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Gastaldon et al. (2022). Withdrawal Syndrome Following Discontinuation of 28 Antidepressants: Pharmacovigilance Analysis of 31,688 Reports from the WHO Spontaneous Reporting Database


Addax

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Drug Safety, 2022, https://doi.org/10.1007/s40264-022-01246-4, Gastaldon et al. 2022

(Drug Safety is peer reviewed journal)

 

Abstract
Introduction Evidence is lacking on withdrawal syndrome related to individual antidepressants and relevant risk factors for severe reactions.


Objective

To ascertain whether antidepressants are associated with an increased reporting of withdrawal syndrome as compared with other medications, and to investigate risk factors for severe reactions.


Methods

This is a case/non-case pharmacovigilance study, based on the VigiBase®, the WHO global database of individual
case safety reports of suspected adverse drug reactions. We performed a disproportionality analysis of reports of antidepressant-related withdrawal syndrome (calculating reporting odds ratio [ROR] and Bayesian information component [IC]). We compared antidepressants to all other drugs, to buprenorphine (positive control), and to each other within each class of antidepressants (selective serotonin reuptake inhibitors [SSRIs], tricyclics and other antidepressants). Antidepressants with significant disproportionate reporting were ranked in terms of clinical priority. Serious versus non-serious reactions were compared.


Results

There were 31,688 reports of antidepressant-related withdrawal syndrome were found. A disproportionate reporting was detected for 23 antidepressants. The estimated ROR for antidepressants altogether, compared to all other drugs, was 14.26 (95% CI 14.08–14.45), 17.01 for other antidepressants (95% CI 16.73–17.29), 13.65 for SSRIs (95% CI 13.41–13.90) and 2.8 for tricyclics (95% CI 2.59–3.02). Based on clinical priority ranking, the strongest disproportionate reporting was found for paroxetine, duloxetine, venlafaxine and desvenlafaxine, being comparable to buprenorphine. Withdrawal syndrome was reported as severe more often in males, adolescents, persons in polypharmacy, and with a longer antidepressant treatment duration (p < 0.05).


Conclusions

Antidepressants are associated with an increased reporting of withdrawal syndrome compared with other drug
classes. When prescribing and discontinuing antidepressants, clinicians should be aware of the potentially different proclivity of withdrawal syndrome across individual antidepressants, and the liability to experience more severe withdrawal symptoms in relation to specific patient characteristics.

 

Link (has link to PDF): https://link.springer.com/article/10.1007/s40264-022-01246-4

 

1988-2012: Prozac @ 60mg (with a few stops and starts)

Fall 2012: Returned to 40mg after discontinuing and horrid withdrawal 

Fall 2013: 40mg Fluoxetine, added 150mg Wellbutrin to treat fatigue 

Winter 2014: Attempting to taper both (too fast)

April 2014: 9mg Fluoxetine + 37.5 Wellbutrin 

Summer 2014: 8 mg Fluoxetine + 0 Wellbutrin (way too fast a drop)

Late summer/Early Fall 2014: Debilitating Withdrawal symptoms 

Fall 2014 - Wellbutrin successfully kicked to the curb but…

Oct- Dec 2014: Panicked reinstatement of Fluoxetine ->30mg - held for 5yrs

Jan 2021: taper to 20mg Fluoxetine  then tapering by 1mg every 2-3 months

Fall 2022 - held at 10mg->December 2022: 9mg->Feb 2023: 8mg ->March 2023: brassmonkey slide begins: 7.8mg -> 7.6 -> 7.4->2 week hold (April)->7.2->7mg->6.8->2 week hold->6.6-> 1-month hold ->(June)-6.5->4-week hold-> (July)-6.4 (discontinued brassmonkey slide and slowed taper)-> (Aug)-6.2->(Sept)-6.0->(Oct)-5.9->(Nov)-5.8->(Dec)-5.7->wave!->(Jan)-5.8 and holding

 

My 2014 withdrawal experience: https://rxisk.org/antidepressant-withdrawal-a-prozac-story/

 

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Keep 'em coming, Addax!  Were you around in the PaxilProgress days?  I swear we didn't have any literature like this back then, or at least I didn't search it out I guess.  

