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Horowitz et al. (2022). Estimating Risk of Antidepressant Withdrawal from a Review of Published Data


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CNS Drugs, 2022, DOI: 10.1007/s40263-022-00960-y. Estimating Risk of Antidepressant Withdrawal from a Review of Published Data. Horowitz et al. 

Adaptation of the brain to the presence of a drug predicts withdrawal on cessation. The outcome of adaptation is often referred to as ‘physical dependence’ in pharmacology, as distinct from addiction, although these terms have unfortunately become conflated in some diagnostic guides. Physical dependence to antidepressants may occur in some patients, consistent with the fact that some patients experience withdrawal effects from these medications. It is thought that longer duration of use, higher dose and specific antidepres- sants affect the risk of antidepressant withdrawal effects as they might cause greater adaptation of the brain. We searched PubMed for relevant systematic reviews and other relevant analyses to summarise existing data on determinants of antidepressant withdrawal incidence, severity and duration. Overall, data were limited. From survey data, increased duration of use was associated with an increased incidence and severity of withdrawal effects, consistent with some evidence from data provided by drug manufacturers. Duration of use may be related to duration of withdrawal effects but data are heterogenous and sparse. Serotonin and noradrenaline reuptake inhibitors and paroxetine are associated with higher risks than other antidepressants, though data for some antidepressants are lacking. Higher doses of antidepressant has some weak association with an increased risk of withdrawal, with some ceiling effects, perhaps reflecting receptor occupancy relationships. Past experience of withdrawal effects is known to predict future risk. Based on these data, we outline a preliminary rubric for determining the risk of withdrawal symptoms for a particular patient, which may have relevance for determining tapering rates. Given the limited scope of the current research, future research should aim to clarify prediction of antidepressant withdrawal risk, especially by examining the risk of withdrawal in long-term users of medication, as well as the severity and duration of effects, to improve the preliminary tool for predictive purposes. Further research into the precise adaptations in long-term antidepressant use may improve the ability to predict withdrawal effects for a particular patient.


Link to full text (Website): https://link.springer.com/article/10.1007/s40263-022-00960-y#citeas


Link to full text (PDF): https://link.springer.com/content/pdf/10.1007/s40263-022-00960-y.pdf?pdf=button


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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  • 2 weeks later...

Thank you for posting this for us, Addax! 


I took from it some good news and bad news.  The good news is that it's unlikely that tapering off Bupropion could be harder than getting off the Venlafaxine, which still makes me shudder to remember.   The bad news is there wasn't enough data for them to draw conclusions about the Bupropion, other than that the length of time I've been on it will put me into a high risk of WD symptoms category.   Makes sense.  


Thanks again, really enjoying these.

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


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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