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.
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.”