Do We Underestimate the Benefits of Antidepressants?

Philip Hickey, PhD
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On April 19, 2014, The Lancet published an article titled Do we underestimate the benefits of antidepressants?, by German psychiatrists Mazda Adli and Ulrich Hegerl.

The Lancet, founded in 1823, is a weekly, general medical journal which since 1991 has been owned by Elsevier, a private, Amsterdam-based, publishing house with offices in the UK, USA, and other countries.

The gist of the article can be gathered from the opening paragraph:

“In the past 5 years, doubts have been raised about the therapeutic effectiveness of antidepressants in patients with depressive disorders, because of the small differences in symptom improvement between antidepressants and placebo recorded in randomised controlled trials (RCTs). With the recent debates about lowering of disease thresholds in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, and the medicalisation of normal bereavement, this scepticism has increased. For the large group of patients with mild depression, the differences between antidepressants and placebo are not thought to be large enough to be clinically significant—ie, at least three points on the Hamilton Depression Rating Scale, HAMD-17.1 Therefore, several guidelines…no longer recommend antidepressants as first-line treatment for patients with mild and moderate depression, and instead generally favour psychotherapy. We are concerned that scepticism about the benefits of antidepressants goes too far, and risks depriving many patients with depression of effective treatment.”

The authors argue that randomized controlled trials (RCT’s), as currently conducted, systematically underestimate the benefits of antidepressants and overestimate the benefits of psychotherapy.  They present six main arguments.

  1. (a)  Trial participants who are actually taking the drug (as opposed to the placebo) have less hope/expectation of benefit, because they know that they might just be taking the placebo.
    (b)  Participants who are actually taking the placebo have more hope of benefit, because they know that they might be taking the drug.
  2. One of the problems with RCT’s is that participants drop out for various reasons.  Most RCT’s deal with non-completers by assuming that their outcome status at the point of drop-out remains the same for the pre-determined period of the study.  This is known as the last observation carried forward (LOCF) technique, and can sometimes underestimate treatment efficacy, because the non-completers dilute the statistical impact of those participants who took the drug and, presumably, steadily improved for the entire period of the trial.
  3. Study participants may not mirror real-life patients.  The authors point out that the prospects of free treatment coupled with financial incentives could result in more “inappropriate and uncompliant” individuals being enrolled in studies than one would find in a typical psychiatric practice setting.
  4. In routine care, practitioners can change the drug and the dosage to meet the emerging needs of the individual, whereas this kind of creative modulation of treatment is often not permitted in RCT’s.
  5. Effect sizes in psychiatric RCT’s are comparable to many effect sizes in general medicine.
  6. The evidence base for psychotherapy is less solid than that for antidepressants.

All of these issues are interesting and debatable.  Any research that involves human activity, thoughts, or feelings is fraught with problems of definition, quantification, and procedures.  Questions can be difficult to formulate, and answers are seldom simple and clear.  Each of the authors’ contentions have been debated at length in the literature, and it is easy to offer counter-arguments.  For instance, with regards to the LOCF issue, it is true that in situations in which treatment is linearly correlated with improvement, LOCF does indeed underestimate treatment efficacy; but in a context in which treatment can also cause deterioration or adverse effects, LOCF can lead to overestimates of efficacy and underreporting of harm.

Similarly with regards to argument number 1 above, it is also widely recognized that a great many trial participants can tell whether they are taking the drug or the placebo – thereby increasing the placebo effect for those taking the drug.

Argument number 3 neglects to point out that the randomization process ensures that there are as many “inappropriate and uncompliant” participants in the placebo group as there are in the drug group.  That’s the purpose of randomization!  And so on.

. . . . . . . . . . . . . . . .

But what’s interesting is that in all the years that pharma-psychiatry was churning out its fraudulent, spurious and self-serving “findings,” I never heard of a single complaint from psychiatry about these kinds of methodological issues.  Now that their drug “treatments” are being exposed as not quite the panacea that they had claimed, they cry “foul!”

It’s also interesting that the article focuses solely on the relative merits of antidepressants vs. psychotherapy, but makes no reference to the much more serious problem – that long-term ingestion of antidepressants is the primary cause of what psychiatry in characteristically self-exculpatory fashion calls treatment resistant depression.

