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Dr. Bob is Robert Hsiung, MD,
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Posted by ttee on September 11, 2007, at 16:06:03
In reply to Re: News - Antidepressants Vindicated?, posted by linkadge on September 10, 2007, at 19:22:25
Relapse From Antidepressant Medication Likely Due to Loss of Placebo Response
Reuters Health Information 2007. © 2007 Reuters Ltd.
Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.By Megan Rauscher
NEW YORK (Reuters Health) Aug 31 - It cannot be assumed that an antidepressant has lost its effectiveness when a patient relapses while continuing on the medication, because the medication might not have been effective in the first place, according to study findings reported in the Journal of Clinical Psychiatry for August.
"We found that the vast majority of relapses occur in presumptive placebo responders," Dr. Mark Zimmerman, director of outpatient psychiatry at Rhode Island Hospital, told Reuters Health.
Some patients with major depressive disorder, similar to other medical disorders, respond to placebo, Dr. Zimmerman explained. "In clinical practice, where everyone is treated with active medication, you do not know if a patient who responds has gotten better because of the active ingredient of the medication or because of the nonspecific effects of treatment (i.e., the placebo response)."
Similarly, relapses that occur during the continuation phase of treatment could be because of true tachyphylaxis or because the initial response to treatment had been a placebo response.
To investigate, Dr. Zimmerman collaborated with Dr. Tavi Thongy on a meta-analysis of four studies involving 750 patients. These were continuation studies of new generation antidepressants that began as placebo-controlled acute-phase studies.
The researchers report that "two different methods of estimating relapse suggested that the majority of relapses in patients taking antidepressants during continuation treatment could be attributed to relapses occurring in patients who were not true drug responders."
This suggests, Dr. Zimmerman told Reuters Health, "that a message can be conveyed to patients who have repeatedly improved on medication and then lost its benefit that perhaps they are more capable than they think in bringing their own resources to bear to improve their depression."
J Clin Psychiatry 2007;68:1271-1276.
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Posted by linkadge on September 11, 2007, at 18:16:47
In reply to Re: News - Antidepressants Vindicated?, posted by jhj on September 11, 2007, at 8:08:39
Untill very recently, drug companies did not need to disclose the trial results on many drugs. They can just keep testing and retesting a drug untill it happens to outperform placebo.
Prime Example:
Go to the GSK clinical trial registry for lamotrigine.
http://ctr.gsk.co.uk/Summary/lamotrigine/studylist.asp
You'd expect that since the drug is FDA approved for bipolar disorder that it outperform placebo right? Wrong. There are like 30 trials resitered there, for things ranging from unipolar depression, bipolar disorder to schizohprenia. Sure there are one or two trials that show the drug is more effective than placebo, but the majority show no such effectiveness.
Also read an article at, about bias on a decent site.
http://www.mcmanweb.com/news.htm
GSK has chosen to be fully honest about disclosing clinical trial informaiton, including those from failed clinical trials, but other companies are not being so open as they know how it will affect public preceptions of drugs.
They likely have failed trials that they are not disclosing. And the FDA does not require that failed trials be used to calculate the overall effectivness of a drug.
Publication bias also affects the viewpoints of the public. Simply put, effective trials get the attention.
A quote from:
http://www.biomedcentral.com/1472-6963/7/64
"The prevailing view amongst psychiatrists is that antidepressant medication is of proven efficacy in reducing the severity and duration of major depression and should therefore be used as its first line of treatment [1]. However systematic reviews of randomised double blind placebo controlled trials of antidepressant medication indicate that differences in outcome between drug and placebo arms are often marginal, and may be exaggerated by selective publication or even deliberate misrepresentation"
A meta analysis of placebo effect in 19 clinical trials.
http://www.geocities.com/oppressionactivist/METAANALYSIS_OF_PLACEBO_htm.htm
Also from:http://www.vaccinationnews.com/DailyNews/June2002/CanPlacebo25.htm
In a soon to be published study, Dr. Arif Khan, a psychiatrist at the Northwest Clinical Research Center in Washington, analyzed the Food and Drug Administration's database of 52 clinical trials in depression, involving nine new antidepressants, conducted from 1985 to 2000. ***Since the agency requires drug companies to report all data from all studies for drugs under development, the database can give a more accurate picture of a new drug's efficacy than the medical journals***, where positive findings are far more likely to be reported than negative ones.
