From: david.j.worrell@gmail.com

Do Antidepressants Work?

The most comprehensive study on them has recently been published, showing mostly modest effects.

http://tinyurl.com/y9vo32tl

By Aaron E. Carroll

March 12, 2018

Antidepressants are widely used, but there are still so many unanswered questions about them.

More people in the United States are on antidepressants, as a percentage of the
population, than any other country in the world. And yet the drugs’ efficacy has been hotly debated.

Some believe that the short-term benefits are much more modest than widely thought, and that harms may outweigh benefits in the long run. Others believe that they work, and that they can be life-changing.

Settling this debate has been much harder than you might think.

It’s not that we lack research. Many, many studies of antidepressants can be found in the peer-reviewed literature. The problem is that this has been a prime example of publication bias: Positive studies are likely to be released, with negative ones
more likely to be buried in a drawer.

In 2008, a group of researchers made this point by doing a meta-analysis of antidepressant trials that were registered with the Food and Drug Administration as evidence in support of approvals for marketing or changes in labeling. Companies had to submit
the results of registered trials to the F.D.A. regardless of the result. These trials also tend to have less data massaging — such as the cherry-picking of
outcomes — than might be possible in journals.

The researchers found 74 studies, with more than 12,500 patients, for drugs approved between 1987 and 2004. About half of these trials had “positive” results, in that the antidepressant performed better than a placebo; the other half were “negative.
” But if you looked only in the published literature, you’d get a much different picture. Nearly all of the positive studies are there. Only three of the negative studies appear in the literature as negative. Twenty-two were never published, and 11
were published but repackaged so that they appeared positive.

A second meta-analysis published that year also used F.D.A. data instead of the
peer-reviewed literature, but asked a different question. Researchers wondered if the effectiveness of a study was related to the baseline levels of depression of its
participants. The results suggested yes. The effectiveness of antidepressants was limited for those with moderate depression, and small for those with severe
depression.

The take-home message from these two studies was that the effectiveness of antidepressants had been overstated, and that the benefit might be limited to far fewer patients than were actually using the drugs.

These points, and more, were made in a paper written by John Ioannidis in the journal Philosophy, Ethics, and Humanities in Medicine in 2008. He argued that the study designs and populations selected, especially the short length of many
studies, biased
them to positive results. He argued that while many studies achieved statistical significance, they failed to achieve clinical significance. He argued that we knew too little about long-term harms, and that we were being presented with biased information
by looking only at published data.

This paper — “Effectiveness of Antidepressants: An Evidence Myth Constructed From a Thousand Randomized Trials?” — sowed lingering doubts about the use of antidepressants and the conduct of medical research. But recently, the most comprehensive
antidepressants study to date was published, and it appears to be a thorough effort to overcome the hurdles of the past.

Researchers, including Dr. Ioannidis this time, searched the medical literature, regulatory agency websites and international registers for both published and unpublished double-blind randomized controlled trials, all the way till the beginning of 2016.

They looked for both placebo-controlled and head-to-head trials of 21 antidepressants used to treat adults for major depressive disorder. They used a
“network meta-analysis technique,” which allows multiple treatments to be compared both within
individual trials directly and across trials indirectly to a common comparator.
They examined not only how well the drugs worked, but also how tolerated the treatment was — what they called acceptability.

They found 522 trials that included more than 116,000 participants. Of those, 86 were unpublished studies found on trial registries and company websites. An additional 15 were discovered through personal communication or by hand-searching review articles.
The authors went an extra step and asked for unpublished data on the studies they found, getting it for more than half of the included trials.

The reassuring news is that all of the antidepressants were more effective than
placebos. They varied modestly in terms of efficacy and acceptability, so each patient and doctor should discuss potential benefits and harms of individual drugs.

Further good news is that smaller trials did not have substantially different results from larger trials.

It also did not appear that industry sponsoring of trials correlated with significant differences in response or dropout rates. But — and this is a big “but” — the vast majority of trials are funded by industry. As a result, this meta-analysis
may not have had enough data on non-industry trials to accurately determine if a difference exists.

There were also signs of “novelty” bias: Antidepressants seemed to perform better when they were newly released in the market but seemed to lose efficacy and acceptability in later years.

The bad news is that even though there were statistically significant differences, the effect sizes were still mostly modest. The benefits also applied only to people who were suffering from major depression, specifically in the short term. In other
words, this study provides evidence that when people are found to have acute major depression, treatment with antidepressants works to improve outcomes in the first two months of therapy.

Because we lack good data, we still do not know how well antidepressants work for those with milder symptoms that fall short of major depression, especially if patients have been on the drugs for months or even years. Many people probably fall into that
category, yet are still regularly prescribed antidepressants for extended periods. We don’t know how much of the benefit received from such use is a placebo effect versus a biological one.