This article is not about science.  It is not, as it purports to be, a discussion of scientific methodology.  A genuine discussion of the six points listed above would have presented both sides of the coin, and many such genuine discussions have been published in the past 50 years, not only in mental health, but in general medicine and other fields.  The Adli and Hegerl article is PR and marketing, and this becomes clear in the final paragraph:

“In summary, the present approach to estimation of the benefits of antidepressant treatments is likely to underestimate the clinical significance of antidepressants and overestimate that of psychotherapy. At the same time, we are experiencing an increasing tendency to medicalise individuals who have emotional reactions to difficult life circumstances but without any clinical signs of depression, and to offer them antidepressants or psychotherapy which might not be appropriate to their needs.…We should be careful not to offer our treatments to the wrong patients, but to provide them consistently to the right patients.”

Note particularly the second sentence:  “… to medicalise individuals who have emotional reactions to difficult life circumstances but without any clinical signs of depression…”

This is just a rewording of the old psychiatric chestnut:  that depression-the-illness is fundamentally different in kind from depression-the-ordinary-feeling-that-we-all-get-when-we-experience-a-loss-or when-life-isn’t-going-too-well.  This is one of the great psychiatric falsehoods because, in practice and in theory, the fact that a person’s depression might be an “emotional reaction to difficult life circumstances” has no bearing whatsoever on whether the individual is assigned a diagnosis, and is prescribed an antidepressant.  The widely-used term “clinical depression” crystallizes this falsehood by creating the impression that such an entity exists (after all, it has a name!), and is fundamentally different from ordinary, everyday depression.  The implication in the authors’ apparently benign and sensible injunction is that psychiatrists should drug clients who have clinical depression, but not those whose depression is merely an emotional reaction to “difficult life circumstances.”

But it’s a meaningless recommendation, because there is no “diagnosis” in the DSM-5 chapter on Depressive Disorders that contains an exclusion clause based on the fact that the depression is a reaction to difficult life circumstances.  Indeed, the whole thrust of DSM and psychiatry for the past fifty years has been that if a person is significantly depressed – for any reason – this is diagnosable as a psychiatric “illness” and should be “treated” with drugs.    Even the tenuous two-month bereavement exclusion of DSM-III and IV has now been eliminated, as the authors themselves noted.

And in fact, DSM-5 specifically cautions practitioners not to rule out the possibility of a major depressive disorder in cases in which people are having understandable reactions to difficult life circumstances.  Here’s a quote from the Diagnostic Criteria section for Major Depressive Disorder (p. 161):

“Note:  Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion A, which may resemble a depressive episode.  Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in addition to the normal response to a significant loss should also be carefully considered.  This decision inevitably requires the exercise of clinical judgment based on the individual’s history and the cultural norms for the expression of distress in the context of loss.”

All that’s needed for a diagnosis to be made is a psychiatrist’s “clinical” and, incidentally subjective, judgment that the vague “diagnostic” criteria are met.

In addition, Axis IV (Psychosocial and Environmental Problems), which had provided practitioners an opportunity to at least identify relevant life circumstances, has also been eliminated.  Psychiatry’s old distinction of endogenous vs. exogenous depression didn’t die a natural death.  Rather it was systematically eliminated by the APA on the ground that it was irrelevant.

The authors’ final cautionary note – not to offer the pills to the wrong “patients,” but to provide them consistently to the right “patients” – is also a meaningless platitude, because within psychiatry’s diagnostic framework, there is no way of distinguishing these two groups on any dimension other than severity, and there is no reliable way of accomplishing even that.  In practice, the assessment of severity, and hence the status of the “diagnosis” is always a function of a practitioner’s subjective opinion, and, also in practice, the pills are given to virtually anyone who can be shoe-horned into a depression “diagnosis,” regardless of precipitating circumstances, which is precisely the state of affairs towards which pharma and organized psychiatry have striven for the past fifty years.

