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Fava, 2018 Discontinuing Antidepressant Drugs: Lesson from a Failed Trial and Extensive Clinical Experience


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Discontinuing Antidepressant Drugs: Lesson from a Failed Trial and Extensive Clinical Experience

Fava G.A.a,b,c · Belaise C.a,c



Scholten et al. [1] reported on the first randomized controlled trial that attempted to prevent relapse in patients with remitted anxiety disorder who discontinued antidepressant drugs (AD) by use of a cognitive-behavioral therapy (CBT) relapse prevention group compared to treatment as usual. The patients who were assigned to CBT received 8 group sessions of relapse prevention, targeting vulnerability factors and discontinuation symptoms. AD were tapered every 2 weeks within 4 months according to a fixed schedule. In the control group (treatment as usual), tapering and discontinuation of AD were carried out without CBT, in individual sessions, according to the same schedule [1]. Primary outcomes were occurrence/reoccurrence of any anxiety disorder or major depressive disorder. Secondary outcome was the success rate of discontinuation of AD. Seventy-three patients were enrolled. Over 16 months there were no significant differences between the CBT group and the treatment as usual group in any of the primary and secondary outcome measures. Despite guidance, only 36% of all participants succeeded in discontinuing AD, and only 28% did not have recurrence. One patient committed suicide. The trial was stopped prematurely for ethical reasons and futility [1]. However, it was certainly not futile and provided important insights into discontinuing AD.


As the authors commented [1], the guidelines’ recommendations to discontinue AD were found neither feasible nor effective in their sample. The investigators, while convinced to apply the best evidence, found out that they had been simply misguided. Withdrawal symptoms and syndromes may occur during and despite slow tapering, do not magically vanish after a couple of weeks from discontinuation and may persist for a long time, leading to postwithdrawal syndromes [23]. In this trial [1], the CBT group was thus stopped when it was more needed, as we are going to discuss below. Further, withdrawal symptoms and syndromes were not adequately assessed and addressed; they might have been misidentified as the occurrence of an anxiety disorder. That specific trial was bound to fail, but alternative routes may be feasible. We will describe the approach to discontinuing AD that we have developed over the years. It has not been tested in controlled trials but may inspire new research efforts in an area that badly needs investigation.

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2005-2008: Effexor; 1/2008 Tapered 3 months, then quit. 7/2008-2009 Reinstated Effexor (crying spells at start of new job.)
2009-3/2013: Switched to Pristiq 50 mg then 100 mg
3/2013: Switched to Lexapro 10mg. Cut down to 5 mg. CT for 2 weeks then reinstated for 6 weeks
8/2013-8/2014: Tapering Lexapro (Lots of withdrawal symptoms)
11/2014 -8/2015: Developed severe insomnia and uncontrollable daily crying spells
12/2014-6/2015: Tried Ambien, Klonopin, Ativan, Lunesta, Sonata, Trazadone, Seroquel, Rameron, Gabapentin - Developed Anxiety disorder, PTSD, and Psychogenic Myoclonus
7/2015-1/2016: Reinstated Lexapro 2 mg (mild improvement, but crying spells still present)

1/2016-5/2017: Lexapro 5 mg ( helped a lot, but poor stress tolerance & depressive episodes)

5/20/2017 - Raised dose to Lexapro 10 mg due to lingering depression(Total of 2 failed tapers & severe PAWS)

9/11/2018 - Present: Still on 10 mg Lexapro and mostly recovered.(Anxiety still triggers Myoclonus.)

10/7/2022 - 20 mg Lexapro (brand only) Plus occasional Klonopin for anxiety and Ambien for insomnia.


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So, at best, approximately 28% of individuals can discontinue at a rapid taper over 4 months.

2005 St John's Wort / 2006-2012 Lexapro 20mg, 2 failed attempts to stop, tapered over 4.5 months in early 2012

January 2013 started Sertraline, over time worked up to 100mg

July 2014 Sertraline dropped from 100mg to 75mg, held for six months, slower tapering until 2019 22 Dec 3.2mg

2020 Sertraline 19 Jan 3.1mg, 26 Jan 3.0mg; 1 Mar 2.9, 7 Mar 2.8, May (some drops here) 24 May 2.5, May 29 2.4, June 21 2.3, June 28 2.2mg,  July 4 2.1mg, July 24 (or maybe a bit before) 2mg, early Nov switched to home made suspension; 29 Nov 1.8mg; approx 25 Dec 1.6mg)

2021 Some time in about Jan/Feb realised probably on more like 1.8mg and poss mixing error in making suspension; doses after 10 Feb accurate; 10 Feb 1.6mg; 7 Mar 1.4, continued monthly

10% drops until 1mg, then dropped 0.1mg monthly.

May 2022,0.1mg, now dropping 0.01mg per week

29 August 2022 - first day of zero!

My thread here at SA: https://www.survivingantidepressants.org/topic/1775-bubbles/page/21/

Current: Armour Thyroid



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That's the most comprehensive analysis I've seen. Very sobering. 

