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Vocapedia > Health > Mental health > Depression > Antidepressants

 

 

 

Prozac: Revolution in a Capsule | Retro Report | The New York Times        22 September 2014

 

When Prozac was introduced in 1988,

the green-and-cream pill to treat depression

launched a cultural revolution that continues to echo.

 

Produced by: Retro Report

Read the story here: http://nyti.ms/XMXik9

Watch more videos at: http://nytimes.com/video

 

YouTube

http://www.youtube.com/
watch?v=qgCFQ5no2jg&list=PL4CGYNsoW2iAOqPtxm4RHo205w_R1IWuH

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

drugs > antidepressants / anti-depressants        UK / USA

 

https://www.nytimes.com/2019/06/21/
health/ketamine-depression-veterans.html

 

https://www.npr.org/sections/health-shots/2019/05/02/
718744068/how-drug-companies-helped-shape-a-shifting-biological-view-of-mental-illness

 

https://www.npr.org/sections/health-shots/2019/04/11/
712295937/ketamine-may-relieve-depression-by-repairing-damaged-brain-circuits

 

 

 

 

https://www.theguardian.com/society/2018/oct/02/
antidepressant-withdrawal-symptoms-severe-says-new-report

 

https://www.npr.org/sections/health-shots/2018/08/29/
642700616/ketamine-a-promising-depression-treatment-seems-to-act-like-an-opioid

 

https://www.theguardian.com/society/commentisfree/2018/jul/19/
drugs-alone-wont-fix-our-epidemic-of-depression

 

https://www.npr.org/sections/health-shots/2018/06/04/
615671405/from-chaos-to-calm-a-life-changed-by-ketamine

 

https://www.nytimes.com/2018/04/07/
health/antidepressants-withdrawal-prozac-cymbalta.html

 

https://www.theguardian.com/science/2018/feb/21/
the-drugs-do-work-antidepressants-are-effective-study-shows

 

https://www.theguardian.com/society/2018/feb/21/
its-official-antidepressants-are-not-snake-oil-or-a-conspiracy-they-work

 

https://www.theguardian.com/science/brain-flapping/2018/jan/24/
antidepressants-please-please-do-not-just-abandon-your-meds-johann-hari

 

 

 

 

https://www.nytimes.com/2017/09/11/
well/mind/paxil-antidepressants-suicide.html

 

https://www.theguardian.com/science/brain-flapping/2017/jul/10/
how-do-antidepressants-actually-work

 

https://www.theguardian.com/commentisfree/2017/jul/08/
antidepressant-effects-psychotherapy-mental-health-crisis-nhs

 

http://www.content.digital.nhs.uk/article/7756/
Antidepressants-were-the-area-with-largest-increase-in-prescription-items-in-2016 - 29 June 2017

 

 

 

 

http://www.npr.org/sections/health-shots/2016/08/29/
491819007/screening-positive-for-depression-
doesn-t-mean-you-ll-get-treatment-study-finds

 

https://www.npr.org/sections/health-shots/2016/08/29/
491819007/screening-positive-for-depression-doesn-t-mean-you-ll-get-treatment-study-finds

 

https://www.theguardian.com/society/2016/jul/05/
antidepressant-prescriptions-in-england-double-in-a-decade

 

http://www.theguardian.com/society/2016/jun/09/
most-antidepressants-not-working-for-children-and-teenagers-study

 

http://www.nytimes.com/2016/06/05/
opinion/sunday/are-opioids-the-next-antidepressant.html

 

http://www.theguardian.com/society/2016/jan/28/
common-antidepressant-could-put-children-at-greater-risk-of-suicide

 

 

 

 

http://www.nytimes.com/2015/09/17/
health/antidepressant-paxil-is-unsafe-for-teenagers-new-analysis-says.html

 

http://www.theguardian.com/science/2015/sep/16/
seroxat-study-harmful-effects-young-people

 

https://www.npr.org/sections/health-shots/2015/07/09/
421203272/some-antidepressants-may-pose-increased-risk-of-birth-

 

https://www.npr.org/sections/health-shots/2015/05/28/
409800015/ketamine-depression-treatments-inspired-by-club-drug-move-ahead-in-tests

 

http://www.theguardian.com/society/2015/apr/21/
mindfulness-based-cognitive-therapy-treatment-chronic-depression-antidepressants

 

http://www.theguardian.com/commentisfree/2015/jan/30/
battle-depression-taught-me-medicine-love

 

 

 

 

http://opinionator.blogs.nytimes.com/2014/10/18/
why-doctors-need-stories/

 

https://www.npr.org/sections/health-shots/2014/06/18/
323329892/warnings-against-antidepressants-for-teens-may-have-backfired

