Peter Kramer is an American psychiatrist specializing in depression, and author of the best-selling book Listening to Prozac. In a long op-ed piece in Sunday’s New York Times “In defense of antidepressants,” Kramer argues that recent attacks in the press on the efficacy of antidepressants (particularly Marcia Angell’s scathing two-part critique of medical psychiatry in the New York Review of Books here and here), are misguided and may be inimical to the treatment of depression. (I’ve discussed my take on Angell’s review on this website.) Kramer’s thesis is this:
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.
I’ve been working my way through the books Angell reviewed, particularly Irving Kirsch’s The Emperor’s New Drugs: Exploding the Antidepressant Myth, to see how much of Angell’s critique was accurate (I’ve also been looking at the primary literature on antidepressants). I don’t claim to have anywhere near Kramer or Angell’s knowledge about antidepressants, and so take this analysis of Kramer’s article in the same way I read Angell’s critique: as one seen through the eyes of a scientist who has a better-than-average knowledge of the literature on depression and antidepressants.
Nevertheless, I found Kramer’s piece, well, depressing: scattered, lacking cohesion, hard to follow, and even a bit misleading. He’s not all gung-ho on antidepressants, but anyone who reads his editorial should also read Kirsch’s book, for Kramer makes several arguments that were already addressed by Kirsch, and neglects some of Kirsch’s important points, like the difference between “active” and “inert” placebos.
Here are what I see as Kramer’s main arguments:
- Some studies show that antidepressants work. He quotes an article which appears to come from Lancet Neurology (Chollet et al. 2011 10:123-130) showing that fluoxetine (the generic name for Prozac) helped significantly improve motor function in French stroke patients.
I have read the original study, which was done in a double-blind trial with placebos, and involved 118 patients. All patients were also given psychotherapy. The study did indeed show a significant drug-induced improvement in motor function over the three months of the study. My quibbles with this analysis are threefold:
1. It did not measure long-term improvement.
2. It did not test whether or not the drug (an SSRI, or “selective serotonin reuptake inhibitor”) had any effect on mental functions, so we don’t know whether its effects—and I don’t deny it had them—involved alleviating depression, making the patients thereby more responsive to treatment, or acting more directly on motor function itself (after all, SSRIs affect neurotransmitters). Thus, the reader might be misled when Kramer follows the description of this study with the statement, “Antidepressants are good at treating post-stroke depression and good at preventing it.” That may be the result of other studies (he doesn’t mention any), but certainly not from the one he describes. It’s also possible that the recovery of motor function itself (and not the drug’s effect on the brain) is what makes the patients less depressed.
3. The placebos were probably not “active” placebos, i.e., those placebos that have side effects, but rather “inert” placebos—those with no side effects, like sugar pills. I suspect that the placebos in this study weren’t active simply because they are not described as active.
Kirsch has made the important point that the “effects” of antidepressants in double-blind trials (which are much smaller than most people assume, often neither statistically nor clinically significant) might well stem from patients’ perception that they are indeed taking the real drug because they experience the common side effects of antidepressants. Inert placebos have no side effects. In other words, when a patient perceives side effects, he concludes that he’s getting a drug that might be efficacious, and improves via an “enhanced placebo effect.”
It’s already well known, and nobody denies, that purely inert placebos, without side effects, themselves have a huge effect in alleviating depression—the famous “placebo effect”. In fact, the “beneficial” effects of antidepressants are usually much smaller than the placebo effect. But when one uses “active” placebos, with side effects, the true drug effect often disappears.
Kirsch argues, then, that inert placebos without side effects are simply not the right controls in studies of depression, since perception of physiological effects enables patients to “break the blind,” and conclude that they’re in the “drug” group rather than the control. Any improvement could occur simply because patients have sussed out that they’re getting treatment.
This is not just speculation, but is supported by several pieces of evidence, including a significantly higher rate of”drug-induced” improvement in studies where all patients get drugs compared to patients who get drugs in placebo studies: the only difference between the two studies is that patients in the first type know they’re getting an antidepressant, and presumably experience side effects. There’s also a huge correlation (0.96 for Prozac!) between the severity of side effects of an antidepressant and alleviation of depression (this is not proof of the ‘side effect’ hypothesis, but supports it). Further, when the placebos are “active”—when they’re substances like atropine that have side effects but aren’t used to treat depression—the difference in improvement caused by antidepressant versus placebo is much smaller (Kirsch reports that only two of nine studies using active placebos showed a significant effect of the drug in alleviating depression.) Kirsch cites other data as well; you can find it on pp. 15-21 of his book.
Kramer also cites another study which, he claims, shows that “elderly female cardiac patients who had emergency operations and were given antidepressants experienced less depression, shorter hospital stays, and fewer deaths in the hospital.” I’ve read that study (Hata et al. Surgery Today 41: pp. 791-794), and as far as I can see, it used no placebos at all. Here’s the relevant line from the methods:
We divided the patients into two groups: group I consisted of 58 patients who had undergone surgery from January 2006 and were prophylactically prescribed 10 mg paroxetine as an SSRI from the first or second postoperative day; group II comprised 59 previous patients who had undergone surgery before December 2005 and had not been administered an SSRI after surgery.
The word “placebo” does not appear in the report, either.
If no placebos were given, not even inert ones (and we already know that inert placebos themselves improve depression far more than no drug at all, with the drug effect being substantially smaller than the placebo effect), then one can’t conclude anything from this study about the effects of the drug. It could all be placebo effect.
It can’t be emphasized strongly enough that double-blind trials (preferably with active placebos) are far better than plain clinical observation in determining whether a drug is efficacious, for the effects of placebos on alleviating depression are strong and well documented. If a doctor gives a patient an antidepressant and she improves, we have no idea whether she’s responding to the drug, to perceiving the drug’s side effects that makes her think it’s “working”, or simply to the fact that she’s being treated by a professional and taking a pill. The testimony of doctors that their patients “appear to improve” when they take an antidepressant are worthless—and by “worthless” I mean they don’t say anything about whether the drug per se is alleviating depression. It’s clear that many doctors do see their patients improve when given antidepressants. And lots of people taking antidepressants have reported improvement (many on my previous thread). Those patients might have felt just as much better had they been taking placeobs.
Given the side effects of antidepressants, and any possible long-term effects on the brain, doctors might start treatment by giving patients placebos, which will often cause big improvement. Unfortunately, I don’t think doctors are allowed to prescribe placebos—and you’d have to hide that fact from the patient, which could be considered unethical.
- The studies on mild depression submitted to the FDA by the drug companies were inadequate and flawed.
Kramer pinpoints several flaws: “quick and sloppy trials” (it seems to me, though, that if a drug really works, then “quick and sloppy trials” would be less likely to demonstrate a drug effect), the fact that patients may exaggerate their initial symptoms to get into a drug study, and the fact that some “patients” might not have been depressed at all, and that these of course wouldn’t show a drug effect.
Kramer might be right here, but I find this an odd criticism. After all, the studies he’s citing were the ones used by the FDA (American Food and Drug Administration) to show that the drugs worked and to support the drugs’ approval. If those studies were flawed, then we shouldn’t be using those drugs at all!
- Other types of studies—not the traditional “double blind” ones—also show positive effects of antidepressants. Here’s Kramer’s description of one type of study:
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.
Unless those placebos are active placebos, the studies are subject to the caveat that the patient’s perception of side effects, not the effects of the drug itself, is an important part of improvement. If the side effects go away because the placebo is inert, the patient may well relapse because of the absence of side effects. Also, the withdrawal of antidepressants often causes pronounced and distressing physical symptoms which could easily make a patient more depressed.
- The news media uncritically focus on studies showing that antidepressants are ineffective. Kramer says:
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. . .
. . . 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.
I’m glad Kramer agrees about the nefarious acts committed by Big Pharma with regard to antidepressants. (I’ve mentioned one of them in my earlier piece: drug companies often don’t submit the trials that don’t work to the FDA. They need submit only two “successful” trials of a drug for approval; and to get those they could conduct as many as they wanted—and keep them secret and unpublished— before you come up with the requisite two.). Too, Kirsch notes that drug companies publish the successful studies in medical journals far, far more often than they do the unsuccessful ones, giving physicians who read journals a biased view of the drugs’ efficacy.
But I think the news media glom onto this story not just because the drugs have celebrity status, but because so many Americans are taking them (antidepressants are the drugs prescribed most often in the U.S.). If you’re not taking them yourself, I bet you know someone who is. And so any questions about their efficacy will naturally be of interest to many people. And I do think the evidence for their efficacy is thin—certainly thinner than most Americans think. Given the huge placebo effects involved in treating depression, the testimony of clinicians that the drugs “work” on their patients seems to me largely worthless. Certainly most of the effects of antidepressants appear to come from the placebo effect accompanying being given a drug, so it’s not quite kosher for Kramer to assert that “antidepressants are not placebos.”
We need to know—and the drug companies and regulatory agencies have not been overly forthcoming about this—whether or not antidepressants work and, just as important, how well and how often they work. That is what the press, and critics like Kirsch, are good for. To say that the press’s digging into the science “causes needless suffering” is not only an unjustified threat, but a red herring—and a dangerous one itself. It was that sort of digging that exposed the problems with the drugs and with Big Pharma.