Dr. Khan found that in only 48 percent of the 52 clinical trials was the antidepressant superior to the placebo.
Linkadge
Posted by linkadge on September 11, 2007, at 18:18:07
In reply to Re: News - Antidepressants Vindicated?, posted by sam123 on September 11, 2007, at 12:41:05
>Link argues AD's are no better than placebo, that >is his experience.
Read my previous thread. Skip to the last paragraph. The emperor's new cloths is also
a good read.
Linkadge
Posted by linkadge on September 11, 2007, at 18:19:17
In reply to Re: News - Antidepressants Vindicated?, posted by Jamal Spelling on September 11, 2007, at 13:42:46
>For example, my own experience has been that >sertaline works much better for me than >citalopram. How is that possible if both were >merely placebos? Shouldn't I then have benefited >equally from both of them?
Perhaps side effects, or lack therof.
Linkadge
Posted by linkadge on September 11, 2007, at 18:20:38
In reply to Re: News - Antidepressants Vindicated?, posted by linkadge on September 11, 2007, at 18:19:17
And BTW, if antidepressants work so great, why are y'all here?
Linkadge
Posted by sam123 on September 11, 2007, at 18:47:38
In reply to Re: News - Antidepressants Vindicated? » sam123, posted by linkadge on September 11, 2007, at 18:18:07
> >Link argues AD's are no better than placebo, that >is his experience.
>
> Read my previous thread. Skip to the last paragraph. The emperor's new cloths is also
> a good read.
>
>
> Linkadge
>
>My point being several here have posted that AD's work for them.
Posted by Phillipa on September 11, 2007, at 21:03:20
In reply to Re: News - Antidepressants Vindicated?, posted by sam123 on September 11, 2007, at 18:47:38
I guess I'm one of those they don't work for but my chemistry is wierdly changing and would like to revisit some I took peri-menopaually as I'm now menopausal and everything is working differently in my body including thyroid gland so meds maybe too? Phillipa
Posted by Deputy Racer on September 11, 2007, at 21:40:55
In reply to Re: News - Antidepressants Vindicated?, posted by linkadge on September 11, 2007, at 18:20:38
> And BTW, if antidepressants work so great, why are y'all here?
>
> LinkadgePlease don't post anything which could lead others to feel accused, put down, or otherwise unwelcome here. This site is about support and education -- including offering support to those who are having success with antidepressant medications.
If you have questions about this or any other policy at this site, please read the FAQ, located at http://www.dr-bob.org/babble/faq.html#civil
Dr Bob, as always, has ultimate authority here. He may choose to revise or reverse any administrative action taken by a deputy.
Deputy Racer
Posted by polarbear206 on September 11, 2007, at 21:57:28
In reply to Re: News - Antidepressants Vindicated?, posted by sam123 on September 11, 2007, at 18:47:38
> > >Link argues AD's are no better than placebo, that >is his experience.
> >
> > Read my previous thread. Skip to the last paragraph. The emperor's new cloths is also
> > a good read.
> >
> >
> > Linkadge
> >
> >
>
> My point being several here have posted that AD's work for them.
>
>
Sam,Just let it go. It's not worth the frustration. Many of us here have success with AD's. I sure have! I am here to support, educate and offer any help I can. It makes me feel good to know that I can give someone hope.
Polarbear
Posted by sam123 on September 11, 2007, at 22:40:36
In reply to Re: News - Antidepressants Vindicated?))SAM, posted by polarbear206 on September 11, 2007, at 21:57:28
>
> Just let it go. It's not worth the frustration. Many of us here have success with AD's. I sure have!
Thanks and you are right. If the best revenge is living well then it follows that the best proof
is also living well. I'll go back to doing that.
Posted by ttee on September 12, 2007, at 0:31:09
In reply to Re: News - Antidepressants Vindicated?))SAM, posted by sam123 on September 11, 2007, at 22:40:36
I think it is appropriate to recall that even when the pills "work,” they don't cure mental illnesses, they merely reduce some of the symptoms of the problem. Perhaps the meds help some get a jump-start leading to recover from other means. We certainly cannot deny that certain drugs affect mood in a positive or negative way, or long term vs. short-term changes. You cannot tell me that when I drink a few beers and I feel a lot better that that is a placebo effect. I am sure the same could be said about someone taking cocaine. I would imagine the acute antidepressant response of Cocaine vs. Placebo would be well defined. What I wonder is if the AD's, like other drugs, are diminished over a longer time frame, due to tolerance. I think that most all of the AD clinical trials for FDA approval are for less than 8 weeks. What happens after 8 weeks? I guess that is what leads us to Babble.