 

http://www.youtube.com/watch?
v=qgCFQ5no2jg&list=PL4CGYNsoW2iAOqPtxm4RHo205w_R1IWuH

 

http://www.theguardian.com/society/2014/may/28/
-sp-antidepressant-use-soared-during-recession-uk-study

 

http://www.theguardian.com/news/datablog/2014/may/28/
rise-in-antidepressant-prescriptions-rates-in-england-get-the-data

 

https://www.npr.org/sections/health-shots/2014/04/28/
307671897/higher-doses-of-antidepressants-may-raise-teen-suicide-risk

 

 

 

 

http://www.theguardian.com/society/2013/nov/21/
prescribing-culture-blame-rise-antidepressants

 

http://www.theguardian.com/society/2013/nov/21/
depression-treatment-antidepressants-europe

 

http://www.theguardian.com/commentisfree/2013/nov/20/
drugs-work-cant-cure-unhappiness-antidepressants

 

http://www.theguardian.com/society/2013/nov/21/
your-experiences-antidepressants-responses

 

http://www.theguardian.com/society/video/2013/nov/20/
taking-tablets-personal-guide-anti-depressants-video

 

http://www.theguardian.com/society/2013/nov/20/
antidepressant-use-rise-world-oecd

 

http://www.theguardian.com/science/head-quarters/2013/aug/15/
antidepressants-depression

 

 

 

 

https://www.npr.org/sections/health-shots/2012/01/31/
146096540/i-wanted-to-live-new-depression-drugs-offer-hope-for-toughest-cases

 

 

 

 

https://www.npr.org/sections/health-shots/2011/10/20/
141544135/look-around-1-in-10-americans-take-antidepressants

 

https://www.npr.org/sections/health-shots/2011/09/13/
140439308/fear-of-antidepressants-leads-people-to-shun-treatment

 

https://www.npr.org/sections/health-shots/2011/08/25/
139943213/why-the-cardiologist-cares-about-your-antidepressant

 

 

 

 

http://www.nytimes.com/2011/07/17/
opinion/sunday/l17dialogue.html

http://www.nytimes.com/2011/07/10/
opinion/sunday/10antidepressants.html

 

http://www.nytimes.com/2010/01/12/
health/12mind.html

 

http://community.nytimes.com/article/comments/2008/04/15/
health/15mind.html

http://www.independent.co.uk/life-style/health-and-wellbeing/
health-news/antidepressant-drugs-udontu-work-ndash-official-study-787264.html

 

http://www.usatoday.com/news/health/2006-12-13-
fda-antidepressants_x.htm

https://www.theguardian.com/society/2006/may/13/
socialcare.medicineandhealth 

 

https://www.theguardian.com/news/2004/jun/14/uk
news

 

https://www.theguardian.com/society/2003/sep/20/
medicineandhealth.lifeandhealth

 

 

 

 

 

 

 

 

 

 

 

 

 

 

USA > drugs > antidepressants / anti-depressants > statistics        UK

 

(...) prescription

of antidepressants

to 34.4 million Americans

in 2013-2014,

up from 13.4 million

just 15 years earlier.

https://www.theguardian.com/society/commentisfree/2018/jul/19/
drugs-alone-wont-fix-our-epidemic-of-depression

 

 

 

 

 

 

 

drugs > antidepressants / anti-depressants > statistics        USA

 

More than 50m prescriptions

for anti-depressants

were written last year (2012)

- a record number.

http://well.blogs.nytimes.com/2014/04/17/
the-antidepressant-generation/

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ketamine        USA

https://www.nytimes.com/2019/06/21/
health/ketamine-depression-veterans.html

 

https://www.npr.org/sections/health-shots/2018/06/04/
615671405/from-chaos-to-calm-a-life-changed-by-ketamine

 

https://www.npr.org/sections/health-shots/2017/03/20/
520169959/ketamine-for-severe-depression-how-do-you-not-offer-this-drug-to-people

 

 

 

 

antidepressants such as Zoloft, Paxil, or other SSRIs        USA

http://www.npr.org/sections/health-shots/2017/09/18/
551020800/xanax-or-zoloft-for-moms-to-be-a-new-study-assesses-safety

 

 

 

 

 

UK > (in 2016), according to NHS Digital,

no fewer than 64.7m antidepressant prescriptions

were given in England alone.        UK

https://www.theguardian.com/commentisfree/2017/jul/08/
antidepressant-effects-psychotherapy-mental-health-crisis-nhs

 

 

 

 

 

Seroxat

- the world's biggest-selling antidepressant        UK

 