Kramer broaches his own theory of depression, which comes from his 2003 book Against Depression:
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.
I haven’t read his book, but his summary above doesn’t make much sense to me. And, at any rate, Kirsch argues (with evidence supporting him) that the effects of antidepressants aren’t really greater in more serious cases, but that the effects of the placebo controls are smaller. That makes the drug-placebo difference (the drug’s “effect”) look larger in cases of more severe depression.
In the end, Kramer does take a more judicious stance. He initially treats depressive patients with psychotherapy and says “I am to use drugs sparingly. They have side effects, some of them serious.” Indeed, for the side effects of psychotherapy are nil.
I’d recommend reading Kirsch’s book, which is not a tirade but a popular presentation of evidence, with lots of citations and references. You can check the data yourself (and I’ll be continuing to do so). If he’s right, then we almost need to go back to square one in assessing the value of antidepressants. That won’t happen, of course, because those drugs are already approved, Big Pharma makes billions of dollars from them, and doctors see that they “work”. But the placebo effect is powerful, and perhaps something should be done about harnessing that as well. After all, taking placebos, at least inert ones, won’t cause you long-term damage.
In fact, the “beneficial” effects of antidepressants are usually much smaller than the placebo effect.
To me, this is really the crux of the matter. If you’ve got loads of conflicting experimental studies – to the point where even different meta-analyses disagree – then the one conclusion you can draw is: if there’s an effect, it’s small. Small enough that experimental noise is a major issue.
And if the benefit is small, you probably shouldn’t be procscribing it a lot. Maybe in some cases, but not to the extent that (IMO) Americans take them.
I agree about how the placebo effect can mask psychological drug effectiveness.
Taking placebos won’t cause long term damage!? Because if the patient kills himself, that’s not damage. And what are these side effects everyone keeps talking about? I’ve been on antidepressants for around 15 years and the only side effects I ever experienced were obviously not part of the beneficial aspect of the drug. What a load of bull this all is. Psychotherapy is a money making scam in the same vein as religion. Mental health care in this country is a joke as it is so let’s try and remove the one thing that actually helps the mentally ill. If you want to fix something perhaps you could work to make mental health care more accessable and do something to help get homeless mentally ill people off the streets. Of course then you would deny them drugs and put them into psychotherapy. In other words, not help them at all.
Did you try psychotherapy? I presume that if you did, it was not effective.
It’s good that the medication is helping.
Interesting question. I was unaware it was possible to take antidepressants without talk therapy. Who would diagnose the problem and monitor the drug’s effectiveness?
I think (I’m not sure about this) that the majority of prescriptions for antidepressants are written not by psychiatrists but by internists and GPs. They might suggest talk therapy, but they can’t mandate it. And these days many psychiatrists—the only therapists allowed to prescribe drugs—don’t engage in talk therapy themselves.
Short answer, yes, it’s eminently possible to take drugs without talk therapy, and I’m sure millions of people do. Talk therapy is expensive and time-consuming!
Not to mention the millions upon millions upon millions of prescriptions written for these drugs for off-label purposes.
A friend of mine recently asked my advice with regard to his medications because he was having unacceptable side effects. The only medication I saw that was a potential problem was Sertraline (another Prozac wanna-be), which was not being prescribed for depression, but for sleep.
He’s off it now and feeling better.
And don’t get me started on Lilly’s new antidepressant, Cymbalta. Quite possibly the “dirtiest” drug I’ve ever seen sail through the approval process.
My son is on Sertraline, he seemed to cheer up a bit but it could easily have been the placebo effect. He is also seeing a psychiatrist but I do wonder whether he should be taking those pills. I took one dose of it myself once, but I felt so ill I would never do it again. I was completely out of action for a couple of days with waves of nausea running up my entire body, it was hideous. It is so hard to know what to do.
Actually, please do get started about Cymbalta. I’m very much interested in your take on the drug. I was prescribed a low dose (3mg/25mg combo)and while it did help me sleep my waking hours were, let us say, less than satisfying (if they could indeed be termed waking hours).
The rules keep changing. In my case, I saw my GP with the problem. He referred me to “the only psychotherapist I trust” who had me see a psychiatrist for the antidepressant prescription who bid me good fortune on my return to my therapist. All three monitored my situation and slowly weaned me from the antidepressants (which were prescribed as, hopefully, a temporary fix. As the talk therapy did its work the Prozac was discontinued. The end result was a repeat of the final therapy session in Good Will Hunting.
If you have not ‘enjoyed’ the fruits of clinical depression I cannot describe the sensation or lack thereof. If you have I’m willing to bet your experience is unlike most, maybe every, other.
I was fortunate. Those in my family who committed suicide quickly or with drink were not. They, to a man (no women) scoffed at any suggestion they had a problem.
have you tried positive affirmations?
i used thinkrightnow.com and their programs to help myself get out of the longest and most difficult depression in my life after failure of my first marriage (i was thinking of killing myself then)
depression is best cured through communication and “tricking” the mind into believing what it seems “refusing to believe”
you are the best doctor to yourself because only you can know your mind best and what medium and “substance” can make your mnind to go “positive” instead of “negative”
once i recovered from the most difficult depression of my life i learned that i should have a certan “mental higeine” and not allow my mind (that is prone to depression) to come “near” it
i am now a “learned optimist” and have mastered a technique of “positive spin” – i constantly look and highlight “positive” side of otherwise “neutral” existance
OK, my knowledge of depression is pretty limited, but I think mild depression is often self-treatable in all sorts of ways. I manage my occasional minor depression(s) with exercise and self-analysis.
For severe/major depression, one needs professional help: drugs, talk therapy, or both. It is dangerous stuff that (as others point out) is often fatal.
I don’t think exercise or affirmations would be nearly enough to deal with major depression. Those are remedies for those who aren’t all that ill.
You’re right, Ray. Exercise and positive affirmations will have no effect on more severe, clinically diagnosable depression.
And positive affirmations are pure woo, plain and simple.
I highly recommend *against* positive affirmations for serious depression. They do not work. I also highly recommend against suggesting them to those with clinical depression. It’s great that they work for you, but they do not work for most people. No responsible therapist or psychiatrist would ever recommend positive affirmations in lieu of real treatment such as psychotherapy and/or antidepressants.
If you watch the commercials, they always say “You MAY experience the following side effects.” Because everyone is a beautiful and unique snowflake and only some percentage of all users of a substance will experience any given side effect. Your experience on its own is anecdotal.
One commonly listed side effect is suicidal ideation. Maybe you don’t get that one; I know at least one person who has (AFIK, this person had never considered suicide before taking meds even when exhibiting depressive symptoms in the first place). That evidence is also anecdotal which shows how poor anecdotal evidence is for actually determining facts about the world.
I would think the Mayo Clinic would be a worthwhile source on antidepressant side effects. If there is some reason to believe that the Mayo Clinic is not a good source, please let me know:
http://www.mayoclinic.com/health/antidepressants/MH00062
Last report I saw (sorry, don’t have the reference and it was some years ago), there were fewer than ten reported suicides while the patients were on Prozac; at the time, more than a million people had taken Prozac.
Suicidal ideation may be much more common, haven’t seen anything on that. But the chances of actually committing it seem lower than the chances of doing it out of out-of-control depression.
If you have suicidal ideation, you need to tell the doctor and get of the med as soon as you can. If you have suicidal ideation while not on meds, you need to do the same thing–tell the doctor and do something to combat it. Your chances of having suicidal ideation during depression are quite high, meds or not. You’ve got to weigh the risks and the benefits of various ways to combat it. And not go into it thinking that meds have no chance of having any benefits, with anyone at all.
“But given the side effects of antidepressants, and their possible long-term damage to the brain, doctors might as well give their patients placebos,”
Exactly what do you mean by “long-term damage to the brain” ?
I provide this information neutrally (at the moment, I’m not taking sides in the debate), but FYI the relevant link from the ones Jerry provides above is —
http://www.nybooks.com/articles/archives/2011/jun/23/epidemic-mental-illness-why/?pagination=false
— and the relevant passages begins with the text “Whitaker’s book is broader and more polemical.” Read from there, til no longer relevant.
Oss
Thanks for the directions to the relevant part of that piece. Based on reading that, it seems that Whitaker fails to make his point. This is certainly the case with antidepressants.
As stated in the article, antidepressants have been in use since the 1950’s. If they caused long-term damage to the brain I think we’d have had this data long ago.
Long-term damage to the brain is reviewed by Robert Whitaker in this article on his blog: Now Antidepressant-Induced Chronic Depression Has a Name: Tardive Dysphoria at http://www.psychologytoday.com/blog/mad-in-america/201106/now-antidepressant-induced-chronic-depression-has-name-tardive-dysphoria
Many of the statistics Angell used were from Whitaker’s book Anatomy of an Epidemic, which maintains antidepressants cause more harm than good. It’s ironic that Whitaker was such a major source for her article but Kirsch’s assertion about the placebo effect is getting all the attention.
