How Much Does it Matter for Patients to Believe They Will Get Well?

Kelly Brogan, MD, ABIHM
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Thanks to the work of Dr. Irving Kirsch, we now know that the majority of the effect of antidepressants is attributable to the “active placebo effect” or the belief that receiving a memified brain-chemical-corrector will actually help alleviate symptoms. As I discuss in this post, evaluation of published and unpublished data, in two metanalysis, demonstrated a non-clinically significant difference between placebo and antidepressants.

A fascinating new study entitled The Role of Patient Expectancy in Placebo and Nocebo Effects in Antidepressant Trials further explores the power of belief in psychiatric treatment. Two fluoxetine (generic Prozac) discontinuation studies including 673 (48-51% of each group) diagnosed depressed outpatients were treated to remission (3 weeks of HDRS< 7) in an open-label (they knew they were receiving fluoxetine)  trial over 12 weeks.

At the 12 week point, all patients were informed that they would be randomized to placebo or continued fluoxetine.

The study identified that change in the first 3 weeks was correlated ( r = -0.46-48, P<.001) with change post-randomization. Impressively, participants continued on fluoxetine and those on placebo BOTH developed worsening depressive symptoms suggestive of two significant interpretations:

1. The initial effect was attributable to placebo since all patients knew they were receiving treatment (open label)

2. The loss of benefit with the introduction of the possibility of being randomized to placebo is the undoing of the placebo effect, or the nocebo effect.

The role of study design (open, placebo controlled, comparator) has been demonstrated to influence patient beliefs about outcomes, and therefore outcomes.

The power of belief and faith in the efficacy of medical treatments cannot be dismissed, and should be leveraged for the implementation of benign, non-habit forming treatments with the potential to confer benefit. The use of medications associated with short and long-term side effects, that primarily ride the placebo effect represents an ethically questionable practice that should be exposed for what it is.

I review some of the primary fallacies underlying current psychiatric practice, celebrate the great thinkers who have pulled th wool from our eyes, and propose a more enlightened approach to treatment in this short talk:

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Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own.

37 COMMENTS

  1. Interesting Article, I think that part of the reason why an army of “Doctors” were so dogmatically insistent that I profess believe in the monoamine hypothesis of depression is because they thought “If she “buys it” then she might get better” (I mean what else can they tell themselves..’this woman’s doomed, and we have no idea what to do’?!)…

    Some sort of enforced Placebo effect…this strikes me as spectacularly misguided and cynical paternalism on their part – and flies in the face of informed consent. Telling your patients ‘fairy stories’ doesn’t = treatment.

    I watched the talk also, to be honest, much of the message sounded as reductionistic as the “serotonin” theory. Just replace the word “serotonin” with “inflammation”? Perhaps I’m just too cynical these days (very real possibility) it just sounds a bit like the ‘shiny new fad’.

    Also, don’t you think there’s a potential for confirmation bias here e.g.:
    – per the Whitaker and Kirsch analysis “all trial studies that purport to show efficacy of psychotropics are badly designed and bias”; but
    – somewhat conveniently…trials that show tumeric is an effective anti-depressant…are, so much better?

    Like I say, maybe just been burned too badly here…

          • We have a saying in my country: “The devils don’t take evil people away” which means that if someone is a sociopathic asshole he/she is likely to live a long and successful life. That is of course not always true but modern society rewards antisocial behaviour on a large scale.

    • My gut feeling is it doesn’t matter what you throw at the “depressed” patient – it only matter if you manage to convince them that it will work. I think antidepressants are just as good as homeopathy, acupuncture, fish oil or whatever else but they also have severe side effects. People complain that giving homeopathy is unethical since it’s basically a placebo but I think it’s more ethical than giving someone Prozac – at least there are no side effects to sugar pills.

  2. Dr. Brogan,

    I’m very happy to see you back. I’ve been reading some of your articles at Green Medicine and other sources, and watched some of your videos too, which have impressed me.

    I’m afraid that I have been guilty of not being as welcoming of you as I should have been in the past when you posted here because I had lots of difficulty understanding a lot of technical language you used and said so. I’m pleased that you have simplified it so those of us without your medical expertise can better appreciate your advice. But, we do tend to be outspoken here at MIA, but in some situations involving those like you with good information and intentions, we can be too outspoken and shoot off the hip! So, I hope you will forgive us for that because based on our experience, we can be easily triggered when not in ours and others’ best interests. Do you have some remedies for that?

    I’m sorry the people posting above don’t appear to be aware of your work because I have been very impressed with it since I think that natural, healthy alternatives are the only solution for severe emotional distress and trauma from social/environmental stressors for the most part that do the body/mind a great deal of harm in the process, causing inflammation and other damage to the body as you say.