Seroxat,

whose generic name is paroxetine,

is in the class of drugs, with Prozac,

termed SSRI

or selective serotonin reuptake inhibitors.
http://www.theguardian.com/society/2003/mar/13/mentalhealth.medicineandhealth

 

http://www.theguardian.com/society/2003/mar/13/
mentalhealth.medicineandhealth

 

 

 

 

selective serotonin reuptake inhibitors    SSRI / SSRIs > Zoloft, Paxil...        UK / USA

http://www.npr.org/sections/health-shots/2017/09/18/
551020800/xanax-or-zoloft-for-moms-to-be-a-new-study-assesses-safety

https://www.theguardian.com/commentisfree/2017/jul/08/
antidepressant-effects-psychotherapy-mental-health-crisis-nhs

 

http://www.guardian.co.uk/culture/2013/may/19/
does-prozac-help-artists-be-creative

 

 

 

 

be on SSRI

 

 

 

 

take selective serotonin

and serotonin-norepinephrin

reuptake inhibitor drugs

to combat depression        UK

http://www.theguardian.com/society/2016/jan/28/
common-antidepressant-could-put-children-at-greater-risk-of-suicide

 

 

 

 

 

Citalopram        UK

https://www.theguardian.com/commentisfree/2017/jul/08/
antidepressant-effects-psychotherapy-mental-health-crisis-nhs

 

 

 

 

depression treatment > ketamine        USA

http://www.npr.org/sections/health-shots/2017/03/20/
520169959/ketamine-for-severe-depression-how-do-you-not-offer-this-drug-to-people

 

http://www.npr.org/sections/health-shots/2015/09/28/
443203592/club-drug-ketamine-gains-traction-as-a-treatment-for-depression

 

http://www.theguardian.com/society/2014/jun/22/
critics-attack-ect-ketamine-therapy-depression

http://www.npr.org/blogs/health/2014/04/03/
298770933/growing-evidence-that-a-party-drug-can-help-severe-depression

 

 

 

 

Prozac        USA

http://www.nytimes.com/2014/05/22/
opinion/depressed-but-not-ashamed.html

 

 

 

 

electroconvulsive therapy    ECT        USA

http://www.nytimes.com/2014/08/16/
opinion/depression-can-be-treated-but-it-takes-competence.html

 

 

 

 

cognitive therapy        UK

 

Mindfulness-based cognitive therapy (MBCT)

was developed from mindfulness techniques,

which encourage individuals

to pay more attention to the present moment,

combined with cognitive behaviour therapy (CBT),

specifically to try to help people

who have recurring depression.

 

It teaches people to recognise

that negative thoughts and feelings will return,

but that they can disengage from them.

 

Rather than worrying

constantly about them,

people can become aware of them,

understand them and accept them,

and avoid being dragged down

into a spiral leading back to depression.

http://www.theguardian.com/society/2015/apr/21/
mindfulness-based-cognitive-therapy-treatment-chronic-depression-antidepressants

 

http://www.theguardian.com/society/2015/apr/21/
mindfulness-based-cognitive-therapy-treatment-chronic-depression-antidepressants

 

 

 

 

 

 

 

 

 

In Defense of Antidepressants

 

July 9, 2011

The New York Times

By PETER D. KRAMER

 

PROVIDENCE, R.I.

IN terms of perception, these are hard times for antidepressants. A number of articles have suggested that the drugs are no more effective than placebos.

Last month brought an especially high-profile debunking. In an essay in The New York Review of Books, Marcia Angell, former editor in chief of The New England Journal of Medicine, favorably entertained the premise that “psychoactive drugs are useless.” Earlier, a USA Today piece about a study done by the psychologist Robert DeRubeis had the headline, “Antidepressant lift may be all in your head,” and shortly after, a Newsweek cover piece discussed research by the psychologist Irving Kirsch arguing that the drugs were no more effective than a placebo.

Could this be true? Could drugs that are ingested by one in 10 Americans each year, drugs that have changed the way that mental illness is treated, really be a hoax, a mistake or a concept gone wrong?

This supposition is worrisome. Antidepressants work — ordinarily well, on a par with other medications doctors prescribe. Yes, certain researchers have questioned their efficacy in particular areas — sometimes, I believe, on the basis of shaky data. And yet, the notion that they aren’t effective in general is influencing treatment.

For instance, not long ago, I received disturbing news: a friend had had a stroke that paralyzed the right side of his body. Hoping to be of use, I searched the Web for a study I vaguely remembered. There it was: a group in France had worked with more than 100 people with the kind of stroke that affected my friend. Along with physiotherapy, half received Prozac, and half a placebo. Members of the Prozac group recovered more of their mobility. Antidepressants are good at treating post-stroke depression and good at preventing it. They also help protect memory. In stroke patients, antidepressants look like a tonic for brain health.