I, too, have only read the reviews, but what first struck me is that Prozac is neither marketed for, nor prescribed for, stroke.
It is prescribed for depression and anxiety. As someone who suffers from both, I can offer only anecdotal data that Prozac doesn’t do a thing for me.
If it helps stroke victims, fine, but let’s quit calling it an “antidepressant” and prescribing it for everyone who feels bad.
Let’s not forget that an *increased* risk of suicide is just one of the many lovely side effects of SSRIs. Try Paxil. It’ll take you there…
Actually I take Paxil and it works really well for me and my generalized anxiety disorder. Just my anecdotal evidence, I guess. I came off Paxil once, the withdrawal symptoms are awful! but then a year or so later I found myself needing to go back on something I tried another SSRI (Lexapro) and despite similar side effects it didn’t do for me what Paxil does. Then I tried some other drugs and they actually made matters worse. So now I am back on Paxil, and I do feel great on it. So yay it works for me! Just not looking forward to ever coming off it, so that is the downside.
But yes, there is a placebo effect that impacts a lot drug trials of this type. I think this is due to the nature of the illness, in that it is hard to define, diagnose and measure improvement from. Also I think that a lot of people that enter into these trials, and a lot of people currently prescribed the drugs, may not even actually have clinical depression or other mental illness, they are maybe just in a bad situation right now. If this is the case then maybe there are lifestyle changes that would be a better strategy, but often people are out for an easy fix and therefore are attracted to the idea of a happy pill. Also, for whatever reason drugs that should in theory work the same (eg SSRIs) for me at least do not work the same in practice. And this is different for everyone, as apparently John can attest to, having had a very bad experience with Paxil.
So I am not convinced the benefit I obtain from Paxil is due to placebo effect. Anecdotal I know, but I am not willing to switch to sugar pills.
At least for minor cases, a doctor should be able to prescribe(? strongly recommend?) something like over-the-counter vitamin D supplements (at label-recommended doses). It has a very, very mild stimulant effect and is quite safe at the levels found in supplements. And, at least in some people, low blood serum levels of vitamin D do cause mild depression, so it would actually cure (not just treat but cure) depression in those people.
I’m sure a competent medical professional should be able to come up with some other sort of safe-yet-active placebos that could be effectively given to patients without violating medical ethics.
Cheers,
b&
Niacin.
Causes flushing. It’s probably good for the heart too (raises HDL).
Niacin also causes the capillaries to become more fragile, easily breaking and thus bruising – you can look like you are constantly being beaten up.
Why does it make them more fragile? I would think it would strength them and make them healthier because of the increased blood flow.
I second the vitamin D recommendation. Very few people these days get enough vitamin D unless they are working outside digging ditches or building houses etc. and they keep finding new things that it does for you, one of which is help maintain mood. In fact with modern diets almost everyone should be taking at least a multivitamin and 1000mg of vitamin D.
I’m fairly certain that, in lieu of a blood test indicating low levels of vitamin D, it would be unethical for a Dr. to prescribe it alone for depression.
I take vitamin D, but then my depression tends to be so severe, I take pretty much everything that has some empirical evidence that supports it’s effectiveness with regards to depression. Of course I don’t take every antidepressant on the market, I only take two of them (because my psychiatrist won’t prescribe me three ; ).
How much sugar is in a sugar pill, anyway? Hopefully not enough to cause a noticeable rise in blood sugar.
Way less than a teaspoon, which is 4 cal. That’s not going to spike anyone’s blood sugar levels.
Plus, “sugar pills” aren’t usually made of sucrose. Some have lactose in them (powdered milk).
Word. Thanks.
Apropos of this, Sam Harris has written an engrossing essay on drugs up on his website at samharris.org
Since these drugs alter the levels of serotonin in the brain, if there’s any degree of adaptation then cutting off the drugs could induce withdrawal symptoms which could mimic depression.
As a (bad?) example, imagine treating aggression with large doses of caffeine. It probably doesn’t help but if you cut it off suddenly, some people will feel irritable and aggressive just because their bodies adapted to the caffeine.
as someone who have been depressed until mid 30ties and who is now forever depression-free i can attest that depression is a cognitive disease and as such should be treated with cognitive therapy only
until we completely and unambiguously know how brain works and how brain chemistry maps into cognitive functions on a 1-to-1 basis the “success” of any antidepressant drug is a coincidence at best
given that human body is self-balancing system introduction of any substances into its environment should be done only when we know how they work and the benefits greatly outweigh the negative effects (think antibiotics in life-threatening situations)
for such complex system as brain the pharmacology solution may be too far in the future and by the time it becomes available depression should be expected to be eradicated through changes of “human condition” alone
Oh sure. I guess your body is a temple, and hence you know what’s best for everybody else.
You may be hit by depression tomorrow, which makes you a liar. Even if the causes are purely cognitive (which there is NO reason to suppose), it might be years or decades before you could lose the symptom through cognitive therapy (distinguishable from spontaneous remission – how?).
So learn to use the shift key and shut up.
When I had my bout with clinical depression twenty five years ago, the three pronged treatment my therapist employed included an antidepressant, talk therapy and behavior modification. She approached the problem as I would have as an engineer trying what she thought best and monitoring the results. (I was unable to work–think–except for a few minutes every hour or so.) She adjusted the antidepressants, talk therapy method and behavior modification as she saw changes, both good and bad.
In a few months the antidepressants were gone and the talk therapy nearly finished, as the behavior modification did its work. since then I have returned to antidepressants once, supervised of course, an occurrence which followed my abandoning the behavior modification method.
Upon returning to my modified behavior, I returned to normal (for me).
My good fortune was to find a therapist who treated me as she observed my behavior, not according to some formula.
No – it doesn’t make the drugs effect “look larger” – it is larger. The problem with antidepressant studies is not that the effects of the drug are small – it is that the placebo effects in depression trials are so high.
Typically, placebo efficacy rates in general trials is around 20%. In antidepressant trials, placebo efficacy can be three times higher!
This is understandable, because simply being in a clinical study improves the depressed patient’s scores on evaluative instruments. They have to get up, get dressed, shower, go out in public, and interact with clinic staff. All of these behavioral changes tend to raise placebo efficacy in the short term.
These placebo effects tend to go down in time, even for patients who continue in clinical trials. Long-term trials tend to more easily demonstrate significant differences between the drug and controls. But most antidepressant trials are short-term, about eight weeks. Please remember, also, that antidepressants may take four weeks to work.
It is therefore not surprising that clinical trials often do not show significant differences between drug and control. If other types of drugs had to be tested against controls that consistently yielded placebo efficacy rates of 50% to 60%, most would have great difficulty achieving FDA approval.
Antidepressants consistently show efficacy in about 2/3 of patients trial in, trial out. It is the high placebo rates which confound demonstration of efficacy, not the fact that antidepressants don’t work. That they do work is pretty apparent to the physicians who prescribe them, and the horrendous rates of depression relapse and suicide which ensue when patients stop treatment is reason to be very very careful before making public proclamations that antidepressants are all a big fraud by greedy pharma. These drugs save lives.
The Cochrane Collaboration, as independent a source as one could hope for, has published more than one meta-analysis which demonstrate the efficacy of antidepressants in the treatment of major depression. That is about as close to a gold standard recommendation as can be found.
Typically, placebo efficacy rates in general trials is around 20%. In antidepressant trials, placebo efficacy can be three times higher!
Yes but so what? So maybe that is also the mechanism behind the success of your “real” drubs.
Long-term trials tend to more easily demonstrate significant differences between the drug and controls.
citation? I think this are exactly the kind of claims that Jerry is looking for to be back up by evidence.
I would also like to see citations for some of the apparently factual statements made in this post.
I was thinking the same thing. I cannot parse what Jerry is saying here.
This is a common criticism and one not to my knowledge addressed by Kirsch. FWIW: Long-term studies are something the FDA should be including in it’s regulatory sweep.
Here is a two year study showing
antidepressant effectiveness in preventing recurrent depression
Keller MB: The prevention of recurrent episodes of depression with venlafaxine for two years (PREVENT) study: outcomes from the 2-year and combined maintenance phases. J Clin Psychiatry 2007; 68:1246–1256
Here’ a useful review to look at
A regulatory apologia: a review of placebo-controlled studies in regulatory submissions of new-generation antidepressants. Eur Neuropsychopharmacol 2008; 18:623–627
Hold the phone…
Since when does the FDA require maintenance trials where a patient is switched from active to placebo?
Every single long-term maintenance trial I’m aware of moves patients who received placebo in the double-blind phase to the active drug in the maintenance phase. In fact, this provides valuable information about whether early treatment is better than delaying therapy in certain conditions.
If there’s a clinical trial of an approved medication that moves patients from active drug to placebo, that would be about as unethical as unethical gets. And if there’s a trial of an investigational drug that deliberately switches patients (cross-over design), that’s not a maintenance trial.
I am wondering on the recurrent suggestion of Coyne that one should look into placebo, which is widely regarded and treated as unethical.
It looks like the age old problem of a scientist that looks into other areas of empirism and thinks he/she “understands and have useful suggestions”.
The usual answer is “butt out, you look ridiculous and You Are Not Helping™”.
