Lexapro vs. Celexa)

It is interesting how professional opinion can be swayed by trends in practice.   Escitalopram (Cipralex, or Lexapro) is a newer antidepressant than citalopram (Celexa).   In fact, citalopram itself is a mixture of "enantiomers," which are molecules that are identical to each other except for being mirror-images of each other geometrically.  In many chemical processes, different enantiomers are formed in fairly equal amounts, as a mixture.   But escitalopram, unlike citalopram, consists of just one of these entantiomers, rather than being a mixture.   Citalopram is literally a mixture of escitalopram with an inactive enantiomer.  Therefore, you literally are taking escitalopram when you are taking citalopram.  You are also taking the inactive enantiomer of escitalopram. 

Here we have it again, that escitalopram has more recently been on patent, while citalopram has been available in a generic form for a longer time.  Of course, there would be many more industry-sponsored research studies done recently on escitalopram. 

There's no doubt about it, that escitalopram can be a good antidepressant.  But many professionals (including in one formal instructive report I recently read), assert that escitalopram is clearly "better" than citalopram.

I think this belief is mainly due to cognitive biases.   There has been much more marketing favouring escitalopram in the past decade.  The trends in practice among psychiatrists tend to favour the personal belief that "escitalopram is better."  Because it is used more often these days than citalopram, any positive report about escitalopram is likely to be more salient.  Also, with recurrent trials of antidepressants, any switch to almost any new agent has a reasonable probability of leading to some improvement, irrespective of the properties of the new agent.  For many people, a given antidepressant does not work well enough.  In this cohort, it is much more likely that a given person would have tried citalopram at some point in the past, and would now be looking at trying escitalopram.  There might be about a 30% chance of the escitalopram helping in this scenario.  For the thousands of people in this group, there would then be hundreds who would have the experience of escitalopram appearing to work better than citalopram.   This feeds the notion that escitalopram is in fact a better antidepressant.

The bias here is that very few people in this cohort would have tried escitalopram first, then tried citalopram later on.   This is because escitalopram is newer, more highly marketed, and is more likely to be used when other antidepressants have not worked.   But the prevailing evidence is that most any new antidepressant (or other therapy) trial has a similar chance of helping, when a previous trial has not helped.  Therefore, I predict that there would be an equal likelihood of citalopram working when escitalopram failed, compared to escitalopram working when citalopram failed.  It is possible that the only reason escitalopram appears to work more commonly is that it is simply used more often!

Some of my patients, over the years, have tried both of these medications.  Some have ended up preferring escitalopram.   Others have ended up preferring citalopram.  For most, there has been no difference, either in side effects or effectiveness. 

Are there any recent research studies which compare the two?  One recent study, by Li et al (2014), reviews and pools results from 3 previous clinical studies.  They conclude that there is no difference in response or remission rates between escitalopram and citalopram:

It is interesting to look at the data from previous studies, including a Cochrane review done in 2012, which conclude that escitalopram is better than citalopram:   The authors slip in the caution that "As with most systematic reviews in psychopharmacology, the potential for overestimation of treatment effect due to sponsorship bias and publication bias should be borne in mind when interpreting review findings."  Yet the reader of this article is left with the impression that escitalopram is much better than citalopram.  

I note that escitalopram is about 30% more expensive than an equivalent dose of citalopram, according to PharmacyCompass, a Canadian service which helps people find the best local prices for medications at local pharmacies.   

In conclusion, I think that with respect to antidepressant choice, there is no doubt that escitalopram is appropriate and works at least as well as other available medications.  But it is not necessarily true that escitalopram is "better."  The problem with this biased view of "betterness" is that it could cause a person (a psychiatrist or patient) to overlook other options, and favour escitalopram as a first choice automatically, and unnecessarily.  It could also cause many to overlook citalopram as a possibility for someone who has unsuccessfully tried escitalopram in the past.

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