Missing a Pivotal Outcome in a Large Cold Turkey Trial of Desvenlafaxine

Peter C. Gøtzsche, MD
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Editor’s note: This article was co-authored by Anders Sørensen.

In June 2014, Arif Khan et al. published a trial of 361 patients randomised to three groups: abrupt versus 1-week taper versus no discontinuation of desvenlafaxine.1 Curiously, although all patients had depression, the readers were told that data on depressive symptoms “are reported elsewhere.”

We were unable to find any such data when we searched on Khan and desvenlafaxine on PubMed. We were also unable to find the protocol for the trial and thought the trial had not been registered, as we did not find it by searching clinicaltrials.gov, and as neither the trial report, nor the PubMed abstract, mention a trial registry identifier.

The trial was funded by Pfizer, and we suspected the data on depression didn’t look good for the company since they had been omitted. Abrupt withdrawal of antidepressants can lead to an abstinence depression in many patients (e.g. an increase in the Hamilton score of at least 8 in a third of the patients treated with drugs with a short half-life).2

We tried to get the missing data from Khan, the corresponding author. Khan informed us that the trial had been registered (NCT01056289). The registry mentioned a secondary, so-called post hoc analysis, which we didn’t find in our searches, as Khan wasn’t one of the authors. This analysis was published in a little-known online journal,3 and there was a table showing depression scores assessed with the Quick Inventory of Depressive Symptomatology Self-Report. Very surprisingly, there were only small differences between the three groups although desvenlafaxine has a half-life of only 11 hours, which would have been expected to cause abstinence depression in many patients exposed to a cold turkey. This paper listed the trial identifier.

We were surprised that Kahn was not an author on the secondary publication, which only had present or former employees of Pfizer as authors. The figures in the online journal were totally unreadable, but we got them from the first author.

Khan informed us that, for the primary publication, he was given data tabulated by Pfizer employees and that he reviewed them and discussed how to present them. This suggests that the academic authors were not involved with data analysis.

We wonder how it can be possible that “Editorial/medical writing support was provided by Kathleen M. Dorries, PhD, of Peloton Advantage and was funded by Pfizer,” at the same time as the authors declare that all six of them “drafted the manuscript.1 Usually, only one person drafts a manuscript and if a medical writer paid by the drug company is involved, it is virtually always that person.

Khan wrote to us that the data are owned by a private company and not the US Government and that all the data are therefore proprietary. We strongly disagree. When patients volunteer for trials, which often involves running a personal risk—which is certainly the case here, where the trial was grossly unethical, as abrupt withdrawal increases the risk of suicide and violence4—the data cannot ethically be said to belong to a drug company. Drug companies have an ethical duty to make all their results public. Researchers should therefore never sign an agreement that the data are owned by a company. They belong to all of us. And researchers should not play hide and seek with the readers by omitting the trial identifier and publishing pivotal data “elsewhere.” All data that are relevant for the patients and their doctors should be published together.

Show 4 footnotes

  1. Khan A, Musgnung J, Ramey T, Messig M, Buckley G, Ninan PT. Abrupt discontinuation compared with a 1-week taper regimen in depressed outpatients treated for 24 weeks with desvenlafaxine 50 mg/d. J Clin Psychopharmacol 2014;34:365-8. ↩
  2. Rosenbaum JF, Fava M, Hoog SL, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomised clinical trial. Biol Psychiatry 1998;44:77-87. ↩
  3. Ninan PT, Musgnung J, Messig M, Buckley G, Guico-Pabia CJ, Ramey TS. Incidence and timing of taper/posttherapy-emergent adverse events following discontinuation of desvenlafaxine 50 mg/d in patients with major depressive disorder. Prim Care Companion CNS Disord 2015 Feb 5;17(1). doi: 10.4088. ↩
  4. Gøtzsche PC. Deadly psychiatry and organised denial. Copenhagen: People’s Press; 2015. ↩

***

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.

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6 COMMENTS

  3. My State government removes any documents that prove their criminal conduct from any legal narrative and then inserts others to create the story they wish to be true before distributing them to lawyers.

    In my instance the documents showing I had been ‘spiked’ with benzos and that the Community Nurse had lied to police and claimed I was his “mental patient” were removed, and others from an old file making it appear I had been a “patient” of this hospital for 10 years were inserted. Thus the victim of serious criminal offences (intoxication by deception, stupefy with intent, kidnapping, conceal evidence….) becomes a paranoid delusional requiring ‘treatment’.

    So why am I not surprised by your revelation Dr Gotzsche?