It takes some extra-ordinary evidence of making the extra-ordinary transition of actually getting it, et cetera.
And there is no such evidence in these articles. Frankly they look emotionally motivated, which is good but not enough.
I thought this other, and I am wrong here. Coyne isn’t actually publishing in the area, so it is legit as long as it goes.
Hmm, ironically it looks like my emotional motivation may have gotten the better of me. I guess the “I’m a scientist, trust me” implication is such a nag.
It’s a matter of definition. By definition a more active person is less depressed than a stay-a-bed. What we don’t know is whether a drug induced activity is the same as a recovery.
I am quite willing to grant anti-depressants ‘efficacy’ if by efficacy one means they have some noticeable physiological effect. The problem with widespread use of antidepressants is that the conditions they are used to treat are poorly understood and poorly defined. It is not at all clear what it means to say a particular drug “works” against depression. Usually what is meant is little more than that a depressed person displays some greater degree of function (i.e. returns to work, cleans the house, takes care of the kids etc.). Generally a person taking anti-depressants is not looking forward to a time when the drug has ‘done its work’ and they can continue on in their lives without the drug. There is no pretense that the drug is curing any condition, merely masking symptoms. They are long term ‘maintenance’ medications. Under the ‘medical model’ this is OK because the symptoms are the condition.
If someone presents with all the symptoms of depression on the death of a loved one they are rarely diagnosed with clinical depression, because the cause of their depression is evident. It is usually clear to everyone that following a death, there is a natural grieving process one goes through, and allowances are made for a period of reduced ‘normal’ functioning.
If, on the other hand, one seeks help for a generalized complaint, such as, “I hate my life,” and cannot point to any single acceptable cause for one’s depression, one is quite likely to receive a diagnosis of clinical depression. But the fact that one is unable to precisely articulate the causes of one’s depression does not imply that such causes do not exist. Add to this a strong social pressure to pretend that “all is well,” and in the U.S. especially, that one lives a blessed life in the greatest of all nations enjoying every conceivable advantage, and the stage is set for the widespread use of drugs to keep depressed people at work and unacquainted with the roots of their depression. Is it merely coincidence that the bulk of anti-depressants were being prescribed for women just as women’s oppression was beginning to be revealed and challenged? Or that many Jews are diagnosed with depression in a society that generally consigns anti-semitism to a past long ago and far away (in spite of christmas trees on the White House lawn and creches at every small town courthouse and public square)?
It seems to me that in order for placebos to ‘work,’ a patient has to buy into the whole medical model thing. They have to believe about themselves that they have some distinct physical condition that can be ameliorated by drugs. An interesting question about placebo that I have never seen anyone address is, when they are effective, why are they not 100% effective? What is going on in the population of people who are not effected by the placebo? What makes them different?
No, one does not have to buy into the medical model thing. Placebos abound. Religion is an obvious example; pets are another.
Things that give us hope and meaning; though what does it for one person may not do it for another. When in terrible pain we will grasp at straws. Modern medicine many times can offer more than straws. Most of us buy into the medical model thing because we know that modern medicine can perform miracles compared with where we stood a few hundred years ago. Someone in the throes of depressive agony will grasp with both hands at a new proffered hope of release from that agony. That’s why the placebo effect is so strong for pain. Just having someone offering something that might help is worth a large fortune. And these are doctors offering something. Billions of dollars and decades of brain power go into searching for treatments that work. These facts are testament to our hope and belief in modern scientific medicine. Maybe the treatment in this trial will be the one; drugs can be powerful placebos but there are always risks and because of this they have to demonstrate that they can do more than merely that.
Where modern medicine doesn’t extend or cannot help folk-placebos abound.
Yes, I think you are right about placebos, but you are confounding ‘modern medicine’ with the ‘medical model of mental illness.’ You cannot seriously suggest that the value of medicine, in general, is the answer to psychiatry’s critics. And you don’t seem to realize that the placebo effect does not support a medical model of mental illness. Critics of psychiatry and the medical model are not anti-science woo-meisters.
I was merely picking up on your expression “medical model thing”. It’s not a phrase I would particularly have thought to use and I don’t particularly want to get drawn into what it is supposed to mean.
Modern psychiatry is where it is at this point in time, in an age of evidence based medicine. I don’t understand what you mean about the placebo effect not supporting a medical model of mental mental illness. I do perceive that some meisters are retreating from claims that their branch of woo isn’t merely the placebo effect and are now pushing it as the woo-factor extraordinaire.
Jerry says
“It’s already well known…that purely inert placebos, without side effects, themselves have a huge effect in alleviating depression….”
I am not a medical or psychiatric practitioner, but how could anything that, in (somewhat) well-run clinical trials, alleviates the diagnosed medical condition, be called a “placebo” or even be described as “purely inert”? If sugar pills alleviated the symptoms better than MyNuMedZ does, then wouldn’t sugar be the “medication” and MyNuMedz the ‘placebo’?
And if medications thought to be placebos have the “side effect” of curing the medical problem, then what right does anyone have to continue thinking that they are ‘purely inert’ placebos? How would it be ethical *not* to prescribe them instead of proscribing them; how would it be ethical to “inform” the patient that they are ‘placebos,’ something most patients would understand to mean “without effect”?
Sounds like a new manifestation of woo to me.
how could anything that… alleviates the diagnosed medical condition, be called a “placebo”…? If sugar pills alleviated the symptoms better than MyNuMedZ does, then wouldn’t sugar be the “medication” and MyNuMedz the ‘placebo’?
Please see:
http://en.wikipedia.org/wiki/Null_hypothesis
In a study intended to assess the efficacy of MyNuMedz, the null hypothesis is that MyNuMedz does no better than a similarly-administered substance with no significant pharmacological effect (2 Cal of sugar shouldn’t have a significant pharmacological effect).
The way the placebo works is not through any sort of biochemical process but by tricking the patient into thinking that something is being done. It’s a form of sleight-of-hand, related to hypnosis or even salesmanship or good acting or the like.
It might help to point out that other common placebos include saline solution for both injectable and inhaled drugs. We know, without a doubt, that a 10cc venous injection of saline solution has absolutely no measurable effect on the human metabolism.
The curious thing is, if, just before giving the injection, you tell the patient that it’ll decrease headache symptoms, a statistically significant number of patients will sincerely report lessening of headaches as opposed to those who got no injection. On the other hand, if you caution the patients that this injection might actually make their headaches worse…well, again, that’s exactly what it’ll do.
An active placebo is something positively known to have absolutely no effect related to the condition being treated but which still presents noticeable side-effects. As Kevin pointed out in his response to me above, niacin — plain ol’ ordinary vitamin B3 — causes skin flushes. A patient in a double-blind study who gets niacin as a placebo might think that the flushing means that they got the active drug, not the placebo, thus triggering the placebo effect.
The placebo effect is real, very important, and not yet thoroughly understood. Not surprisingly, it’s also a hot topic of research.
Cheers,
b&
You folks (Dan and Ben above) are saying that it is a placebo because it has no known pharmacology to alleviate the disease, and therefore, if it does in fact alleviate the disease, it is “tricking the mind (or “tricking the patient).” Ok, that’s my wikipedian understanding of placebo effect.
Now, I’ve just read in the OP (a) that there is no known pharmacology about why some, at least, of the so-called antidepressants work, and (b) that so-called placebos (also with no known pharmacology) often have alleviation rates approaching those of the medZ.
And I’m still curious why you two think that it was the medZ that were clinically tested, and not the “placebo.”
Maybe, just maybe, “tricking the mind” is a valid way to treat depression? The comment on “positive affirmations” above suggests that (without the pejorative aspects of “tricking.”)
I think the point I’m trying to make is that if you, a medical practitioner treating a patient, have two identical little white pills at hand, both of which with similar “cure” rates, but one with no known side effect, while the other has some potentially nasty side effects, AND if you can honestly tell the patient about EITHER of the pills: “This drug has been shown in clinical trials to be effective in alleviating symtoms like yours,” then how can you ethically prescribe the nastier of the two pills just because think the other one shouldn’t work, even though it does?
When clinical trials reveal no significant difference between a drug and a placebo, the conclusion is not that the placebo is effective, but that the drug is ineffective.
For a physician, the response should be to prescribe neither (with the intent of using them for active treatment) and instead use non-pharmacological treatment modalities (such as, in the case of depression, cognitive behavioral therapy). (Or, of course, if some other drug has proven to be more effective than a placebo, to use that instead.)
It may well be advised for the physician to prescribe a placebo of some sort as part of the therapy — see the discussions above about using vitamins as placebos. This gets into tricky ethical problems, though, and is probably avoided by the overwhelming majority of physicians. There’s a fine line between suggesting that something mild can have slightly-more-than-mild effects and abusing the patient-doctor trust.
The subject of this particular debate is whether or not SSRIs actually are more effective than placebos.
I think we can all agree that the effectiveness of SSRIs is somewhere between that of penicillin on (large classes of) bacterial infections and homeopathic tinctures on…well, anything. The questions are where they lie on that spectrum and the situations where they are and aren’t effective.
