Sugar pills, antidepressants, and the miracle of the human brain

[drwex]

Chasing other links I stumbled across this:

As a proportion of the drug response, the placebo response was constant across different types of [antidepressant] medication (75%), and the correlation between placebo effect and drug effect was .90. [...] These data raise the possibility that the apparent drug effect (25% of the drug response) is actually an active placebo effect.

In English: it's possible that all reported effects of antidepressant medication are placebo effects. It's quite likely that 75% of reported effects are placebo.

More recently, these authors replicated the work using studies from the FDA database. FDA studies are done as part of drug approval processes. They're generally not published in refereed literature and there have been accusations that they're slanted in favor of the drugs. That is, the studies are done in order to speed drugs through the approval process and may overreport positive effects and underreport negatives. So in theory you'd see a larger effect for ADs if you analyzed these studies. In fact:

Kirsch et al. reported an 18% difference between drug and placebo.

The debate is actually fairly nuanced. There's been some good work recently looking (via MRI) at the neurochemical mechanisms triggered by placebos. There is some evidence that the difference between AD and placebo increases with the severity of depression, though that might be due to differences between active and inert placebos - people with serious depression are often familiar with the side effects of ADs and can recognize when given a sugar pill that doesn't have the expected side effects.

Nobody's claiming that ADs don't work. The claim is that they do work... and sugar pills work, too.

Title: "Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication."
Authors: Kirsch, Irving; Sapirstein, Guy
Publication: Prevention & Treatment. 1(1), Jun 1998
<http://content.apa.org/journals/pre/1/1/2>

Title: "The emperor's new drugs: An analysis of antidepressant medication data submitted
 to the U.S. Food and Drug Administration."
Authors: Kirsch, I., Moore, T. J., Scoboria, A., & Nicholls, S. S.
Publication: Prevention & Treatment, 5, art. 23
<http://journals.apa.org/prevention/volume5/pre0050023a.html>

Comments

[hlmt.livejournal.com]

Well, I don't think you should be surprised at ppl being mad, since your plain English -seems- to lead to the corollary that 75%, and possibly 100%, of mental illness (or at least mental illness that is relieved by the use of antidepressants) is (pun aside) in the users' head.

I'm sure you can see why that would piss someone off. =)

[drwex]

As I said, I didn't write these studies. I did translate the abstract, but that is in fact what the abstract says. People may take offense at "placebo effect" but that's what it is. What the studies show is that if you give people with mild to moderate depression a non-AD (placebo) you get effective treatment, just as if you'd given them an AD.

I can't stop people thinking "placebo effect" means "is in your head" because... well that's what it DOES mean. It doesn't mean you're a fool or dupe. If people want to get offended over their own implications associated with the phrase I can't stop that either.

As I said, there's starting to be MRI work tracing the neurochemical bases for placebo effects. I found a reference to Mayberg's article titled The functional neuroanatomy of the placebo effect but you might not want to read that because, among other things, she found that there were some significant similarities in brain chemistry changes between placebo and SSRI groups. There were also significant differences. What we don't know is whether one matters more than the other.

[ariesd.livejournal.com]

What the studies show is that if you give people with mild to moderate depression a non-AD (placebo) you get effective treatment, just as if you'd given them an AD.
That is B.S. personally. You can pretty much change your diet in any way, eat all fat, eat all carbs, eat all protein, etc and you will lose weight for a short period of time.

How long did these studies go on for?

Most researchers with a clue would I hope know that AD and CBT work is a long term approach, not something that is over in the span of a month or what could be tested for in a trial of this type.

I think this is bad science in general. SSRI's and eating Carbohydrates will do the same thing. SO sugar pills don't surprise me. Hell if you know what an SSRI does you will know there are many ways to achieve that effect w/o the pill.

Sorry, this is a bad study, I would like to see it researched for a much longer period of time and on drugs and I think actual lying to some and telling them they are getting a placebo when they are not would be extremely valuable to see if the efficacy is impacted.

