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Berwian, 2017 Predicting relapse after antidepressant withdrawal - a systematic review.

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ADMIN NOTE E-mail sent to lead author of paper with cc to journal editor.


Dr. Berwian —


I read with interest your paper Psychol Med. 2017 Feb; 47(3): 426–437. Predicting relapse after antidepressant withdrawal – a systematic review.


I believe the conclusion of your paper is correct, medicine cannot predict who will relapse after discontinuation of antidepressants. However, I must make a very important point: If you look closely at the 13 studies you included in your review, you will see that not a single one includes a protocol for distinguishing relapse from antidepressant withdrawal or discontinuation syndrome.


Instead, all of them evaluated post-discontinuation condition on some kind of depression scale. If a patient was feeling poorly from withdrawal symptoms, he or she had no choice but to indicate that somehow in the context of “depression” — even if the symptoms were the very common dizziness, disorientation, "brain zaps", nausea, or sleeplessness, all withdrawal symptoms that are not relapse of depression but might cause anyone to feel down.


Failure to identify withdrawal symptoms and the consequent misdiagnosis as relapse has confounded all studies of antidepressant efficacy and relapse after discontinuation. This may be why you found predictive value of these studies to be very weak.


Given that physicians, even academic psychiatrists, are so poorly informed about gradual tapering techniques and identifying withdrawal symptoms, it may very well be that the most common outcome of antidepressant discontinuation is not “relapse” but withdrawal syndrome.


In fact, true relapse in such situations may be rare, and millions of people have been erroneously continued on chronic antidepressant treatment for years merely to avoid withdrawal symptoms.


Please consider this should you follow up on your 2017 publication.



Psychol Med. 2017 Feb;47(3):426-437. doi: 10.1017/S0033291716002580. Epub 2016 Oct 27.

Predicting relapse after antidepressant withdrawal - a systematic review.

Berwian IM1, Walter H2, Seifritz E1, Huys QJ1.


Abstract and free full text at https://www.ncbi.nlm.nih.gov/pubmed/27786144


A substantial proportion of the burden of depression arises from its recurrent nature. The risk of relapse after antidepressant medication (ADM) discontinuation is high but not uniform. Predictors of individual relapse risk after antidepressant discontinuation could help to guide treatment and mitigate the long-term course of depression. We conducted a systematic literature search in PubMed to identify relapse predictors using the search terms '(depress* OR MDD*) AND (relapse* OR recurren*) AND (predict* OR risk) AND (discontinu* OR withdraw* OR maintenance OR maintain or continu*) AND (antidepress* OR medication OR drug)' for published studies until November 2014. Studies investigating predictors of relapse in patients aged between 18 and 65 years with a main diagnosis of major depressive disorder (MDD), who remitted from a depressive episode while treated with ADM and were followed up for at least 6 months to assess relapse after part of the sample discontinued their ADM, were included in the review. Although relevant information is present in many studies, only 13 studies based on nine separate samples investigated predictors for relapse after ADM discontinuation. There are multiple promising predictors, including markers of true treatment response and the number of prior episodes. However, the existing evidence is weak and there are no established, validated markers of individual relapse risk after antidepressant cessation. There is little evidence to guide discontinuation decisions in an individualized manner beyond overall recurrence risk. Thus, there is a pressing need to investigate neurobiological markers of individual relapse risk, focusing on treatment discontinuation.



Table 1 is the list of the studies included in the above review, with their evaluating instruments: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244448/table/tab01/


Also see pdf of Table 1 at https://drive.google.com/open?id=13FmKRp4wSlJ4vkbdh2mcqIhXuwxPy0qP

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Do any studies of withdrawal include people treated for conditions other than depression or anxiety?  Antidepressants are used for so many physical disorders including premature ejaculation, low blood pressure, etc. It would be interesting to see cases like that included. 

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@Altostrata Just bless you for caring so deeply here and for persevering so tenaciously in your efforts to educate prescribers and others.  It is amazing to me.  Hopefully soon those following behind us will reap the benefits of your work and the work of the other staff here and not find themselves in  situations such as ours.  I copy these to take to my doctor.  Thank you for sharing!  

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Thank you, Rabe.


How does your doctor respond?

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