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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 21 of 21. This is the beginning of the thread.
Posted by jrbecker76 on October 12, 2010, at 18:24:12
http://www.reuters.com/article/idUSLDE69B0BZ20101012
Pfizer depression drug ineffective, may be harmful -study
7:01pm EDT
* Review of 13 trials says Edronax is ineffective
* Most data from clinical trials were not published
* Researchers say results show "striking" publication bias
* Pfizer says stands by drug as "effective treatment option"
By Kate Kelland
LONDON, Oct 13 (Reuters) - Pfizer's (PFE.N: Quote, Profile, Research, Stock Buzz) antidepressant reboxetine is an "ineffective and potentially harmful" drug and published data on it overestimates the benefits and underplays the risks, a study by German researchers said on Wednesday.
In a review published in the British Medical Journal, researchers from the German Institute for Quality and Efficiency in Health Care (IQWiG) found that nearly three quarters of the data on patients who took part in trials of reboxetine was not published until now -- a factor they said underlined the urgent need for mandatory publication of all clinical trial results.
Reboxetine, sold under the brand name Edronax, has been approved for the treatment of major depressive disorder in many European countries since 1997 but doubts have been raised about its effectiveness on the basis of recent studies and rejection of the application for approval in the United States in 2001.
"It is not a major drug in depression but every patient that is treated with an ineffective drug is one too many," said Beate Wieseler of IQWiG's department of drug assessment, who led the study. "Depression is a severe disease and there are effective drugs available, so if a patient is given an ineffective drug, that is unacceptable."
Reboxetine is one of the first in a class of anti-depressant drugs called selective serotonin re-uptake inhibitors, or SSRIs.
A Pfizer spokesperson said the drug was "an effective treatment option" for acute depression and said the U.S. drugmaker would review the BMJ studies and "provide further comment after completing the review".
The German team analysed the results of 13 trials of reboxetine, including eight previously unpublished trials from Pfizer, and concluded that overall the drug was ineffective as a treatment for depression and may have harmful side effects.
They found no significant difference in benefit for patients taking reboxetine when compared with patients taking a placebo, or dummy pill.
The team also said trial data showed that patients taking the Pfizer drug also did worse than those taking the SSRI Prozac, known generically as fluoxetine, in terms of side effects that were bad enough to prompt them to stop taking the drug.
"Published data overestimated the benefit of reboxetine versus placebo by up to 115 percent and reboxetine versus SSRIs by up to 23 percent, and also underestimated harm," they wrote in the study.
The researchers also noted that data on 74 percent of patients in trials had not been published until now.
Wieseler said the study's findings were a "striking example of publication bias" and experts commenting on the findings agreed they highlighted an unacceptable situation.
"Clinicians treating patients with depression absolutely need the full picture in order to help their patients make the right choices about the various treatments that are available," said Anthony Cleare, a consultant psychiatrist at the Maudsley Hospital and Institute of Psychiatry at King's College London.
Pfizer said it "discloses the results of its clinical trials to regulatory authorities all around the world".
"These regulatory authorities carefully balance the risks and benefits of each medication and reflect all important safety and efficacy information in the approved product labelling," it said in an emailed statement.
In an editorial about the study, BMJ editors Fiona Godlee and Elizabeth Loder said the medical evidence base was being "distorted by missing clinical trial data" and called for urgent action to restore trust.
"Full information about previously conducted clinical trials involving drugs, devices and other treatments is vital to clinical decision-making," they said. "It is time to demonstrate a shared commitment to set the record straight." (Editing by Greg Mahlich)
Posted by huxley on October 12, 2010, at 21:38:26
In reply to Study: Reboxetine found ineffective,may be harmful, posted by jrbecker76 on October 12, 2010, at 18:24:12
Well what do you know. An independant study finds a medication innefective and harmful.
Posted by weatherfreak on October 12, 2010, at 21:49:33
In reply to Study: Reboxetine found ineffective,may be harmful, posted by jrbecker76 on October 12, 2010, at 18:24:12
jrbecker this is not directed at you in anyway, it's one of many MAJOR flaws in the article. I will never understand how these things get published without proper research from the journalist.
Quote from article, "Reboxetine is one of the first in a class of anti-depressant drugs called selective serotonin re-uptake inhibitors, or SSRIs." Totally wrong
Reboxetine is not an SSRI, it's an NRI and has NOTHING to do with serotonin. (from wiki)- reboxetine is a norepinephrine reuptake inhibitor (NRI); it does not inhibit the reuptake of serotonin.
I get so angry at the people who write these articles and have very important information completely wrong.
I took reboxetine for a while, it is known to poop out quickly if it works for you and it did for me. I stayed on it for 3 months and had some very unpleasant side effects from it but it lifted me out of a black hole so I put up with it. It's not an ineffective drug either. It just doesn't work for some people.