Posted by jhj on September 12, 2007, at 0:44:11
In reply to Re: News - Antidepressants Vindicated?, posted by sam123 on September 11, 2007, at 12:41:05
I am seeing improvement far past placebo response and there are posters here who have been on AD's a long time and find they do work.
I agree completely.I have social phobia,GAD and dysthymia for at least 15 years and i have tried at least 20 drugs of various classes but with no effect.So,they are like placebo to me and i many time get angry that no treatment is working for me.But,i have read posts here as well as seen people who vouch for the efficacy of antidepressants.I do not think all of them would have reacted the same way if they had been on placebo.So,ADs are better then placebo definitely though they are not working for me.
Posted by jhj on September 12, 2007, at 8:28:45
In reply to Re: News - Antidepressants Vindicated? » sam123, posted by linkadge on September 11, 2007, at 18:18:07
Link argues AD's are no better than placebo, that >is his experience.
It is not his experience as per him. read this one.
but I can argue that placebos work as well as antidepressants in most clinical trials becuase that is fact based.
Please see last two words "fact based" whatever it menas.
Posted by jhj on September 12, 2007, at 9:17:23
In reply to Re: News - Antidepressants Vindicated?, posted by linkadge on September 11, 2007, at 18:20:38
And BTW, if antidepressants work so great, why are y'all here?
I am here certainly to know about the experiences of other people suffering from depression and other mental illnesses and learn about the effectiveness of different treatments.I would not have come here,had i known that placebo works as well as antidepressants.
You can get an idea of the gravity of the placebo effect by typing in antidepressant + placebo into your favorite search engine.
I have tried this search before and i am sure many of us have tried it.But,previously i did not know the method of segregating "decent" sites from "biased" sites.
Lastly the revolutionary findings like the similarities between suicide and stock market crash should be presented to the entire world and do not deserve to be known by only people visiting such sites.I think this is sufficient for nobel committee to give nobel prize both in medicine and economy for the same theory which has not happend before in 107 years of nobel history.But,there are some issues here too.
1.FDA and health authorities around the world are cheating people by not banning the antidepressants. If placebo is able to give same benefits with out giving any side effects,then health authorities should make it clear to people not to waste their money for the benefits of few pharma companies.
2. There are going to be some negetive repurcussions for the world economy if facts have proved that antidepressants are no better then placebo.The reason is that millions of employees,share holders and other stake holders of giant phrama companies around the globe would be in miserable conditions due to closure of these companies. And one can only imagine the condition of pdoctors around the world because they would be left with no option but to wonder in the streets with begging bowl in their hands to make their ends meet.
I would request everybody not to consider this post sarcastic because this is written out of genuine appreciation and respect.Thanks.
Posted by Larry Hoover on September 12, 2007, at 9:25:56
In reply to Re: News - Antidepressants Vindicated?, posted by sam123 on September 10, 2007, at 10:44:43
>
> >
> > I think the figures are compelling.
> >
> > Lar
> >
>
> Thanks Lar, yes very compelling. Wow, a 49% increase in sucide rates in the Netherlands
> while SSRI prescriptions for youths decreased
> by approximately 22% in both the United States and the Netherlands.I think, perhaps, that you misunderstood me. I meant Figures literally, as in the graphical evidence, rather than the data figures. Still, it's the same evidence, simply presented in a different way.
An old trick I learned from an excellent prof was to hold my completed graph of data points up close to my face, and to look across the dataset at a shallow angle. You can quite easily estimate an appropriate regression line for the set, and also readily identify outlier datapoints. You can do the same thing with these figures, on the computer screen. When you look at the figure for U.S. suicide trends in this way, the latest data point stands quite apart from the others.
A similar procedure for the Netherlands dataset is less conclusive, as there is greater variability about the line of central tendency. Nonetheless, the more typical way of viewing the graph reveals the dramatic upturn in incidence.
The authors of this paper spend quite a bit of time discussing pretty much any possible explanation for the change in trends, and IMHO the only plausible one remains the change in SSRI utilization.
Lar
Posted by Larry Hoover on September 12, 2007, at 9:38:45
In reply to Re: News - Antidepressants Vindicated? » sam123, posted by linkadge on September 10, 2007, at 14:06:09
> >And yet in the real world suicide rates for >teens and children are at the highest rates in >more than a decade during a period where >prescribing AD's for this age group declined.
