Withdrawal/discontinuation effects of antidepressants – Inside Health 22/10/19

a history of antidepressant withdrawal

1950s – class of drug called tricyclics started to be used for depression

reports of withdrawal side effects in medical literature in 1960s and 70s suggesting slow withdrawals

https://journals.sagepub.com/doi/10.1177/070674376601101S27

another class of drugs called MAOIs – again not commonly used nowadays for depression, available in 1950s onwards, lots of interactions

but again reports of withdrawal effects  in 1960s and 70s

https://www.ncbi.nlm.nih.gov/pubmed/14154787

https://journals.lww.com/psychopharmacology/fulltext/2011/02000/Advances_Pertaining_to_the_Pharmacology_and.13.aspx?casa_token=5RyMD-FAWm0AAAAA:Ip5_dPn4AHnWj-12kZUtGYwiDfvwHFc08dCrTCOLKPFdHzDgPaOl6GxkvSxVTVfYxWMpsvDxs8zsKw_f-O6AEtyfNqs

then in late 1980s (1988) Fluoxetine put onto the market

atypical venlafaxine in 1993 (two different receptors serotonin and norepinephrine)

early 90s started seeing studies looking at ‘interruption ‘ syndrome

https://www.ncbi.nlm.nih.gov/pubmed/10827885 – single blind stoppages

Drugs and Therapeutics Bulletin 1999 

https://dtb.bmj.com/content/37/7/49.info

“Before withdrawing an antidepressant, patients should also be warned of the possibility that stopping treatment can itself lead to a cluster of symptoms which are commonly referred to as a ‘discontinuation syndrome’.

can occur with any antidepressant; they usually start abruptly within a few days of stopping the drug and resolve quickly (usually within 24 hours) if the drug is restarted. In general, it should be possible to distinguish discontinuation syndromes from true relapse of depression, which is uncommon in the first week after stopping treatment and resolves more slowly when the drug is restarted. On the other hand, re-emergent symptoms of depression may be a feature of the discontinuation syndrome itself,15 so the distinction is not always clear-cut. Ignorance of discontinuation reactions could have led, in the past, to some overestimation of relapse rates when antidepressants were withdrawn.”

Then American Family Physician in 2006 https://www.aafp.org/afp/2006/0801/p449.html 

many reports of discontinuation reactions with SSRIs.13,18 Typically symptoms begin within 24-72 hours of stopping the drug and last 1-2 weeks, but occasionally much longer.19

Studies specifically designed to assess discontinuation symptoms with SSRIs commonly report rates of around 20% or more.

Then

Yellow card scheme – paroxetine most notified out of SSRIs re adverse effects and most severe withdrawal effects https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2125.1996.00498.x

NICE guideline in 2009

“usually mild and self limiting over about one week”

dispute 2018

review article (much criticised)  

letter from critics wrote about harms and benefits of antidepressants

https://www.thetimes.co.uk/article/stigma-and-efficacy-of-taking-antidepressants-0zvsg560x

RCPsych then said 

May 2019 https://www.rcpsych.ac.uk/docs/default-source/improving-care/better-mh-policy/position-statements/ps04_19—antidepressants-and-depression.pdf?sfvrsn=ddea9473_5

Discontinuation of antidepressants should involve the dosage being tapered or slowly decreased to reduce the risk of distressing symptoms, which may occur over several months, and at a reduction rate that is tolerable for the patient. Whilst the withdrawal symptoms which arise on and after stopping antidepressants are often mild and self-limiting, there can be substantial variation in people’s experience, with symptoms lasting much longer and being more severe for some patients. Ongoing monitoring is also needed to distinguish the features of antidepressant withdrawal from emerging symptoms which may indicate a relapse of depression.

updated guidance from NICE  says now

Explain that whilst the withdrawal symptoms which arise when stopping or reducing antidepressants can be mild and self-limiting, there is substantial variation in people’s experience, with symptoms lasting much longer (sometimes months or more) and being more severe for some patients. [2019]

other things also of note

interesting informed views on how to reduce 

history of ADs

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428540/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136031/

https://www.nice.org.uk/guidance/cg90/chapter/1-Guidance#treatment-choice-based-on-depression-subtypes-and-personal-characteristics

also say

When stopping an antidepressant, gradually reduce the dose, normally over a 4-week period, although some people may require longer periods, particularly with drugs with a shorter half-life (such as paroxetine and venlafaxine). This is not required with fluoxetine because of its long half-life.

1.9.2.3

https://www.karger.com/Article/FullText/370338

2001

https://link.springer.com/article/10.2165%2F00002018-200124030-00003

Discontinuation symptoms have received little systematic study with the result that most of the recommendations made here are based on anecdotal data or expert opinion. Research is needed to provide a firm evidence base for future recommendations

Click to access PIIS2215-0366(19)30219-6.pdf

NICE guidelines

https://www.nice.org.uk/guidance/cg90/chapter/1-Guidance#treatment-choice-based-on-depression-subtypes-and-personal-characteristics

Comments are closed.