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For Those Still Convinced Antidepressants Have Non-Placebo Value

with 13 comments

Even though meta-analyses of antidepressant studies have repeatedly shown that antidepressants’ effects are barely distinguishable from placebo, many opponents of suicide rights still point to meds as a proper course of action for those who wish to die. Those unlucky enough to be hospitalized after a suicide attempt (like me) are still administered antidepressants in hospital – by force, if necessary.

Anyone who still thinks antidepressants have non-placebo value should listen to this 20-minute interview with Dr. Irving Kirsch, the lead investigator on the major meta-analyses of antidepressant drugs.

Major points:

  1. The serotonin hypothesis is “dead in the water.” Studies have repeatedly failed to demonstrate that serotonin deficiency is responsible for depression.
  2. The effects of antidepressants are indistinguishable from placebo, especially when data is included from studies that have not been published because they did not get a positive result. (Dr. Kirsch and others obtained these unpublished studies using the Freedom of Information Act.) Both the publication bias in general, and specific monetary incentives, are implicated.
  3. Antidepressants’ “effects” are independent of the drug mechanism. Antidepressants that work on inhibiting serotonin reuptake have the same effect as antidepressants that work on other neurotransmitters or even other chemicals; that is, their effect is indistinguishable from placebo.
  4. Antidepressant “effects” are independent of dosage.
  5. SSRIs (selective serotonin reuptake inhibitors) show the same level of response as SSREs (selective serotonin reuptake enhancers) – that is, drugs with the opposite mechanism show the same result!
  6. Contrary to my previous suppositions, the antidepressants’ effects are dismal regardless of the severity of depression. Severely depressed patients (who make up most of the study groups!) are not significantly more likely to respond to antidepressants than less severely depressed individuals.

As Dr. Kirsch puts it, “that’s what I call a placebo.”

The next time you see someone recommend drugs as a course of therapy for depression, please point them here, or to the podcast.

Meanwhile, the only drug that consistently cures depression in laboratory studies is only available on the black market.

(In the interests of full disclosure, I take one of these yummy placebos every day – citalopram. Similarly, millions of people feel better every day by using quack therapies such as chiropractic, homeopathy, and prayer. The folks making money off those therapies feel even better.)


Written by Sister Y

March 7, 2011 at 6:12 pm

13 Responses

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  1. Sis Y-
    I hate to ask the obvious, but if you don't buy that it's effective (except insomuch as a placebo is “effective”), why do you continue taking it? Does the placebo work if you doubt that it's anything more than a placebo? I know that a lot of meds, including SSRIs, can have rather unpleasant side effects, which I'd think would further deter a skeptic. So I'd love to hear why you continue the course. For what it's worth, my bf, who's deeply concerned about my ongoing depression and suicidality, has been imploring me to begin a regime of the same thing you're on. I don't wanna. Am I crazy? Or is everyone else crazy?


    March 8, 2011 at 3:07 am

  2. This may sound strange, but the more you can “feel it working,” the less you have to “believe.” A very bitter drink makes a great placebo simply because it tastes so bad, you seem to experience it working. I can, to some degree, feel my drugs working. The citalopram, especially in combination with cannabis, seems to increase the pleasurability of exercise.

    From time to time, I forget to take it for a few days, and if that happens to coincide with me feeling down, I can attribute it to not taking the drug, and immediately get some forward-looking relief from that (“ah, I'll feel better when I get back on my meds.”)

    Much more important to my well-being than the drug is heavy aerobic exercise – there is laboratory evidence for the antidepressant effects of that, but telling a depressed person to exercise is just mean. The citalopram feels a lot like Ritalin at first – lots of energy you need to work off. It's not pleasant, but it can get you exercising, which is pleasant.

    Sister Y

    March 8, 2011 at 3:46 am

  3. There is enough evidence that placebos could work even if you tell people they’re taking placebos.


    March 8, 2011 at 12:54 pm

  4. isn't this rather odd? the patient has to “believe” to get the medicine to work?

    you just have to believe in it 😉


    March 8, 2011 at 12:56 pm

  5. Anonymous – interesting!

    We consistently overestimate the power of our conscious thought processes.

    Sister Y

    March 8, 2011 at 5:03 pm

  6. “We consistently overestimate the power of our conscious thought processes.”

    There it is in a nutshell. The idea that our minds are unified is somewhat of a delusion of the self-correcting process itself. In reality, there are all kinds of things going on in there, conflicting things knitted together through the processes of idealization and memory editing. We aren't always who we think we are.