Incidentally

The article concludes with the following disclosure statement:

“MA [Mazda Aldi] has received grants or research support from Aristo, Servier, and Bristol-Myers Squibb; honoraria for speaking from Deutsche Bank, the Johanniter Order, East German Savings Banks Association, Pusch Wahl Legal Lawyers, HRM Forum, Helios Media, Lundbeck, Bristol-Myers Squibb, Boehringer Ingelheim, Servier, Aristo, Viiv, and Gilead; travel grants from the Alfred Herrhausen Society, Lundbeck, and Servier; and has been a consultant to Deutsche Bank, Bristol-Myers Squibb, Aristo, Merz, and Lundbeck. UH [Ulrich Hegerl] has received funding from health insurance companies (Barmer BEK, Central Versicherung); is or has been a member of advisory boards for Lilly Deutschland, Lundbeck, Otsuka, and Takeda, and has received honoraria for speaking from Bristol-Myers Squibb, Medice Arzneimittel, and Roche Pharma.”

* * * * *

This blog first appeared on Philip Hickey’s website
Behaviorism and Mental Health

34 COMMENTS

  1. Excellent article.

    The methodological naivete of not just psychiatric, but most medical, research is something that needs to be highlighted more often. Of course, it is not simple naivete, but as this article points out, a convenient fig leaf which, when it suits, is discarded, or in this case, a complete volte face takes place.

    On a minor point, it is always amusing to me that the professional classes like to disguise their apparent distaste for money by calling a fee an “honorarium”.

  2. The bottom line is this: simply put, the so-called “antidepressants” do nothing for depression and are dangerous to both mental and physical health. They numb you so that you don’t feel. Too many people are so scared of having to deal with their sadness that they’d rather be emotional zombies.

    • Elia,

      Thanks for coming in. your 2011 paper does indeed address these issues cogently and comprehensively. For readers, here’s a quote:

      “In the meantime, the widespread and often long-term use of these agents needs to be reconsidered. This is particularly worrisome given the limited knowledge of side effects with long-term treatment…Of further concern is the suggestion that some patients exposed to long-term antidepressants drugs may experience worse mood and related symptoms in the long run, possibly through tachyphylactic effects…”

      Well worth reading!

  3. We know a self-fulfilling prophecy is a prediction that directly or indirectly causes itself to become true, by the very terms of the prophecy itself, due to positive feedback between belief and behavior.

    Belief: I am depressed cause my brain is broken. The ad on T.V told me so.

    Behavior: I will just mope around, my brain is broken nothing I can do, I need those pills.

    This article just had me thinking about when I went to treatment for substance ‘abuse’ after the medical profession made me an ‘addict”(dependent on benzos).

    Every single person that went in to see that physician assistant was put on SSRI’s unless they refused them, usually Zoloft or Welbutrin . This one reckless prescriber has likely started well over 1000 people on anti depressants over the years. I called her out on it, what are you doing giving everyone this crap ? I am trying to help them… They have anxiety or are depressed and it helps them stay of alcohol and drugs of abuse she said in so many words. This was before I ever started posting or reading MIA but I gave her a lecture on informed consent and told her about the evidence SSRIs cause alcohol cravings. http://davidhealy.org/out-of-my-mind-driven-to-drink/

    Maybe these drugs can lift some people out of a real hopeless deep hole of depression but the way so many medical people start people down the road of psychiatric drugs cause “maybe’ you have a little depression and this drug ‘may’ help creating new mental patients faster than the assembly line at ford motors creats cars is just messed up.

    • Copy_cat,

      Thanks for coming in. Thirty years ago there was a deep distrust of psychiatrists in the AA/NA community. I think this has been significantly eroded by psychiatric promotion of the concept of duel diagnosis. The “logic” goes like this: “You have two illnesses: addiction to a substance, for which the treatment is abstinence; and depression (or anxiety, or ADHD, or whatever), for which the treatment is to take a drug.”

      There truly is no human problem that psychiatry can’t make ten times worse.

