Some People With Depression Actually Do Worse With Medication, Study Finds

By Genevra Pittman

NEW YORK (Reuters Health) - According to a new look at past antidepressant trials, up to a fifth of patients on Cymbalta and similar medications may actually do worse than those given drug-free placebo pills.

Researchers found that patients' symptoms over the first couple months of antidepressant use separated them into "responders," who got progressively better, and "non-responders," who didn't improve with treatment but may still have suffered side effects.

However, "It's difficult to say a priori who will be in which group," Ralitza Gueorguieva, the study's lead author from the Yale University School of Medicine in New Haven, told Reuters Health.

The findings highlight the importance of identifying as soon as possible which patients will and won't respond to certain drugs, her team said.

The researchers combined data from seven studies that randomly assigned patients to receive Eli Lilly's drug Cymbalta (known generically as duloxetine), other antidepressants, or a placebo pill for two months. Those trials involved a total of about 2,500 people with major depression.

People getting the placebo tended to report small, gradual improvements in depression symptoms. On the other hand, those on Cymbalta or another antidepressant fell into one of two categories: most had steeper, steady improvements in depression symptoms, but a sizeable chunk didn't seem to get any better.

About four in five patients on all antidepressants were responders. For Cymbalta in particular, about 84 percent of patients improved and 16 percent did not.

Medication responders saw significantly bigger improvements in their depression symptoms than patients assigned to the placebo. Non-responders, however, did worse.

Differences between antidepressant responders and non-responders were seen as early as a week or two into treatment, and the researchers wrote in their Archives of General Psychiatry report that initial improvements seem to predict who will have a better outcome on Cymbalta, along with the other drugs.

"You know within the first couple weeks of starting a treatment who's the most likely to benefit because they're already starting to show improvement," said Dr. Michael Thase, a psychiatrist from the University of Pennsylvania Perelman School of Medicine who wasn't involved in the new study.

"The first few weeks are revealing, and obviously if the patient's getting worse instead of better, I would use that as a strong indicator that this particular treatment isn't likely to work," he told Reuters Health.

"I think this finding holds true for the antidepressants that are most commonly used today," he said of the gap between responders and non-responders.

Thase pointed out that side effects of antidepressants, such as stomach problems and poor sleep, could make some patients score lower on measures of depression -- perhaps explaining the worse symptoms seen in non-responders compared to placebo patients.

He added that if patients don't benefit from a first antidepressant, they could still respond to a different type of drug, although the chances fall with each successive treatment attempt.

Another scientist said the latest research has been trying to pick out certain patient characteristics -- genetics or specific depression and anxiety symptoms, for instance -- that could help determine who will end up in the responder category, and who won't see any benefit from individual drugs.

"If you can identify people who would be potential responders to a particular medication...it would be a great, huge advantage for the field," said C. Hendricks Brown, who has studied depression treatments at the University of Miami Miller School of Medicine, but wasn't linked to the new research.

Gueorguieva agreed. "Identifying variables that are associated with response is a very important question that we haven't quite tackled," she said.

One of the study's authors is an employee of Eli Lilly and another is on the company's scientific advisory board.

SOURCE: http://bit.ly/uFgdie Archives of General Psychiatry, online December 5, 2011.

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Comments

[RedDog79]

10:44 AM on 12/14/2011

duh. when the warning labels on these medications cause more problems then they help. why take them.

[eskeeemo]

02:51 PM on 12/12/2011

I suffered depression a while back and, thankfully, I had a doctor who wasn't quick to push drug-treatment on me. She gave me one month of Xanax, to combate the anxiety I was having at night, and to help me catch up on my sleep (amazing how catching up on my rest was the biggest step forward in fighting the depression!). She, also, suggested that I see a phsychiatrist to get to the root of what was causing me the anxiety and the depression. She said that if I wasn't feeling any better at the end of the month, that we could then talk about drug methods. I took her advice and never did need the drugs. Honestly, they scared me more than the anxiety did. To this day, I do get occasional bouts of anxiety and mild depression, but I learned tools to cope. I wonder how many people who suffer depression and/or anxiety are given drug free options first.

