SSRI: Are they *really* that different?

[DD214_DOC]

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So this debate came up with residents and an attending during didactics. Basically, Stahl taught us that SSRIs different greatly not only in their pharmacokinetics and dynamics but also their affinity for specific neurotransmitters, or that some are more, "activating" than others.

At any rate, we have a new attending who made the bold statement that he used to believe this, but clinically he has noticed little to no difference in SSRIs other than pharmakinetic/dynamic properties and that the common-held belief that one is more, "activating" than another is hogwash inferred from certain patients who simply have had a different response that could have occurred with any SSRI.

I mean to fiddle around on pubmed and see what studies are out there investigating this sort of thing but did not have time, and I'm not going back to the hospital on the weekend.

Thoughts? Are they really that different? Is the difference clinically significant? Are the "differences" simply individual-specific reactions or responses?

 

[firedoor]

Thoughts? Are they really that different? Is the difference clinically significant? Are the "differences" simply individual-specific reactions or responses?

My guess is that the differences are largely related to pharmacokinetic and individual-specific responses. Perhaps Prozac is an exception due to its unique 5-HT2C antagonism among the SSRI's. (I also think that 20 mg is often too high of a starting dose and that's probably significant also [http://forums.studentdoctor.net/archive/index.php/t-795088.html]).

Stahl likes to talk about sigma receptors and god bless him for it, sincerely, but I'm unclear of the clinical relevance as related to SSRI's. People knock him but I've learned a lot from his articles/books.

Paxil does have the baggage of H-1 and cholinergic receptor antagonism, which is a reason I often avoid prescribing it.

I do buy that clinically significant differences exist between Lexapro and Celexa, at least in terms of initial onset of therapeutic and side effects. It is noted the links below involve rats and the company which produces escitalopram:

http://www.cipralex.co.il/sitecontent/ExternalFiles/217.pdf

http://www.sciencedirect.com/science/article/pii/S0028390803001382

Personally, I believe Lexapro does have some benefits over Celexa especially in terms of onset of action, likely due to the functionally antagonistic effects of R-citalopram on SERT. Whopper once mentioned that could be of benefit, as anecdotally some patients cannot tolerate the activating effects of Lexapro, whereas they can tolerate those of Celexa. I have noticed this in practice with several patients. Perhaps the most important differences between the two relate to the initation of therapy and in severe depression:

Is escitalopram really relevantly superior to citalopram in treatment of major depressive disorder? A meta-analysis of head-to-head randomized trials.

http://www.ncbi.nlm.nih.gov/pubmed/20162747

[Escitalopram is more effective than citalopram for the treatment of severe major depressive disorder].

http://www.ncbi.nlm.nih.gov/pubmed/15107719

I still prescribe a lot of Celexa.

In general, while as an aggregate the SSRI's are more similiar than dissimiliar, individual-specific response differences are relevant and my guess is that such differences have much to do with pharmacokinetic and pharmacodynamic factors (individual-specific differences in binding-affinities related to polymorphisms in SERT configuration [i.e. the lock and key model]). A failure of one SSRI does not preclude the failure of another. And I wouldn't discount psychoanalytic factors in individual-specific responses either.

Not to digress, but relatedly I take exception with the common belief that Wellbutrin is necessarily more "activating/stimulating" than the SSRI's. I have also not put to rest in my mind the clinically important differences between SSRI's and SNRI's (beyond pain). Despite the initial overhyped claims that SNRI's have clinical superiority to the SSRI's, I often wonder if SNRI's are not underused in psychiatry.

 

[Suedehead]

I choose an ssri using astrology and cross my fingers whenever I hand over the rx.

 

[Suedehead]

and i'm only halfway kidding

 

[IAmAUser]

.

