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Wilson and Lader, 2015 A review of the management of antidepressant discontinuation symptoms

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Ther Adv Psychopharmacol. 2015 Dec;5(6):357-68. doi: 10.1177/2045125315612334.
A review of the management of antidepressant discontinuation symptoms.
Wilson E1, Lader M2.

Abstract and free full text at http://www.ncbi.nlm.nih.gov/pubmed/26834969PDF at http://tpp.sagepub.com/content/5/6/357.full.pdf

Strong evidence supports the existence of a discontinuation syndrome following the withdrawal of antidepressant medication, particularly second-generation antidepressants. The syndrome is a common phenomenon and guidance as to best avoid the symptoms is essential for both practitioners and patients. The current study reviewed the available literature on the best methods of discontinuation for antidepressants in order to avoid or prevent the occurrence of any unpleasant side effects associated with antidepressant withdrawal. Accordingly, an electronic search of the PubMed/MedLine database and Google Scholar was conducted to find relevant literature published within the last 10 years. From this, 18 related articles were identified; five clinical studies, one case series, one consensus panel's recommendations and 11 literature reviews. Of the articles reviewed there is a general consensus as to tapering the drug slowly over a period of weeks or months. Also, in those patients who experience severe symptoms the drug should be reinstated and discontinued more gradually. The discontinuation syndrome does not occur as frequently or severely with longer-acting agents such as fluoxetine and therefore it is recommended that switching to this drug prior to withdrawal may be advisable. The articles reviewed also emphasize the need for patient education and reassurance throughout the discontinuation process. One in particular adds that cognitive behavioural therapy may be a useful tool in easing the patients' distress. However, this review highlights the lack of controlled data to support the available guidelines. Furthermore, the guidance which is available is somewhat conflicting. Research approaches should address this issue as well as develop appropriate methods of withdrawal for specific drugs.
 

Edited by Altostrata
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Synchronicity, I was just about to post this.

 

Malcolm Lader has long written about benzo withdrawal.

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From the paper:

 

....

Blier and Tremblay stating that the rate at which SSRI treatment is terminated and the duration of treatment appear to be key factors in predicting discontinuation symptoms [Blier and Tremblay, 2006]. They suggest that SSRI discontinuation symptoms may arise from the rapid decrease in serotonin (5-HT) availability when treatment ends abruptly but also note that the discontinuation syndrome may not be mediated exclusively through 5-HT receptors; they propose that the noradrenaline and the cholinergic systems also play a key role [Blier and Tremblay, 2006].

....

Although there remains some debate as to the biological mechanisms underlying the antidepressant discontinuation syndrome, there is substantial agreement that it can occur following the withdrawal of any antidepressant and is a common phenomenon amongst a wide range of antidepressants including TCAs, MAOIs, and SSRIs, particularly with more-potent and shorter-acting SSRIs such as paroxetine and SNRIs such as venlafaxine [Tartakovsky, 2011]. Studies have shown that this withdrawal reaction is a genuine syndrome experienced at least by some patients and therefore does present a clinical concern. Due to the soaring prescription rates of drugs such as these and the prevalence of depression globally, guidance on the treatment of this disorder is necessary, especially for discontinuation, as adverse effects appear to be a common phenomenon experienced during drug withdrawal. According to Ogle and Akkerman, at present the literature available as well as the package insert guidance is vague and somewhat generic [Ogle and Akkerman, 2013].

....

Overview

A review of this literature shows a general consensus towards tapering the dose of the drug over time, although the taper rates recommended vary somewhat between the articles reviewed. For instance, two of the articles suggest that reducing the dosage by 25% per week is sufficient to avoid discontinuation symptoms [McHugh and Krishnadas, 2011; Edwards, 2006] whilst another more cautiously recommends tapering over 6-8 weeks [Warner et al. 2006]. Phelps nevertheless proposes even longer rates of gradual dose reduction, adducing evidence from narcolepsy studies which show 3 months as being necessary for cataplexy rates to return to baseline [Phelps, 2011]. The author argues that this period is required for the body to ‘normalize’ during discontinuation and recommend 4 months in order to reduce relapse rates and symptoms associated with drug withdrawal [Phelps, 2011]. Many of the guidance articles reviewed state explicitly that there is conflicting opinion as to the optimum duration of gradual dose reduction [Haddad and Anderson, 2007; Ogle and Akkerman, 2013] and the evidence base for tapering antidepressants is weak. Of the five clinical studies reviewed, only two [Himei and Okamura, 2006; van Geffen et al. 2005] recommend tapering the drug over time as a result of findings that abruptly withdrawing medication significantly increases the likelihood of a discontinuation syndrome. Only one randomized control trial [Tint et al. 2008] investigates the effects of tapering schedules, however, with the authors reporting no significant difference between a 3-day and 14-day taper rate. Nevertheless, the compared taper schedules are relatively short in this study and sample size is small.

