Tumbling Further Down the Rabbit Hole of Antidepressant Withdrawal Research

James Davies, PhDJohn Read
18
1530

For those still interested in the recent antidepressant withdrawal debate, here is a new and important installment.

Before we get to the essential part, let us first recall that our systematic review in Addictive Behaviors (2018) showed, among other things, that around half of people who stop antidepressants experience withdrawal. This conclusion was critiqued in a blog by Joseph Hayes and Sameer Jauhar, to which we responded by pointing out the blog’s many serious errors and misrepresentations (see our response here).

Our response to that blog, however, did not deal with one of Hayes and Jauhar’s core criticisms: that our systematic review had failed to include five randomised control trials (RTCs). (These RCTs were: Baldwin 2004a1 & 2004b2; Lader 20043; Montgomery 20034 & 20045.) They alleged that these five trials, while primarily focusing on the effectiveness of antidepressants, also contained data on the ‘incidence’ of withdrawal — that is, on how common withdrawal actually is. Had we included this data in our review, Hayes and Jauhar contended, the number of people suffering antidepressant withdrawal would have been lower than we reported, perhaps by around 10% (we infer this 10% from the tables they produced in their original blog critique). It was therefore either remiss or dishonest of us, they implied, not to include data from these studies.

Today, we would like to deal briefly with this particular blog criticism, not merely to show how groundless it is, but more importantly because, by doing so, we gain crucial insight into how shadowy and ethically suspect antidepressant withdrawal research can get when viewed up close.

The first thing to notice when looking at these five ‘studies’ is that the pharmaceutical company, Lundbeck, funded all of them. Additionally, all five studies were undertaken and written (either entirely or in part) by employees of Lundbeck, who reached the conclusion that their antidepressants were superior to competitor drugs.

The second thing to note about these studies is that three of them were not published as full studies at all. Rather, they were published as short ‘research supplements’ — each at around 300 words. For those who do not know much about ‘research supplements’, they are basically industry-funded study-summaries that some journals will publish in return for an industry fee. Needless to say, the obvious conflicts of interests these supplements involve6 as well as the serious challenges they pose to anyone wanting to assess their methods properly (supplements don’t provide enough detail for that), are just two among numerous ethical and scientific reasons as to why many credible journals, such as Lancet, now refuse to publish them.7

The third and most disconcerting revelation about these five ‘studies’ and by extension the so-called evidence upon which Hayes and Jauhar base their critique, is that none of the five studies actually contain any data on the incidence of antidepressant withdrawal. To repeat, these five studies do not contain the very data that Hayes and Jauhar alleged we overlooked.

While this, of course, explains why we did not include these studies in our systematic review, it does not explain why Hayes and Jauhar claimed the data was there. We can only surmise that Hayes and Jauhar did not actually check these five studies. Rather, they simply quoted a Lundbeck-funded article, published three years later (by Baldwin et al. 20078), which somehow ‘cites’ data from these original five studies that were never included in them.

Two implications of this arise:

Firstly, and most obviously, by basing their arguments on such dubious foundations, Hayes and Jauhar invalidate many of their core criticisms, such as their view that the overall incidence rate from the RCTs is closer to 40% rather than our 50%, as well as their suggestion that we were not thorough (or even worse, were biased) by not including these five RCTs.

The second implication concerns why such research practices are ever permitted at all. How can a later article cite data from company-funded ‘studies’ that don’t actually report that data (let alone report the mechanisms by which that data was gathered)? And how can individuals, journals and professional communities permit or make use of these suspect practices while also receiving financial succour from the companies set to benefit from them?

Both implications can only add to the growing disquiet within the professional and service user communities as to the impoverished state of psychiatry’s withdrawal research. Where such research exists it is scattered and minimal (and, by design, minimises withdrawal effects). And where such research exerts influence it appears to do so less on behalf of patients (whose withdrawal often lacks proper recognition and support) than on those who promote, defend or evermore widely prescribe this class of psychopharmaceutical.