When I learned that my friend was not on antidepressants, I suggested he raise the issue with his neurologists. I e-mailed them the relevant articles. After further consideration, the doctors added the medicines to his regimen of physical therapy.

Surprised that my friend had not been offered a highly effective treatment, I phoned Robert G. Robinson at the University of Iowa’s department of psychiatry, a leading researcher in this field. He said, “Neurologists tell me they don’t use an antidepressant unless a patient is suffering very serious depression. They’re influenced by reports that say that’s all antidepressants are good for.”

Critics raise various concerns, but in my view the serious dispute about antidepressant efficacy has a limited focus. Do they work for the core symptoms (such as despair, low energy and feelings of worthlessness) of isolated episodes of mild or moderate depression? The claim that antidepressants do nothing for this common condition — that they are merely placebos with side effects — is based on studies that have probably received more ink than they deserve.

The most widely publicized debunking research — the basis for the Newsweek and New York Review pieces — is drawn from data submitted to the Food and Drug Administration in the late 1980s and the 1990s by companies seeking approval for new drugs. This research led to its share of scandal when a study in The New England Journal of Medicine found that the trials had been published selectively. Papers showing that antidepressants work had found their way into print; unfavorable findings had not.

In his book “The Emperor’s New Drugs: Exploding the Antidepressant Myth,” Dr. Kirsch, a psychologist at the University of Hull in England, analyzed all the data. He found that while the drugs outperformed the placebos for mild and moderate depression, the benefits were small. The problem with the Kirsch analysis — and none of the major press reports considered this shortcoming — is that the F.D.A. material is ill suited to answer questions about mild depression.

As a condition for drug approval, the F.D.A. requires drug companies to demonstrate a medicine’s efficacy in at least two trials. Trials in which neither the new drug nor an older, established drug is distinguishable from a placebo are deemed “failed” and are disregarded or weighed lightly in the evaluation. Consequently, companies rushing to get medications to market have had an incentive to run quick, sloppy trials.

Often subjects who don’t really have depression are included — and (no surprise) weeks down the road they are not depressed. People may exaggerate their symptoms to get free care or incentive payments offered in trials. Other, perfectly honest subjects participate when they are at their worst and then spontaneously return to their usual, lower, level of depression.

THIS improvement may have nothing to do with faith in dummy pills; it is an artifact of the recruitment process. Still, the recoveries are called “placebo responses,” and in the F.D.A. data they have been steadily on the rise. In some studies, 40 percent of subjects not receiving medication get better.

The problem is so big that entrepreneurs have founded businesses promising to identify genuinely ill research subjects. The companies use video links to screen patients at central locations where (contrary to the practice at centers where trials are run) reviewers have no incentives for enrolling subjects. In early comparisons, off-site raters rejected about 40 percent of subjects who had been accepted locally — on the ground that those subjects did not have severe enough symptoms to qualify for treatment. If this result is typical, many subjects labeled mildly depressed in the F.D.A. data don’t have depression and might well respond to placebos as readily as to antidepressants.

Nonetheless, the F.D.A. mostly gets it right. To simplify a complex matter: there are two sorts of studies that are done on drugs: broad trials and narrow trials. Broad trials, like those done to evaluate new drugs, can be difficult these days, because many antidepressants are available as generics. Who volunteers to take an untested remedy? Research subjects are likely to be an odd bunch.

Narrow studies, done on those with specific disorders, tend to be more reliable. Recruitment of subjects is straightforward; no one’s walking off the street to enter a trial for stroke patients. Narrow studies have identified many specific indications for antidepressants, such as depression in neurological disorders, including multiple sclerosis and epilepsy; depression caused by interferon, a medication used to treat hepatitis and melanoma; and anxiety disorders in children.

New ones regularly emerge. The June issue of Surgery Today features a study in which elderly female cardiac patients who had had emergency operations and were given antidepressants experienced less depression, shorter hospital stays and fewer deaths in the hospital.

Broad studies tend to be most trustworthy when they look at patients with sustained illness. A reliable finding is that antidepressants work for chronic and recurrent mild depression, the condition called dysthymia. More than half of patients on medicine get better, compared to less than a third taking a placebo. (This level of efficacy — far from ideal — is typical across a range of conditions in which antidepressants outperform placebos.) Similarly, even the analyses that doubt the usefulness of antidepressants find that they help with severe depression.