Cheers,
b&
Well, sometimes these trials include a “no placebo” option in which the patient gets no pills (I guess there is still doctor consultation). And for the antidepressants, those trials show, according to Kirsch, a VERY LARGE improvement in depression of placebo over no treatment, and a substantially smaller increase of drug over placebo (none if you use an “active placebo”). So one can indeed conclude that the placebo is effective and the drug less effective or even ineffective. That’s why I think that somehow there should be a way to treat depression initially by taking advantage of the placebo effect. “First do no harm.”
You know, something else occurs to me.
People get depressed when their lives suck. I don’t think there’s any question about that — your spouse dies, you lose your home, you get in a car wreck, you’re a very strong candidate for depression. And for excellent reason, I might add.
But people’s lives don’t just suck because something major happened. Some people’s lives suck because they hate their jobs or their families. Even if they have not-bad jobs and loving families, their lives may still suck because they’re spending all their most productive hours at work when they really want to be writing poetry or tending a garden or teaching their nieces how to ride their bikes.
I wonder: how many people are depressed for perfectly legitimate reasons — namely, their lives suck, for one reason or another — and yet they’re taking drugs rather than doing something to make their lives not suck?
When you get to the numbers of people being medicated for depression these days, especially coupled with the general state of the economy, I have to conclude that what a non-trivial number of these people need most is not drugs. And if they’re going to use drugs rather than solve their problems, I have to wonder if they wouldn’t be better off with something more recreational.
Oh — one more thing. Negative feedback loops can be a bitch. If you hate your boss, you might get depressed. Your depression might give your boss an excuse to fire you, making you even more depressed. Now, because you’re depressed, you can’t find a new job. No job, no mortgage payments, and you’re now on the street — a most legitimate reason to be depressed if ever there were one. But are the drugs the answer, or a good strategy to get a job with a boss you don’t hate?
Cheers,
b&
P.S. Yes, yes. I know. Depression has many causes. This is just one of those possible causes. There are others. b&
“…I think that somehow there should be a way to treat depression initially by taking advantage of the placebo effect.”
Like what? Lying to the patient about his/her medical treatment? No one had better *ever* try that on me or on anyone. The patient has to be in charge of choosing their treatment and making informed decisions.
If a doctor did administer a placebo, and the patient committed suicide or was hospitalized, how far do you think that “I was lying to him about his treatment, trying for a placebo effect” will go in court?
Especially if any medicine whatsoever has shown even the slightest advantage over placebo?
Jerry said:
“…And for the antidepressants, those trials show, according to Kirsch, a VERY LARGE improvement in depression of placebo over no treatment, and a substantially smaller increase of drug over placebo (none if you use an “active placebo”). So one can indeed conclude that the placebo is effective and the drug less effective or even ineffective…”
How do you conclude that the drug is “ineffective” when it outperforms the placebo – which you conclude IS effective?
“How do you conclude that the drug is “ineffective” when it outperforms the placebo – which you conclude IS effective?”
Excellent question. Jerry? Care to answer?
And it is absolutely unethical to prescribe a placebo for a potentially fatal illness. Antidepressants do outperform placebos. Kirsch acknowledges this but downplays it (“No statistically significant difference” in the active placebo studies, yet he doesn’t provide the actual stats. How hard would it be to do so?; and “In only 2 out of 9 of the active placebo studies did antidepressants outperform antidepressants to a statistically significant degree.” And how many times did the placebo outperform the antidepressant? ZERO! And yet, Jerry, you conclude that the placebos work better than antidepressants and SHOULD be prescribed for an indescribably horrible condition and potentially fatal condition?!
What on earth are you thinking?
I think #12 covers that, placebo works temporarily but those dreaded “long-term effects” of actual drugs stay. Maybe you can save lives with placebo, but numbers say you say many more with medicine!
No, that’s not what I’m saying. I’m talking about a particular hypothesis — the hypothesis that MyNuMedz does something, anything, to alleviate symptoms of depression.
Alternative hypotheses: -the ingestion of any pill has clinical benefits; -attention paid by doctor to patient has clinical benefits; -being given a pill by a medical professional has clinical benefits. To eliminate these alternate hypotheses you need to do a clinical trial that checks what effect these hypotheses have on the outcome. That entails using something known not to have pharmacological effects as a placebo.
You’re right that a lot of the drugs being clinically tested don’t have a known pharmacology, but there’s a difference between not having a known pharmacology and being known not to have a pharmacology. We EXPECT SSRIs to have a pharmacological effect even if we don’t understand the effect from end to end.
You’re mixing up clinical efficacy with TESTING clinical efficacy. You might be right that placebos are a better treatment, but that’s irrelevant to the problem of determining WHETHER placebos are a better treatment.
I think there’s a great amount of underestimation of the destruction that psychiatric medicines can relieve.
Medicines are effective in cases of schizophrenia, bipolar disorder, and severe, even catatonic, depression. That is beyond question. A lot of these patients are so out of their minds that they’re not aware that they’re even taking medicines, let alone together enough to have believe that it’s going to help and experience a placebo effect. Talk therapy isn’t an option when you can’t understand language, and can’t talk understandably yourself. (Ever seen anyone in a manic episode?)
These diseases are so agonizing, life-destroying, and deadly that almost any kind of side effect is better. Of course, people have the option to choose whether they prefer living with the side efffects or the therapeutic effects, but in many cases there’s no question which they prefer. The agony is so great that they’d do anything, even suicide.
Bipolar has the highest suicide rate of any mental illness. Before lithium, it was one in four. That is so far higher than any psychiatric medicine that the med is overwhelmingly worth trying. People spend their lives going in and out of hospitals, without the chance to build any kind of a lfe. That’s a hell of a lot more money going into the pockets of Big Medicine.
*Who cares* if it’s a placebo effect that’s supplying the relief? If doctors can’t prescribe actual placebos without the patient’s knowledge (quite unethical), then for goodness sake, let them prescribe what they can.
You may say, oh, these medicines are most often prescribed for more borderline cases. But, if they work in major cases, they definitely ought to be tried for minor ones. Even less severe depression is unbearable and often completely disruptive. If anything helps, bring it on. Again, if side effects are too great, they can choose to stop the medicine and try something else. Even a little improvement in mood (caused by whatever!) may allow patients to work and progress with their talking therapies. Then the med can be stopped, and the therapies take over.
This is a conversation that needs to be had. Patients need to be able to weigh the options in psychiatric treatment (if they’re in any state of mind to do so). But blanket condemnations (“psychiatric medicines are a scam”) are only going to discourage people who truly need them to turn away, and a lot of needless death, agony, and life-destruction will be the result.
Also, the first antidepressant medicine was discovered during an anti-tuberculosis trial. The doctors were not treating the patients for depression, so there was no expectation of any antidepressant effect. However, one was observed, and the trial surely wasn’t filled with people who all had severe mental illness.
Surely the med should have produced placebo benefits in the patients’ tuberculosis? Not their depression? At the time, it was not thought that any medicine could be an antidepressant, no medical model there.
Bipolar neither. No one thought to try lithium for the express purpose of treating bipolar. No medical model there, no placebo effect. Yet the benefit was observed all the same, enough for the deliberate use of lithium as a mood stabilizer to be tried.
The older classes of antidepressants are all reportedly more effective than the newer ones (I’d like to see the studies on those older medicines–how much more effect might they show than placebo?). But, they had truly vicious side effects (you could literally drop dead from eating the wrong foods if you were taking MAO inhibitors). So, the new antidepressants are now the first-line treatment. Perhaps going back to the old ones should be considered, if these new ones are not more effective than placebo? Someone should find out how much better the old ones worked.
“I think there’s a great amount of underestimation of the destruction that psychiatric medicines can relieve.”
Indeed! Depression is a seriously life-threatening condition with perhaps 30 % (? can’t remember) mortality. And in numbers it is the number 4 ~ 5 killer in Sweden I think. Which can make _anyone_ depressed. :-/
To discuss efficacy and side-effects is of course important, but to suggest we can move away from any working methods without massive amount of study is premature. (“we almost need to go back to square one in assessing the value of antidepressants. That won’t happen, of course, because those drugs are already approved,”)
When circulation system or cancer treatments started out they had massive side effects and deaths. But people sloughed on without any re-assessing, and society is the better for it.
Ironically as some point out it may be the drive to alleviate side effects that makes the new generations of antidepressants marginal!
I think you allow your urgency to save lives to prevent you from seeing a bigger picture. I have no doubt that psychiatric drugs have saved some lives. But I also have no doubt that they have destroyed some lives especially some children’s lives who, once tracked into the psychiatric system, may never get free of it.
Cogent criticism of modern psychiatry begins with diagnosis. You claim that manic-depressives have a high suicide rate, but there’s no lab test for manic-depression. It’s just a label slapped on someone by a psychiatrist. There is a certain amount of circular reasoning that goes on in psychiatry. If someone presents with suicidal ideation they are going to be diagnosed. Then later if they kill themselves, they are said to have been the victim of their mental illness.
Criticisms of psychiatry have been swept aside for decades with the passionate cry that “mental illness kills people” and “we must give them drugs to save lives.” It is just an emotional appeal. It has a silencing effect—only a cretin would object to saving lives—and distracts people from taking a hard look at the actual practices of psychiatry.
