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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 16 of 16. This is the beginning of the thread.
Posted by Neal on March 6, 2001, at 1:06:13
A Vanderbilt study has found that Prozac and the antipsychotic Zyprexa work better together on treatment-resistant depression patients than either drug alone. Twenty-eight patients were given either Prozac and a placebo, Zyprexa and a placebo, or the two drugs together. After eight weeks, researchers found a "minimal" improvement with Prozac, a "modest" improvement with Zyprexa, and a "significant" improvement with the combination.
Posted by JohnX on March 6, 2001, at 2:49:42
In reply to Prozac Zyprexa Study, posted by Neal on March 6, 2001, at 1:06:13
> A Vanderbilt study has found that Prozac and the antipsychotic Zyprexa work better together on treatment-resistant depression patients than either drug alone. Twenty-eight patients were given either Prozac and a placebo, Zyprexa and a placebo, or the two drugs together. After eight weeks, researchers found a "minimal" improvement with Prozac, a "modest" improvement with Zyprexa, and a "significant" improvement with the combination.
This doesn't seem too unexpected. Ideally it seems
one would like a really clean SSRI that blocks the
5ht-2 receptor. Currently there is no medication that does this. Serzone effectively blocks 5ht-2
receptors, but is a weak SSRI and NRI and also
blocks alpha-1 adrenergic receptors which can cause depressive feelings. I'm wondering to
what extent the low dose d2-receptor antagonism
in zyprexa may help depression?I read a few abstracts on new compounds that will
hopefully be more targeted at blocking 5ht-2
receptors while acting as strong SSRI's or 5ht-1
agonists. Hopefully these meds will be quicker
acting with fewer side effects and better response
rates.Zyprasidone looks like a potentially excellent
anti-depressant or complement to an anti-depressant too.Would be interested in any updates.
-John.
Posted by JohnL on March 6, 2001, at 5:16:12
In reply to Re: Prozac Zyprexa Study » Neal, posted by JohnX on March 6, 2001, at 2:49:42
> > A Vanderbilt study has found that Prozac and the antipsychotic Zyprexa work better together on treatment-resistant depression patients than either drug alone. Twenty-eight patients were given either Prozac and a placebo, Zyprexa and a placebo, or the two drugs together. After eight weeks, researchers found a "minimal" improvement with Prozac, a "modest" improvement with Zyprexa, and a "significant" improvement with the combination.
>
I have always felt that Prozac+Zyprexa is a great combination. Not sure why. There just seems to be some synergy with them that turns out to be very helpful for a whole wide range of symptoms, especially for people who have had less than adequate results with straight forward antidepressant therapy.Prozac+Zyprexa dramatically raises levels of serotonin, norepinephrine, and dopamine. Zoloft+Zyprexa raised only dopamine. Risperdal+Prozac also raised neuro levels, but not as impressively or as efficiently as Prozac+Zyprexa.
The two drugs tend to have counteracting side effects which is an added bonus. While Prozac generally causes side effects of insomnia and/or anxiety, Zyprexa counters both of those, allowing for good sleep and reduced anxiety. Weight loss is common with Prozac while weight gain is common with Zyprexa. They help to cancel each other out. Not for everyone of course. Mileage varies. But generally speaking.
Either Prozac or Zyprexa alone can be ok. But when results are just ok, the combination can remarkably improve results. It's almost as if the sum is greater than the two parts.
John
Posted by Cam W. on March 6, 2001, at 8:35:41
In reply to Re: Prozac Zyprexa Study, posted by JohnL on March 6, 2001, at 5:16:12
That study was a good tie-in for Lilly (both drugs are manufactured by them), and "surprize", it was funded by them. ;^) Actually clozapine and risperidone have both shown to work in augmenting SSRI antidepressants, as well. - Cam
Posted by steve on March 6, 2001, at 13:36:33
In reply to Re: Prozac Zyprexa Study, posted by Cam W. on March 6, 2001, at 8:35:41
> That study was a good tie-in for Lilly (both drugs are manufactured by them), and "surprize", it was funded by them. ;^) Actually clozapine and risperidone have both shown to work in augmenting SSRI antidepressants, as well. - Cam
Someone brought it up on a newgroup that Prozac and Zyprexa are both metabolized by the same enzyme. The conclusion that was drawn was that it would be better to take meds that don't inhibit the same enzyme, but that's to be taken with a grain of salt.
Since you brought up the Lilly angle, I was thinking that you could also add some of their insulin for the tried and proven insulin coma therapy. That way you'd get a Lilly trifecta, and presumably bring a smile to Randall Tobias' face.