In fact, antidepressants appear to have effects across the depressive spectrum. Scattered studies suggest that antidepressants bolster confidence or diminish emotional vulnerability — for people with depression but also for healthy people. In the depressed, the decrease in what is called neuroticism seems to protect against further episodes. Because neuroticism is not a core symptom of depression, most outcome trials don’t measure this change, but we can see why patients and doctors might consider it beneficial.

Similarly, in rodent and primate trials, antidepressants have broad effects on both healthy animals and animals with conditions that resemble mood disruptions in humans.

One reason the F.D.A. manages to identify useful medicines is that it looks at a range of evidence. It encourages companies to submit “maintenance studies.” In these trials, researchers take patients who are doing well on medication and switch some to dummy pills. If the drugs are acting as placebos, switching should do nothing. In an analysis that looked at maintenance studies for 4,410 patients with a range of severity levels, antidepressants cut the odds of relapse by 70 percent. These results, rarely referenced in the antidepressant-as-placebo literature, hardly suggest that the usefulness of the drugs is all in patients’ heads.

The other round of media articles questioning antidepressants came in response to a seemingly minor study engineered to highlight placebo responses. One effort to mute the placebo effect in drug trials involves using a “washout period” during which all subjects get a dummy pill for up to two weeks. Those who report prompt relief are dropped; the study proceeds with those who remain symptomatic, with half getting the active medication. In light of subject recruitment problems, this approach has obvious appeal.

Dr. DeRubeis, an authority on cognitive behavioral psychotherapy, has argued that the washout method plays down the placebo effect. Last year, Dr. DeRubeis and his colleagues published a highly specific statistical analysis. From a large body of research, they discarded trials that used washouts, as well as those that focused on dysthymia or subtypes of depression. The team deemed only six studies, from over 2,000, suitable for review. An odd collection they were. Only studies using Paxil and imipramine, a medicine introduced in the 1950s, made the cut — and other research had found Paxil to be among the least effective of the new antidepressants. One of the imipramine studies used a very low dose of the drug. The largest study Dr. DeRubeis identified was his own. In 2005, he conducted a trial in which Paxil did slightly better than psychotherapy and significantly better than a placebo — but apparently much of the drug response occurred in sicker patients.

Building an overview around your own research is problematic. Generally, you use your study to build a hypothesis; you then test the theory on fresh data. Critics questioned other aspects of Dr. DeRubeis’s math. In a re-analysis using fewer assumptions, Dr. DeRubeis found that his core result (less effect for healthier patients) now fell just shy of statistical significance. Overall, the medications looked best for very severe depression and had only slight benefits for mild depression — but this study, looking at weak treatments and intentionally maximized placebo effects, could not quite meet the scientific standard for a firm conclusion. And yet, the publication of the no-washout paper produced a new round of news reports that antidepressants were placebos.

In the end, the much heralded overview analyses look to be editorials with numbers attached. The intent, presumably to right the balance between psychotherapy and medication in the treatment of mild depression, may be admirable, but the data bearing on the question is messy.

As for the news media’s uncritical embrace of debunking studies, my guess, based on regular contact with reporters, is that a number of forces are at work. Misdeeds — from hiding study results to paying off doctors — have made Big Pharma an inviting and, frankly, an appropriate target. (It’s a favorite of Dr. Angell’s.) Antidepressants have something like celebrity status; exposing them makes headlines.

It is hard to locate the judicious stance with regard to antidepressants and moderate mood disorder. In my 1993 book, “Listening to Prozac,” I wrote, “To my mind, psychotherapy remains the single most helpful technology for the treatment of minor depression and anxiety.” In 2003, in “Against Depression,” I highlighted research that suggested antidepressants influence mood only indirectly. It may be that the drugs are “permissive,” removing roadblocks to self-healing.

That model might predict that in truth the drugs would be more effective in severe disorders. If antidepressants act by usefully perturbing a brain that’s “stuck,” then people who retain some natural resilience would see a lesser benefit. That said, the result that the debunking analyses propose remains implausible: antidepressants help in severe depression, depressive subtypes, chronic minor depression, social unease and a range of conditions modeled in mice and monkeys — but uniquely not in isolated episodes of mild depression in humans.

 

BETTER-DESIGNED research may tell us whether there is a point on the continuum of mood disorder where antidepressants cease to work. If I had to put down my marker now — and effectively, as a practitioner, I do — I’d bet that “stuckness” applies all along the line, that when mildly depressed patients respond to medication, more often than not we’re seeing true drug effects. Still, my approach with mild depression is to begin treatments with psychotherapy. I aim to use drugs sparingly. They have side effects, some of them serious. Antidepressants help with strokes, but surveys also show them to predispose to stroke. But if psychotherapy leads to only slow progress, I will recommend adding medicines. With a higher frequency and stronger potency than what we see in the literature, they seem to help.