>
> That doesn't mean anything yet. Only time will tell if one is actually causing the other. I'm sure the rate of prescriptions to adults has declined a bit too, has there been a corresponding increase in adult suicide?There is some adult data included in the full-text. I highly recommend that you consider it.
> Like I said before, there could a reverse plaecbo effect at work wherby the precieved loss of a effective treatment is increasing depression.
>
> In order to truely determine if antidepressants are infact reducing suicde rates there would need to be a double blind placebo controlled study on the likelyhood of suicide, which is unlikely to happen due to ethics.
>
> LinkadgeI think there's more evidence already collected, from large ecological studies conducted in the U.K. They demonstrated a relatively brief uptick in suicidal events during the immediate period upon introducing the antidepressant treatment. However, if the longer view is taken (i.e. past the first 6 or 8 weeks), suicidal events were dramatically reduced. It was also discovered that the most critical period for suicidality comes immediately before treatment is initiated, a finding comfirmed by Veterans Administration data recently published.
If you consider the more typical long-term treatment found in normal clinical practise, the limitation of most published studies to data obtained during the first six, eight, or twelve weeks of treatment actually biases the data towards capturing the treatment-emergent uptick in suicidality, which is an effect common to every class of antidepressants. In fact, it is just this effect that spurred the development of the SSRIs, as the prior generation of antidepressants, the TCAs, are far more toxic in overdose.
I think there is a major logical flaw in generalizing from short-term efficacy trials to the broader experiences of depressives obtaining treatment in the community. There is likely nothing more artificial than a clinical trial. The simple act of controlling variables reduces generalizability. The more controlled, the less generalizable the resultant data become.
Lar
Posted by Larry Hoover on September 12, 2007, at 9:49:29
In reply to Re: News - Antidepressants Vindicated? » sam123, posted by linkadge on September 10, 2007, at 14:20:38
> >Wow, a 49% increase in sucide rates in the >Netherlands
> >while SSRI prescriptions for youths decreased
> >by approximately 22% in both the United States >and the Netherlands.
>
> But does't that kind of favor my point though? Why does the increase in rate of suicide exceed the rate of drop in prescriptions?No, there are other explanations more consistent with the available data. Undertreatment of depression and suicidality in general, coupled with reduction in prescription rate (remember, we do not reach 100% of depressed people), would produce exactly such a dataset.
> One would need to know if the individuals who were killing themselves were ones who were previously taking antidepressants?
No, again, because these are population statistics. We don't need to know which subjects were identified and which were not, nor which were treated and which were not.
Lar
Posted by Larry Hoover on September 12, 2007, at 9:50:59
In reply to Re: News - Antidepressants Vindicated?, posted by linkadge on September 10, 2007, at 14:22:31
> Its not compelling at all (IMHO).
>
> Check back in a year and the suicide rate will level out regardless.The data for 2005 will be available in December of this year. We'll know soon enough.
Lar
Posted by sam123 on September 12, 2007, at 9:55:54
In reply to Re: News - Antidepressants Vindicated? » linkadge, posted by Larry Hoover on September 12, 2007, at 9:38:45
> If you consider the more typical long-term treatment found in normal clinical practise, the limitation of most published studies to data obtained during the first six, eight, or twelve weeks of treatment actually biases the data towards capturing the treatment-emergent uptick in suicidality, which is an effect common to every class of antidepressants. In fact, it is just this effect that spurred the development of the SSRIs, as the prior generation of antidepressants, the TCAs, are far more toxic in overdose.
>
Thanks Lar.The STAR*D study was a much longer study.
http://www.nimh.nih.gov/healthinformation/stard.cfm
My understanding is if people were not successful in phase 1 they moved to phase 2, ect. Med choices
were random within each phase.
5. What were the results?A. In most clinical trials of treatment for depression, the measure of success (outcome) is called "response" to treatment, which means that the person's symptoms have decreased to at least half of what they were at the start of the trial. In STAR*D, the outcome measure was a "remission" of depressive symptoms—becoming symptom-free. This outcome was selected because people who reach this goal generally function better socially and at work, and have a better chance of staying well than do people who only achieve a response but not a remission.
In level 1, about one-third of the participants reached remission and about 10-15 percent more responded, but did not reach remission. Still, these are considered good results because study participants had high rates of chronic or recurrent depression and other psychiatric medical problems.