 

[billypilgrim37]

In child, we have good evidence that fluoxetine works and that paroxetine does not work. We know that sertraline and the citaloprams have fewer drug interactions for our medically ill kids. We know that the Columbine kids were on fluvoxamine when they went on their rampage. So are they very different? Well, no. They have somewhat different titrations. Some come in liquid and others don't. The side effect profiles are not amazingly different, but significantly different. They have remarkably different profiles at other receptor systems, but clinically who knows. Sertraline hits dopamine hard enough you would expect it to have some differential clinical effects, though I don't think anybody sees this practically. Sertraline tears your stomach up more than the others do. Withdrawing from paroxetine feels like absolute hell. Clinically, I have seen much more activation with fluoxetine than other agents, especially in autism populations (zero data to support this that I'm aware of). Now, you're not allowed to use citalopram at high enough doses to treat some percentage of your patient population. Around here, citalopram, paroxetine, and fluoxetine are on the 4 dollar pharmacy plans, sertraline is more expensive but not too bad, and escitalopram is just a bad marketing ploy (until a few years from now when it's on the 4 dollar plans, and I suddenly forget all of my biases against it).

They are different enough that your choice might matter sometimes, nevermind the transference issues that some of the meds evoke. The word "Prozac" can elicit a wide variety of reactions from parents, from "that's been around forever" and "I know a billion people who have been on that" to "that's that drug they invented to steal kids' souls after Ritalin steals their hearts."

 

[OldPsychDoc]

In child, we have good evidence that fluoxetine works and that paroxetine does not work. We know that sertraline and the citaloprams have fewer drug interactions for our medically ill kids. We know that the Columbine kids were on fluvoxamine when they went on their rampage. So are they very different? Well, no. They have somewhat different titrations. Some come in liquid and others don't. The side effect profiles are not amazingly different, but significantly different. They have remarkably different profiles at other receptor systems, but clinically who knows. Sertraline hits dopamine hard enough you would expect it to have some differential clinical effects, though I don't think anybody sees this practically. Sertraline tears your stomach up more than the others do. Withdrawing from paroxetine feels like absolute hell. Clinically, I have seen much more activation with fluoxetine than other agents, especially in autism populations (zero data to support this that I'm aware of). Now, you're not allowed to use citalopram at high enough doses to treat some percentage of your patient population. Around here, citalopram, paroxetine, and fluoxetine are on the 4 dollar pharmacy plans, sertraline is more expensive but not too bad, and escitalopram is just a bad marketing ploy (until a few years from now when it's on the 4 dollar plans, and I suddenly forget all of my biases against it).

They are different enough that your choice might matter sometimes, nevermind the transference issues that some of the meds evoke. The word "Prozac" can elicit a wide variety of reactions from parents, from "that's been around forever" and "I know a billion people who have been on that" to "that's that drug they invented to steal kids' souls after Ritalin steals their hearts."

I think I'll just hand this out from now on instead of giving my 1 hour lecture on antidepressants to the med students...

Adding, of course, the excellence of fluoxetine's infinite half-life when treating homeless chemically dependent types who are likely to go on and off their med randomly.

 

[whopper]

They are very different but also have one underlying similarity.

No matter how much you know about them, if you've never tried them on a specific patient, you won't know what it will do. The data available only gives us guidelines on how it will work on a population, not specific individuals. You could, for example, give the med with the least amount of side effects on person x, and that person will not be able to tolerate it, but then give them the one with the most amount of side effects, and the person does well on it.

Knowing the pharmacology does give us a best educated guess in recommending a specific SSRI, but don't do so under a false guise that the med is the best one available for the patient. Best educated guess is still better than shot in the dark. While these numbers aren't based on science, for me, based on clinical experience/gutt feeling compared to other docs I've seen who just give out one SSRI to every single patient, it's like having a 55% chance vs 15% chance of getting the patient the best med for them.

For this reason it is very important for patients and doctors to record what each med and at what dosages.