    • There is this insane notion that a drug the doctors prescribes is good and safe while the street drugs are all bad and harmful. In fact there is often very little difference, in some cases maybe even for the street drugs (marihuana seems pretty harmless in comparison to most psych drugs, though it can also cause psychotic episodes).
      Prescribing someone a legal narcotic in order to keep them from illegal narcotics (or legal but not assumed to be medicine) is laughable and dangerous in the same time. These drugs should all be treated equally – there are real health benefits to pot and alcohol and probably even to psych drugs but not in the way they’re used now.
      Imagine you go to a doctor with “depression” and he prescribes a glass of scotch twice a day to relax you? You’d think he’s an idiot trying to get you addicted. But if you substitute scotch with benzos, which in a way are much stronger and have more side effects and really make you high, then it’s suddenly OK. Funny world we live in…

  4. Dr. Hickey, Thanks for targeting the malfeasance so systematically and keeping your method plain for the critique of the orthodox hype. By the way, compared to ordinary, average depression, clinical depression is just what your billed for and the disease that lets you express gratitude for getting labelled with it, right?

  5. “The Adli and Hegerl article is PR and marketing”

    Ulrich Hegerl is all over the German media. He is using his role as the chairman of the German Alliance Against Depression (Stiftung Deutsche Depressionshilfe / Bündnis gegen Depression) for doing PR. In a 2010 interview he said that the media coverage of the Kirsch et al meta-analysis will lead to more suicides.

    He is a pain in the ass. Doing his job professionally by twisting every fact in a way that it fits their message, which he repeats over and over again. From the website of the German Alliance Against Depression:

    “depression can hit anyone”
    “depression has many faces”
    “depression is treatable”

    For the German readers, a presentation they did in 2008:

    http://www.krisendienst-mittelfranken.de/dgs/weckwerth.pdf

  6. Thank you once again, Dr. Hickey, for pointing out the psychiatric propaganda. For me, an antidepressant given under the guise of a “safe smoking cessation med” caused “brain zaps,” odd dreams, and odd sexual side effects. And these adverse drug side effects were then misdiagnosed as “bipolar.” Resulting in a whole bunch of major drug interaction induced anticholinergic intoxication poisoning to cover up that misdiagnosis, not to mention the defamation of character.

    I was getting my hair cut the other day, and talking to my stylist about my research and the fraud within the psychiatric industry. She kept nodding in agreement. Finally, she chimed in, “I’m on an antidepressant and I feel like a zombie.” She went on to explain that her family was filled with “bipolar” and “depressed” people, and she was told at the age of 16 that she had a “chemical imbalance” in her brain and had to take these drugs for the rest of her life … but there were no blood tests done to verify the diagnosis … and she wants to have children some day. So we went on to discuss how the antidepressants can cause birth defects, and it’s important she gets off the drugs with the help of a qualified medical professional, but it may be hard to do after twelve years.

    It’s the lies to get people to take these drugs; it’s the fact they’re coercing young children onto these drugs; and it’s the lies to cover up the adverse effects of the psych meds, that make the psycho / pharmaceutical industries so evil.

      • in the interests of accuracy i feel you should point out that there are no blood tests to confirm a diagnosis of depression or bipolar affective disorder. the idea of a “chemical imbalance” is a commonly used explanation of how the drugs are presumed to have their effect, by the people who believe them to work, especially 12 years ago.

        nobody should simply be left on medication for 12 years, they should be followed up regularly and the need for medication reviewed, among other things.

  7. If you told your grandmother you were depressed what would she tell you to do?

    If you told your grandmother you had lost your job, would she tell you to go out and drink a bottle of whiskey?
    There are 57 million anti depressant prescriptions in the UK each year – this has got to be drug pushing, because its not genuine illness.

  8. Depressed , how about adding “Abilify” ?

    2mg 30 tablets $717.30
    10mg 30 tablets $717.30
    20mg 30 tablets $1,011.76
    http://www.truemedcost.com/abilify-price/

    2014 Mercedes E350 Cabriolet $699/mo*+tax

    P01 Package: Hard-drive-based navigation, 10GB Music Register, harman/kardon® Logic 7® surround-sound system with Dolby Digital 5.1, SiriusXM Radio with 6-month All Access trial, SiriusXM Traffic and Weather, Enhanced Voice Control for audio, telephone and navigation, AIRSCARF® neck-level heating system, Rear view camera
    http://www.mbencino.com/specials/new/

    Imagine if the did a study on the effects of Abilify Vs a new Mercedes on a persons depression. If the results are better why not a nice new car ? The cost is the same to the person or their insurance company anyway.