My own beliefs aside, it is dangerous for the press to hammer away at the theme that antidepressants are placebos. They’re not. To give the impression that they are is to cause needless suffering.

As for my friend, he had made no progress before his neurologists prescribed antidepressants. Since, he has shown a slow return of motor function. As is true with much that we see in clinical medicine, the cause of this change is unknowable. But antidepressants are a reasonable element in the treatment — because they do seem to make the brain more flexible, and they’ve earned their place in the doctor’s satchel.

 

Peter D. Kramer

is a clinical professor of psychiatry at Brown University.

In Defense of Antidepressants,
NYT,
9.7.2011,
http://www.nytimes.com/2011/07/10/
opinion/sunday/10antidepressants.html

 

 

 

 

 

Popular Drugs May Help

Only Severe Depression

 

January 6, 2010
The New York Times
By BENEDICT CAREY

 

Some widely prescribed drugs for depression provide relief in extreme cases but are no more effective than placebo pills for most patients, according to a new analysis released Tuesday.

The findings could help settle a longstanding debate about antidepressants. While the study does not imply that the drugs are worthless for anyone with moderate to serious depression — many such people do seem to benefit — it does provide one likely explanation for the sharp disagreement among experts about the drugs’ overall effectiveness.

Taken together, previous studies have painted a confusing picture. On one hand, industry-supported trials have generally found that the drugs sharply reduce symptoms. On the other, many studies that were not initially published, or were buried, showed no significant benefits compared with placebos.

The new report, appearing in The Journal of the American Medical Association, reviews data from previous trials on two types of drugs and finds that their effectiveness varies according to the severity of the depression being treated.

Previous analyses had found a similar pattern. But the new study is the first to analyze responses from hundreds of people being treated for more moderate symptoms, as are most people who seek care.

“I think the study could dampen enthusiasm for antidepressant medications a bit, and that may be a good thing,” said Dr. Erick H. Turner, a psychiatrist at Oregon Health and Science University. “People’s expectations for the drugs won’t be so high, and doctors won’t be surprised if they’re not curing every patient they see with medications.”

But Dr. Turner added, “The findings shouldn’t dampen expectations so much that people refuse to even try medication.”

A team of researchers, including psychologists who favor talk therapy and doctors who consult widely with drug makers, performed the new analysis, using government grants. The group evaluated six large drug trials, including 728 men and women, about half of them with severe depression and half with more moderate symptoms.

Three of the trials were of Paxil, from GlaxoSmithKline, a so-called S.S.R.I., and the other three were of imipramine, an older generic drug from the class known as tricyclics. The team, led by Jay C. Fournier and Robert J. DeRubeis of the University of Pennsylvania, found that compared with placebos, the drugs caused a much steeper reduction in symptoms of severe depression (cases scoring 25 or higher on a standard scale of severity, putting them in the top quarter of the sample). Patients with scores of less than 25 got little or no added benefit from the medications.

“We were able to give an overall estimate of effectiveness for the first time in this more moderate severity range, from 14 to 20 on the scale, in which there’s no question that doctors would likely consider prescribing medication,” Dr. DeRubeis said.

His co-authors included Steven D. Hollon and Dr. Richard C. Shelton of Vanderbilt University, Sona Dimidjian of the University of Colorado, Dr. Jan Fawcett of the University of New Mexico and Dr. Jay D. Amsterdam of Penn.

The effects of other popular S.S.R.I.’s like Lexapro and Prozac are not likely to be much different than those of Paxil, experts said.

Dr. DeRubeis and others said antidepressants’ inability to outperform placebos against moderate symptoms stemmed partly from the sustained attention that patients in drug trials received from top doctors — which itself can help relieve symptoms, drug or no drug. For some people, too, the drugs’ side effects may cancel any benefit.

“The message for patients with mild to moderate depression,” Dr. DeRubeis said, “is, ‘Look, medications are always an option, but there’s little evidence that they add to other efforts to shake the depression — whether it’s exercise, seeing the doctor, reading about the disorder or going for psychotherapy.’ ”

    Popular Drugs May Help Only Severe Depression, NYT, 6.1.2010,
    http://www.nytimes.com/2010/01/06/health/views/06depress.html

 

 

 

 

 

Mind

Who Are We?

Coming of Age on Antidepressants

 

April 15, 2008

The New York Times

By RICHARD A. FRIEDMAN, M.D.