You are not describing how psychiatry actually works. I was diagnosed, once upon a time, and told that I would be taking drugs for the rest of my life. And then there’s “nobody” (post #3) who thinks his drugs are ‘successful’ because he has been taking them for fifteen years with no end in sight. Just couple of anecdotes, I know… but similar anecdotes are legion. I don’t doubt your good intentions, but your view is simplistic.
Another perplexing article in a subject where we have science and medicine to replace precisely speculation such as using placebo. It is also considered unethical.
– Use of antidepressants doesn’t need “defending”. Many trials says it works from animal models to epidemic observation, and this article test that particular claim without being able to reject it.
[Especially odd is this: “the effects of antidepressants aren’t really greater in more serious cases, but that the effects of the placebo controls are smaller.”]
Antidepressants have saved many lives compared to placebo AFAIU statistics. IIRC articles, locally [Sweden] scientists are arguing for massive more use because of that.
– An alternative is, presumably, CBT. Placebo is not an alternative I believe, not allowed in medicine for ethical reasons. Using placebo is an entirely different question than antidepressants as such.
– “any possible long-term effects on the brain”.
Well, that _is_ the point. This is an irrelevant folk medicine argument against active chemical agents.
– “the nefarious acts committed by Big Pharma with regard to antidepressants.”
Conspiracy theories? Really, and I have asked this before, how is this different from anti-vaxx.
Now I _am_ going to engage in “defending”, because besides being a witless accusation, the response has some cogent points:
1. The possibility to admit successful trials only looks to be a system failure, and its possibility is “the nefarious acts” of the responsible government.
2. Conversely any pharmaceutical that releases a drug that is a failure, and we have a recent example, is set on a course to bankruptcy. Now the problem of 1 shouldn’t affect 2, but as we all know it happens. Presumably it isn’t the conspiracy of The Company that doesn’t benefit from this in the end, but the efforts of project workers et cetera that benefits from rigging the system.
Au contraries, the use of antidepressants very much needs to be defended. Moreover, the whole ideology of ‘mental illness’ needs to be defended. For instance you claim anti-depressants ‘work’ in animal models… who diagnosed the lab rats to be suffering from clinical depression? Or what can you possibly mean when you say it ‘works’ in animal trials? You can only mean that administering the drugs has some kind of measurable effect on the animal, but who says the effect is “good” or “desirable.” Did the rats tell you that? The most animal trials can tell you is that a drug has some efficacy. But that does not automatically translate into ‘works.’ It tells you nothing of the desirability of the drugs effect or the wisdom of prescribing it.
And what are the epidemics you refer to? The only epidemics of mental illness that I am aware of are the ones that occur when a new psychiatric condition is first defined (invented) and suddenly thousands of peeps who were perfectly fine before are suddenly part of an epidemic of dysfunction that (co-incidentally?) expands the market for psychiatric services. When was there an epidemic of depression that did not coincide with some new form of treatment being released, such as the prozac epidemic?
I have no first hand knowledge about antidepressants from reading or experience. This article makes me sceptical. But, given that this is a cat lover’s website, I thought I’d share an anecdote.
A good friend of mine recently moved in with his girlfriend. She owns a cat that gets ‘separation anxiety’ when she leaves the house for work during the day and confuses her bed for a litter box. She has apparently come to terms with this through various approaches. A combination of plastic covers and tolerance I believe. He wasn’t up for that. Their vet recommended antidepressants and they seem to work. No idea what drug though nor what else changed in the house. The vet also spoke about taking the cat for acupuncture too though, so I don’t think the prescription was given based upon scientific evidence.
A quick google search just suggested that the placebo effect works on animals too?!?
Regarding the issue of active placebos versus antidepressants, the issue is a bit more complicated than you let on.
First, a Cochrane review in 2004 by Moncrieff et al of TCA’s versus active placebos found the following: “Combining all studies produced a pooled estimate of effect of 0.39 standard deviations (confidence interval, 0.24 to 0.54) in favour of the antidepressant measured by improvement in mood. There was high heterogeneity due to one strongly positive trial. Sensitivity analysis omitting this trial reduced the pooled effect to 0.17 (0.00 to 0.34).” In other words, there was a benefit, but it was small to moderate in terms of effect size. If there was no difference between active placebos and antidepressants, then there would be, well, no difference, not a small or moderate one.
Second, the placebo response rate is basically identical between active versus inert placebos. One would expect that active placebos would have a higher response rate, but in reality, this does not occur when data is pooled. See Quitkin’s article at the American Journal of Psychiatry (2000; 157(3): 327-337), which is available online at http://ajp.psychiatryonline.org/cgi/content/full/157/3/327. In that review, the active placebo response rate was around 25-30%, which is essentially identical to the placebo response rate in most clinical trials that use inert placebos. That is the opposite of what you would expect if side effects were driving efficacy.
I think that the more nuanced position is that antidepressants do work for severe depression, but that their effect size has been exaggerated by key opinion leaders and drug companies. At best, they have a small to moderate effect size, which is still something, but nowhere near good enough. And if you want to say that only treatments with large effect sizes should be used in medicine, then you can throw out psychotherapy, as well, because its effect sizes are similar to those of antidepressants. That would have the ironic effect of there being nothing at all that we can do for severely depressed individuals. In addition, if you want to go that route, then you might as well throw out a huge chunk of modern medicine, because most medical interventions have moderate efficacy, at best.
A whole other issue is whether their benefits, which are real, are worth the costs, and to do that one would have to look at the alternatives and factor in their efficacy, their tolerability, their risks, their availability, their cost, and so on. It may turn out that their efficacy is not worth their cost, but that is a different argument from their being ineffective altogether. However, this slippery slope argument can become easily problematic. After all, one can argue that scientific knowledge itself is not worth the risk of malicious or ignorant human beings using that knowledge to destroy our species and millions of others on the planet.
Finally, with regards to side effects, your contention that psychotherapy and placebos have no side effects is incorrect. Look at Table 4 from a NEJM study that compared Sertraline, CBT, combination and placebo for childhood anxiety, available online for free at http://www.nejm.org/doi/full/10.1056/NEJMoa0804633#. You see that every treatment arm had adverse outcomes. The point is that every intervention has a benefit and a cost, and there are no free lunches in medicine, i.e. no treatment modalities that have only benefits and no risks or adverse effects. The point is to negotiate with one’s patients modalities that maximize the benefits and minimize the risk, according to their individual contextual circumstances.
If you want an even-handed review of psychiatry, then I would recommend Joel Paris’ “Prescriptions for the Mind” and Daniel Carlat’s “Unhinged”. They are both reputable psychiatrists who are aware of both the strengths and limitations of psychiatry, and offer constructive criticisms of this discipline. Certainly, psychiatry pretends to have more certainty and knowledge than is warranted, but that is no reason to jettison the entire profession. Rather, it should be acknowledged that we are in the early stages of understanding mental illness, more akin to our understanding of medical illnesses in the 19th century. Given that fact, a great deal of humility is necessary in psychiatric care, and we should be honest about how little we actually know.
Send them on vacation, throw them a party, take them on a walk in the woods, listen to them talk about their lives, buy them a balloon, send them to camp, teach them an instrument or an art, dance with them, hold their hands, cry with them, cook and eat a fine meal with them… you show a remarkable lack of imagination concluding we either drug them or nothing. And yes, the efficacy of these types of things has not been shown, but under the current medical model their efficacy will never be tested. Drugs are preferred because they are not labor intensive and do not require any social commitment to the patient. They are the perfect expression of our (post) industrial society.
I don’t mean to sound hostile. I appreciate you last paragraph, especially. There is no chance that we, as a society, will jettison psychiatry. It serves us too well. But we do have a hope of transforming it into something a little less dehumanizing.
I would say that I wish it was as easy as throwing someone a party or taking them for a walk or just listening to them. Sure, anything is worth a try, but in my experience, when someone is severely depressed, they can barely even get out of bed, let alone go on a vacation or attend a party, and even when they do, they invariably describe them as awful and useless.
And this is not unexpected, especially since part of the depressive syndrome is a highly negative interpretive framework that distorts their life experience into nihilistic perspectives. Part of why therapy works is not just that they have the experience of a caring and compassionate individual who takes them seriously as a valued individual, which helps to attenuate the low self-esteem that goes with depression, but also that they make concrete suggestions about alternative ways to interpret their experiences by looking at the various distortions and misinterpretations that they are prone to. And when you add a behavioral component that has them gradually increasing their level of meaningful and significant life activities, then that helps, as well. Adding a mindful and meditative component, as is available in mindfulness-based CBT, DBT, and ACT is also a bonus, because it helps foster a non-judgmental attitude towards their mental states rather than seeing them in a critical light and becoming fused with them as necessary truths of life.
As you can see, I do not suffer from a lack of imagination, and try to keep my toolbox as varied as possible, but I prefer to use techniques and modalities that have some demonstrated efficacy, even if that efficacy is far less than I would prefer. And this also falsifies your claim that I endorse drugs or nothing to treat depression. I endorse whatever has been shown to work, and so far that includes medications, psychotherapy, bibliotherapy, behavioral activation, and so on.