And I add this only because I see this problem so many times. Per studies, antidepressants usually only work at higher dosages. A patient on Prozac 20 mg Q daily x 2 years with no benefit doesn't mean that Prozac doesn't work. It could work at higher dosages. For that reason, I tend to automatically have the patient raise the dosage from the starting dosage to the next higher dosage before they even see me next unless they have questions or want to address side effects.

 

[sunlioness]

I agree with the dosing, which is why I am still not thrilled about the new Citalopram guidelines. 60mg was a dose I went to all the time.

I do generally try to avoid paroxetine because of the weight gain issues (though I just had a patient referred to me on paroxetine 20 QID and quetiapine. Yikes! She had gained all kinds of weight) and escitalopram because of the cost (though I'll be really excited when it goes generic).

 

[kugel]

In child, we have good evidence that fluoxetine works and that paroxetine does not work. We know that sertraline and the citaloprams have fewer drug interactions for our medically ill kids. We know that the Columbine kids were on fluvoxamine when they went on their rampage. So are they very different? Well, no. They have somewhat different titrations. Some come in liquid and others don't. The side effect profiles are not amazingly different, but significantly different. They have remarkably different profiles at other receptor systems, but clinically who knows. Sertraline hits dopamine hard enough you would expect it to have some differential clinical effects, though I don't think anybody sees this practically. Sertraline tears your stomach up more than the others do. Withdrawing from paroxetine feels like absolute hell. Clinically, I have seen much more activation with fluoxetine than other agents, especially in autism populations (zero data to support this that I'm aware of). Now, you're not allowed to use citalopram at high enough doses to treat some percentage of your patient population. Around here, citalopram, paroxetine, and fluoxetine are on the 4 dollar pharmacy plans, sertraline is more expensive but not too bad, and escitalopram is just a bad marketing ploy (until a few years from now when it's on the 4 dollar plans, and I suddenly forget all of my biases against it).

They are different enough that your choice might matter sometimes, nevermind the transference issues that some of the meds evoke. The word "Prozac" can elicit a wide variety of reactions from parents, from "that's been around forever" and "I know a billion people who have been on that" to "that's that drug they invented to steal kids' souls after Ritalin steals their hearts."

This is a good one-paragraph summary, though I don't know anything about the autism pop'n. Retail price is an issue. Although your patients may currently have access to whatever you Rx, that will not always be true, even for your current patients. Most patients will move or change insurance over time. When the day comes that they have to pay retail price (even for one month), they are likely to skip medicines that cost a lot. In addition to fluoxetine and citalopram because they are on the $4 lists, I often use sertraline because of the ability to fine-tune dosing with 25mg increments. I especially use it in medically complicated or older pt's because of the low-drug interaction profile, similar to citalopram but with more dosing options.

Other than the few things noted above, and the half-life issues, I believe any other differences are clinically irrelevant. Although the other differences may be true, the patient differences are larger. If the differences in individual patient tolerance/response are larger than the medication differences, how could you ever utilize/minimize those other medication differences? The noise in the data will be larger than the signal.

A very wise 7th grade history teacher once told me,
"A difference that makes no difference is no difference."
(We still don't know why he intruded on our pre-school nap time just to tell us that!)

 

[whopper]

The citalopram 60 mg thing is bothersome. It's been out for decades and only now they find a problem? I've literally had hundreds of patients on 60 mg Q daily and none of them had cardiac problems as far as I'm aware, several of these patients being on telemetry or frequent EKGs due to already existing heart problems.

I've yet to see the exact data showing this is a problem. All the data I've seen points to statements provided by the manufacturer, but not the actual real data.

I'm also sure there is a higher risk at 60 mg Qdaily, just like I'm sure there's a higher risk of getting into a car accident at 35 MPH vs. 15 mph, though that in and of itself shouldn't make it so that the med has a recommendation across the board to not take it at 60 mg Q daily, just like there shouldn't be a law outlawing driving over 15 mph.

 

[zenman]

and i'm only halfway kidding

I actually tell patients that truthfully I'll just throw it at them and see what happens.