 

“I’ve grown up on medication,” my patient Julie told me recently. “I don’t have a sense of who I really am without it.”

At 31, she had been on one antidepressant or another nearly continuously since she was 14. There was little question that she had very serious depression and had survived several suicide attempts. In fact, she credited the medication with saving her life.

But now she was raising an equally fundamental question: how the drugs might have affected her psychological development and core identity.

It was not an issue I had seriously considered before. Most of my patients, who are adults, developed their psychiatric problems after they had a pretty clear idea of who they were as individuals. During treatment, most of them could tell me whether they were back to their normal baseline.

Julie could certainly remember what depression felt like, but she could not recall feeling well except during her long treatment with antidepressant medications. And since she had not grown up before getting depressed, she could not gauge the hypothetical effects of antidepressants on her emotional and psychological development.

Her experience is far from unique. Since their emergence in the late 1980s, serotonin reuptake inhibitors like Prozac and Zoloft have become some of the most widely prescribed drugs in the world, for depressed teenagers as well as adults. Because depression is often a chronic, recurring illness, there are certain to be many young people, like Julie, who are coming of age on these newer antidepressants.

We know a lot about the course of untreated depression, probably more than we do about very long-term antidepressant use in this population. We know, for example, that depression in young people is a very serious problem; suicide is the third-leading cause of death in adolescents, not to mention the untold suffering and impaired functioning this disease exacts.

By contrast, the risk of antidepressant treatment is small. A 2004 review by the Food and Drug Administration, analyzing clinical trials of the drugs, did show an elevated risk of suicidal thinking and nonlethal suicide attempts in young people taking antidepressants — 3.5 percent, compared with 1.7 percent of those taking a placebo. But since the lifetime risk of actual suicide in depressed people ranges from 2.2 to 12 percent, risk from treatment is dwarfed by the risks of the disease itself.

Still, what do we know about the effects of, say, 15 to 20 years of antidepressant drug treatment that begins in adolescence or childhood? Not enough.

The reason has to do with the way drugs are tested and approved. To get F.D.A. approval, a drug has to beat a placebo in two randomized clinical trials that typically involve a few hundred subjects who are treated for relatively short periods, usually 4 to 12 weeks.

So drugs are approved based on short-term studies for what turns out to be long-term — often lifelong — use in the world of clinical practice. The longest maintenance study to date of one of the newer antidepressants, Effexor, lasted only two years and showed the drug to be superior to a placebo in preventing relapses of depression.

What do I say to a depressed patient who is doing well after five years on such a drug but can’t stop without a depressive relapse and who wants reassurance that the drug has no long-term adverse effects?

I usually say that we have no evidence that the drug poses a risk with long-term use; and since the risk of untreated depression is much greater than the hypothetical risk of the drug, it makes sense to stay on it.

This large gap in our clinical knowledge is compounded by the public’s growing and well-founded skepticism about research sponsored by drug makers. A study in the January 2008 issue of The New England Journal of Medicine, involving 74 clinical trials with 12 antidepressants, found that 97 percent of positive studies were published, versus 12 percent of negative studies.

Clearly, physicians and the public need much better data on the safety and efficacy of drugs after they hit the market, which at present consists mainly of anecdotes and case reports.

Congress recently reauthorized the Prescription Drug User Fee Act, which will expand the F.D.A.’s post-marketing drug surveillance, though I think it did not go far enough in mandating the use of powerful epidemiological strategies to monitor drugs over the long term.

Beyond these concerns, there are other important issues to consider in long-term use of antidepressants, especially in young people. One patient, a woman in her mid-20s, told me that she felt pressured by her boyfriend to have sex more often than she wanted. “I’ve always had a low sex drive,” she said.

For the past eight years she had been taking Zoloft, which like all the antidepressants in its class is known to lower libido and to interfere with sexual performance. She had understandably mistaken the side effect of the drug for her “normal” sexual desire and was shocked when I explained it: “And I thought it was just me!”

This just underscores how tricky it can be to use psychotropic drugs during adolescence — when the brain is still developing, when one’s identity is still work in progress.

The drugs save lives, and we often have no choice but to use them — even if we have questions about their long-term use. But the questions are big ones, and we owe it to our patients to try to answer them.
 


Richard A. Friedman is a professor of psychiatry
at Weill Cornell Medical College.

Who Are We? Coming of Age on Antidepressants,
NYT,
15.4.2008,
http://www.nytimes.com/2008/04/15/health/15mind.html

 

 

 

 

 

Antidepressant Studies Unpublished

 

January 17, 2008

The New York Times

By BENEDICT CAREY

 

The makers of antidepressants like Prozac and Paxil never published the results of about a third of the drug trials that they conducted to win government approval, misleading doctors and consumers about the drugs’ true effectiveness, a new analysis has found.