[Doobydoobs]

10:41 AM on 12/12/2011

The pharmaceutical companies are desperate to minimise and exclude placebo effects as much as they possibly can, by hook or crook, because antidepressants so often don't show any real benefit over them. The middle author, a drug company man, appears to have done prior stuff on improving 'signal detection'.

They appear to be trying to pave the way for a methodology whereby those who don't respond to the medication can be routinely excluded from the main comparison with placebo. That comparison is then more likely to show a "significant" (STATISTICALLY) difference in favour of the antidepressant (and that's already based on an average, which may itself hide that some large percentage of responders didn't actually respond any better than those on placebo - in fact maybe only a minority did, maybe a sort of opposite 1/5 to the group who got worse).

That's in addition to the usual issue here - they don't give any indication in the journal abstract as to the effect size, which is what indicates whether the difference over placebo is PRACTICALLY SIGNIFICANT, which is the crucial thing. And all of this is just about effects over a few months, so it says nothing about whether there's any real long-term benefit of course.

[ThinkCreeps]

05:09 AM on 12/12/2011

"Writer fails to understand statistics shock"

[chiara0]

04:40 AM on 12/12/2011

Well that's a big Duh. Many drugs have a combination of side effects that are the very same symptoms for which they supposedly alleviate.

[farmilyman]

04:19 AM on 12/12/2011

It's probably because the testing on mice was for anxiety.....not depression.

[MissMiniMonster]

12:26 AM on 12/12/2011

This doesn't shock me at all. I worked at a state-funded outpatient mental health clinic for a while and a lot of the clients I saw seemed to get worse as the psychiatrist messed around with different medications trying to find the right one that would make any difference. We tend to overmedicate without treating some of the underlying causes (life situations, etc) and I'm glad to see that this is finally starting to be acknowledged. I once quit going to a doctor when she wanted to put me on depression meds after my father died instead of referring me to a grief counselor.

[WoodsideCraig]

12:12 AM on 12/12/2011

So if I read this right you can skip the drugs and their awful side effects and still get better. That seems like a better option.

I don't trust drug companies.

[eskeeemo]

02:54 PM on 12/12/2011

It's true! I did! I briefly took anti-anxiety medicine to help me get the sleep I was missing due to the depression and anxiety, but other than that, I jsut saw a shrink who helped me get to the root of what was bugging me, and then taught me how to cope. Those drugs scare me and every time I se the ads that rattle off longer and longer lists of nasty side effects, I wonder which is worse - the depression or the drugs to fight the depression?!

[AnnainLA]

06:49 PM on 12/11/2011

A few days ago , Tyler Brehm shot at people at the Hollywood and Sunset intersection . His girlfriend says that he had just started taking pyshciatric drugs. If he hadn't taken these drugs, he might still be alive and people would not have been terrorized .

[AnnainLA]

05:57 PM on 12/11/2011

Antidepressant trials arer never really double blind because the drugs cause so many side effects that all of the patients know whether they are taking the placebo or the drug. Properly analyzed tests of antidepressants show them to be ineffective in the short run and damaging in the long run. The tests of antidepressants are paid for by the drug company that manufactured the drugs and they often conduct many , many trials until two show an effect however minor or unrelated to depression . For example , some drugs win approval because they increase sleep or appetite or something unrelated to decrease in feelings of sadness. Hundreds of billions of dollars are made by drug companies so they will do anything to spin their worthless products.

www.antidepressantsfacts.com/pinealstory.htm
Before you take psychiatric drugs, you should read books by Peter bregin MD , Marcia Angell MD, Joseph Glenmullen MD and others.