Posted by ItsJustMe on March 6, 2001, at 14:37:40
In reply to Prozac Zyprexa Study, posted by Neal on March 6, 2001, at 1:06:13
I'm not saying that the combo doesn't work better, but 28 patients is hardly a study.
> A Vanderbilt study has found that Prozac and the antipsychotic Zyprexa work better together on treatment-resistant depression patients than either drug alone. Twenty-eight patients were given either Prozac and a placebo, Zyprexa and a placebo, or the two drugs together. After eight weeks, researchers found a "minimal" improvement with Prozac, a "modest" improvement with Zyprexa, and a "significant" improvement with the combination.
Posted by Sunnely on March 6, 2001, at 19:33:39
In reply to Prozac Zyprexa Study, posted by Neal on March 6, 2001, at 1:06:13
Neal,
I'm with Cam on this (see his post above). Since this study was funded by Lilly (maker of both Prozac and Zyprexa), not surprise with the result. In fact, one of the researchers is in the payroll of Lilly (Tollefson).
Lilly is trying to squeeze everything it could from Prozac and Zyprexa. Prozac's patent has expired and generic Prozac (fluoxetine) will soon be available (much cheaper). Zyprexa is sure to face stiff competition from the now available ziprasidone (Geodon), not known to cause weight gain, diabetes, elevated triglycerides.
How do you think Sarafem and Prozac Weekly came about? Weekly Prozac capsule, which contains 90 mg of fluoxetine is supposed to be the equivalent of 20 mg Prozac daily. Using pharmacokinetic modeling to select an optimal dose for once-weekly regimen, investigators discovered that 90 mg weekly resulted in a mean steady blood concentrations of Prozac comparable to those achieved with daily doses of 20 mg. Lilly then formulated an enteric-coated preparation that delays release of Prozac to minimize stomach distress. You will save a bundle if you can tolerate (no stomach distress) taking 90 mg of generic fluoxetine weekly instead of taking Weekly Prozac of Lilly. (Note: Weekly Prozac is not indicated for the treatment of acute depression but as a maintenance treatment of depression in remission.)
This kind of ploy is nothing new to the pharmaceutical companies. Ever heard of Depakote or divalproex sodium by Abbott? Except for the coating and the generic name (divalproex sodium) being registered so it could be patented (and no switching allowwed), no difference from Depakene (valproic acid), except the latter is much cheaper. The coating in Depakote is supposed to minimize the GI distress, although most patients generally tolerate Depakene (valproic acid).
Sarafem is another ploy of Lilly to squeeze more money from the loss of revenue from Prozac's eventual demise. Sarafem is Prozac (fluoxetine)! If your doctor prescribes Sarafem for PMDD, pharmacist can't switch it to generic Prozac (once available). On the other hand, a prescription for Prozac can be switched to generic fluoxetine.
+++++++++++++++++++++++++++++++++++++++
> A Vanderbilt study has found that Prozac and the antipsychotic Zyprexa work better together on treatment-resistant depression patients than either drug alone. Twenty-eight patients were given either Prozac and a placebo, Zyprexa and a placebo, or the two drugs together. After eight weeks, researchers found a "minimal" improvement with Prozac, a "modest" improvement with Zyprexa, and a "significant" improvement with the combination.
Posted by Cam W. on March 6, 2001, at 20:02:57
In reply to Re: Prozac Zyprexa Study » Neal, posted by Sunnely on March 6, 2001, at 19:33:39
> This kind of ploy is nothing new to the pharmaceutical companies. Ever heard of Depakote or divalproex sodium by Abbott? Except for the coating and the generic name (divalproex sodium) being registered so it could be patented (and no switching allowwed), no difference from Depakene (valproic acid), except the latter is much cheaper. The coating in Depakote is supposed to minimize the GI distress, although most patients generally tolerate Depakene (valproic acid).
>Sunnely - Actually, although divalproex (Depakote™ - U.S.; Epival™ - CDN) is a gimicky valproic acid, there is a slight difference besides the coating. Divalproex is 2 valproic acid molecules joined together that dissociates in the intestine, avoiding stomach upset; hence "di"-valproex. Therefore, Abbott can justify calling this a "different" drug.
HMOs and Provincial Formularies are getting around these pharmaceutical company ploys by only paying for the "least expensive equivalent" medication in a particular drug class; hence they will only pay for valproic acid, rather than ther more expensive divalproex. I guess this is the equivalent of nature's "Darwinian arms race". - Cam
Posted by Sunnely on March 6, 2001, at 20:40:09
In reply to Re: Prozac Zyprexa Study, posted by Cam W. on March 6, 2001, at 20:02:57
Hi Cam,
Thanks for the info on the structural make up of Depakote. I always value your info and opinion. Thanks for all the great posts.