 

Tapering schedules

Most articles reviewed agree that tapering is unnecessary for patients who have been taking an antidepressant for 4 weeks or less as this is insufficient time to develop a withdrawal reaction [Ogle and Akkerman, 2013; Haddad and Anderson, 2007; Edwards, 2006]. They also agree that if discontinuation symptoms are severe, the drug should be reintroduced and a slower taper initiated [Ogle and Akkerman, 2013; Lader, 2007; Zarowitz, 2006; Schatzberg et al. 2006; Reid and Cameron, 2009; Warner et al. 2006; Edwards, 2006]. Baldwin and colleagues argue that duration of treatment has no association with incidence of discontinuation syndrome [Baldwin et al. 2007] and two of the reviewed publications suggest that the half-life of the drug plays a more pivotal role than the taper rate [Tint et al. 2008; Montgomery et al. 2004]. They also suggest that for antidepressants with shorter half-lives, such as venlafaxine and paroxetine, a more gradual dose reduction would be advisable as a result of the associated severe discontinuation syndrome [Tint et al. 2007; Montgomery et al. 2004]. Likewise, in a few of the articles [Ogle and Akkermann, 2013], a distinction was made between fluoxetine and other antidepressants due to its relatively long half-life and active metabolite. As a result, suggestions that a taper from this drug was possibly unnecessary were made [Schatzberg et al. 2006; Warner et al. 2006] along with recommendations of switching to fluoxetine prior to discontinuation in some cases [Schatzberg et al. 2006; Warner et al. 2006; Muzina, 2010]. Muzina adds that a more rapid tapering may also be possible in cases where doses are low prior to withdrawal [Muzina, 2010] and two studies [Haddad and Anderson, 2007; McHugh and Krishnadas, 2011] also note that some antidepressants, including paroxetine, are available in liquid formulations enabling a more precise and graduated taper.

....

Although there are few studies available, the guidance they provide does possess substantial face validity. From the available literature there is a general consensus that the best method is to taper the drug slowly in order to avoid discontinuation symptoms. At present, the most recent antidepressant guidelines advise this method and recommend a minimum period of a 4-week taper following long-term treatment, preferably over months for a planned withdrawal of antidepressant medication [Cleare et al. 2015]. However, as highlighted, some debate remains as to the optimum taper schedule implemented. McHugh and Krishnadas add that individuals vary in their propensity to experience discontinuation symptoms and there should be no time pressure on the tapering period when an antidepressant is being terminated altogether [McHugh and Krishnadas, 2011]. Despite this, the question of methods of discontinuation will remain an ongoing issue....

....

Tapering can also be facilitated by liquid formulations for precision in very gradual dose reductions, whilst tapering strips are now available for some antidepressants, including paroxetine, in which each strip contains a slightly lower dose on each consecutive day [Groot, 2013]. Another potential method of avoiding unnecessary discomfort during discontinuation may come from the use of specialist nurses that have been trained in antidepressant discontinuation. This strategy has been trialled previously for benzodiazepine withdrawal, with one study in particular reporting that, after a period of one year, two thirds of patients had successfully ceased taking the medication [Lopez-Peig et al. 2012]. Finally, treatment should also be kept as short as possible with the aim of complete discontinuation.

....

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Note: Schatzberg et al, 1997 and Schatzberg et al, 2006 were "expert consensus" panels outright sponsored by Eli Lilly (Prozac) and Wyeth (Effexor) respectively, and should have been excluded from this survey.

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Very good....the part about using specialist nurses trained in antidepressant discontinuation to provide comfort and hopefully knowledge. I shall keep my license active. And continue to print off articles. For the cause! Must fix printer soon or switch to another one.

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I wonder how many other authors have conflicts of interest . some of the statements seem misinformed.

 

1. Most articles reviewed agree that tapering is unnecessary for patients who have been taking an antidepressant for 4 weeks or less as this is insufficient time to develop a withdrawal reaction [Ogle and Akkerman, 2013; Haddad and Anderson, 2007; Edwards, 2006].

What were the 'most articles' ...pharma sponsored propaganda.

Healys research and my own experience is at odds with this.

