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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by steve2 on October 23, 2001, at 22:34:12
Anyone know if there are any new antidepressants on the horizon?
Posted by Mitch on October 24, 2001, at 8:30:03
In reply to Any new AD's in the making?, posted by steve2 on October 23, 2001, at 22:34:12
> Anyone know if there are any new antidepressants on the horizon?
You may know about these already, but Lilly is coming out with duloxetine which is similar to Prozac but enhances norepinephrine to a greater extent. Also, Forrest is planning a "cleaner" version of Celexa (escitalopram). Those two are the closest to getting to market from what I have read here.
Posted by steve2 on October 24, 2001, at 16:54:22
In reply to Re: Any new AD's in the making? » steve2, posted by Mitch on October 24, 2001, at 8:30:03
Do you know when they are anticipated for release?
> > Anyone know if there are any new antidepressants on the horizon?
>
> You may know about these already, but Lilly is coming out with duloxetine which is similar to Prozac but enhances norepinephrine to a greater extent. Also, Forrest is planning a "cleaner" version of Celexa (escitalopram). Those two are the closest to getting to market from what I have read here.
Posted by daveman on October 25, 2001, at 22:22:47
In reply to Re: Any new AD's in the making? (Mitch), posted by steve2 on October 24, 2001, at 16:54:22
Okay, I've been reading about this "new" Celexa for awhile now. But I've yet to figure out what's so "new". As I've been stable on plain old Celexa for almost a year, I'm curious to learn what the "new" version offers. Thanks for any responses.
Dave
Posted by Sunnely on October 26, 2001, at 22:42:31
In reply to What's new about the new Celexa?, posted by daveman on October 25, 2001, at 22:22:47
> Okay, I've been reading about this "new" Celexa for awhile now. But I've yet to figure out what's so "new". As I've been stable on plain old Celexa for almost a year, I'm curious to learn what the "new" version offers. Thanks for any responses.
>
> Dave**************************************************
S-Citalopram
Many biologically active compounds are made up of racemic mixtures. The selective serotonin reuptake inhibitor (SSRI) citalopram (Celexa) is a mixture of an S and an R enantiomer. The reuptake inhibitory activities of citalopram appear to reside in the S enantiomer, making S-citalopram a highly selective SSRI, with no effect on catecholamine reuptake. S-citalopram is active in animal models of antidepressant activity, and in vitro studies suggest it has low likelihood of pharmacokinetic drug interactions.
A study of almost 500 outpatients with major depression compared two doses of S-citalopram, 10 mg/day and 20 mg/day; racemic citalopram (Celexa), 40 mg/day; and placebo in an 8-week, double-blind, random-assignment protocol. Both doses of S-citalopram were greater in efficacy than placebo, with a suggestion of higher efficacy with the 20 mg/day dose than at 10 mg/day. Racemic citalopram was also statistically superior to placebo in efficacy, but S-citalopram at both doses produced greater mean changes than citalopram in key outcome measures at endpoint.
The 10 mg/day dose of S-citalopram was better tolerated than citalopram, 40 mg/day. The rates of discontinuation due to adverse events were 10.4% for S-citalopram, 20 mg/day; 8.8% for citalopram; 4.2% for S-citalopram, 10 mg/day; and 2.5% for placebo. The frequency of treatment-emergent adverse events was only slightly higher for patients in the S-citalopram 10 mg/day group versus patients in the placebo group (79.0% versus 70.5%, P = NS), and comparable between S-citalopram, 20 mg/day, and citalopram, 40 mg/day (85.6% versus 86.4%). The most common adverse events in the active treatment groups were nausea, diarrhea, insomnia, and dry mouth.
In an analysis of three studies with over 1300 subjects, the main adverse event showing the difference between S-citalopram, 10 to 20 mg/day and placebo was insomnia, which occurred at incidences of 9% and 4%, respectively.