    In contrast to Anonime above, I am very much aware of many great studies showing that tumeric is like a magic potion/medicine that helps prevent and treat many health problems in addition to creating great health per Green Medicine and many other sources. Moreover, even if tumeric didn’t turn out to be as effective as the studies have indicated so far, at least it is a natural substance that will do no harm.

    That certainly is not true of biopsychiatry’s toxic drugs not only known to cause much brain and body damage along with early death by an average 25 years in ADULTS, so it much be way worse for children, but also known to make the supposed “mental health” problems they pretend to treat based on bogus DSM stigmas that even Dr. Thomas Insel, Head of NIMH, has admitted to be invalid, far worse and permanent in the long run along with all the other harm they do per Robert Whitaker after much examination of the literature and many others like Dr. Grace Jackson in her great books like Rethinking Psychiatric Drugs.

    Anyway, I am thrilled about any doctors seeking natural, healthy alternatives even if they must write a prescription to start walking/exercising; eat healthy per Dr. Joel Fuhrman’s best selling book, Eat to Live; stop smoking and other poison habits, etc.

    Dr. Hyla Cass has been active in such natural health with books like Natural Highs and others plus her web site in promoting natural remedies for severe emotional/bodily stress stigmatized as “mental illness.” The famous, highly regarded Dr. Andrew Weil and others take this approach as well, so you are in good company. I also find Dr. Mark Hyman with his functional (holistic) medicine quite impressive too.

    I hope you will be patient with people here since they and/or loved ones have suffered much harm from biopsychiatry and medicine in general due to much life destroying stigma and corruption in main stream medicine. Again, I am very pleased you’ve decided to post here again.

    Finally, if you haven’t explored it already, I highly recommend that you check out the web site Alternative Mental Health/Safe Harbor since it includes tons of natural remedies for what are stigmatized as “mental illness” to push toxic drugs in main stream biopsychiatry, so perhaps you might find useful information there and/or contribute some yourself to spread your name and expertise around. I especially appreciate your focus on women’s health since that gets much short shrift in main stream medicine as exposed in many books with most studies done by and for men.

    I look forward to seeing and reading more of your articles at MIA in the future. Thanks for posting at MIA again.

  3. HI Donna,

    Actually, when I took Tumeric, it caused GI bleeding. Yes, that was the culprit because when I stopped the product, the problem ceased.

    Many people during withdrawal and post withdrawal are quite sensitive to supplements which sadly, many of us have found that alternative folks do not understand. Not saying that Dr. Brogan is like that because I am not totally familiar with her work although I am impressed that she understands that meds are not the answer. But my point is that even supplements aren’t harmless in susceptible individuals.

    I do have to agree with Anomine that blaming depression on inflammation sounds as reductionist as the serotonin theory. When Dr. Brogan was on Peter Breggin’s Show and made this type of claim, I could tell that Dr. Breggin was quite skeptical although he didn’t say it outright.

    I just think that just because someone isn’t a mainstream psychiatrist doesn’t mean they should get a free pass as far as their theories being questioned. Of course, it should be done in a respectful manner.

    • I totally agree with you. Some people who are opposed to pharma drugs (and for many good reasons) tend to overestimate the “power of nature” and the fact that natural substances also can cause health problems. Take garlic – a source of powerful antimicrobial activity. Personally, I use it everytime I have throat infections and it really helps to prevent a lasting sickness or speeds up recovery. However, there are people who’s digestive system or liver do not tolerate it. I’ve heard the same story about LSD and THC somehow being better than psych drugs. It may well be the case in some instances but they also cause ill health effects that the pharma drugs are famous for. The same goes probably for any medicine out there, natural or not. I think the main point is that for so-called “mental illnesses” the real way to solve most problems is social and life style changing and not one or the other wonder drug.

  4. I for one am interested in the role of inflammation, immune system, cytokines, etc, in depression and other mental issues. It’s at least an interesting thing to think about. You don’t have to say it’s all about inflammation or cytokines, or that you’re kind of born with an unrepairable bad immune system and that makes go mad. Many of the more “extreme anti-biological anti-psychiatrists” admit that things such as prolonged stress, social issues, bad nutrition and lack of sleep may cause mental issues. Well, there’s certainly also some biological ways these social and other issues cause issues. Prolonged bodily inflammation, cytokines, immune system, etc, may be one thing that is being modulated by lack of sleep, social problems, etc. It may well be related to at least some cases of depression, psychosis5, etc.

    • For instance, after years of self-experiment and study, I’ve developed a system for myself which works quite well. It consists mainly of diet (low carb paleo style), meditation, zen and yoga style exercises, “science” of creating new habits, hiking and trekking, and related issues. Actually these all are related in some way or another. I think one possible way they have actually helped me may have to do with inflammation, through the effects caused in my body through diet, exercise, meditation, etc. I don’t know for sure, but it makes sense. Of course there are many other changes on many different levels as well. For instance, a low carb diet may in the end be more “energy efficient” way to supply energy for the brain, maybe it facilities more GABA. Not to mention, for instance, the social level issues, etc. These different levels and things are often interrelated in many ways. So of course I don’t think inflammation is the only explanation of depression, but it’s one interesting thing to consider in this mesh.