 

2. Baldwin and colleagues argue that duration of treatment has no association with incidence of discontinuation syndrome [Baldwin et al. 2007]

 

If this is correct then this contradicts 1.

 

3. As a result, suggestions that a taper from this drug was possibly unnecessary were made [Schatzberg et al. 2006; Warner et al. 2006] along with recommendations of switching to fluoxetine prior to discontinuation in some cases [Schatzberg et al. 2006; Warner et al. 2006; Muzina, 2010].

Well a Lilly employee would say this wouldnt they.

 

4. Muzina adds that a more rapid tapering may also be possible in cases where doses are low prior to withdrawal [Muzina, 2010]

Oh boy!!

 

 

3. and two of the reviewed publications suggest that the half-life of the drug plays a more pivotal role than the taper rate [Tint et al. 2008; Montgomery et al. 2004].

Some more reviewed publications sponsored by pharma? We all know people on prozac and lexapro struggle just as much as everyone else with wdl.

 

4. whilst tapering strips are now available for some antidepressants, including paroxetine, in which each strip contains a slightly lower dose on each consecutive day [Groot, 2013].

This sounds like its  going to trigger trouble.

 

5. Finally, treatment should also be kept as short as possible with the aim of complete discontinuation.

Be good to tell the docs this. Easier said than done.

 

6. Another potential method of avoiding unnecessary discomfort during discontinuation may come from the use of specialist nurses that have been trained in antidepressant discontinuation.

Why ? Is it asking too much for doctors to understand this? I know of no other profession where people are paid so highly yet get to so easily avoid all responsibility.

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As you can see, there are a lot of guesses but little is known.

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yep, if this is the best they can come up with in Dec 15 lets call it Jan 16, then it truly is a tragic situation.

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Tijdschr Psychiatr. 2013;55(10):789-94.
[Taperingstrips for paroxetine and venlafaxine].
[Article in Dutch]
Abstract
BACKGROUND:

Tapering strips can be used for the gradual reduction of the dose of certain types of drugs such as antidepressants and benzodiazepines. The strips contain a slightly lower dose on each consecutive day. This prevents the withdrawal symptoms still experienced by too many patients and lowers the risk of relapse.

AIM:

To make tapering strips of antidepressant drugs available for patients in need of a tapering-off procedure.

METHOD:

The Consensusgroup Tapering studied the literature and consulted with experts to find out whether the plan to make tapering strips of paroxetine and venlafaxine available for patients is feasible.

RESULTS:

The Cinderella Therapeutic Foundation (www.cinderella-tx.org), a not-for-profit organisation which aims to give patients access to orphan drugs and treatments, wants to make tapering strips of paroxetine and venlafaxine available since these are the two antidepressants that cause the most problems. The process of producing, packaging and checking the tapering doses is <span class="abbreviation">iso</span>-certified; each strip is provided with a bar-code and can be followed and traced. Therefore the strips will conform to current safety regulations.In view of the large number of patients taking paroxetine and venlafaxine there is likely to be a considerable demand for tapering strips.

CONCLUSION:

From a financial, marketing and practical point of view, the introduction of tapering strips is feasable. Patients will derive considerable benefits. The paroxetine strips will be produced first and are expected to be available from December 2013.

Strips supposedly to be made by this company

http://www.cinderella-tx.org/en/

 

They have paxil tapering strips but effexor tapering strips are not yet ready. 

http://www.cinderella-tx.org/en/2013/12/30/tapering-paroxetine-better-safer-taperingstrip/

 

They also produce low dose naltrexone 

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" Antidepressant discontinuation syndrome is more likely with a longer duration of treatment and a shorter half-life of the treatment drug. "

 

http://www.aafp.org/afp/2006/0801/p449.html

 

The importance of understanding and recognizing antidepressant discontinuation syndrome is threefold: (1) though typically mild, antidepressant discontinuation syndrome symptoms are associated with significant discomfort, work absenteeism, other psychosocial problems, and may on rare occasions be severe enough to require hospitalization1012; (2) failure to recognize antidepressant discontinuation syndrome may result in medical and psychiatric misdiagnosis, potentially exposing patients to unnecessary diagnostic investigations or potentially risky medical interventions; (3) patients may be unwilling to use psychotropic medications in the future, thereby increasing their vulnerability to future relapses of depressive or anxiety disorders

 

Though this article is from 2006 it has some interesting tables some you can see and some you can't such at this one

"There are no clear, validated tapering recommendations. However, Table 527 offers one expert's recommendations for tapering rates."

TABLE 5

The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item, see the original print version of this publication.

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btdt, stop posting off-topic in the Journals forum.

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