    • I’m quite certain the new car would always work better. And come to think of it, if you complain to a psychiatric professional that their drugs are making you worse, they just put you on more and more.

      But if you start complaining about the cost, and asking for free samples. Well, that’s how I finally got my psych doctor to wean me off the meds.

      I mention this in the event anyone is having a hard time getting a doctor to help them wean off the meds. But, of course, you have to pretend you’re doing much better (even if you’re on 6 drugs, all with major drug interaction warnings that they cause anticholinergic intoxication). And, of course, you must pretend weaning you off the meds is all the doctor’s idea, too. What a joke psychiatrists are.

    • During my only involuntary commitment to date, after my only psychotic episode, I was prescribed Abilify (among a host of other drugs I refused to take). I saw it being advertised so knew it was pricey, but YOW! You’d think insurance companies would have a problem with paying for that, but I guess it’s still cheaper than two hours of talk therapy.

      It was advertised as an adjunct to antidepressants, and I wasn’t depressed, so I asked the smug psychiatrist why he was prescribing it. I don’t remember his answer, it was mushy and not particularly logical. It wasn’t even specific. ‘Blah, blah, blah, other uses…’

      I wonder what the mark-up was on Abilify. Seems that the hospital could make some pretty pennies off the still patented drugs. I finally told him I would take lithium (because it was cheap, close to natural, and didn’t cause strange symptoms). Since I was making sure he didn’t like me, he agreed and I went home two days later. I didn’t refill the scrip, because I only needed sleep and time to process what had happened to me in the comfort of my own home, with my BFF.

      • RE “after my only psychotic episode, I was prescribed Abilify ”

        Of course you were, so was I after showing up at the E.R with panic attacks from all the other pills I was put on.

        You are better off having a “psychotic” episode in Nigeria than in the U.S. Why? Because third-world countries have better recovery rates for so-called mental illness than the United States and other industrialized nations that keep their psychiatric patients “maintained” on the drugs. In the United States, one “psychotic” episode will almost always land you in psychiatric wasteland for the rest of your life. It is psychiatry itself that created the chronicity in so-called mental illness.

        That’s the anatomy of the epidemic. I don’t understand why this is not front page news or why the majority doctors themselves aren’t doing anything.

        Re “because I only needed sleep”

        When I was in the hospital they would violate peoples right to undisturbed rest with blood pressure checks at 6:30 am , how incredibly stupid ! Forced wakeups for people who are trying to recover from psychosis most often caused by a lack of sleep.

        Psychiatry: Total morons.

    • New car or: money to pay your bills, to send your kids to collage, to be able to quit on of your 2-3 jobs and actually have time for yourself, to go to psychotherapy, to get a hobby, to go on holidays…
      Drugs have never cured anyone of their life problems. Money can’t help with every case of “depression” but it certainly can make things better for some folks:
      http://www.dailymotion.com/video/xyytgr_bbc-this-world-america-s-poor-kids-720p-hd-6-3-13-360p_news
      minutes: 16.30 to 17.20
      Says it all…

    • Copy_cat
      In England the prescriptions are free or subsidised, so everyone is paying, and they don’t even know it. While seemingly genuine people go on television talking about how mental illness is deprived of resources. It is deprived – but not in the way they say.

  9. Well, the disclaimer at the end says it all, reading articles like that is just like reading drugs adverts and trying to discuss them based on presented information.
    Funny how they never consider the risk/benefit ratio of putting someone on an “anti-depressant” in term of side effects. Ones like suicide, mania and psychosis for instance, not to mention the physical effects.

  10. Dear madmom
    I sent an account of my psychiatric drug experience to the university that runs the psychiatric unit where I was treated many years ago. They were conducting a study on depot injection medication. Google in ‘Near Fatal Modecate Experience’ and you should find it.

    I made full recovery from not taking my medication (very slowly).