I see, I didn’t properly connect your comment about there being nothing else we could do to your remark about throwing out small effect treatments. I apologize for misreading you.
Also, I never meant to suggest that a single kind act could overthrow the habits of a lifetime. I was merely trying to point out there there are whole classes of response to depressed people that might be appropriate but that cannot be properly evaluated under the current system. I think that point still stands.
I must add that I appreciate your eclectic toolbox and am very sorry to have impugned your imagination. Still, I think you are missing part of the picture of modern psychiatry. Because what you outline, and correct me if I’m wrong about this, a person who, for whatever reasons has developed poor framing for the events of his life who can be trained to reframe events in a more positive way, though from a certain point of view could be said to be empowering, from another point of view is classic blaming the victim. If there is a social dimension to the condition (and I think the current wide extent of it argues that there is), that is, if depression is to some degree a response to a failing social structure, then your approach, though it may have some benefit for any individual lucky enough to work with you, will do nothing to stem the tide of future cases, and will miss (perhaps!) an important Truth (with a capital ‘T’) about what is actually going on with depressed people, what it actually ‘means’ to be depressed. You have, it seems to me, reduced the meaning of depression to something like ‘ignorance of how to stay happy in a failing social structure (given any particular biological makeup).’
I would argue for a more ecological approach. By all means teach people how to stay happy in a chaotic world, but let’s put a little attention as well on changing the environment and not focus entirely on changing individuals, thus allowing the environment to go unchallenged. True empowerment encourages people to organize all of their world, not just their private inner worlds.
“Send them on vacation, throw them a party, take them on a walk in the woods, listen to them talk about their lives, buy them a balloon, send them to camp, teach them an instrument or an art, dance with them, hold their hands, cry with them, cook and eat a fine meal with them…”
Are you serious? The hallmark of clinical depression is anhedonia – the inability to experience pleasure, so NONE of these suggestions would work for a severely depressed person and it’s naive (and offensive) to suggest otherwise. You might as well suggest that a severely depressed person pull themselves up by their own bootstraps as your above suggestions are equally (un)helpful.
Kramer
What a joke! Repressed Memory Therapy as false memory has ruined lives. Maybe Kramer is talking about more mainstream psychotherapies such as “Existential Therapy” and “Energy Therapy” which only separate people from their money.
Oops.
I misattributed that odd statement to Kramer instead of Coyne.
Yes. And the therapeutic effects of psychotherapy can also be nil.
They treated bipolar with psychotherapy alone for decades. The successful-suicide rate was 1 in 4 (the attempted suicide rate was 1 in 3, and the depressed mood was much more dangerous.)
In patients treated with lithium, the suicide rate is seven times lower.
Which treatment would you rather bet your life on? How about your patient’s life?
Oy.
I’ve been using Zoloft since 1995, in order to tamp down suicidal thoughts and a kind of free-floating anger.
A side effect of the drug was a drastic reduction in my desire to run. I went from 1500+ miles per year to less than 300 and gained almost 20 lbs.
Each time I tried to wean myself off of the drug or if I missed two or more doses, the anger would come back.
I tried behavior modification, attitude modification, etc to no avail. I confess that I even tried Deepak Chopra tapes. Nada.
Lately I’m trying 100mg per day plus lots of caffeine.
I think the stuff works for me. I fell out of a moving car (it was slowing down for a light) when I was 5 or 6 and fractured my skull.
Brain injury studies of WWII and Korean War vets showed a correlation between an injury and depression, usually 40 years or so after the injury. That’s kind of what happened with me. In ’95, I was 45.
What a deeply depressing thought.
Swallowing an inert pill whilst listening to a deeply compassionate woo-man or woo-woman telling me how my own mind-body self-healing energy will make me all better again. Really, truly it will.
Kirsch was one of the authors of “Placebos Without Deception” published by PLoS late last year. The study was dissected by David Gorski on his Science Based Medicine blog.
http://www.sciencebasedmedicine.org/index.php/placebo-effects-without-deception-well-not-exactly/#more-9339
Gorski doesn’t think that the study justifies its title. Nor do I. A lot of deception was going on, consciously or otherwise.
Kirsch admitted that their paper was misleading where it said that the placebo was tested against a no-treatment control group. The control group received exactly the same therapeutic support as the placebo group; the only difference was the absence of the preparatory pep-talk about the scientifically proven benefits and subsequent administration of placebo pills.
What was not made clear was that the clear benefits of placebo are found when compared with no treatment groups. For example, people on waiting lists for treatment. In placebo controlled trials patients are normallyy told of the exact probablity that they may receive an active as opposed to inert pill. The greater the probability the greater is the placebo effect.
In Placebos Without Deception the placebo group were told simply that the pills they were going to receive had been scientifically proven to help people with Irritable Bowel Syndrome by means of mind-body, self-healing powers.
So the placebo group were given a booster dose of placebo – the spiel about the mysterious power of the placebo – to add to the therapeutic effect of warm sympathetic support. Many doctors think that the therapeutic relationship entirely accounts for the placebo effect. Nothing in this study indicates otherwise.
Kirsch believes that giving the inert pills was not part of the therapeutic relationship. I think he’s wrong.
To know for sure, what Kirsch and his co-researchers should have done was to have a placebo control group not told that the placebo pills that they were to be given had been scientically proven to work for IBS. That is misleading as I have shown. This control group would simply be told that they would be given an inert pill, not expected to have an effect – as in the standard procedure for placebo controlled trials.
I would be most surprised if this control group reported greater benefits than the non-placebo group; after all, in a standard placebo controlled trial a patient knows that there is a chance that he/she may receive an active substance. In Kirsch’s trial there was zero probabilty of that.
“It is important that clinical trials, particularly those dealing with subjective conditions like depression, remain double-blind, with neither patients nor doctors knowing whether or not they are getting a placebo. That prevents both patients and doctors from imagining improvements that are not there, something that is more likely if they believe the agent being administered is an active drug instead of a placebo.”
Marcia Angell in her NY Review
Books piece The Epidemic of Mental Illness: Why?
So what does Kirsch and his co-researchers do? They tell patients that although the pills they will be given are inert in themselves the act of taking them is sufficient to produce self-healing benefits.
Assuming that the doctors and patients believe what the doctors are saying, what is to stop patients and doctors from imagining improvements that are not there?
Nothing.
” A lot of deception was going on, consciously or otherwise.”
I’ve only started reading Kirsch’s book, but so far the above statement has been true for the book, too. Kirsch’s writing also has a sort of “gotcha” tone to it. While initially perusing the book, I read snippets of chapters whose titles interested me – in particular “The Myth of Chemical Imbalance.” There he writes as though the fact that depression is *not* caused by a chemical imbalance of serotonin (the primary neurotransmitter he focusses on in this book), norepinephrine, or dopamine is something that he’s newly uncovered. This is simply not true. It’s been known since the 70’s or 80’s, the antidepressant commercials of 90’s and 00’s notwithstanding. He also seems to be seriously undereducated in psychopharmacology which is really a shame as it (further) lessens his credibility.
Very pertinent item over at Orac: Dangerous placebo medicine for asthma
http://scienceblogs.com/insolence/2011/07/dangerous_placebo_medicine_in_asthma.php#more
A study showing extraordinary differences between objective and subjective measures of placebo treatment against Albuterol for asthma. The placebo and sham acupuncture (which has been shown to be as effective as veram (sic) acupuncture) did no better than the no treatment group objectively, and got nowhere close to the bronchodilator as an effective treatment.
On the subjective testing both placebo and sham acupuncture almost as effective as Albuterol.
The results are really quite stunning.
The lead author, Ted Kaptchuk was a co-author with Kirsch in the study mentioned above.
Now it’s just a thought but those studies referred to by Kirsch, for depression, showing placebos to be nearly as efficacious as drugs – were they subjectively or objectively measured, I wonder?
As a small pilot study the results would end a prospective drug’s life stone dead. However, the NEJM have a Deepak Chopra clone quoting quantum theory in defense of placebos saying that subjective testing is more suitable for: migraine, schizophrenia, back pain, depression, asthma, post-traumatic stress disorder, neurologic disorders such as Parkinson’s disease, inflammatory bowel disease and many other autoimmune disorders.
God, or better yet, reason and solid, hard, objective evidence save us from placebo-woo.
It gets worse. A commenter at Orac spotted that the trial protocol said that subjects would be told that they would receive active or inactive acupuncture. If the trial followed the protocol then they all received sham acupuncture whilst under the impression that they might be having needles inserted into them. They were deceived again!
What are the objective measures used for depression? Cheers.
I would say that I wish it was as easy as throwing someone a party or taking them for a walk or just listening to them. Sure, anything is worth a try, but in my experience, when someone is severely depressed, they can barely even get out of bed, let alone go on a vacation or attend a party, and even when they do, they invariably describe them as awful and useless.