However, Depakote's generic name as "divalproex sodium" and not valproic acid was a "marketing coup," says Stephen R. Saklad, Pharm.D., Editor of the Psychopharmacology Update (Nov. 1998 issue), Manisses Communications, Providence, R.I. The following is his full comments on this matter.
"Technically, Depakote's generic name is divalproex sodium, not valproic acid. However, this was a marketing coup by Abbott, not science. Depakote uses a "2:1 coordination salt" of valproic acid and sodium (in a 2 to 1 ratio, respectively) instead of the acid itself as is used in Depakene, the original product. This was done to extend the patent life. At the same time, Depakote was enteric coated to reduce stomach upset. The two changes are unrelated, but only Depakote contains the newly patented salt. Abbott convinced the United States Adopted Names (USAN) committee to assign them a new generic for this salt. They therefore were able to have a product with a different generic and avoid substitution with another company's generic valproic acid. Divalproex doses are expressed in mg equivalent to valproic acid. In the blood, after either form is absorbed, the molecule exists in the ionized form: valproate. I usually refer to either one as valproate for this reason."
+++++++++++++++++++++++++++++++++++++++++++++++++
> > This kind of ploy is nothing new to the pharmaceutical companies. Ever heard of Depakote or divalproex sodium by Abbott? Except for the coating and the generic name (divalproex sodium) being registered so it could be patented (and no switching allowwed), no difference from Depakene (valproic acid), except the latter is much cheaper. The coating in Depakote is supposed to minimize the GI distress, although most patients generally tolerate Depakene (valproic acid).
> >
>
> Sunnely - Actually, although divalproex (Depakote™ - U.S.; Epival™ - CDN) is a gimicky valproic acid, there is a slight difference besides the coating. Divalproex is 2 valproic acid molecules joined together that dissociates in the intestine, avoiding stomach upset; hence "di"-valproex. Therefore, Abbott can justify calling this a "different" drug.
>
> HMOs and Provincial Formularies are getting around these pharmaceutical company ploys by only paying for the "least expensive equivalent" medication in a particular drug class; hence they will only pay for valproic acid, rather than ther more expensive divalproex. I guess this is the equivalent of nature's "Darwinian arms race". - Cam
Posted by dj on March 7, 2001, at 0:33:46
In reply to Re: Prozac Zyprexa Study » Neal, posted by Sunnely on March 6, 2001, at 19:33:39
> Zyprexa is sure to face stiff competition from the now available ziprasidone (Geodon), not known to cause weight gain, diabetes, elevated >triglycerides.
Great comments and cutting through the marketing distortions, guys!! However, despite the low sample suppose there is a grain of truth to the conclusions then would Geodon (which I've never heard of - available in Canada, Cam?) be potentially a good substitute for Zyprexa (which I've also never heard of) and if so what should this combo be potentially good for dealing with - treatment resistant depression??
Also, what about a Wellbutrin - Prozac combo. - what are the benefits and downfalls of that in comparism, besides being an energizing combo. I believe I put on some pounds while using that combo. but then I was pretty sedentary and down at the time and it did get my energy up but left me feeling off mentally, still...
Sante!
dj
Posted by SLS on March 7, 2001, at 6:57:16
In reply to Re: Prozac Geodon combo? - Cam » Sunnely, posted by dj on March 7, 2001, at 0:33:46
Hi Steve.
Regarding combining Wellbutrin and Prozac, I can't characterize its statistical comparison to combinations of Wellbutrin with the other SSRIs. Wellbutrin is considered to be almost a universal augmentation agent. It can be combined with just about everything, including MAO-inhibitors. Many people have had success combining it with Zoloft. A particularly efficacious combination seems to be that of adding Wellbutrin to Effexor. I don't know to what extent Wellbutrin would offset the weight-gain that some people experience with SSRIs, but I imagine that it can help by suppressing appetite somewhat.
I share your thoughts regarding Geodon (ziprasidone). It is touted as being a new Zyprexa without the weight gain. You probably already know this, but Geodon possesses a sort of purified buspirone (Buspar) property to stimulate postsynaptic (somato-dendritic) serotonergic autoreceptors. Buspirone is considered by some to be occasionally effective as an augmenting agent to antidepressants.