Posted by Phillipa on October 13, 2010, at 0:07:39
In reply to Re: Study: Reboxetine found ineffective,may be harmful, posted by weatherfreak on October 12, 2010, at 21:49:33
Not quite sure but feel JR Becker is a researcher he visits infrequently but always glad to read his findings. Phillipa
Posted by huxley on October 13, 2010, at 0:56:24
In reply to Re: Study: Reboxetine found ineffective,may be harmful, posted by weatherfreak on October 12, 2010, at 21:49:33
bad journalism is not the issue here for me.
The fact that a pharma company has AGAIN distorted trial results by not using all the clinical trial data is the issue.
They seem to have no quarms holding back important health information in the quest to sell as much of their product as possible.
Even if it means that mine or your health is sacraficed in the process.
People seem to be to happy to take the approach that 'depression is a serious problem, dont question the meds'
Yes depression is a serious problem, that does not give anyone the right to prescribe drugs on false pretense knowing very well that they could harm more than they could help.
Posted by SLS on October 13, 2010, at 6:15:25
In reply to Re: Study: Reboxetine found ineffective,may be harmful, posted by huxley on October 13, 2010, at 0:56:24
I couldn't find it in the article. What were the harmful effects that were referred to?
I had a terrible reaction to reboxetine. It produced a suicidal state with anxiety. I try not to generalize my experiences to others, though. However, I have not seen more than a handful of people take reboxetine while posting on Psycho-Babble. I think one person had a robust response. However, I think that the population of posters here is weighted towards people from the US, where reboxetine is not available. My impression of reboxetine, all in all, is that it is not as effective as the tricyclics, despite robust NE reuptake inhibition properties. Regarding the selectivity of these drugs for NE, desipramine works. Strattera doesn't. I don't think reboxetine does either.
- Scott
Posted by ed_uk2010 on October 13, 2010, at 13:15:46
In reply to Re: Study: Reboxetine found ineffective,may be harmful, posted by SLS on October 13, 2010, at 6:15:25
Reboxetine has been on the market in the UK for years, but it's very rarely prescribed. I don't think psychiatrists rate it highly.
Posted by weatherfreak on October 13, 2010, at 20:46:20
In reply to Re: Study: Reboxetine found ineffective,may be harmful » weatherfreak, posted by Phillipa on October 13, 2010, at 0:07:39
> Not quite sure but feel JR Becker is a researcher he visits infrequently but always glad to read his findings. Phillipa
Phillipa, my 1st line was clearly pointing out that my response was not directed to jr at all.
It was the article itself. I think you need to read my post again. The article itself is wrong, not jr. That's all I was pointing out. I was not referring to jr at all. It's always good to read articles, but unfortunately that had a major flaw in it which you can check out for yourself, that all I was saying.
If you read the article, it said reboxetine is a SSRI, it isn't at all. Google it if you don't believe me.
Posted by Phillipa on October 13, 2010, at 21:36:02
In reply to Re: Study: Reboxetine found ineffective,may be harmful » Phillipa, posted by weatherfreak on October 13, 2010, at 20:46:20
Sorry I guess I will wonder if a typo? Phillipa
Posted by weatherfreak on October 14, 2010, at 2:02:53
In reply to Re: Study: Reboxetine found ineffective,may be harmful » weatherfreak, posted by Phillipa on October 13, 2010, at 21:36:02
No it's not a typo Phillipa it's just really bad research on the author's behalf. It should have been double checked by a sub editor, as reboxetine is not a SSRI like Prozac as it states. It's an NRI like Strattera. There is only a few NRI's on the market, that's why it really stood out to me.
I just find that I can't take any article seriously when there's a mistake like that in it.
It's no different than saying that Luvox is a TCA.
Posted by BrainDamage on October 14, 2010, at 5:37:29
In reply to Re: Study: Reboxetine found ineffective,may be harmful, posted by ed_uk2010 on October 13, 2010, at 13:15:46
I've Very Rarely heard of people responding well to Reboxetine
It seems to be one of the most hated Psych medsViloxazine was actually an older drug, which worked in a simililar way & actual,ly seemed much more effective
However it was discontinued, of patent I suppose, perhapse the main reason
Posted by Jay_Clockwork_Angels on October 14, 2010, at 11:44:13
In reply to Re: Study: Reboxetine found ineffective,may be harmful, posted by SLS on October 13, 2010, at 6:15:25
> I couldn't find it in the article. What were the harmful effects that were referred to?
>
> I had a terrible reaction to reboxetine. It produced a suicidal state with anxiety. I try not to generalize my experiences to others, though. However, I have not seen more than a handful of people take reboxetine while posting on Psycho-Babble. I think one person had a robust response. However, I think that the population of posters here is weighted towards people from the US, where reboxetine is not available. My impression of reboxetine, all in all, is that it is not as effective as the tricyclics, despite robust NE reuptake inhibition properties. Regarding the selectivity of these drugs for NE, desipramine works. Strattera doesn't. I don't think reboxetine does either.