In published trials, about 60 percent of people taking the drugs report significant relief from depression, compared with roughly 40 percent of those on placebo pills. But when the less positive, unpublished trials are included, the advantage shrinks: the drugs outperform placebos, but by a modest margin, concludes the new report, which appears Thursday in The New England Journal of Medicine.

Previous research had found a similar bias toward reporting positive results for a variety of medications; and many researchers have questioned the reported effectiveness of antidepressants. But the new analysis, reviewing data from 74 trials involving 12 drugs, is the most thorough to date. And it documents a large difference: while 94 percent of the positive studies found their way into print, just 14 percent of those with disappointing or uncertain results did.

The finding is likely to inflame a continuing debate about how drug trial data is reported. In 2004, after revelations that negative findings from antidepressant trials had not been published, a group of leading journals agreed to stop publishing clinical trials that were not registered in a public database. Trade groups representing the world’s largest drug makers announced that members’ companies would begin to release more data from trials more quickly, on their own database, clinicalstudyresults.org.

And last year, Congress passed legislation that expanded the type of trials and the depth of information that must be submitted to clinicaltrials.gov, a public database operated by the National Library of Medicine. The Food and Drug Administration’s Web site provides limited access to recent reviews of drug trials, but critics say it is very hard to navigate.

“This is a very important study for two reasons,” said Dr. Jeffrey M. Drazen, editor in chief of The New England Journal. “One is that when you prescribe drugs, you want to make sure you’re working with best data possible; you wouldn’t buy a stock if you only knew a third of the truth about it.”

Second, Dr. Drazen continued, “we need to show respect for the people who enter a trial.”

“They take some risk to be in the trial, and then the drug company hides the data?” he asked. “That kind of thing gets us pretty passionate about this issue.”

Alan Goldhammer, deputy vice president for regulatory affairs at the Pharmaceutical Research and Manufacturers of America, said the new study neglected to mention that industry and government had already taken steps to make clinical trial information more transparent. “This is all based on data from before 2004, and since then we’ve put to rest the myth that companies have anything to hide,” he said.

In the study, a team of researchers identified all antidepressant trials submitted to the Food and Drug Administration to win approval from 1987 to 2004. The studies involved 12,564 adult patients testing drugs like Prozac from Eli Lilly, Zoloft from Pfizer and Effexor from Wyeth.

The researchers obtained unpublished data on the more recently approved drugs from the F.D.A.’s Web site. For older drugs, they tracked down hard copies of unpublished studies through colleagues, or using the Freedom of Information Act. They checked all of these studies against databases of published research, and also wrote to the companies that conducted the studies to ask if specific trials had been published.

They found that 37 of 38 trials that the F.D.A. viewed as having positive results were published in journals. The agency viewed as failed or unconvincing 36 other trials, of which 14 made it into journals.

But 11 of those 14 journal articles “conveyed a positive outcome” that was not justified by the underlying F.D.A. review, said the new study’s lead author, Dr. Erick H. Turner, a psychiatrist and former F.D.A. reviewer who now works at Oregon Health and Sciences University and the Portland Veterans Affairs Medical Center. His co-authors included researchers at Kent State University and the University of California, Riverside.

Dr. Turner said the selective reporting of favorable studies sets up patients for disappointment. “The bottom line for people considering an antidepressant, I think, is that they should be more circumspect about taking it,” he said, “and not be so shocked if it doesn’t work the first time and think something’s wrong with them.”

For doctors, he said, “They end up asking, ‘How come these drugs seem to work so well in all these studies, and I’m not getting that response?’ ”

Dr. Thomas P. Laughren, director of the division of psychiatry products at the F.D.A., said the agency had long been aware that favorable studies of drugs were more likely to be published.

“It’s a problem we’ve been struggling with for years,” he said in an interview. “I have no problem with full access to all trial data; the question for us is how do you fit it all on a package insert,” the information that accompanies many drugs.

Dr. Donald F. Klein, an emeritus professor of psychiatry at Columbia, said drug makers were not the only ones who can be reluctant to publish unconvincing results. Journals, and study authors, too, may drop studies that are underwhelming.

“If it’s your private data, and you don’t like how it came out, well, we shouldn’t be surprised that some doctors don’t submit those studies,” he said.

Antidepressant Studies Unpublished,
NYT,
17.1.2008,
http://www.nytimes.com/2008/01/17/health/17depress.html

 

 

 

 

 

 

 

 

 

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