    • Hi Hermes,

      I don’t totally disagree with you. My problems with chronic sleep deprivation are definitely causing inflammation, no doubts about it.

      But where I have a problem with the inflammation theory in general is it just seems another way to generally medicalize the condition of depression without taking into account people’s life circumstances. For example, before I ever started psych med, I am sure I had inflammation due to a bad diet. But the main factor was my life circumstances were bad and that needed to be addressed instead of my being put on a psych med cocktail.

      AA

      • Yes, I definitely don’t disagree with any of that. At least my point of view is that inflammation, cytokines, etc, may be one thing that happens in the body of someone who has some severe mental issues such as not getting sleep. For instance, life circumstances such as prolonged stress, problems with people, getting isolated, etc, change all kinds of things inside the body too, such as they may increase stress hormones, change the proportion of cytokines and so on the biological level. I think the levels of social, biological, spiritual, subjective experience, political, etc, are all very much inter-related. For instance, in my own case, I think my “problems” were also in a big part caused by prolonged social issues (parenting, issues as a kid in school, etc).

        • AA,

          I totally agree that the environmental/social issues like abuse, bullying, mobbing, sexism, racism and other growing oppression and inequality by the 1% that has been the force behind the latest eugenics oppression by biopsychiatry must be addressed if only by validating the victims for starters.

          The reason is that when people are suffering great stress and trauma from such factors, they are more inclined to do self destructive things like smoking, overeating, failure to exercise, isolating, drugs/alcohol and other toxic habits in a vain attempt to alleviate or obliterate the suffering and trauma.

          So, as Dr. Judith Herman, Psychiatrist and trauma expert and author of the classic TRAUMA AND RECOVERY has acknowledged, one’s psychological and physical safety must come first before any psychological or physical treatments can be useful as when a woman is with an abusive, battering spouse or in people are in any type of combat conditions.

          At the same time, a compassionate doctor could try to convince the sufferer that the more they engage in toxic habits like drug abuse and junk food, they will be far worse off and far less able to cope and survive while giving their abusers, scapegoaters all the more ammunition to use against them while not shaming and blaming the victims for their all too understandable but misguided attempts to cope or escape their agony.

          So, I think both the environmental and health conditions need to be considered. I also agree that there is no “one size fits all” approach, which is one reason biopsychiatry has been such a dismal failure since we are all unique human beings they are treating like the unfeeling, narcissistic robots that they’ve become in this life destroying paradigm. It is obvious that anyone who can do what mainstream psychiatry does to people has to have completely eliminated any and all of their conscience, humanity and decency!

          I still am a great advocate of natural medicine, but I never suggested leaving one’s brains at the door of any doctor since one should always thoroughly research any medical and other advice offered and understand that it may be more or less effective for some than others. Just because one person has an allergy or problem with tumeric or peanuts does not mean that everyone will suffer the same problems, but those who do better avoid the offending substance or face the consequences.

          I guess I was thinking of this article in terms of the traumatic events many at MIA have suffered that can be so harmful, one can have what has been called a stress breakdown with much harmful physical impact on the body that leads to inflammation.

          Also, I’ve read that now many diseases including Alzheimer’s are thought to be related to inflammation, so it is an important issue in medicine though not the only cause of what is dubiously called “mental illness.”

          • Thanks Donna, what you say makes total sense. You have to be in good shape health wise to address your bad circumstances and hitting both the environmental and the health issues is the way to do it.

            I guess I am so leery because of the bad experiences I have had with “alternative” folks. Sheesh, I getting to the point where I don’t trust anybody. Not good.

    • As to inflammation as an issue that leads to “mental illness,” the anti-inflammatory drugs are “notorious” for their adverse effects. I personally was miss-medicated with egregious drug cocktails by a neurologist who supposedly knew “everything about the meds,” who thought my “mental illness” was due solely to the ADRs of a NSAI, according to his medical records. He did eventually wean me off all his drugs because a decent doctor took me off my NSAI, and he claimed “rec’d disorder” – from supposed “bipolar.” My point is, the anti inflammatory drugs are problematic.

      • Any drug is problematic, especially when taken long-term and directed at poorly defined target (inflammation is a very simplistic notion about the complex processes that happen in the immune system – there are many types of inflammation involving multitude of different cells and molecules).
        As for giving drugs for stress-related mental illness – it may work in some cases, at least in short term but in the end the best solution is to tackle the underlying problem. It doesn’t really matter how stress causes mental issues – removing stress should be the target and not the symptoms of the unhealthy lifestyle.

