Common Statistical Method Conflates Withdrawal with Relapse

Researchers argue that common study methods for psychiatric drugs may inadvertently minimize withdrawal effects and inflate drug efficacy.


Survival analysis is a statistical technique often used to test whether psychiatric drugs prevent relapse. But, in a new article in BMJ Evidence-Based Medicine, researchers write that it is inappropriate to use it for that purpose.

The researchers were Joanna Moncrieff at University College London, Janus Christian Jakobsen at the University of Southern Denmark, and Max Bachmann at the University of East Anglia.

They note that while this method may be appropriate for some situations when it comes to psychiatric drug studies, it is prone to conflating withdrawal with relapse and can lead to misleading conclusions. Thus, they suggest it should be avoided for these studies. The researchers write:

“We suggest that survival analysis should not be routinely employed in trials of interventions aimed at relapse prevention in long-term psychiatric conditions.”

In survival analysis, researchers generally compare one, or both, of the following: whether there are more relapses off the drug and whether those relapses happen sooner.

The first question is a vital one: do people taking the psychiatric drug being studied suffer fewer relapses? But the problem is that discontinuing the drug leads to withdrawal effects, which are often counted as relapse, especially in drug trials. So, because of withdrawal, people who discontinue the drug appear to relapse more—even though it is actually drug withdrawal.

The second question is more troubling: what if there are the same number of relapses over time, but the relapses happen sooner for those who discontinue the drug? And again, many of those “relapses” in the discontinuation group may actually be drug withdrawal effects.

Moncrieff, Jakobsen, and Bachmann suggest that in this situation, although the drug looks better statistically, it is not necessarily worth the adverse effects of the drug. That is, if the same number of people ultimately relapse whether they are taking the drug or not, then the drug may not be worth it—even though it looks better statistically.

The researchers note that there has been no research into whether a slightly delayed relapse is a clinically relevant outcome. So they ask whether patients would opt to continue the drug indefinitely if they knew their chances of relapse were the same if they stopped it.

“The clinical relevance of a temporary delay in relapse in a long-term psychiatric condition that may last for decades has not been established, and statistically significant results are a questionable basis for implementing an intervention that may be of limited importance to patients,” they write.

To clarify this, the researchers use two examples. The first is a study of whether antipsychotic drugs prevented relapse after the first episode of psychosis. At the 18-month follow-up, it seemed that the risk of relapse was greater for those who had discontinued the drug. But at the 7-year follow-up, the risk of relapse had flipped—it was now greater for those who remained on the drug.

The second example involves using esketamine for relapse prevention in treatment-resistant depression. In the first eight weeks, people who did not take the drug had higher relapse rates. But by about the 9-month mark, there was no difference between the groups in terms of relapse risk. The researchers write:

“Evidence of a withdrawal effect has a bearing on the cost-benefit analysis of starting treatment, and is particularly important in view of the fact that acute trials of esketamine have not demonstrated a clinically relevant effect.”

Ultimately, they argue that survival analysis is misleading and should be avoided in trials of psychiatric relapse prevention. Additionally, they point to the importance of long-term follow-up since withdrawal effects bias the short-term results.



Moncrieff, J., Jakobsen, J. C., & Bachmann, M. (2021). Later is not necessarily better: limitations of survival analysis in studies of long-term drug treatment of psychiatric conditions. BMJ Evidence-Based Medicine. (Link)


  1. “Common Statistical Method Conflates Withdrawal with Relapse”

    Definitely, the “mental health professionals” – in a hubris filled manner – admitted that they didn’t know anything about the common withdrawal symptoms of the antidepressants, in 2005.'Brain_shivers'_From_chat_room_to_clinic

    And, of course, all their hubris filled ignorance – of the common adverse effects of the drug classes they force onto innocent people – did result in a massive societal iatrogenic “bipolar epidemic.”

    And the psychiatrists’ solution to these staggering in scope, crimes / malpractice against millions, was to take this DSM-IV-TR disclaimer out of their DSM5 “bipolar” diagnostic “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.”

    Yes, definitely there’s a societal problem with the so called “mental health professionals” confusing the adverse and withdrawal symptoms of their drugs, with their “invalid” DSM disorders.

    Report comment

    • And, thank you so much Peter, for reporting on the fact that both the antidepressants and antipsychotics can create “psychosis,” via anticholinergic toxidrome. I’m not certain yet whether you’ve reported on the fact that the antipsychotics can also create the negative symptoms of “schizophrenia,” via neuroleptic induced deficit syndrome.

      But I do know the globalist banksters already know, that those of us on MiA have destroyed the scientific validity of even “the sacred symbol of psychiatry.” Which has historically always been used as their way of discrediting those who stood against their systemic, criminal banking system. As eluded to at the end of this truthful talk.

      Report comment

  2. People often cite the horrendous withdrawal symptoms and how those can seem like a breakdown but if my own experience is akin to anyone elses I initially felt on top of the world alot of the time. Lifting the veil of sedation would do that but perhaps also the derailed brain goes through an ecstatic rocket launch phase prior to abrupt crash landing in the several months of insufferable smashed up pandemonium.

    If drug trials are taking people off antipsychotics and pepping them with new pills in a week where the rocket launch occurs then maybe one or two of those patients will possibly be so manic and full of revival that they might link feeling fabulous, after a decade of miserable sedation, to such new pills.

    This may mean that most approved antipsychotics come on to the market from causing nothing fancier than the patient’s own post antipsychotic “well” feeling, a feeling that is actually a dangerous level of mania.

    For drug box leaflets that read…

    “effective at treating depression”

    instead read…

    “effective at doing nothing to abort the rocket launch of the patient’s manic sense of “betterness” from withdrawal.

    Lots of psyche drugs may come from someone elses “high”, a high that has nothing to do with the drugs pushed onto the pharma shelves.

    T’would be like taking an alcoholic person off drink and waiting for them to get sober and lucid and then giving a drug and claiming it causes a feeling of super wellness and clarity of thinking.

    Removal of what causes illness cures that illness, it does not mean any added crumbs of faff were “the cure”.

    “Curiouser and curiouser”, said Alice.

    Report comment