Most antidepressants trials only last a few weeks, far too short a time for the most serious side effects such as tardive dyskinesia, akathesia, epilepsy, dystonia, diabetes etc to appear

[pinetrale]

10:28 PM on 12/11/2011

If your talking strictly antidepressanst and not antipsychotics you really shouldn't be getting those kinds of side effects. The newer antidepressants are only about 10% more effective than the older ones, going from 70%-80% efficacy. There is a lot of debate weather the atypical antipsychotics actually should be given approval as antidepressants, maybe as adjuncts to one, but not the main one. I agree with the poster who says going to a psychologist weekly, whether it be CBT or traditional talking therapy is a good idea when starting a new antidepressant so they can evaluate how your doing rather than wait a month or three to see the prescribing psychiatrist. Maybe the shooter was starting one, apparently given to him by a pharmaceutical person? what ever that means. Bad medicine there. Still someone has to be awfully mean to act out such impulses on innocent drivers like that so something was really wrong with that guys personality and soul to do that. That was more than just drugs. Hopefully, if one can find a good psychopharmacologist, a psychiatrist who specializes in medications for depression, anxiety, bipolar, schizophrenia, they can make a more accurate diagnosis and pick the right treatment. Its still trial and error, so yes, weekly followup is the right way to go (HMO's). Also proper diet and sleep and regular exercise are some of the cheapest simplest medicines to add in.

[wrobbins]

04:20 AM on 12/12/2011

For the most common type of antidepressant, the SSRIs, all of the side effects you've listed are extraordinarily rare.

[AnnainLA]

02:43 PM on 01/03/2012

Dr Kessler , former head of the FDA admits that reporting of side effects is about obne percent. Trials on new antidepresssants usually are domne for a few weeks , too short a time for these effects to occur.
When people have symptoms of neurological damage , they typically don't make the connection between their symptoms and the psychiatric drugs they are taking and doctors never admit( and are often unaware) that their patient's symptoms are caused by psychiatric drugs.
Newsweek did a story on what they called "conversion hysteria" and said that several million people in the US have it . The symptoms are suspiciously like the side effects of antiodepressants but Newsweek never made the connection.

[Antonio Robinson]

05:00 PM on 12/11/2011

not bad

[madcityy]

03:06 PM on 12/11/2011

THIS IS ALARMINGGGGGGGGGGGGGGGGGGGGGGGGGGGG

GET OFF THESE TYPE DRUGSSSSSSSSSSSSSSSSSSSSSSSSSS

[John Di Saia]

12:15 PM on 12/11/2011

Is this really all that surprising? Medication doesn't fix everything.

[eskeeemo]

02:56 PM on 12/12/2011

Medication should go hand in hand with other treatments. It seems that people tend to rely solely on the meds and never get to the root of their depression.

[missy40mouse]

12:28 PM on 12/14/2011

I know that there are those who suffer from depression where the depression IS NOT based on circumstances. Something is just wrong with their brains. In those cases, there is not a "root" (like having marriage troubles, etc.) that can be fixed.

[Jeanne Ball]

09:45 AM on 12/11/2011

Many people who come to learn meditation these days are suffering from either depression or anxiety, and looking for an alternative to taking drugs. Not all meditation practices effect these disorders, but research has found that some do reduce depression and anxiety significantly. Check out this study http://psychcentral.com/news/2010/04/08/transcendental-meditation-for-depression/12685.html

[DrB516]

09:17 AM on 12/10/2011

It is noteworthy that Cognitive Behavioral Therapy (CBT) has been found to be as effective as medication for treating depression. As a psychologist for over 34 years I have not been against the use of medication for depression or other mental health conditions. For some people, with some conditions, it may help. However, most psychotropic medications are meant to be a "temporary" aid, not the "Magic Pill" that makes problems disappear forever. Using medication may temporarily benefit people who also get psychotherapy. Using medication alone rarely works, because if your life's situation doesn't change, when you stop taking the medication, the symptoms return. Since many people get depressed during the holidays, prepare yourself for dealing with the holiday by checking out my free article called, "A Psychological Christmas Present" at http://jamesbarrickphd.com/APsychologicalChristmasPresent.en.html

[DrB516]

09:23 AM on 12/10/2011

Sorry for the mistake. It's DrJ516. My apologies.