        • Well, actually my inflammation was only in my ankle, and is likely due to the fact that my PCP didn’t want to approve a second surgery on my broken ankle to take the metal plates out, since (unbeknownst to me at the time) her husband was the “attending physician” at the “bad fix” on that broken ankle.

          I thought tackling the underlying cause (in my case, getting the foreign matter that is causing the inflammation out of my body) would have been the best solution. It’s a shame the medical community (and insurance companies) are so greedy they’d rather harm people in the long run (by keeping foreign objects in a patient’s body and with “life long” drugs), rather fix the problems they created in the short term.

  5. Actually I think this is all wrong…… Because getting well is not an idea, and there is no comparison between observing yourself getting well and having an idea of what its supposed to look like.

    Lots of people begin to act as if they are well because its so much easier than actually getting well. This will prevent them from actually getting well and in fact makes more difficulty for them…

    Another powerful thing is observing other people like you getting well, and observing them doing what they need to do to get there.

    Its not an abstract idea, and its not one that I think can be measured with ideas, but rather emotionally. After all your the expert o0 yourself. Not the psychiatrist.

  6. AA, since there is no reply button under your post responding to me, I am posting here to thank you for your response. You are not alone in being suspicious and lacking in trust regarding the claims of medical experts and for good reason.

    Here is a great article form Green Medicine about how mainstream medicine takes a Mafioso approach to perpetrate its death agenda while doing all in its ill gotten power to continue its disease mongering/creation/maintenance at the expense of its so called patients while attacking and smear campaigning those in alternative medicine with natural, healthy practices in many cases that actually maintain health and prevent disease. Often, out and out coercion, false accusations, mobbing, bullying, destruction and silencing of its more effective, honest competitors are the tactics of the main stream medicine guilds willing to do anything to maintain their power, status and wealth at the cost of many lives. Now, I am not saying this is a black and white issue with all the good guys in alternative medicine and all the bad ones in main stream medicine, but statistics do prove that millions of people die each year due to the toxic effects of main stream medicine’s dangerous, questionable drugs taken as prescribed while there are few if any deaths due to healthy diets, vitamins, good health supplements, exercise, etc.

    http://www.greenmedinfo.com/blog/do-you-believe-offit

  7. Dear Dr Brogan,
    I like to watch you talking, because you explain things so well.
    I have wondered how anti depressants that have the same effect as placebos can cause long term mental illness, but you go on to explain why this, in your video.

    I came off depot medication (Fluphenazine Decanoate) 30 years ago and have experienced chemically induced withdrawal syndrome. I was getting attacks of fear and panic. I noticed that if I was able to stand back from my thinking the fear got much worse, but in the end softened. I noticed that when I was in the ‘fear’ my mind was like an ‘operating system’ that followed a very distressing path, but outside of the fear my mental ‘operating system’ was reasonable. So, I made full recovery.

    I suffered from continual sadness for many years as well – Buddhist breathing meditation is the only thing that I can identify as getting me off the hook, and making me happy.

    For me the solutions were in the psychologolical or emotional approach but everything that worked could have been found in Buddhism.

    I think you are right when you suggest that the mainstream chemical treatments cause long term mental illness.

  8. I would love to see a study on the “placebo/nocebo effects” of telling a client/patient that they have a chemical problem in their brain that they have no control over, vs. telling them that depression is a pretty common phenomenon, happens to lots of people for very good reasons, and that most people recover pretty quickly with some help. I’d bet anything that what the doctor says is wrong with you and what your prognosis is has a direct impact on the outcome.

    —- Steve

  9. These insights and talking points via Kirsch’s important argument inter-relate perfectly to the eternal quest for altered states, via thrills or drugs or fasting and sweats and such things. People very naturally take notice of the fact that besides changing things in life, you can change your affect, you attitude, your reasons for reacting at all, and so on. How painfully obvious is it that the “War on Drugs” approach and prohibitionistic psychological propaganda campaign in support of FDA approval and doctor prescribed substance use as the sole option in life exists to hide the full range of considerations and stop questions that confront the mainstream authorities.?

    • Copy Cat — Good day, sir. Listen, I got interested in your remark here first time I saw it. The context, what you were relating it to when you thought of it–do you remember?

      I am swamped with re-expereincing today–had a near wipe-out on my bike due to an aggressive trucker some time ago, had no idea it traumatized me until I got off Lithium and the fragmentary nature of my attention to things and the detached feelings associated with numerous recollections became clear.

      I know it bothers the anti-abolitionist factionalists that we disagree that anything mainstream about the industry should pass inspection, including their novel re-interpretations of others’ pains, but if what you were adding to the discussion here had to do with some deficient goals or modes of intervention, please elaborate.

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