Personally, I sometimes wonder if for some people, a number of their serotoninergic (5-HT) pathways are actually over-active or poorly regulated in that direction. A property often focused on regarding the mechanism of actions of certain antidepressants is the antagonism (blockade) of postsynaptic 5-HT2a receptors. It is proposed that this serotonin *inhibiting* regulatory property is partially responsible for the antidepressant properties of Serzone, Remeron, Desyrel, Zyprexa and Risperdal. Like Zyprexa and Risperdal, Geodon also antagonizes these receptors. However, Geodon also serves to agonize (stimulate) the 5-HT1a receptors which inhibits the neuron even further. I guess it is possible that a drug that exhibits both of these properties might produce a synergism that would make Geodon a more efficacious augmenting agent than Zyprexa or Rispersal. Of course, this is nothing more than a "soft" argument. Perhaps some of our more pioneering people will give us some answers as to whether or not is effective in real life.
Regarding stimulation versus inhibition of serotonergic neurons, perhaps any "push" or "pull" of the serotonin system trips a reset mechanism to force a reregulation of these neurons to nominal operation.
Just my morning mental calisthenics...
- Scott
Posted by dj on March 7, 2001, at 9:10:53
In reply to Re: Prozac Geodon combo? - Cam, posted by SLS on March 7, 2001, at 6:57:16
> Hi Steve.
..I guess it is possible that a drug that exhibits both of these properties might produce a synergism that would make Geodon a more efficacious augmenting agent than Zyprexa or Rispersal. Of course, this is nothing more than a "soft" argument. Perhaps some of our more pioneering people will give us some answers as to whether or not is effective in real life.
>
> Regarding stimulation versus inhibition of serotonergic neurons, perhaps any "push" or "pull" of the serotonin system trips a reset mechanism to force a reregulation of these neurons to nominal operation.
>
> Just my morning mental calisthenics...Well Scott.
Other than the fact that you've mistaken my posting for Steves, you seem to have done some 'heavy' lifting of the micro-bio. effects/impacts of these formulations. I don't know about pioneers (though Cam's Alberta does have that rugged, unsettled sense to it ; ) but I'd be interested in hearing other knowledgable folks comment on the combo(s) I cited and their synergies, to see if their comments mirror yours and perhaps Cam will know about Geodon's availability in Canada or appropriate subs. if it isn't but such a combo. is effacious (my two dollar word for the day...)
dj
Posted by Eric on March 7, 2001, at 10:48:59
In reply to Prozac Zyprexa Study, posted by Neal on March 6, 2001, at 1:06:13
> A Vanderbilt study has found that Prozac and the antipsychotic Zyprexa work better together on treatment-resistant depression patients than either drug alone. Twenty-eight patients were given either Prozac and a placebo, Zyprexa and a placebo, or the two drugs together. After eight weeks, researchers found a "minimal" improvement with Prozac, a "modest" improvement with Zyprexa, and a "significant" improvement with the combination.
What else would you expect them to say though? Both drugs are made by Eli Lilly and obviously Eli Lilly wants to sell as much of both meds as possible. This study was sponsored by Eli Lilly.Instead, what Eli Lilly should be really doing is trying to R & D new psychiatry meds specifically for treatment resistant depression and for psychotic depression. Because there is a percentage of treatment resistant patients who have major trouble combining psych medications...some people just cannot do that.
Actually Seroquel is a superior neuroleptic augmentor compared to Zyprexa in many cases because Seroquel does not use the 2D6 liver enzyme for drug metabolism.
Seroquel is least likely to cause pharmacokinetic drug interactions when combined with antidepressants. It also causes less weight gain compared to Zyprexa.
Posted by dj on March 7, 2001, at 22:39:49
In reply to Re: Prozac Zyprexa Study, posted by Eric on March 7, 2001, at 10:48:59
So what about good combos with Prozac??? Any insights to share on that front??
Posted by Cam W. on March 8, 2001, at 8:39:32
In reply to Synrgstic combos that work well, 2gthr, Cam, Sun??, posted by dj on March 7, 2001, at 22:39:49
> So what about good combos with Prozac??? Any insights to share on that front??
dj - Roll the dice and take your pick. A lot of case reports, but nothing definitive, yet. I believe that lithium has been shown to be a good augmenter of Prozac. - Cam
Posted by dj on March 8, 2001, at 11:48:37
In reply to Re: Synrgstic combos that work well, 2gthr, Cam, Sun?? » dj, posted by Cam W. on March 8, 2001, at 8:39:32
> > So what about good combos with Prozac??? Any insights to share on that front??
>
> dj - Roll the dice and take your pick. A lot of case reports, but nothing definitive, yet. I believe that lithium has been shown to be a good >augmenter of Prozac. - CamI am sooo tired of rolling the dice and coming up short...or worse off for the roll...
This is the end of the thread.
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