Show 8 footnotes

  1. Baldwin DS, Hindmarch I, Huusom AKT, Cooper J (2004a). Escitalopram and paroxetine in the short and long-term treatment of major depressive disorder (MDD). International Journal of Neuropsychopharmacology 7 (Suppl. 2), S168–S169.
  2. Baldwin DS, Huusom AKT, Mæhlum E (2004b). Escitalopram and paroxetine compared to placebo in the treatment of generalised anxiety disorder (GAD). European Neuropsychopharmacology 14 (Suppl. 3), S311.
  3. Lader M, Stender K, Burger V, Nil R (2004). The efficacy and tolerability of escitalopram in 12- and 24-week treatment of social anxiety disorder: a randomised, double-blind, placebo-controlled, fixed-dose study. Depression and Anxiety 19, 241–248.
  4. Montgomery SA, Durr-Pal N, Loft H, Nil R (2003). Relapse prevention by escitalopram treatment of patients with social anxiety disorder (SAD). European Neuropsychopharmacology 13 (Suppl. 4), S364.
  5. Montgomery SA, Huusom AKT, Bothmer J (2004a). A randomised study comparing escitalopram with venlafaxine XR in patients in primary care with major depressive disorder. Neuropsychobiology50, 57–64.
  6. Lundh A, Barbateskovic M, Hróbjartsson A, Gøtzsche PC. (2010) Conflicts of interest at medical journals: the influence of industry-supported randomised trials on journal impact factors and revenue – cohort study. P L o S Medicine. 2 (1);7(10):e1000354. https://doi.org/10.1371/journal.pmed.1000354
  7. The perils of journal and supplement publishing. Lancet 2010; 375(9712): 347. DOI:https://doi.org/10.1016/S0140-6736(10)60147-X
  8. Baldwin DS, Montgomery SA, Nil R, Lader M. (2007) Discontinuation symptoms in depression and anxiety disorders. International Journal of Neuropsychopharmacology. 1;10(1):73-84.

18 COMMENTS

  1. So where is everybody?

    The first thing to notice when looking at these five ‘studies’ is that the pharmaceutical company, Lundbeck, funded all of them

    Probably the only truly significant date necessary. Still I read on to learn of the “pro”-AD study which offers no actual data, and the rabbit hole allusion became utterly apt. Maybe future studies can be based on nothing but algorithms, like with stocks.

  2. You mean to tell me that when all my doctors proclaimed with 100% certainty that the common symptoms of antidepressant discontinuation syndrome were “bipolar,” that was malpractice? (sarcasm)

    https://en.wikipedia.org/wiki/Antidepressant_discontinuation_syndrome

    I now know it was blatant malpractice, even according to the DSM-IV-TR at the time. It’s a shame the psychiatrists aren’t intelligent enough to even read their DSM “bible.”

    “Note: Manic-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, electroconvulsive therapy, light therapy) should not count toward a diagnosis of Bipolar I Disorder.”

    I’m pretty certain this disclaimer was taken out of the DSM5 to spite Robert Whitaker for pointing out America’s completely iatrogenic “childhood bipolar epidemic.” And to prevent malpractice suits due to all this massive in scope psychiatric malpractice against children, and likely millions of adults.

    But I do know my doctors were ignorant of at least one, very disconcerting physical symptom of antidepressant discontinuation syndrome in 2002, because this doctor points out the ignorance of all the doctors about this common symptom of antidepressant discontinuation in this 2004 article.

    https://www.researchgate.net/publication/247806326_'Brain_shivers'_From_chat_room_to_clinic

    I love the conclusion of that article. But that article is a confession that none of the doctors knew brain zaps were a common symptom of antidepressant discontinuation syndrome in 2004. How embarrassing our “mental health professionals” must learn about the common withdrawal symptoms of the antidepressants from the patients online, and they’re scared of their clients researching online “without our control.” Can we say our “mental health professionals” are control freaks? The satanic “omnipotent moral busy bodies” that C.S. Lewis forewarned us about?

    But I agree, we should not be silent about “the impoverished state of psychiatry’s withdrawal research.” Because “Where such research exists it is scattered and minimal (and, by design, minimises withdrawal effects).” Which has resulted in massive in scope psychiatric malpractice, especially in the United States.

    “And where such research exerts influence it appears to do so less on behalf of patients (whose withdrawal often lacks proper recognition and support) than on those who promote, defend or evermore widely prescribe this class of psychopharmaceutical.” And, no doubt, removing that disclaimer about the antidepressants from the “bipolar” definition in the DSM5 will result in a lot more psychiatric iatrogenesis = malpractice.

    It’s a shame the American psychiatric DSM writers thought the solution to massive societal psychiatric malpractice – the completely iatrogenic “childhood bipolar epidemic” – was to change their DSM to make that blatant iatrogenesis acceptable harm of their clients. Truly the American DSM5 writers are disgusting human beings, whose goal is to harm their clients for profit, not help them.

