I’ll TRY to keep this brief… People with mood or anxiety disorders are often treated with SSRI’s or SNRI’s. In fac, such meds are the appropriate treatment for anxiety disorders, not ‘benzos’– a topic that I have already discussed in a prior post.  The SSRIs are ‘selective serotonin reuptake inhibitors’ and SNRIs are ‘serotonin and norepinephrine reuptake inhibitors.’  In general, SNRIs are more potent;  psychiatrists often start with and SSRI or maybe try one and then if necessary a second SSRI, and THEN go on to an SNRI if the patient doesn’t find adequate symptom relief.  SNRIs are chosen as a second option because they tend to be, in general, more difficult to tolerate.  The difficulty usually consists of  short period of ‘activation’ when the medication is first started;  patients will complain of a couple days of irritability or insomnia for example.  Both SSRIs and SNRIs are very well tolerated after a few days or at most weeks have passed on the medication.

The few days of side effects to SSRIs and SNRIs comes from a nonspecific effect of an increase in brain serotonin– NOT from the therapeutic actions of the medication.  When people taking an SSRI or SNRI say ‘I don’t like how it makes me feel’, they are feeling something that is NOT going to be around when actual therapeutic actions occur, several weeks in the future.

I will use brand names for this post;  the brand name for citalopram is Celexa.  Lexapro is the brand name for ‘escitalopram.’  The brands of SSRIs include both of those medications, and also Zoloft, Paxil, Prozac, Luvox, and some names for products in other countries (and I feel like I am forgetting one).  The brand names for SNRI’s in the US are Cymbalta, Effexor, and Pristiq.  This talk, though, is primarily about Lexapro and Celexa.

Celexa was (is) a very good SSRI.  Some SSRIs cause weight gain (Paxil), sedation  (Paxil), weight loss (Prozac), activation or insomnia (Prozac), or nausea (Zoloft)… but Celexa does not cause significant amounts of any of those side effects.  Like all other SSRIs (except, perhaps, Lexapro), Celexa requires at least a few weeks to start working.  Eventually Celexa went ‘off patent’ and became an inexpensive generic– four bucks at WalMart, as a matter of fact.  Around the time Celexa went generic it was replaced by an antidepressant that is very similar, called Lexapro.  So now a frequent issue is whether Lexapro, at ‘brand prices’ of over $100 per month, is worth the money over Celexa, at $4 per month.  What does that extra money get you?  I am not going to be able to give a solid answer to that question, but I will show why the question is there, so that perhaps you can make a better decision yourself.

As I will show in a minute, the two drugs are more than ‘similar’– they are almost identical.  Both medications treat depression and anxiety– of that there is NO doubt.  There have been studies that show that Lexapro works faster than Celexa;  that Celexa takes about 4 weeks to work whereas Lexapro works in as fast as 2 weeks.  There are also those who believe that Celexa has more side effects– a bit more weight gain perhaps, or some sedative effects.  This issue is not absolutely ‘cut and dried’.  The studies favorable to Lexapro have usually been supported by the manufacturer of Lexapro.  On the other hand, I have no doubt that the people doing the studies were honest about the work they have done– my concern is that if you look for something long enough, you will find it by chance alone.  And I do not know how many studies have looked for a positive difference of Lexapro over other SSRIs in order to come up with studies that showed the desired finding.  After reading the research and prescribing the medications over the years, I believe that it is clear that Lexapro is a more desirable medication;  it probably works faster with slightly fewer side effects.  Is it worth the money?  That depends on who is buying it and who it is being given to.  For my I will pay for Lexapro if the difference is only a copayment of 20 bucks.  If insurance won’t cover Lexapro, I will have them try Celexa first.  For me, Celexa is fine– but if I had a moderate to severe depression that was not getting better on Celexa, I would pay for Lexapro.  From my experiences with Medicare and my reading about the language of the bill being debated in Congress today, along with my understanding of Tom Daschl’s book and the comments off the current President of the US, I would be SHOCKED if Lexapro were available for people on any ‘public option’.  This is the type of savings that the administration seems to believe will make a difference in the price of health care.  I think it might help a little bit, but I think that many people will be angry when they gain ten pounds on Celexa and find that they cannot take Lexapro.  But they can always exercise– and then the problem is solved.  There is enough to argue about even if we take all of what I just said as fact– which is why everyone is arguing right now!