And this is not unexpected, especially since part of the depressive syndrome is a highly negative interpretive framework that distorts their life experience into nihilistic perspectives. Part of why therapy works is not just that they have the experience of a caring and compassionate individual who takes them seriously as a valued individual, which helps to attenuate the low self-esteem that goes with depression, but also that they make concrete suggestions about alternative ways to interpret their experiences by looking at the various distortions and misinterpretations that they are prone to. And when you add a behavioral component that has them gradually increasing their level of meaningful and significant life activities, then that helps, as well. Adding a mindful and meditative component, as is available in mindfulness-based CBT, DBT, and ACT is also a bonus, because it helps foster a non-judgmental attitude towards their mental states rather than seeing them in a critical light and becoming fused with them as necessary truths of life.
As you can see, I do not suffer from a lack of imagination, and try to keep my toolbox as varied as possible, but I prefer to use techniques and modalities that have some demonstrated efficacy, even if that efficacy is far less than I would prefer. And this also falsifies your claim that I endorse drugs or nothing to treat depression. I endorse whatever has been shown to work, and so far that includes medications, psychotherapy, bibliotherapy, behavioral activation, and so on.
That said, I agree that psychiatry can be dehumanizing in its focus on biology to the exclusion of psychology and social factors. In theory, psychiatrists are supposed to adhere to the biopsychosocial approach to mental illness, but in practice, due to financial and time constraints, they fail to do so.
I think it would be worthwhile to keep in mind that “depression” is not a monolithic phenomenon.
Your post applies very well to major depression. But antidepressants are prescribed in large part to people whose depression is minor, not major. And I’m sure you’d agree that, as applicable as your post is to major depression, it’s rather inapplicable to minor depression.
Somebody who can get out of bed, who does go to work yet who’s depressed and taking SSRIs may well respond better to a party or a vacation or a walk on the beach than to medication. And they’d probably respond even better still to solving the cause of their depression (get a new job / spouse / life etc.).
But, again. That’s minor depression, not major depression.
Cheers,
b&
Actually, Ben, the condition is known as “major depression”, which comes with different amounts of severity. The severity is determined by various instruments (series of standardized questions).
There are other types of depressions which are recognized separately, like dysthymia, bipolar, SAD, and atypical depression (which is actually quite common).
There is no medical entity known as “minor depression”.
Thanks for the clarification.
I hope it should be clear from context what I meant by the term, even if it is not something defined by the medical literature.
Cheers,
b&
Agreed. My post only applies to major depression, especially of the more severe variety. The mild to moderate range of depressive syndromes is best addressed by time, support, and psychotherapy rather than medications. And for severe major depression, the best treatment is a combination of medications and psychotherapy.
For reference here’s the APA Practice Guidelines for treatment of Major Depressive Disorder.
http://www.psychiatryonline.com/pracGuide/pracguideChapToc_7.aspx
I would draw attention to section 2: Formulation and Implementation of a Treatment Plan; and section 3: Review and Synthesis of Available Evidence.
Sorry, that should be section 5:Review and Synthesis of Available Evidence.
Robert Whitaker – whose book was one of those under review by Maria Angell – has responded to Kramer here…
http://www.psychologytoday.com/blog/mad-in-america/201107/the-new-york-times-defense-antidepressants-0?page=2
Dr. Coyne, you will be very interested in this paper from the perspective of evolutionary psychology: Paul Andrews, et al. Blue again: Perturbational effects of antidepressants suggest monoaminergic homeostasis in major depression. (2011), available at http://www.frontiersin.org/evolutionary_psychology/10.3389/fpsyg.2011.00159/abstract
Dr. Andrews found similar results to Kirsch. I have been corresponding with Dr. Andrews and Dr. Kirsch. My contention is the placebo effect is only partly responsible for the statistical evidence of antidepressant efficacy.
The rest of the statistical discrepancy is antidepressant withdrawal syndrome misdiagnosed and reported as “relapse” in these studies — in the plus column for antidepressant efficacy — when it should have been reported as an adverse effect — in the minus column for efficacy.
The bookkeeping error indicates efficacy where there isn’t efficacy.
This pervades the entire literature of antidepressant efficacy, going back to the beginning, as NONE of these studies contained a protocol to distinguish withdrawal syndrome from relapse. (This addressed in passing in Deshauer et al. (2008).)
With an incidence of 20%-80%, antidepressant withdrawal syndrome confounds all studies and statistics finding antidepressant efficacy.
My argument is summarized here http://t.co/WNmTvMf and http://t.co/mPzwHXT in comments
I run a Web site, http://SurvivingAntidepressants.org, supporting people tapering off antidepressants and those with prolonged withdrawal syndrome after quitting.
What you are calling “prolonged withdrawal syndrome” is just the return of their depression.
Your website appears to push religion and spirituality as a response to organic illness.
This is just a witchhunt.
Very sorry, you are incorrect on both counts.
You may find documentation of prolonged withdrawal syndrome here: http://survivingantidepressants.org/index.php?/topic/368-papers-about-prolonged-antidepressant-withdrawal-syndrome/
Currently, Dr. Carlotta Belaise, a colleague of Dr. Giovanni Fava, is gathering patient reports of prolonged antidepressant withdrawal syndrome for journal articles.
Specifics are at http://survivingantidepressants.org/index.php?/topic/530-researchers-seek-prolonged-antidepressant-withdrawal-cases/
SurvivingAntidepressants.org is not affiliated with any religious organization and does not “push” any religious solution to the suffering caused by withdrawal syndrome.
Because there is no medical treatment for this iatrogenic condition, sufferers cope with symptoms the best they can. For some, this can be mindful meditation, for others, CBT or other psychotherapeutic techniques.
Conceivably, others might find solace in a recognized religion, although no one has presented that yet. As SurvivingAntidepressants.org is a peer support site, members are free to make any constructive suggestions they wish in order to help others.
I wrote a critical discussion of this blog post (where I looked at expectancy side-effects of inert placebos, Kirsch and effect size, negative side effects of psychotherapy and a few other things) called “Why Jerry Coyne is Still Wrong about Antidepressants”: http://debunkingdenialism.wordpress.com/2011/08/21/why-jerry-coyne-is-still-wrong-about-antidepressants/
Unfortunately you are wrong. 😉
Stunningly naive “analysis” on your blog, Emil Karlsson.
For one thing, adverse effects from SSRIs are probably understated in the literature, not overstated. The sexual dysfunction alone is estimated to affect about 50% of those taking SSRIs. While some don’t miss their sex lives, others find this very distressing indeed.
FYI, see http://tinyurl.com/3o4k3j5 — a site for antidepressant withdrawal syndrome. Read these case histories and come to the conclusion adverse effects of SSRIs are negligible.
If anything Kirsch has understated the lack of efficacy of SSRIs, as he has not taken withdrawal syndrome misdiagnosed as relapse into consideration. Those cases “relapsed” off SSRIs were counted as evidence of efficacy rather than adverse effects.
Lastly, take a look at http://1boringoldman.com, where a psychiatrist is painstakingly taking apart study after study regards SSRIs and other psychiatric drug, and finding unmistakeable signs of deliberate misrepresentation in the pro-drug research you seem to so deeply trust.
As I am unable to post comments on Emil Karlsson’s site I thought I would write here. In support of his views he is fond of giving details of the study NEJM (Walkup et. al. 2008), that compared the efficacy of sertraline (an SSRI) alone, cognitive behavioral therapy (CBT) alone, placebo, and sertraline and CBT together and the results where: improvement with CBT alone (59.7%), sertraline alone (54.9%) where both better than placebo (23.7%) and a combination of CBT and sertraine (80.7%) was the best option.
Having had a quick read of this study I have suspicions to it’s validity.
1. The study uses the anti-depression drug sertraline, Zoloft, to ascertain it’s usefulness in improving anxiety and panic attacks in children aged 7 -13 (mean age 10). Nothing to do with depression. The methodology used, subjective checklists to determine improvement will be more problematic.
2. The placebo group was half the size of the other groups.
3. Children who had previously taken Zoloft without effect were excluded from the trial. Why? Wouldn’t this change the results in favour of the drug over placebo?
4. Everyone on the combination study knew that Zoloft was being taken. There was no combination/placebo testing. Why not?
5. The improvements in the placebo group were very high suggesting problems with the methodology?
6. The were no differences between side effects experienced by those on the drug and placebo. Given the side effects documented by Pfizer on Zoloft I find this result strange.
7. Those running the trial worked for pharma companies. (not necessarily a problem).
Comments back welcome.
cheers.
Nick
Peter Kramer is proof of evil. SSRIs ruined my life! Psychiatry is quietly spread with the power of the elite and 1% to dumb us down and profit off us with unnatural medications that are worse than anything natural you could ever ingest.
Psychiatry would not be bad if they didn’t exploit and abuse anyone they deemed needed help from, and if they didn’t put children on highly dangerous drugs like Ritalin for their own profit. Humanity is not a bunch of mental cases waiting for a chemical to fix their unique traits. Everything has a casue and effect, and believe me when I say psychiatry’s abuse on me has created a monster.
Kirsch: “Déjà vu All Over Again”.
http://blogs.plos.org/mindthebrain/2012/12/26/the-antidepressant-wars-a-sequel-how-the-media-distort-findings-and-do-harm-to-patients/