I asked Dr. Ioannidis if the results of this new study were as radical as many news articles had suggested. He confirmed that this was a much-larger meta-analysis — with about 10 times more information — than the ones from a
decade ago, with more
unpublished data and more antidepressants covered. He’s also hopeful that future studies will be even better at informing individual-level responses, which might help to see if some patients benefit substantially even when others
don’t seem to
benefit at all.

But he thought that some of the exuberance in the news media might be a little overblown. “I am afraid that some news stories gave very crude interpretations that may be misleading, especially when their titles were too absolute, like ‘the drugs work�
��, ‘the debate is over’ and so forth,” he said. “The clinical (as opposed to statistical) significance of the treatment effects that we detected will continue to be contested, and it is still important to find ways that one can identify the
specific patients who get the maximum benefit.”

Even with so much research on antidepressants, there are still many unanswered questions. It’s unclear if drug companies would be interested in the results,
or indeed why they would be. The drugs are already being widely used, and no regulatory agency
is requiring more data. If patients want answers, they will need to demand the research themselves.

***

I've been concerned with this issue most of my life, not because I take antidepressants but because many of the people I've cared for did.
And I've been skeptical of the benefits since I was about 12 years old.
This debate is far from over. Not with:

"the vast majority of trials are funded by industry"

and...

"There were also signs of “novelty” bias"

and... most importantly,

"even though there were statistically significant differences,
***the effect sizes were still mostly modest***."

and...

“The clinical (as opposed to statistical) significance of the
treatment effects that we detected will continue to be contested"

and...

"we still do not know how well antidepressants work for those
with milder symptoms that fall short of major depression, especially
if patients have been on the drugs for months or even years.
Many people probably fall into that category, yet are still
regularly prescribed antidepressants for extended periods.
We don’t know how much of the benefit received from such use
is a placebo effect versus a biological one."

and...

"there are still many unanswered questions"

and yet...

"no regulatory agency is requiring more data"

Doctors and companies have been pushing these psych meds relentlessly
for decades. I remain skeptical even after this large study which
indicates that while such meds may help many, the effect is... modest.

It's a barely adequate "solution" to human mental health.
That's what I've always thought; and I still think so.

.

--- SoupGate-Win32 v1.05
* Origin: www.darkrealms.ca (1:229/2)

From: thangolossus@gmail.com

On Mon, 12 Mar 2018 17:14:11 -0700 (PDT), "Jeremy H. Denisovan" <david.j.worrell@gmail.com> wrote:

Do Antidepressants Work?

The most comprehensive study on them has recently been published, showing mostly modest effects.

http://tinyurl.com/y9vo32tl

By Aaron E. Carroll

March 12, 2018

Antidepressants are widely used, but there are still so many unanswered questions about them.

More people in the United States are on antidepressants, as a percentage of the population, than any other country in the world. And yet the drugs’ efficacy has been hotly debated.

Some believe that the short-term benefits are much more modest than widely thought, and that harms may outweigh benefits in the long run. Others believe that they work, and that they can be life-changing.

Settling this debate has been much harder than you might think.

It’s not that we lack research. Many, many studies of antidepressants can be

found in the peer-reviewed literature. The problem is that this has been a prime example of publication bias: Positive studies are likely to be released, with negative ones
more likely to be buried in a drawer.

In 2008, a group of researchers made this point by doing a meta-analysis of antidepressant trials that were registered with the Food and Drug Administration as evidence in support of approvals for marketing or changes in labeling. Companies had to

submit the results of registered trials to the F.D.A. regardless of the result. These trials also tend to have less data massaging — such as the cherry-picking of outcomes — than might be possible in journals.

The researchers found 74 studies, with more than 12,500 patients, for drugs approved between 1987 and 2004. About half of these trials had “positive” results, in that the antidepressant performed better than a placebo; the other half were “

negative.” But if you looked only in the published literature, you’d get a
much different
picture. Nearly all of the positive studies are there. Only three of the negative studies appear in the literature as negative. Twenty-two were never published, and 11 were published but repackaged so that they appeared positive.

A second meta-analysis published that year also used F.D.A. data instead of the peer-reviewed literature, but asked a different question. Researchers wondered if the effectiveness of a study was related to the baseline levels of depression of its

participants. The results suggested yes. The effectiveness of antidepressants was
limited for those with moderate depression, and small for those with severe depression.

The take-home message from these two studies was that the effectiveness of antidepressants had been overstated, and that the benefit might be limited to far fewer patients than were actually using the drugs.

