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

[Addax]

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

 

[j1290]

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.   

[Addax]

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.