The difference between the two medications is difficult to understand… and yet very simple once you get the point.  Look at your two hands–  one is ‘right handed’ and the other is ‘left handed’.  Most medications consist of two ‘halves’, a right and left-handed form.  Your two hands are in many ways identical– the same tissue, the same genes, the same structure.  And yet they are different in that one is the mirror image of the other.  A batch of chemicals contains right and left handed molecules because chemical reactions produce a 50/50 mix of both right and left forms.  It is hard to separate them from each other, as they both act the same way in electrical fields and they both are the same size and shape– so you can’t just make some type of ‘filter’ that separates out just the active form. But when the chemicals are used in the body, they usually work at ‘receptors’, where they must ‘fit’ in order to cause something to happen.   And if you try to stick your right hand into a left glove, you have problems.  Same in the body;  one ‘half’ binds to the receptor and is effective, and the other half does not fit, and is inactive.  In other words, half of most of the medication you use does not do anything.

This is the case with Lexapro and Cexexa.  Celexa consists of both varieties of the molecule– the right and left forms.  But Lexapro is only the potent, active variety– the left-handed molecule.  When you are taking Celexa you are taking two chemicals that are mirror images of each other;  one of the chemicals binds to the proper site and blocks serotonin reuptake, and the other chemical is the mirror image of the active chemical, and probably doesn’t do much of anything.  If you take Lexapro, you are taking ONLY the active form.  So if you take 20 mg of Celexa, half of what you are taking– 10 mg– is Lexapro.

Both are 'Citalopram'; one half is 'Lexapro'

This would imply that a person could just take twice as much Celexa and get the same effect as Lexapro, right?  Maybe.  The problem is that some studies suggest that Lexapro is more than twice as potent as Celexa– that it is actually about 4 times as potent.  The only way that could be the case is if for some reason the inactive half is doing something bad– not just doing ‘nothing’, but maybe getting in the way of the active half.  The inactive half might also cause side effects that are not caused by the active half, explaining why some people find that Celexa causes them to gain weight or get sleepy, while Lexapro does neither.  What do I think?  I t hink that it is easy to get too tied up in the chemical issues.  Both medications are effective, with some minor differences between them.  I’ll stick with my earlier comments about it depending on who is taking/paying for the medications.  I think there are implications, though for ‘choice’ when it comes to health care.  I also recognize that if pharmaceutical companies cannot profit from their discoveries, then there will be fewer discoveries.  Most of the profits of pharmaceutical companies go right to where we should all want them to go– to research efforts for more effective, safer medications.  And if some team of scientists find a cure for something, they should benefit financially– just as Bill Gates became a billionaire for his work with computer operating systems.

I think I’ll leave it there before I say something controversial.  Lexapro or Citalopram– you get to decide.  Perhaps the bigger question– the one that is being debated in Congress right now– is SHOULD you get to decide?  I’m not taking a position on that question– but the people who are debating the health care reform should recognize– and admit– that THEY are taking a position on that question.

Just a quick comment tonight about an interesting report from the American Academy of Child and Adolescent Psychiatry 56th Annual Meeting– in Hawaii, of all places (gnashing my teeth in jealousy, but it should pass in a few minutes!).  As you may or may not know, my practice is split between classic psychiatry (med management and/or psychotherapy from a psychodynamic perspective), treatment of addictions (primarily opiate dependence), and treatment at the interface of chronic pain, psychiatry, and addiction.  Compared to the fatal nature of opiate dependence and the epidemic of cases locally and across the nation, I view pot-smoking as a relatively minor vice for most people.  I have met a number of people who seem to be able to smoke pot fairly regularly without significant harmful sequelae– although I would not be surprised if the pot use is costing something–  a reduction in marital intimacy or in one’s relationship with one’s children, for example.

On the other hand there are clearly people who have negative consequences from use of THC.   One thing that has always stood out, at least in patients I have followed, is that people who are depressed and who are regular pot smokers do not seem to benefit all that well from SSRI‘s– or from other treatments, for that matter.  I have assumed that the reason is more psychological than chemical– that since pot-smokers tend to be more sedentary, and tend to lack good coping skills other than smoking marijuana to deal with stress (whereas non-pot-smokers may deal with stress by exercising, meditating, or taking up a new hobby), they are simply harder to pull out of the ‘funk’ that depressed people are in.  But at the meeting in Hawaii, docs from the University of Pittsburgh School of Medicine reported partial data from a larger study that showed a reduced treatment response to antidepressants by patients using moderate amounts of alcohol or marijuana.

File this report in the ‘evidence backing up common sense’ drawer.  It was not a huge surprise, but it is always a good thing when the science is consistent with the general opinion on a topic.  This was not the case, as some of you may remember, when it came to breast implants and autoimmune conditions– and about a million other things that the media warns us about, that eventually turns out to be a bunch of baloney.  In the case of pot smoking and reduced response to antidepressants, seems that there isn’t much baloney going around.

JJ

Casual Cannabis, Alcohol Use Reduces Treatment Efficacy in Adolescents With Major Depression