These points, and more, were made in a paper written by John Ioannidis in the journal Philosophy, Ethics, and Humanities in Medicine in 2008. He argued that the study designs and populations selected, especially the short length of many

studies, biased
them to positive results. He argued that while many studies achieved statistical significance, they failed to achieve clinical significance. He argued that we knew too little about long-term harms, and that we were being presented with biased information by looking only at published data.

This paper — “Effectiveness of Antidepressants: An Evidence Myth Constructed From a Thousand Randomized Trials?” — sowed lingering doubts about the use of antidepressants and the conduct of medical research. But recently, the most comprehensive

antidepressants study to date was published, and it appears to be a thorough effort to
overcome the hurdles of the past.

Researchers, including Dr. Ioannidis this time, searched the medical literature, regulatory agency websites and international registers for both published and unpublished double-blind randomized controlled trials, all the way till the beginning of 2016.

They looked for both placebo-controlled and head-to-head trials of 21 antidepressants used to treat adults for major depressive disorder. They used a

“network meta-analysis technique,” which allows multiple treatments to be compared both within
individual trials directly and across trials indirectly to a common comparator.
They
examined not only how well the drugs worked, but also how tolerated the treatment was — what they called acceptability.

They found 522 trials that included more than 116,000 participants. Of those, 86 were unpublished studies found on trial registries and company websites. An additional 15 were discovered through personal communication or by hand-searching review

articles. The authors went an extra step and asked for unpublished data on the studies
they found, getting it for more than half of the included trials.

The reassuring news is that all of the antidepressants were more effective than placebos. They varied modestly in terms of efficacy and acceptability, so each patient and doctor should discuss potential benefits and harms of individual drugs.

Further good news is that smaller trials did not have substantially different results from larger trials.

It also did not appear that industry sponsoring of trials correlated with significant differences in response or dropout rates. But — and this is a big “but” — the vast majority of trials are funded by industry. As a result, this meta-analysis

may not have had enough data on non-industry trials to accurately determine if a
difference exists.

There were also signs of “novelty” bias: Antidepressants seemed to perform

better when they were newly released in the market but seemed to lose efficacy and acceptability in later years.

The bad news is that even though there were statistically significant differences, the effect sizes were still mostly modest. The benefits also applied only to people who were suffering from major depression, specifically in the short term. In other

words, this study provides evidence that when people are found to have acute major
depression, treatment with antidepressants works to improve outcomes in the first two months of therapy.

Because we lack good data, we still do not know how well antidepressants work for those with milder symptoms that fall short of major depression, especially if patients have been on the drugs for months or even years. Many people probably fall into that

category, yet are still regularly prescribed antidepressants for extended periods. We don’t know how much of the benefit received from such use is a placebo effect versus a biological one.

I asked Dr. Ioannidis if the results of this new study were as radical as many

news articles had suggested. He confirmed that this was a much-larger meta-analysis — with about 10 times more information — than the ones from a
decade ago, with more
unpublished data and more antidepressants covered. He’s also hopeful that future
studies will be even better at informing individual-level responses, which might help to see if some patients benefit substantially even when others don’t seem to benefit at all.

But he thought that some of the exuberance in the news media might be a little

overblown. “I am afraid that some news stories gave very crude interpretations that may be misleading, especially when their titles were too absolute, like ‘the drugs
work’, ‘the debate is over’ and so forth,” he said. “The clinical (as
opposed to
statistical) significance of the treatment effects that we detected will continue to be contested, and it is still important to find ways that one can identify the specific patients who get the maximum benefit.”

Even with so much research on antidepressants, there are still many unanswered

questions. It’s unclear if drug companies would be interested in the results,
or indeed why they would be. The drugs are already being widely used, and no regulatory agency
is requiring more data. If patients want answers, they will need to demand the research themselves.

***

I've been concerned with this issue most of my life, not because I take >antidepressants but because many of the people I've cared for did.
And I've been skeptical of the benefits since I was about 12 years old.
This debate is far from over. Not with:

"the vast majority of trials are funded by industry"

and...

"There were also signs of “novelty” bias"

and... most importantly,

"even though there were statistically significant differences,
***the effect sizes were still mostly modest***."

and...

“The clinical (as opposed to statistical) significance of the
treatment effects that we detected will continue to be contested"

and...

"we still do not know how well antidepressants work for those
with milder symptoms that fall short of major depression, especially
if patients have been on the drugs for months or even years.
Many people probably fall into that category, yet are still
regularly prescribed antidepressants for extended periods.
We don’t know how much of the benefit received from such use
is a placebo effect versus a biological one."

and...

"there are still many unanswered questions"

and yet...

"no regulatory agency is requiring more data"

Doctors and companies have been pushing these psych meds relentlessly
for decades. I remain skeptical even after this large study which
indicates that while such meds may help many, the effect is... modest.