It took an average of six weeks of treatment for participants to improve enough to reach a response and nearly seven weeks of treatment for them to achieve a remission of depressive symptoms. In addition, participants visited their care providers an average of five to six times. Participants who achieved remission stayed on the treatment for an average of 12 weeks before going on to a 12-month follow-up period.
In the level 2 switch group, about 25 percent of participants became symptom-free. All three of the switch medications performed about the same and were equally safe and well-tolerated. In the add-on group, about one-third of participants became symptom-free. Those who added bupropion experienced less troublesome side effects and slightly more reduction of symptoms than those who added buspirone.
In levels 2 and 3 where participants were allowed to either add-on or switch medications, most participants found only one or the other treatment strategies acceptable. Because most participants did not agree to be randomly assigned to one or the other treatment strategy, the findings of the add-on and switch approaches cannot be compared. It is likely, however, that people being treated in the real world also tend to limit their treatment preferences to switching or adding on medications. In addition, the people in the switch and add-on groups were a little different. The group who chose and were assigned to a switch medication had more problematic side effects while taking the preceding medication (citalopram) than the group who chose and were assigned to an add-on medication.
Level 2 also included cognitive psychotherapy as a switch or add-on treatment. Results for the psychotherapy treatment are not yet available.
In the level 3 switch group, 12 to 20 percent of participants became symptom-free, and the two medications used fared about equally well, suggesting no clear advantage for either medication in terms of remission rates or side effects. In the add-on group, about 20 percent of participants became symptom-free, with little difference between the two treatments. However, the T3 treatment was associated with fewer troublesome side effects than lithium.
In level 4, seven to 10 percent of participants became symptom-free, with no statistically significant differences between the medications in terms of remission, response rates or side effect burden. However, those taking the venlafaxine-XR/mirtazapine combination experienced more of a reduction in depressive symptoms than those taking the tranylcypromine. Also, those who were treated with tranylcypromine were more likely to discontinue the treatment citing side effects as the reason. It is also possible that the dietary restrictions associated with taking an MAOI could have limited its acceptability as a treatment.
In conclusion, about half of participants in the STAR*D study became symptom-free after two treatment levels. Over the course of all four treatment levels, almost 70 percent of those who did not withdraw from the study became symptom-free. However, the rate at which participants withdrew from the trial was meaningful and rose with each level—21 percent withdrew after level 1, 30 percent withdrew after level 2 and 42 percent withdrew after level 3.
3. What were the treatments used in the study?A. In level 1, participants were given the antidepressant citalopram (Celexa) for 12 to 14 weeks. Those who became symptom-free during this time could move on to a 12-month follow-up period during which the citalopram was continued, and patients were monitored. Those who experienced intolerable side effects or did not become symptom-free during this level could go on to level 2.
Citalopram is representative of the class of antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs). It was chosen as the first treatment because it generally is not associated with troublesome withdrawal symptoms when it is stopped, is easy to administer (once a day), and has been shown to be safe for older adults and medically fragile patients. It does not appear to interact unfavorably with other medications that some participants may have been taking for other medical problems.
Level 2 was designed to help determine an appropriate next treatment step if the first step did not work. Thus, in level 2, participants had the option of switching to a different medication or adding on to their existing citalopram.
Those who joined the "switch" group were randomly assigned to either sertraline (Zoloft), bupropion-SR (Wellbutrin), or venlafaxine-XR (Effexor). These medications were chosen for comparison because they represent three different types of medications. Sertraline is an SSRI, the same class as the citalopram used in level 1. Bupropion belongs to another class of antidepressant medications that work on different neurotransmitters than SSRIs. Venlafaxine is a "dual-action" medication that works on two neurotransmitters at the same time.
Those who joined the "add-on" group were prescribed either the non-SSRI antidepressant bupropion-SR (Wellbutrin), or buspirone (BuSpar), which is not an antidepressant but enhances the action of an antidepressant medication. Participants could also switch to, or add on, cognitive psychotherapy.
As in level 1, those who became symptom-free with their level 2 treatment could continue with that treatment and entered the follow-up period. Those who did not become symptom-free, or who experienced intolerable side effects, could continue on to level 3.