Pristiq tapered over 8 months ending Spring 2011 after 18 years of polydrugging that began w/Zoloft for fatigue/general malaise (not mood). CURRENT: 1mg Klonopin qhs (SSRI bruxism), 75mg trazodone qhs, various hormonesLitigation for 11 years for Work-related injury, settled 2004. Involuntary medical retirement in 2001 (age 39). 2012 - brain MRI showing diffuse, chronic cerebrovascular damage/demyelination possibly vasculitis/cerebritis. Dx w/autoimmune polyendocrine failure.<p>2013 - Dx w/CNS Sjogren's Lupus (FANA antibodies first appeared in 1997 but missed by doc).

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Twenty years ago, this journal anticipated the current medical scenario dominated by corporate interests which result in self-selected academic oligarchies that influence clinical and scientific information. 


Members of special interest groups, by virtue of their financial power and close ties among themselves, have the task of systematically preventing dissemination of data which may be in conflict with their interests.


Corporate powers fused with academic medicine to create an unhealthy alliance that works against objective reporting of clinical research, sets up meetings and symposia with the specific purpose of selling the participants to sponsors, and substantially controls journals, medical associations, and related foundations (through direct support and/or advertising). The growth of evidence-based medicine, with its emphasis on systematic reviews and guidelines, provided an ideal ground for multiplying the effects of financial conflicts of interest in medicine.


In the early nineties, when the reports on withdrawal syndromes upon discontinuing SSRI began to appear, it was crucial to downplay such occurrences. At that time, the commercial plan was to extend the use of SSRI to other psychiatric disorders and to prolong their administration to the longest possible time. Awareness of the occurrence of dependence would have run counter to such a strategy. A concerted action became operational:


(a) Withdrawal reactions were promptly renamed as discontinuation syndromes, as if they were different from what was known about other psychotropic drugs, such as BZD. There was no evidence to support that dependence was different with SSRIs and SNRIs. Indeed, in our clinical experience it is far more difficult to discontinue a drug such as paroxetine or venlafaxine than any BZD. Both physicians and patients were taught that the problem could have appeared only with abrupt discontinuation of AD and that, if symptoms arose, they had to be considered signs of relapse, with prompt readministration of the AD.


(b) BZD, because of their widespread use and their limited cost, were a major obstacle to the introduction of the new AD in anxiety disorders. In anxiety disorders, when directly compared to AD, BZD were found to be more or as effective and with fewer side effects. 
A commercial war was thus started: the dependence potential of BZD was dramatized, and their prescription was hindered in all possible ways, despite the clinical value of this class of medication. Physicians thus learned that BZD were bad and could cause dependence, whereas AD were devoid of such effects. This was probably the most spectacular achievement of propaganda in psychiatry.


(c) Prolongation of pharmacological treatment with the claim to maintain the clinical responses obtained in the short term was another commercial target for SSRI and SNRI. The evidence supporting this strategy was mainly based on clinical trials where remitted patients were randomized to drug continuation or placebo, without any differentiation between withdrawal syndromes and relapse. Thus, in the group that underwent drug tapering and discontinuation, we have no way to know how many of the relapses were actually withdrawal and postwithdrawal syndromes. As a result, the efficacy of AD in preventing relapse in depression compared to placebo relies on hiding the existence of withdrawal syndromes that are misinterpreted as new illness episodes.


(d) Special interest groups operating in funding agencies and medical journals made sure that iatrogenic components of depression could not get attention and funding, even though these phenomena may explain a large part of clinical outcomes, such as chronicity.


An important research question arises with withdrawal phenomena related to SSRI and SNRI: are these distressing but self-limiting reactions or are they signs of something else? They may be manifestations of behavioral toxicity (the oppositional model of tolerance), potentially related to loss of clinical effects, increased vulnerability to relapse, resistance when treatment is reinstituted, unresponsiveness, paradoxical effects.


A major consequence of these commercial strategies has been that patients experiencing anguish and mental pain of withdrawal syndromes have not received appropriate medical attention and have been forced to refer themselves to websites, groups, associations, which had the recognized merit of providing support but could not offer the medical competence that was required, particularly as to medical comorbidities. Professional organizations and scientific societies have major responsibilities in not assuring proper care to people in need of it.”

Medication before problems: Took Paxil 60-100mg from 2003 to 2014 for OCD.
1) Last pill taken November 2014, horrendous withdrawal started six weeks later.

2) Re-instated successfully @ 20mg May 2015, but accompanied by severe anhedonia, loss of emotion, apathy, and fatigue

3) Switched to Prozac, Viibyrd, Zoloft, Nefazadone, Cymbalta, Nardil in attempt at abating WD symptoms while not re-introducing anhedonia. Each one either failed to relieve WD or brought back anhedonia. So re-stabilized on Paxil at 15mg

4) Tapered down to 7.5mg as of October 2016. More energy, anhedonia/loss of emotions remains apart from short windows.

5) May 2017 - down to 3.5mg of Paxil (no other meds)
6) Early 2018 - added 8mg of Prozac
7) January 2019 - down to 1.05 Paxil / 5mg Prozac and continuing

8) October 2019 - down to 0.2mg Paxil / 3mg Prozac

9) November 2019 - down to 0.1mg Paxil / 3mg Prozac 

10) March 2020 - done with Paxil, 2.5mg Prozac

11) April 2021 - 0.03mg Prozac

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