>
>
> - Scott
>
>
>Scott:
I don't like to generalize and I hate making assumptions (not good science..lol) but from my anecdotal evidence, and seeing a number of posts regarding Strattera and Reboxetine, it seems some of the NE reuptake inhibitors can create a bit more risk of suicide. I think it may be the initial more activating factor.
I wonder how they compare when added to an SSRI, as I imagine you may get a good response with the dual reuptake inhibition. One med I am thinking of adding to my Prozac is maprotiline. Desipramine did not provide much in the way of depression relief for me.
Jay
Current meds:
Prozac 80mg qd
Lyrica: 150mg bid
Topomax: 100mg bid
Risperidal: 1mg bid
Clonazepam: 1mg qid
Posted by SLS on October 14, 2010, at 18:05:18
In reply to Re: Study: Reboxetine found ineffective,may be harmful » SLS, posted by Jay_Clockwork_Angels on October 14, 2010, at 11:44:13
> > I couldn't find it in the article. What were the harmful effects that were referred to?
> >
> > I had a terrible reaction to reboxetine. It produced a suicidal state with anxiety. I try not to generalize my experiences to others, though. However, I have not seen more than a handful of people take reboxetine while posting on Psycho-Babble. I think one person had a robust response. However, I think that the population of posters here is weighted towards people from the US, where reboxetine is not available. My impression of reboxetine, all in all, is that it is not as effective as the tricyclics, despite robust NE reuptake inhibition properties. Regarding the selectivity of these drugs for NE, desipramine works. Strattera doesn't. I don't think reboxetine does either.> I don't like to generalize and I hate making assumptions (not good science..lol) but from my anecdotal evidence, and seeing a number of posts regarding Strattera and Reboxetine, it seems some of the NE reuptake inhibitors can create a bit more risk of suicide. I think it may be the initial more activating factor.
>
> I wonder how they compare when added to an SSRI, as I imagine you may get a good response with the dual reuptake inhibition. One med I am thinking of adding to my Prozac is maprotiline. Desipramine did not provide much in the way of depression relief for me.
>
> Jay
>
> Current meds:
>
> Prozac 80mg qd
> Lyrica: 150mg bid
> Topomax: 100mg bid
> Risperidal: 1mg bid
> Clonazepam: 1mg qidDo you ruminate much? Looking at your medication, it would seem that you are fighting against obsessions, rumination, and social anxiety. That's a rough guess, but I am curious as to what you are attempting to treat. I like Topamax. I have seen it work wonders for mixed-state bipolar disorder. Where does it fit in your treatment?
- Scott
Posted by Jay_Clockwork_Angels on October 14, 2010, at 22:08:15
In reply to Re: Study: Reboxetine found ineffective,may be harmful » Jay_Clockwork_Angels, posted by SLS on October 14, 2010, at 18:05:18
not depression relief for me.
> >
> > Jay
> >
> > Current meds:
> >
> > Prozac 80mg qd
> > Lyrica: 150mg bid
> > Topomax: 100mg bid
> > Risperidal: 1mg bid
> > Clonazepam: 1mg qid
>
> Do you ruminate much? Looking at your medication, it would seem that you are fighting against obsessions, rumination, and social anxiety. That's a rough guess, but I am curious as to what you are attempting to treat. I like Topamax. I have seen it work wonders for mixed-state bipolar disorder. Where does it fit in your treatment?
>
>
> - ScottScott:
Well, today another med change at docs. I am on Abilify now, 5mg, hope to go up to 15...then more if needed.
The mixed state BP is partially what I am trying to treat, since I have the dysphoric type of mania. I do too occasionally get more classic manic symptoms, but I can catch it before it gets worse. The idea here is to hammer that internal restless/anxiety down...really deep. This combo has done the job, but Risperdal is just like taking candy now. Abilify has had a very positive effect on me in the past, and now I am going to stick with it. What do you think?
Best,
Jay
Posted by SLS on October 15, 2010, at 5:04:48
In reply to Re: Study: Reboxetine found ineffective,may be harmful » SLS, posted by Jay_Clockwork_Angels on October 14, 2010, at 22:08:15
So much for guesswork...
:-)
Don't forget about Trileptal. I have conversed with people for whom it was a miracle antimanic agent. Some of these people were ultra-rapid cycling bipolar II.
Good luck with the Abilify. Its a good drug in my opinion. I will be very curious to see how well it works as an antimanic for you. It is a proven antidepressant adjunct.