In level 3, which like level 2 was designed to compare medications that are thought to work differently in the brain and produce different results, participants again had the option of either switching to a different medication or adding on to their existing medication. Those who chose to switch their medication were randomly assigned to either mirtazapine (Remeron) — a different type of antidepressant — or to nortriptyline (Aventyl or Pamelor) — a tricyclic antidepressant—for up to 14 weeks. Both work differently in the brain than the SSRIs and other medications used in levels 1 and 2.
In the level 3 add-on group, participants were randomly prescribed either lithium — a mood stabilizer commonly used to treat bipolar disorder — or triiodothyronine (T3) — a medication commonly used to treat thyroid conditions — to add to the medication they were already taking. These medications were chosen because they have been shown to boost the effectiveness of antidepressant medications.
In level 4, participants who had not become symptom-free in any of the previous levels (and therefore considered to have highly treatment-resistant depression) were taken off all other medications and randomly switched to one of two treatments — the monoamine oxidase inhibitor (MAOI) tranylcypromine (Parnate) or the combination of venlafaxine extended release (Effexor XR) with mirtazapine (Remeron). These treatments were chosen for comparison because previous research had suggested that they may be particularly effective in people who had not received sufficient benefit from other medications.
http://www.nimh.nih.gov/healthinformation/stard-treatment-flowchart.pdf
Posted by Larry Hoover on September 12, 2007, at 10:25:34
In reply to Re: News - Antidepressants Vindicated? » jhj, posted by linkadge on September 11, 2007, at 18:16:47
> GSK has chosen to be fully honest about disclosing clinical trial informaiton, including those from failed clinical trials, but other companies are not being so open as they know how it will affect public preceptions of drugs.
I did some very detailed analyses of a number of paroxetine trials from that database, for example, and what I discovered was that there were some very poorly conducted trials, particularly in the early years. They really didn't know how to do them, early on, and some of the data was simply of poor quality. You cannot attribute a failed statistical outcome to the medication having failed, when methodology was so poor. GIGO. Garbage in, garbage out.
> They likely have failed trials that they are not disclosing. And the FDA does not require that failed trials be used to calculate the overall effectivness of a drug.
>
> Publication bias also affects the viewpoints of the public. Simply put, effective trials get the attention.Of course they do. That's the whole point of publishing. But aren't you ignoring the fact that the drugs are approved? Have you ever read a set of briefing notes for an FDA approval? It is far from a rubber stamp process. All data are considered.
> A meta analysis of placebo effect in 19 clinical trials.
>
> http://www.geocities.com/oppressionactivist/METAANALYSIS_OF_PLACEBO_htm.htmI can show you a Preskorn reference that has SSRIs as a group better than placebo at P < 10^-40. http://www.preskorn.com/books/ssri_s4.html Table 4.4.
I'm sure your reference was not free from selection bias, also.
> Also from:
>
> http://www.vaccinationnews.com/DailyNews/June2002/CanPlacebo25.htm
>
> In a soon to be published study, Dr. Arif Khan, a psychiatrist at the Northwest Clinical Research Center in Washington, analyzed the Food and Drug Administration's database of 52 clinical trials in depression, involving nine new antidepressants, conducted from 1985 to 2000. ***Since the agency requires drug companies to report all data from all studies for drugs under development, the database can give a more accurate picture of a new drug's efficacy than the medical journals***, where positive findings are far more likely to be reported than negative ones.But all data are considered in the FDA analysis. That's why they require their submission.
You'll also note that the data go back to 1985. Which means the studies were sometimes initiated much earlier than that. They didn't know what they were doing back then. Clinical trial procedures were in their infancy, and no one had any idea that the process of conducting a clinical trial would produce such a robust placebo effect. I've taken part in clinical trials, and let me assure you, the standard of care received in one is far, far superior to what I have received from my own family physician. Moreover, as a Canadian, I do believe my physician's care is superior to that received from "treat 'em and street 'em" "you've got five minutes, what do you want" HMO doctors in the U.S. Clinical trials do not represent real life.
> Dr. Khan found that in only 48 percent of the 52 clinical trials was the antidepressant superior to the placebo.
I prefer to present Khan's own words.
http://www.psychiatrictimes.com/p000429.html
(Me: It's important to emphasize that subjects receiving placebo pills in antidepressant trials are *not* untreated.)
