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Quilichini et al. (2022). Comparative effects of 15 antidepressants on the risk of Withdrawal Syndrome: A real-world study using the WHO pharmacovigilance database


Addax

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Journal of Affective Disorders, 2022, https://doi.org/10.1016/j.jad.2021.10.041, Quilichini et al.

 

Abstract

Background

While case reports and clinical trials reported withdrawal syndrome after reduction and/or discontinuation of antidepressant drugs, no large study has been conducted to compare the risk between the different antidepressants.

 

Methods

Using data recorded from January 1st, 1988, and December 31st, 2020 in VigiBase®, the World Health Organization's Global Individual Case Safety Reports database, we performed disproportionality analysis to investigate the risk of reporting withdrawal syndrome in patients treated by short half-life antidepressants compared with patients treated by long half-life antidepressants. In addition, we aimed to better inform clinical practice by comparing 15 antidepressants for the risk of reporting withdrawal syndrome.

 

Results

Among the 338,498 reports with antidepressants of interest, we found 15,507 cases of withdrawal syndrome. Short half-lives antidepressants were associated with an increased risk of reporting a withdrawal syndrome compared to long half-life antidepressants (ROR 5.38; 95% CI 5.16–5.61). The risk was higher for 18–44 years old (ROR 6.88; 95% CI 6.17–7.62), women (ROR 1.38; 95% CI 1.33–1.43) and patients treated with Paroxetine, Desvenlafaxine, Venlafaxine and Duloxetine.

 

Limitations

The limitations of this study stem from the case-reporting process.

 

Conclusions

This large observational study in a real-world setting suggests that the use of short half-life antidepressants increases the risk of reporting withdrawal syndrome compared to long half-life antidepressants. Among the most common antidepressants, paroxetine and serotonin-noradrenaline reuptake inhibitors are associated with a greater risk of reporting withdrawal syndrome, while agomelatine and vortioxetine present a lower risk. Additional studies are needed to corroborate our results.


web link (and link to PDF): https://www.sciencedirect.com/science/article/abs/pii/S0165032721011253

 

 

Edited by Addax

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->(Feb)-6mg and holding.

 

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

 

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Very interesting, Addax!   Glad this is being studied.  Bupropion doesn't seem to get much coverage. I hope the word gets out about how hard it can be to get off these things, and these studies are a great direction.  

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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5 hours ago, j1290 said:

Bupropion doesn't seem to get much coverage.

No it doesn’t. It’s kind of surprising given evidence that coadministration of bupropion with ADs that are also metabolized by CYP450 2D6 can increase the other AD’s plasma levels and half-life by decreasing the other AD’s clearance (like it increases the other drugs potency). In theory, This relationship has the potential to really muck up tapering and therefore withdrawal if bupropion has been being taken with an AD metabolized by CYP450 2D6.  But with more attention to AD withdrawal, I bet we’ll see more on bupropion.

Edited by Addax

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->(Feb)-6mg and holding.

 

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

 

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This is something I really would like to understand. I'm newly tapering off of 20 mg of Paxil but still on 150 mg Bupropion. I know Paxil is a potent 2D6 inhibitor -- I found this out the hard way when a cardiologist prescribed a beta-blocker that sent my heart-rate down to 39 bpm! They ask for your medication history then don't bother to check for toxic interactions. Yay health care. Anyway, I thought tapering off the Paxil was more critical but am now wondering how the Bupropion might, as you put it, "muck up my tapering." 

1997 - 1/22/23 Paxil - 20 mg * 1/22/23 - 18 mg * 2/19/23 - 16.2 mg * 3/31/23 - 14.6 mg * 5/9/23 - 13.1 mg * 6/11/23 - 11.8 mg * 8/17/23 - 10.6 mg * 9/18/23 - 10 mg

 

1997 - present Wellbutrin 150 mg

non-psychiatric: Metoprolol, Rosuvastatin, Omeprazole, Eliquis

Magnesium Glycinate - 100 mg

 

 

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10 hours ago, possum said:

Anyway, I thought tapering off the Paxil was more critical but am now wondering how the Bupropion might, as you put it, "muck up my tapering."


It’s tough to say whether or how much it would or will since there is not much information on it out there. For me I think the awareness of potential for “muck up” might have slowed me down in the past. Or maybe I would have tapered Fluoxetine first because it sounds like tapering the bupropion first might have been causing a simultaneously taper of Fluoxetine. Of course I don’t know that to be true. I’m theorizing using limited information. Ultimately, Alto and the SA staff offer the most well informed guidance on these issues. 

Edited by Addax

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->(Feb)-6mg and holding.

 

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

 

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