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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by scatterbrained on April 17, 2005, at 23:42:20
Relapse prevention with gepirone ER in outpatients with major depression.
Keller MB, Ruwe FJ, Janssens CJ, Sitsen JM, Jokinen R, Janczewski J.
Department of Psychiatry and Human Behavior, Brown University, Providence, RI 02906, USA. martin_keller@brown.edu
To evaluate long-term efficacy and tolerability of the serotonin 5-HT1A receptor agonist, gepirone extended release (ER), a multicenter, randomized, placebo-controlled relapse prevention study was performed in patients with recurrent major depression (DSM-IV criteria). Patients 18 to 70 years, with a primary diagnosis of recurrent major depression (DSM-IV; 296.3) and a screening and baseline HAMD-17 total score >/=20 were eligible. After a 3- to 14-day (dependent on pretrial medication) single-blind placebo washout period, eligible patients entered an 8- or 12-week (depending on time to remission) open-label gepirone ER treatment period. They initially received a dose of 20 mg/d gepirone ER and were titrated to a dose of 40 to 80 mg/d. Patients who achieved remission (HAMD-17 total score </=8) were randomized to double-blind continuation of their gepirone ER treatment or placebo for 40 to 44 weeks. The primary end point was a comparison of the relapse rates between gepirone ER and placebo. Relapse was defined as a HAMD-17 total score >/=16 or discontinuation for lack of efficacy. A total of 420 patients were treated in the open-label phase. Of these, 303 (72.1%) completed the open-label phase and 250 (59.5%) fulfilled the criteria for remission and were randomized into the double-blind continuation phase (gepirone ER: n = 126; placebo: n = 124). The mean (+/-SD) final titrated dose of gepirone ER was 61.9 (+/-17.0) mg/d in the double-blind continuation phase. The relapse rate in the gepirone ER group was statistically significantly lower than that in the placebo group, 23.0% versus 34.7%, respectively (P = 0.024). During the open-label phase, adverse events that occurred in more than 5% of patients were nausea (15.7%), dizziness (13.1%), headache (12.9%), insomnia (6.2%), and vertigo (6.0%). During the continuation phase, the incidence of newly or re-emerging adverse events was similar with gepirone ER (43.7%) and placebo (42.7%). Adverse events different from those occurring during the open-label phase were not apparent. All adverse events occurred in less than 5% of patients with the exception of flu syndrome and headache.In conclusion, gepirone ER at a dose range of 40 to 80 mg/d is effective for relapse prevention in patients with recurrent major depression. It is well tolerated during long-term treatment for up to approximately one year.
Posted by linkadge on April 18, 2005, at 12:27:26
In reply to Relapse prevention with gepirone ER, posted by scatterbrained on April 17, 2005, at 23:42:20
What is the status of this drug ??
Linkadge
Posted by zeugma on April 18, 2005, at 15:56:20
In reply to What is the status of this drug ??, posted by linkadge on April 18, 2005, at 12:27:26
as far as I know, gepirone has been shelved everywhere, in the place where brofaromine, adinazolam, and other seemingly promising drugs have gone. I would not expect to see it turn up anywhere as a marketed AD, since it has received official thumbs-down from the FDA. A shame, since gepirone could have been a viable alternative to existing treatments for so many people.
-z
Posted by scatterbrained on April 18, 2005, at 17:00:07
In reply to Re: What is the status of this drug ?? » linkadge, posted by zeugma on April 18, 2005, at 15:56:20
Since it got the thumbs down from the FDA for depression, is it going to be marketed under any other context, for example anxiety,etc? If so, it seems logical to assume that it will be prescribed off label for depression as long as the drug is being produced. Does anybody know why it got the thumbs down?
Posted by zeugma on April 18, 2005, at 17:45:04
In reply to Re: What is the status of this drug ?? » zeugma, posted by scatterbrained on April 18, 2005, at 17:00:07
> Since it got the thumbs down from the FDA for depression, is it going to be marketed under any other context, for example anxiety,etc? If so, it seems logical to assume that it will be prescribed off label for depression as long as the drug is being produced.>
Anxiety, it seems, is being reconceptualized as part of bipolar disorder. For example, I have seen it asserted that Generalized Anxiety Disorder and BP II are co-extensive. What this will mean in practical terms is that meds such as Lyrica, which are GABAergic and anticonvulsant, will be increasingly used for anxiety disorders, due to suspicion that anxiety is a manifestation of a bipolar disorder. Drugs such as the azapirones, of which buspirone is the only representative in clinical use, will be shelved, and not used for any indication whatsoever. IMHO this is unfortunate for several reasons:
buspirone is probably the least-efficacious member of this class of drugs;
the pharmacokinetics of the azapirone class practically dictate that they be available in ER formulation, but while such a formulation has been prepared for buspirone, and would improve its therapeutic potential considerably, it will not see the light of day either because the drug has gone off patent;
the reconceptualization of GAD as a species of bipolar is another instance of psychiatry marching rapidly backwards. Since the azapirones, unlike the AC's, have proven, if modest, efficacy in depression, they are unlikely to be used for anxiety if this symptom is viewed as a manifestation of bipolarity. I agree that GAD is a dubious category, but I think that subsuming it under bipolarity compounds whatever error brought it into the DSM in the first place.