Data from these trials suggest GREATER and FASTER symptomatic improvement in depression among patients treated with S-citalopram than with citalopram. There is also a suggestion that S-citalopram is faster in reducing anxiety symptoms in depression than citalopram and that the higher dose of S-citalopram will reduce anxiety to a greater degree.
As occurred with the Prozac brand of fluoxetine, the Celexa brand of citalopram will soon lose patent protection. Patenting an enantiomer gives the manufacturer an opportunity to profit from patent protection for a much longer period. R-fluoxetine was believed to be the clinically active enantiomer of fluoxetine, but hopes for its reaching market were dashed when problems developed, possibly related to an adverse event.
We should know before long whether S-citalopram will come to market in the U.S. and other countries. If so, it is likely to be priced comparably to other new antidepressants but much higher than the generic racemic citalopram. Will the cost be worth it, and how will S-citalopram compare to other antidepressants? Will S-citalopram at doses sufficient to optimize efficacy be more tolerable than generic citalopram? The science is interesting, but the clinical implications and health care economics will undoubtedly gain greater attention. We eagerly await more information.
From: Biological Therapies in Psychiatry, Alan J. Gelenberg, M.D., August 2001.
P.S. I've heard once S-citalopram labeled as the "Super" Celexa. We'll find out soon if it lives up to this billing.
Posted by Daveman on October 29, 2001, at 22:16:01
In reply to Re: What's new about the new Celexa? » daveman, posted by Sunnely on October 26, 2001, at 22:42:31
Thanks for posting that article! It was a bit technical but basically answered my question. I'm surprised to hear that Celexa is going generic soon; I thought it was newer than Paxil. I'm sure my insurance plan will be glad to hear it:)
Dave
Posted by JohnX2 on October 31, 2001, at 4:49:52
In reply to Thanks Sunnely!, posted by Daveman on October 29, 2001, at 22:16:01
Paxil is actually going to be one of the
last to go off patent from the SSRI's.It will be interesting to see if the new
celexa lives up to its claims.If the article was technical heres a simple explanation.
Basically any chemical can have what is called
stereoisomers. These are 2 different versions
of the same chemical with the same formula,weight,
etc. But they are mirror images. Kind of like
superman and bizarro superman. The 2 isomers
(sometimes called levo or dextro), often have
radically different therapeutic qualities.
The chemicals are mirror images, if you looked
at there structures in a mirror they would fit
identically (like if you put your two hands
together). But obviously your left hand is not
the same as your right hand (hence the difference).
Other chemicals dont have this properties. Suppose
we compared two tennis balls. They are mirror images
and they are one in the same, hence no stereo-isomers.One example is dextro-amphetamine which will have a
pro-dopaminergic stimulant effect. But its mirror
image levo-amphetamine does not have such a strong
effect.Eli-Lilly tried this with Prozac (weeding out the
inactive isomer in hopes to reduce side effects), but
if my memory serves me correct it didn't help much.Anyways, with all these anti-depressants coming
off patent, guess what, the race to come out
with improved versions is accelerated by the
pharmaceutical manufacturer's!-john
> Thanks for posting that article! It was a bit technical but basically answered my question. I'm surprised to hear that Celexa is going generic soon; I thought it was newer than Paxil. I'm sure my insurance plan will be glad to hear it:)
>
> Dave
Posted by SLS on October 31, 2001, at 7:31:34
In reply to Re: Thanks Sunnely! » Daveman, posted by JohnX2 on October 31, 2001, at 4:49:52
Hi John.
> Eli-Lilly tried this with Prozac (weeding out the inactive isomer in hopes to reduce side effects), but if my memory serves me correct it didn't help much.
Lilly stated that they discontinued r-fluoxetine because of treatment-emergent cardiovascular side effects (prolongation of QT interval) at the highest dosage tested. They really shot themselves in the foot here. They tested the r-enantiomer at dosages equivilant to the racemate, even though 1/2 that amount would have been biologically equivilant. Lilly decided not to invest the time and money to conduct the trials at lower dosages that would be required for FDA approval. The program would be delayed by two years.
- Scott
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