From the referenced article:
"The less-than-impressive results in these and other studies also calls to mind the fact that patients assigned to placebo treatment in clinical trials are not "getting nothing." The capsule they receive is pharmacologically inert but hardly inert with respect to its symbolic value and its power as a conditioned stimulus. In addition, placebo-treated patients receive all of the commonly employed treatment techniques: a thorough evaluation; an explanation for their distress; an expert healer; a plausible treatment; expectation of improvement; a healer's commitment, enthusiasm and positive regard; and an opportunity to verbalize their distress. "(Me: He goes on to include a very important warning about the interpretation of the data arising from antidepressant clinical trials. Note particularly the concluding statement of the second paragraph.)
"A cautionary note is indicated about the generalization of these data to the clinical management of depressed patients. The less-than-impressive difference between drug and placebo in this and other studies of clinical trials does not speak directly to the effectiveness of antidepressants in clinical practice. Participants in antidepressant clinical trials are a highly select group and are not representative of the general population of depressed patients. They are not actively suicidal, they are almost always outpatients who are moderately rather than severely or mildly depressed, and they are free of comorbid physical or psychiatric illness. They are likely to have a higher placebo response rate than more severely ill depressed patients. "
"Furthermore, the primary aim of these studies is not to assess the optimal effect of antidepressants, but rather to rapidly assess efficacy of new drugs so they can be brought to the market. Therefore, dose, duration and diagnosis in clinical trials are not necessarily ideally suited to identify the optimal effects of antidepressants. Accordingly, clinical trials may identify the lower bound of the effect size compared to placebo. "
I'd also like to add that it is a fallacy to conclude that the absence of significant difference between groups in a clinical trial means there is no true difference. The absence of evidence (of a difference) is not evidence of the absence (of a difference). It only means that one was not found, in the limited and selected population under study, under the artificial constraints of the study methodology. It is incorrect to generalize from a null finding. Period.
Lar
Posted by Larry Hoover on September 12, 2007, at 10:51:00
In reply to News - Antidepressants Vindicated?, posted by jrbecker76 on September 8, 2007, at 21:40:40
> Web address: http://www.sciencedaily.com/releases/2007/09/070907095628.htm
>
> related story:
> http://www.nytimes.com/2007/09/07/health/07suicide.html?_r=1&oref=slogin
>
> Newer Antidepressants Led To Less, Not More, Teen SuicidesI'd like to drag the discussion back to the original topic.
The FDA invoked the black box warning based on what I believe to be a political decision, because we want to protect our children from any plausible harm. But the facts do not support the decision made.
In the entire dataset for pediatric antidepressant trials, there was not a single completed suicide. In the many tens of thousands of subjects, there is not one single case from which to generalize. And yet we did.
Prior to the warning, statistical analyis of the adolescent suicide data across the U.S. had shown a clear protective effect of SSRI prescription with respect to suicide. In fact, the relationship was sufficient to develop a regression equation of the form y= mx + b, where y is suicide incidence, m is a negative value (-0.23 suicides/1% increase in SSRI utilization), and b (the intercept) the probably non-zero suicide rate if all vulnerable subjects were treated.
Factorial analysis of the predictors of adolescent suicide have never been shown to even include SSRI use. Alcohol use is a powerful predictor, however. Why do we view these two drugs so differently?
I looked at the whole thing back in 2004 http://www.dr-bob.org/babble/20040915/msgs/392320.html, back before the FDA warning came out, and I haven't seen any reason to reconsider.
I've said it many times before, and I'm going to say it again: The problem is not in the drugs themselves, but in how they are managed. The drugs are blunt instruments, which although powerful, can be used safely. I'll close with the concluding statement of the authors of the study which opened this discussion:
"If the FDA’s goal is to ensure that children and adults treated with antidepressants receive adequate follow-up care to better detect and treat emergent suicidal thoughts, the current black box warning is not a useful approach; what should be considered instead is better education and training of physicians."Lar
Posted by Larry Hoover on September 12, 2007, at 11:51:53
In reply to Re: News - Antidepressants Vindicated? » jrbecker76, posted by Larry Hoover on September 12, 2007, at 10:51:00
I just discovered some information that I did not know, about the FDA analysis of the pediatric SSRI trials. It seems that despite screening prior to entry, 29% of subjects were suicidal before the drug trials. Moreover, only spontaneous reports of suicidality were utilized in considering the black box warning.....although only 4% reported such thoughts. In the majority of studies, standard suicidality questionnaires were used, and they revealed a consistent reduction in suicidality during the study period. Induction of suicidality was not observed. :-/
Lar
P.S. I unwittingly exaggerated the subject pool for these studies, suggesting there were tens of thousands. In fact, there were about 4400.