- Scott
Posted by linkadge on October 15, 2010, at 16:37:02
In reply to Study: Reboxetine found ineffective,may be harmful, posted by jrbecker76 on October 12, 2010, at 18:24:12
>They found no significant difference in benefit >for patients taking reboxetine when compared >with patients taking a placebo, or dummy pill.
That statement could apply to most antidepressants out there.
Linkadge
Posted by linkadge on October 15, 2010, at 16:40:35
In reply to Re: Study: Reboxetine found ineffective,may be harmful, posted by SLS on October 13, 2010, at 6:15:25
>My impression of reboxetine, all in all, is that >it is not as effective as the tricyclics, >despite robust NE reuptake inhibition >properties. Regarding the selectivity of these >drugs for NE, desipramine works. Strattera >doesn't. I don't think reboxetine does either.
Norepinephrine reuptake inhibition is probably not relavant to the effects of any antidepressant IMHO.
Why a potent selective NRI like straterra or reboxetine is not an antidepressant seems to argue that norepinephrine reuptake inhibition is of little theraputic relavance.
Linkadge
Posted by linkadge on October 15, 2010, at 16:47:26
In reply to Re: Study: Reboxetine found ineffective,may be harmful » Jay_Clockwork_Angels, posted by SLS on October 15, 2010, at 5:04:48
Tyrosine hydroxylase (the enzyme which synthesizes norepinephrine) is elevated in depression.
Depression (especially that associated with stress/anxiety) has been linked to an overactivity of the central noradrenergic system.
The following article discusses how paroxetine increases activity of the locus coeruleus in juvenile rats - a model of paroxetine induced suicidality (?)
see: http://www.ncbi.nlm.nih.gov/pubmed/20357759
"Both clinical and preclinical evidences indicate that the principal noradrenergic cell group in the brain, the locus coeruleus (LC), is overactive in depressives and that, conversely, effective AD treatments decrease the activity of LC neurons. We report here that short-term (2 and 4 days) administration of PAR produces an increase in the activity of LC neurons (spontaneous firing rate and sensory-evoked responses) in young rats, contrary to the 'therapeutic' decrease in activity typically observed in adult rats."
Posted by SLS on October 16, 2010, at 5:23:33
In reply to Re: Study: Reboxetine found ineffective,may be harmful, posted by linkadge on October 15, 2010, at 16:47:26
Yes. I can see how you came to your conclusions. As you so often point out, tricyclics like desipramine (known as a selective NE reuptake inhibitor) do a great many other things pharmacologically. So really, desipramine is selective as a reuptake inhibitor of amines, but is not selective if one takes other properties into consideration.
What properties of desipramine do you think contribute to its antidepressant effect?
Thanks.
- Scott
Posted by linkadge on October 16, 2010, at 9:17:35
In reply to Re: Study: Reboxetine found ineffective,may be harmful » linkadge, posted by SLS on October 16, 2010, at 5:23:33
>What properties of desipramine do you think >contribute to its antidepressant effect?
Of course, I don't really know anything for sure, but based on some reading the TCAs have other common effects including:
- Monoamine receptor blockade (5-ht2,3,7 receptor antagonists have antidepressant effects)
- Increased sensitivty of limbic dopamine d2/d3 receptors (even surmontil)
- weak-moderate MAOI activity (maoa < maob)
- opioid activity, kappa, delta, mu, etc
- ion channel blockade
- muscarinic (esp. m1 antagonism)
- direct interaction with HPA axis (?)
- modification of phospholipid (cellular) activity
- sigma receptor agonism
- TRK-a/b agonism (amitriptyline)
- weak gaba transporter inhibition
- metabolite of desipramine is more serotonin selective
- NMDA receptor antagonism (synergy with sigma agonism)
- dopamine reuptake inhibition (stronger with desipramine than other tcas)
- antihistamine effects (histamine activity is overactive in some animal models of depression)
- interaction with adenosine receptors (TCAs potentiate the activity of adenosine through inhibition of the adenosine transporter - relavance to anxiety disorders)
- other, more fundamental properties ?
Linkadge
Posted by medamorphosis on October 16, 2010, at 17:48:31
In reply to Re: Study: Reboxetine found ineffective,may be harmful » SLS, posted by linkadge on October 16, 2010, at 9:17:35
Reboxetine? I liked it! Ok, I came off it because it really isn't that great for depression. But if you have 'get up and go' problems then it can certainly help to combat that. Good replacement for caffeine- I couldn't tolerate caffeine whilst on reboxetine. But I could march 2 miles into town and back with ease. Cleared the mind too. A slow working stimulant seems a more acurate description than an antidepressant.
Makes me wonder if it could be benificial taken along side drugs which tend to 'zombify' you throughout the day, i.e. mirtazepine. Hmmm...
And lets not forget that, when taken along side an MAOI its been shown to protect against the hypertensive effects of consuming tyramine. As do other NRIs.
It has its uses.med
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