    Especially since trying to cure the common adverse and withdrawal effects of the antidepressants by adding the “bipolar treatments,” the antipsychotics, will likely make the clients “mad as a hatter,” via anticholinergic toxidrome.

    https://en.wikipedia.org/wiki/Toxidrome

    And our DSM5 writers still have not included this known antidepressant/antipsychotic induced toxidrome (and a toxidrome is a known way to poison a person) into the DSM, so it will always be misdiagnosed as one of the billable, but “invalid,” DSM disorders.

    https://www.nimh.nih.gov/about/directors/thomas-insel/blog/2013/transforming-diagnosis.shtml

    Especially since anticholinergic toxidrome mimics the positive symptoms of “schizophrenia.” And the antipsychotics create symptoms that mimic the negative symptoms of “schizophrenia” too, via neuroleptic induced deficit syndrome. Which is also conveniently left out of the DSM billing code “bible.”

    https://en.wikipedia.org/wiki/Neuroleptic-induced_deficit_syndrome

    Psychiatry is just one gigantic iatrogenic illness creation system. This medical betrayal, on such a huge societal scale, is appalling. And to create a DSM that intentionally encourages poisoning people, in order to make them “mad as a hatter,” is disgusting.

    Thank you for pointing out these problems with the psychiatric lack of knowledge base, Drs. Read and Davies.

  3. Thank you for your work, keep it up !

    “The first thing to notice when looking at these five ‘studies’ is that the pharmaceutical company, Lundbeck, funded all of them.”

    Meaning: they aren’t worth the paper they are printed on.

    A company that gets to decide whether or not their products are safe and effective (products which will make them billions), how on earth can that go wrong…

  4. Dear authors,
    your review is completely biased and bad science. I, too, think that antidepressants should not be used due to inefficacy and that withdrawal is a problem. We need to apply sound science here though. You are doing this cause a disservice.
    You cannot use incidence numbers without comparing to Placebo. This is like saying Antidepressant work in 80 % of people , because 80 % of patients in the antidepressant-arm showed a “response” – this is misleading. There are many other sources of bias in your review, see here:
    https://ksrevidence.com/a-systematic-review-into-the-incidence-severity-and-duration-of-antidepressant-withdrawal-effects-are-guidelines-evidence-based/
    Best regards,
    CV

  5. Of all the RCTs done on antidepressant efficacy and “discontinuation” studies purporting to demonstrate that people relapse when off the drugs, very few — perhaps 3 out of hundreds — contain any protocols for identifying withdrawal symptoms.

    For example, the 2006 STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study, which over 7 years switched about 3,000 people from one antidepressant to another in search of the most effective treatment for depression, reported 0 (zero) cases of withdrawal syndrome — a result that defies belief. (It has long been established that one may suffer withdrawal syndrome even when taking a replacement drug.)

    (The STAR*D study’s methodology and statistical analysis have been heavily criticized. Yet, many doctors believe it is the gold standard for antidepressant treatment and to this very day are merrily switching people from one drug to another regardless of withdrawal effects.)

    All of these studies contain methods to measure “depression.” If a patient, having no other way to report withdrawal symptoms, quite logically conveys the discomfort by marking up the depression questionnaire, the data from these studies would be replete with false positive results supporting the presupposition that what happens after discontinuation is “relapse.”

    And this is so.

    (Most patients in these trials would not be aware they are experiencing withdrawal symptoms; most likely, they thought they were experiencing some new species of mental disorder.)

    That so few studies even differentiated withdrawal syndrome from relapse indicates that assumptions about antidepressant efficacy and the conclusion that people often relapse when off the drugs are incorrect. Most likely, a big chunk — maybe even most — of that “relapse” is withdrawal symptoms.

    What most likely happens after discontinuation of a psychiatric drug taken for a month or more is most likely withdrawal rather than “relapse.”

    References
    Haddad, et al., 2000, Misdiagnosis of antidepressant discontinuation symptoms.
    Deshauer, et al., 2008, Selective serotonin reuptake inhibitors for unipolar depression: a systematic review of classic long-term randomized controlled trials.
    Baldessarini, et al., 2010, Illness Risk Following Rapid Versus Gradual Discontinuation of Antidepressants.