[drwex]

How long did these studies go on for?

The study periods I saw were six weeks and six months. I believe that under six weeks you may not get the full effect of an AD. Can't say why the six month period was picked.

what could be tested for in a trial of this type.

That was one of the reasons for replicating the work with the FDA database. If you wish to say (as the Feds do) that the FDA study criteria are sufficient to establish the safety and effectiveness of a drug that is to be prescribed to patients then it's a very strange claim to then say "well those studies are no good."

That said, you're not the first one to say this. Certainly there's a body of objection to Kirsch that says "if you measure in a properly constructed study you do see significant differences." Fair enough, but then the onus is on the claimant both to state what a proper study would be and to say why a study is sufficient to get a drug approved and onto the market but somehow is not sufficient to distinguish its effect from a placebo effect.

actual lying to some and telling them they are getting a placebo when they are not would be extremely valuable to see if the efficacy is impacted.

There are two problems with that. One, as I mentioned earlier, is that you have a very hard time getting approval for a study protocol that bald-faced lies to people. You can mislead or conceal, but lying it pretty much right out because it destroys informed consent. Two, it messed with the notion of double-blind. The point is that not only does the patient not know what pill they're getting, the administering person doesn't know either. That removes effect and observational biases. (Or at least reduces them; again, see the discussion of active vs inert placebos.)

[sweetmmeblue.livejournal.com]

> I would like to see it researched for a much longer period of time and on drugs and I think actual lying to some and telling them they are getting a placebo when they are not would be extremely valuable to see if the efficacy is impacted.

But that can't be done. Not with the ethical considerations. There was a big tadoo after the Tuskeegee trials and others of the 60's and 70's where peole were lied to, harmed and in some cases, allowed to die in the name of research.

As for the long term vs short term, with mild to moderate depression there is a long term benefit even with plecbos. In my work, once a client has called to make an appointment there is always a lift in some of the depression. It's called the "hope effect". What happens is that once a person knows they are going to get help they relax a bit, find more strangth cause help is about to be there, find more cope and remember coping mechanisms. One of the things I always do with new clients is ask them how much better things got from the time they made the hone call to the time they came in. Same numbers as the plecebo trials, about 75% say things got noticebly better. I then talk to them about what they did and what made them better. 10% of those where things got better don't stay in therapy long or, when it comes time for the first appointment, don't show because they no longer need the help.

The 25 where things don't get better usually need something more than just hope. Many of those benifit from some chemical assistance because the combination of therapy (and it may not be CBT) and drugs is much more useful to that group than any other and better than drugs alone.

I read studies like these when I was in school as a way of keeping in mind that drugs are over-used and over-emphasised and a person's strengths were downplayed.

All that said... are anti-depressants and other drugs useful? Yes, when used correctly. The person who trained me on anti-depressants said there are 3 kinds of people that benifit from the drugs. 1) use for a year and get off them to set the chemical balance back on track. 2) may use short term every so often (4-6 months) across a life time. 3) on them all the time becasue the chemicals in the brain need that extra help. She also said that accounted for about 40% of the people being prescribed anti-depressants. The other 60% may not need them for as long as they are being given them, were given them by laze doctors and therapists, may have asked for them and think they need a magic fix pill, may be addictted to them, may have fogotten how to cope off of them and are uninterested in learning....

Everyone is different. Studies are not designed to account for the individual. Studies are designed to try and put everyone into boxes. As with all things YMMV. That does not make the study any less valuable to the mental health community in general. It may just make it less valuable to you.

[ariesd.livejournal.com]

yes but Tuskeegee was purposefully to harm patients and observed the results.

In a study people know they may or may not get a placebo. All I am saying is tell the group that is getting the placebo they are getting the real drug and vs versa. See if that knowledge actually skews the results.

I think we are always surprised when the placebo works because it is just that a placebo. I'm curious if the drug wouldn't work if they thought they weren't getting it. The reverse of the placebo effect.