 

I liked that they acknowledged "...the impact of withdrawal symptoms on quality of life and social functioning may be highly disabling...."

 

Glad to hear that this is being discussed in the right circles.   I'd love to hear something about truly long term use like 10+ years but I haven't seen that survey yet.   

I am not a doctor and do not offer any medical advice, only my own experience.  Consult your physician.

2011-2015 tapered off 300MG of Effexor.  Back in the Paxil Progress days.  No rebound.   

2005-2021:  450 mg Bupropion XL Daily

2021 Buporopion May 450mg/June 400mg/July 375mg/Aug 10th 360mg/

2021 Dec - 150mg IR, 3x day = 450mg Bup, Heritage manufacturer-yellow color pill. 

2022 May 3 - 3 x 150mg IR Bup, Avet brand(pharmacist said they merged with Heritage-orange color) -migraines

REINSTATED-BACK TO MY LAST STABLE DOSE/TIME RELEASE

2022 June 5 - switched back to 3 x 150mg XL one time per day= 450 mg total Bup-Apotex brand

CURRENT TAPER 2022 Aug 31 - 450MG to 412MG IR Bup//Sep. 28, 2022: 412mg to 375mg//Oct 26, 2022: 375mg to 365 mg//Nov 21, 2022: 365mg to 327mg//Dec 27, 2022: 327 mg to 290 mg//Dec 31, 2022:  290mg to 262mg//Jan 28, 2023:  262mg to 190mg//Feb. 19, 2023:  190mg to 140mg//Mar. 18, '23:  140mg to 100mg//

 

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17 hours ago, j1290 said:

I'd love to hear something about truly long term use like 10+ years but I haven't seen that survey yet. 


Ditto. With 30+ years of Fluoxetine use, I keep an eye out for research on long term use of SSRIs and SNRIs. 

 

17 hours ago, j1290 said:

I swear we didn't have any literature like this back then, or at least I didn't search it out I guess.  


There was relatively little research on adverse affects and withdrawal from SSRIs and SNRIs until very recently. Unfortunately, the research that was published decades ago related adverse effects and withdrawal symptoms did not get much, if any, attention. Maybe someone will stumble across a plethora of unpublished research data and put out a meta analyses. 

1988-2012: Prozac @ 60mg (with a few stops and starts)

Fall 2012: Returned to 40mg after discontinuing and horrid withdrawal 

Fall 2013: 40mg Fluoxetine, added 150mg Wellbutrin to treat fatigue 

Winter 2014: Attempting to taper both (too fast)

April 2014: 9mg Fluoxetine + 37.5 Wellbutrin 

Summer 2014: 8 mg Fluoxetine + 0 Wellbutrin (way too fast a drop)

Late summer/Early Fall 2014: Debilitating Withdrawal symptoms 

Fall 2014 - Wellbutrin successfully kicked to the curb but…

Oct- Dec 2014: Panicked reinstatement of Fluoxetine ->30mg - held for 5yrs

Jan 2021: taper to 20mg Fluoxetine  then tapering by 1mg every 2-3 months

Fall 2022 - held at 10mg->December 2022: 9mg->Feb 2023: 8mg ->March 2023: brassmonkey slide begins: 7.8mg -> 7.6 -> 7.4->2 week hold (April)->7.2->7mg->6.8->2 week hold->6.6-> 1-month hold ->(June)-6.5->4-week hold-> (July)-6.4 (discontinued brassmonkey slide and slowed taper)-> (Aug)-6.2->(Sept)-6.0->(Oct)-5.9->(Nov)-5.8->(Dec)-5.7->wave!->(Jan)-5.8 and holding

 

My 2014 withdrawal experience: https://rxisk.org/antidepressant-withdrawal-a-prozac-story/

 

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