    For instance, I am ostensibly an atheist and an unbeliever in any sort of conscious-centered predestination. And yet, I constantly catch myself looking for happenings or patterns in the existential flux that might tell me I'm moving in the right direction. So, I am still moved by that which I supposedly don't believe exists. The placebo effect is a powerful phenomenon. Furthermore, since everything seems to be the result of physical processes, can't we perhaps label 'placebo' as merely a drug of another sort?

    On the other hand, if we find it works too well it'll probably become restricted and eventually outlawed.


    March 8, 2011 at 5:39 pm

  7. The growing body of studies on the influence of the ovulatory cycle on the behavior of both sexes is an especially piquant exposé on the vanity of consciousness and introspection.


    March 8, 2011 at 8:05 pm

  8. Rob, agreed.

    In other news, playing with human pheromones with a consenting partner is hella fun.

    Sister Y

    March 8, 2011 at 8:21 pm

  9. For what it's worth, here's a link to Floyd Bloom's 2010 critique of Kirsch:

    Basically, Bloom argues that the high placebo effects documented in Kirsch's metaanalyses reflect a widespread recruitment bias for FDA trials in this area, and that Kirsch fails to account for a core body of early research in which the clinical effectiveness of antidepressants was more rigorously established, such as in several cited trials where fairly robust effects were documented in placebo-controlled studies. He claims that Kirsch ignores the results and methodological significance such studies.

    I'm rooting for Kirsch (largely because his conclusions are consonant with my considered view that sociogenic and psychogenic causes lie behind many profound social behaviors and beliefs), but I think there is still room for good faith skepticism regarding the null hypothesis. (I know there are giant corporate interests at stake, but mavericks have biases too.)

    One thing I'm curious about (and someone here can probably educate me): when it is stated, in the context of studying antidepressant treatments of depression, that a study is placebo-controlled, does this necessarily mean that the study is double-blind? Scientifically, this would seem important, but I can think of ethical reasons why single-blind designs might be preferred, despite the potential to corrupt results.

    In the interview, I think Kirsch is too credulous in (apparently) accepting the claim that antidepressants increase the risk of suicide. Perhaps caution is warranted, but from all I've read the data for this claim is questionable while the incentive for publicity — and litigation — is great.


    March 9, 2011 at 2:26 am

  10. In all fairness, there is a serious qualification in the results of these 'antidepression drugs are just placebos'-meta studies that gets mentioned but then dropped in follow-up discussions: the placebo effect was not confirmed for sufferers of severe depression.

    That is, for those with severe depression the drugs really work (that is, if they do work, which they don't always do)


    The researchers said that the drug was more effective than a placebo in severely depressed patients (my bold)


    For less severely depressed patients, the antidepressants were found to work no better than placebos (my bold)

    This is an extremely important qualification. If antidepressants are useless for 'the vast majority of patients', this is because they should not have been prescribed to the 'vast majority' in the first place. Antidepressants are being prescribed for every man and his dog feeling a bit down; and it's useless for them.

    But for seriously depressed people antidepression drugs can be a life-saver and it upsets me that people quote the meta study results so selectively.

    Someone close to me suffers from real depression and I have seen with my own eyes what effect drugs have made. Against my vehement protestations this person is now also receiving monthly ECT. After many months of this barbaric and ill understood 'treatment' I cannot refute what my eyes see; he changes from close to a zombie-like automaton to an actual human being after treatment.

    I for one am very happy that health insurers don't jump on this 'it's all a placebo' bandwagon, because if they stop paying for the treatment I think suicide would indeed be the only option left for him.

    If he would take that route, I'd be happy for him. It's his body, his mind, his consciousness, his unhappiness. I have no gripe with someone taking his/her life if they don't find it worthwhile to live. Don't know what a fight about the placebo effect has to do with that moral right.


    March 23, 2011 at 11:57 am

  11. I apologise, I see the original post specifically addresses the issue I raised above and quotes an article which says the opposite. Many articles I've read have reported different results. He-said, she-said.

    And I can't expect people to attach much importance to my personal experience.

    Got a bit carried away, sorry.


    March 23, 2011 at 4:28 pm

  12. Anonymous, I feel you. Personal experience is a strong motivator for action. Unfortunately, it is not a very scientific way to evaluate cause and effect. As one of my boyfriends says, “the plural of anecdote is not data.”

    Still, I don't pretend to be beyond such things. I take my pill almost every day. And I use marijuana for antidepressant effects, which has definitely not been proven to help in controlled laboratory situations.

    Sister Y

    March 24, 2011 at 3:19 am

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