From: http://www.parentsmedguide.org/physiciansmedguide.pdf
The Use of Medication in Treating Childhood and Adolescent Depression: Information for Physicians
Prepared by the American Psychiatric Association (APA) and American Academy of Child and Adolescent Psychiatry (AACAP)"What Prompted the FDA Warning?
In 2004, the FDA reviewed 23 clinical trials involving more than 4,300 child and adolescent patients who received any of nine different antidepressant medications. No suicides occurred in any of these studies. Most of the studies that the FDA examined used two measures to assess suicidal thinking and behavior.
1) All used "Adverse Event Reports," which are reports made by the research clinician if a patient (or their parent) spontaneously shares thoughts about suicide or describes potentially dangerous behavior. The FDA found that such “adverse events” were reported by approximately 4% of all children and adolescents taking medication compared with 2% of those taking a placebo. One of the problems with using this approach to measuring suicidal thinking is that most teenagers do not talk about their suicidal thoughts unless they are asked, in which case no report is filed.
2) In 17 of the 23 studies a second measure was also available. These were standardized forms asking about suicidal thoughts and behaviors completed for each child or teen at each visit. In the views of many experts these measures are more reliable than event reports. The FDA's analysis of the data from these 17 studies found that medication neither increased suicidality that had been present before treatment, nor did it induce new suicidality in those who were not thinking about suicide at the start of the study. In fact, on these measures, all studies combined showed a slight reduction in suicidality over the course of treatment. Although the FDA reported both sets of findings, they did not comment on the contradiction between them.Hence, the 2% and 4% spontaneous report rates need to be understood in the context of findings from community samples cited previously in which as many as half or more of teenagers with major depression are thinking about suicide at the time of diagnosis and some 16% to 35% have made a previous suicide attempt.
Although only nine medications were re-examined in the analysis, the FDA applied the labeling changes to all antidepressant medications. This was done on the basis of the advisory committee’s perception that currently available data are inadequate to exclude any single medication from being potentially associated with the same increased risk for spontaneous reports of suicidal thinking and/or behavior found in the 23 studies."
Posted by rskontos on September 12, 2007, at 18:43:50
In reply to Re: News - Antidepressants Vindicated? » jrbecker76, posted by Larry Hoover on September 12, 2007, at 10:51:00
If the FDA’s goal is to ensure that children and adults treated with antidepressants receive adequate follow-up care to better detect and treat emergent suicidal thoughts, the current black box warning is not a useful approach; what should be considered instead is better education and training of physicians."
Lar, I think this is the gist and the most important point you have made in this thread. For all the studies and conclusions, you are right that the drugs are blunt instructions and used well and carefully, they can be helpful. Doctors need to be better educated. I think releasing drugs so quickly with the FDA only requiring 12 weeks of trials it is imperative that doctors be highly educated and prescribe judiciously. Then and only then, can we all hope that the drugs are safe for all that need them. For me, with my anxiety disorder or illness or whatever you want to call it, and my bad experience with AD's I am so hesitant to go to another doctor to get another drug to help me, yet that is probably what I need to do. First, though I need to find a new doctor. The argument here should not really be are AD's vindicated but how about how they are used. This seems to be the real issue. At least for me it is. The black box warning only seems to get the monkey off the backs of the doctors and the manufacturers and place it back on the very people that really shouldn't have to be the ones deciding should I take it or is it the right one for me? Don't get me wrong I feel we need to be educated but what has the black box warning done is cause many people just to back off. We need to be better informed, but so do the doctors that prescribe these drugs. I think with children we should be extra cautious naturally. I know from my own experience that my daughter's doctors always said medicating a child was tougher than an adult. So erring on the side of caution is good but parents need solutions too. I have been in the tough situation where no meds were working and no one had an answer either. It is a tough issue all the way around but I think you hit the nail on the head with your statement of educating doctors more. Thanks for your insight. RK
Posted by Phillipa on September 12, 2007, at 20:14:57
In reply to Re: News - Antidepressants Vindicated?))SAM, posted by ttee on September 12, 2007, at 0:31:09
Finally someone said what I've been thinking so long. Thanks for saying that. Phillipa
Posted by Phillipa on September 12, 2007, at 20:33:03
In reply to Re: News - Antidepressants Vindicated?))SAM » ttee, posted by Phillipa on September 12, 2007, at 20:14:57
Also definitely agree with educating the docs more. Phillipa ps who should educate them?
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