It's a barely adequate "solution" to human mental health.
That's what I've always thought; and I still think so.

I have some significant misgivings about SSRI's based on family
experience where a member of my family was incorrectly
(inappropriately?) prescribed, almost reflexively, zoloft (a prozac
type SSRI).

She was not depressed and this stuff sent practically sent her into
insanity and she is, and was, a prosaic uncomplicated person. She
decided to cold turkey the pills and came off them after reducing the
dosage for around a month or so. This was against GP advice but it
worked. This was over a decade ago and she has never looked back and
will never take any form of AD again, ever.

All I can say is in my family member's case, the SSRI did not work
because she was not clinically depressed in the first instance, nor
has she ever been.

On another note, I have a lot of experience with amphetamines, having
taken them for jollies in my younger days for around 5 years or so
(only on weekends, perhaps twice a week, never intravenously, and
usually for great sex and partying). There is no possibility of a
depressed person remaining depressed when on the "whizzer" - whether
it be ritalin, off market speed, ice, methphindrate, ecstasy or
whatever in its many forms. Why not hit the really bad, clinically
diagnosed cases of depression with a couple of months worth of
dexamphetamine at low, measure and prescribed dosage? I can guarantee
that pesky depression will disappear immediately.

My personal view as a man who is independent and individualistic
(slider would call me an "outsider") is that the entire panoply of
depressive diseases may well exist, in reality, but in days past there
was no time for our ancestors to wallow in self pity and
self-absorbtion - they were far too busy fucking well surviving!!

It's a malady of the rich first world. I wonder what the rates of
suicide due to depression are in third world countries where every
moment is spent on survival? This is only my view but I think people
are far to introspective nowdays and lack proper perspective. When
I'm down, and we all get that way from time to time it's part of the
human condition, I think of the fucking cosmos and nature and how damn
small we all are in that context. I think of people like Hawking who
not only survived massive insults to the physical organism but thrived
in spite thereof. I think then of a person who has convinced
themselves there is no point going on who puts a bullet in their brain
because they are "depressed". A nice week spent in the outdoors,
looking at the stars at night and the wonders of nature in the day
might just cure the malaise...


As democracy is perfected, the office of the president
represents, more and more closely, the inner soul of the
people. On some great and glorious day the plain folks of
the land will reach their heart’s desire at last, and the
White House will be adorned by a downright moron.

——— H. L. MENCKEN ———


---
This email has been checked for viruses by Avast antivirus software. https://www.avast.com/antivirus

--- SoupGate-Win32 v1.05
* Origin: www.darkrealms.ca (1:229/2)

From: david.j.worrell@gmail.com

I have pet peeves of my own regarding people on psych meds.

One: many of them are sedentary. You need exercise!
Regular exercise can make a big difference physically and mentally.

Two: many eat an unhealthy diet. Eat nutritious food regularly.
Eating junky all the time has bad effects physically and mentally.

Three: regularly experience the beauty of the natural world.
Sitting inside forever twiddling electronic devices can make
everything start to seem unreal.

Four: learn how to quiet your thoughts. (And how to question
your thoughts, skeptically.) If your thoughts start running away
in weird directions, quiet your mind. Then go for a long walk
and open your eyes. :)

I think that if most people just make sure to do all four of those
simple things first they probably won't ever need pysch meds.
There may be people this 'prescription' doesn't work for -
but I almost never see people truly try it.

.

--- SoupGate-Win32 v1.05
* Origin: www.darkrealms.ca (1:229/2)

From: allreadydun@gmail.com

Jeremy wrote:

I have pet peeves of my own regarding people on psych meds.

One: many of them are sedentary. You need exercise!
Regular exercise can make a big difference physically and mentally.

Two: many eat an unhealthy diet. Eat nutritious food regularly.
Eating junky all the time has bad effects physically and mentally.

Three: regularly experience the beauty of the natural world.
Sitting inside forever twiddling electronic devices can make
everything start to seem unreal.

Four: learn how to quiet your thoughts. (And how to question
your thoughts, skeptically.) If your thoughts start running away
in weird directions, quiet your mind. Then go for a long walk
and open your eyes. :)

if you are reading this out in cyber world i have one
more thing to add to this. And i got to tell you that
this one thing was the ticket that really made it work.
Don't identify with the content of your thought(s). Don't
identify with what is NOT you. A vast majority of our thoughts
are just bogus hot air. Useless actually.

I think that if most people just make sure to do all four of those
simple things first they probably won't ever need pysch meds.
There may be people this 'prescription' doesn't work for -
but I almost never see people truly try it.

and turn the tv off, it's ALL bullshit, all of it.

--- SoupGate-Win32 v1.05
* Origin: www.darkrealms.ca (1:229/2)