    In the above example the fraudulent documents sent to the lawyers were accompanied by an “Internal Memo” authorising the “editing” of the file by the Clinical Director of the hospital. Perhaps he works for a Pharma Company and is doing a bit of “editing” for them?

    Editing and fraud are two different matters, and it is my contention that changing legal narrative in documents is the latter. My government who is authorising this “editing” does not agree because police can’t find their copy of the Criminal Code, and the Chief Psychiatrist doesn’t understand what a burden of proof is, so is being derelict in his duty to protect ‘consumers, carers and the community’, and allowing arbitrary detentions and the use of known torture methods, concealed by making it appear to be medicine. Kidnapping and torture become “referral”, “detention” and “assessment” with a change of status from citizen to “mental patient” and allows the later slander of any complainants. Ask our current Minister for Health how this works if details are required, as it is his method of dealing with complaints.

    Have police retrieve the proof and ignore the complaint. If police fail to retrieve the proof ignore the complaint anyway, despite it being criminal to do so. A Chief Psychiatrist who doesn’t understand a burden of proof? That sounds insane, but of course if I didn’t have these documents I couldn’t prove what he knew, that they are concealing the ‘spiking’ of citizens to bring them under the powers of the Mental Health Act by using police referrals to conceal the torture. It’s a win win situation, except for the ‘patient’ who, as we know matters zero in the scheme of things. The ‘spiking’ of citizens and enabling of the corrupt practice of ‘verballing’ providing carte blanche to detain and force drug anyone they wish.

    Not that anyone is prepared to do anything about it. Though they do seem to be prepared to speak out about abuses occurring in other parts of the world, while walking past the Guantanamo franchises set up in our community. Mind you, the point I made to the hospital Operations Manager before she ‘fuking destroyed’ me and my family was that they couldn’t do what they are doing in Guantanamo, it would actually meet Article 1.1 definition of Torture, rather than constitute an “enhanced coercive measure” so popular in these places these days. Waterboarding is not considered an assault and therefore may only reach the standard of ‘soft torture’, the ‘spiking’ consists of an assault under the Criminal Code (assault against persons) and therefore DOES meet the standard of ‘hard torture’.

    Still, what do you do when they’re killing inconvenient truths in the E.D. with ‘hotshots’?

    • Add to this the fact the my government is silencing journalists via raids by Federal Police to identify whistleblowers with invalid warrants. And of course they then refuse to destroy or dispose of the ‘information’ they have gathered from such unlawful raids……

      https://www.abc.net.au/news/2020-04-15/annika-smethurst-wins-afp-fight-high-court/12147706

      So the idea of the public becoming aware that citizens are being tortured is highly unlikely. Especially when even lawyers can be given instructions by the State which over ride the instructions of their clients, and will then aid and abet in the misconduct.

      Brings a whole new meaning to “we’re all in this together” huh? Still, they wanted Euthanasia by popular vote, i’m certain if the public were asked they would support the use of torture too. Pity we can’t put it to the vote and get an idea of who is for and against it really.

      Count me out.

      From little things, big things grow. I’m sure that if left unrestrained (as psychiatry has been where I live eg The Man of Lawlessness) then these methods will expand rather quickly because it is much cheaper than having to deal with the legal ramifications of torturing citizens (and meeting Articles which require public officers to be trained in what is and is not torture. Ignorance of the law being a valid excuse according to our Minister despite the conditions of the Convention. [note no emergency provisions, and no superior authority]. You don’t get to kill victims of torture. Though I do note that not one of them has denied that this was torture in writing, that would expose them to a breach of the Convention, in writing. They know it’s torture and to deny it would expose their deliberate negligence). And what better way to bring the population under control than to kill anyone who is inconvenient to the narrative you wish to propagate? I’m sure the National Socialists had every intention of stopping when they had finished with the ‘mental defectives’, but it just sort of got out of hand. It tends to take on a life of it’s own really from what I saw.

  4. Peter thank you.

    You are a true researcher and analyst. You can live with that, despite what happens.
    We all know what happens when someone disagrees with false presentations, hidden realities or facts.
    What the coverups, the lies really expose is the basis of the whole operation.

    If we have to manipulate or lie even a little bit, the whole cannot be trusted.
    That is what happened from the outset. It was always based on presenting to “know” “something”, that was not really not the “something” in the first place and is the basic reason why nothing works to fix the “something”, and why lies are used to maintain.

    It really would be less uncomfortable to be a researcher or psychiatrist or medical doctor if we could drop pretense of knowledge and admit lack of understanding.

    We should be and are beyond thankful for those who have no fear to stand up. The measure of a man.

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