Please note that these are merely my opinions, and are likely to be hotly disputed by many others on this board. But you are unlikely to see geprirone prescribed anywhere for any reason.
-z
Posted by scatterbrained on April 18, 2005, at 19:20:08
In reply to Re: What is the status of this drug ?? » scatterbrained, posted by zeugma on April 18, 2005, at 17:45:04
ZEUGMA said..."the reconceptualization of GAD as a species of bipolar is another instance of psychiatry marching rapidly backwards. Since the azapirones, unlike the AC's, have proven, if modest, efficacy in depression, they are unlikely to be used for anxiety if this symptom is viewed as a manifestation of bipolarity. I agree that GAD is a dubious category, but I think that subsuming it under bipolarity compounds whatever error brought it into the DSM in the first place."
From my understanding, GAD is also increasingly being understood as a manifestation of depression not just bipolar. So, it doesn't make any sense why a drug like gepirone, which is sort of like a more potent version of buspar but with antidepressant properties(overly simplefied i know), would not be embraced by psychiatry for conditions such as atypical depression, PTSD(which apparently unlike GAD, is considered it's own entity), and especially augmentation for treatment resistent depression.
With an increasing number of "cocktails" being used for psychiatric conditions, and buspar considered a first line treatment for antidepressant augmentation,as well as a treatment for SSRI induced anorgasmia, it just boggles my mind why something more potent and in that same family or drugs would be just cast aside and forgotten.
Posted by zeugma on April 18, 2005, at 19:39:00
In reply to Re: What is the status of this drug ?? » zeugma, posted by scatterbrained on April 18, 2005, at 19:20:08
> ZEUGMA said..."the reconceptualization of GAD as a species of bipolar is another instance of psychiatry marching rapidly backwards. Since the azapirones, unlike the AC's, have proven, if modest, efficacy in depression, they are unlikely to be used for anxiety if this symptom is viewed as a manifestation of bipolarity. I agree that GAD is a dubious category, but I think that subsuming it under bipolarity compounds whatever error brought it into the DSM in the first place."
>
> From my understanding, GAD is also increasingly being understood as a manifestation of depression not just bipolar. So, it doesn't make any sense why a drug like gepirone, which is sort of like a more potent version of buspar but with antidepressant properties(overly simplefied i know), would not be embraced by psychiatry for conditions such as atypical depression, PTSD(which apparently unlike GAD, is considered it's own entity), and especially augmentation for treatment resistent depression.
>
> With an increasing number of "cocktails" being used for psychiatric conditions, and buspar considered a first line treatment for antidepressant augmentation,as well as a treatment for SSRI induced anorgasmia, it just boggles my mind why something more potent and in that same family or drugs would be just cast aside and forgotten. >>you are not the only one whose mind is boggled:
http://www.dr-bob.org/babble/20040621/msgs/360253.html
Posted by Cecilia on April 19, 2005, at 2:55:18
In reply to Re: What is the status of this drug ?? » scatterbrained, posted by zeugma on April 18, 2005, at 19:39:00
The most frustrating thing is that I`ve never read any official explanation of why this drug was not approved. Not the usual request for more studies-just "not approved". Doesn`t the FDA have to give SOME kind of explanation, even if it`s a lie? They`re as secretive as the papal conclave. Cecilia
Posted by Ritch on April 19, 2005, at 9:54:29
In reply to Re: What is the status of this drug ?? » scatterbrained, posted by zeugma on April 18, 2005, at 17:45:04
>...Anxiety, it seems, is being reconceptualized as part of bipolar disorder. For example, I have seen it asserted that Generalized Anxiety Disorder and BP II are co-extensive. What this will mean in practical terms is that meds such as Lyrica, which are GABAergic and anticonvulsant, will be increasingly used for anxiety disorders, due to suspicion that anxiety is a manifestation of a bipolar disorder. Drugs such as the azapirones, of which buspirone is the only representative in clinical use, will be shelved, and not used for any indication whatsoever...
Z, that's an interesting statement there. I clearly have bipolar disorder, and when I tried buspirone it did *lower* anxiety, but it "shifted" it into anger and worsened rage problems. I think it had to do with the metabolite's alpha2-antagonist activity (other a2-antagonists do the same thing to me). I was hoping that gepirone would lack this activity and actually *help* the anxiety associated with my bipolar disorder. So, in my case I think it is a pity it isn't available, because I thought it held promise as a non-benzo anxiolytic that is also NOT a monoamine reuptake inhibitor that could treat my anxiety *without* worsening my bipolar disorder.--- Mitch
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