0924-6479/18/$35.00 © 2018 - lOS Press and the authors. All rights reserved

•Address for correspondence: Dr Tom Stockmann, Department of Research and Development, NELFf NHS FoundationTrust, 1st floor, Maggie Lilley Suite, Goodrnayes Hospital, Barley Lane, mord, Essex 103 8Xl, UK. Tel.: +44 0300 55512001Ext: 53623; Mobile: +4407834395310; E-mail: Tom.stockmann@nelft.nhs.uk.

Antidepressant use is high and increasing. In2012, 13% of the population of the United States wereprescribed antidepressants, a figure that had almost doubled since the year 2000 [1]. The majority ofthese prescriptions were for antidepressants classified as SSRls or SNRIs. There are similar trendsacross the world [2], with the number of prescriptions for antidepressants in the United Kingdom morethan doubling since 2005 [3].

There is now clear evidence that a variety of symptoms can result from the discontinuation of allantidepressant classes [4]. They have been observed to be more common in drugs with a shorter half­life, such as venlafaxine and paroxetine, and if the antidepressant had been taken for eight weeksor longer before withdrawal [5]. Common symptoms following SSRI withdrawal include dizziness,nausea, fatigue, anxiety, headache, electric shock-like symptoms, sweating, insomnia and nightmares[6]. There is comparatively less research on SNRI withdrawal, however, and little data on the natureof the symptoms from the user's perspective.

1. Introduction

Keywords: Antidepressant, SSRI, SNRI, antidepressant withdrawal, online report

Abstract.BACKGROUND: Antidepressant withdrawal symptoms are well-recognised, but their potential duration remains uncertain.OBJECTIVE: We aimed to describe the characteristics of withdrawal associated with two popular classes of antidepressants,including duration.METHODS: We analysed the content of a sample of posts on an antidepressant withdrawal website. We compared thecharacteristics of withdrawal associated with SSRIs and SNRIs, including time of onset, duration and nature of symptoms.RESULTS: 110 posts about SSRI withdrawal, and 63 concerning SNRI withdrawal, were analysed. The mean duration ofwithdrawal symptoms was significantly longer with SSRls than SNRIs: 90.5 weeks (standard deviation, SD, 150.0) and 50.8weeks (SD 76.0) respectively; p=0.043). Neurological symptoms, such as 'brain zaps,' were more common among SNRIusers (p= 0.023). Psychosexuallgenitourinary symptoms may be more common among SSRI users (p= 0.054).LIMITATIONS: The website aims to help people with antidepressant withdrawal, and is therefore likely to attract peoplewho have difficulties. Length of prior use of antidepressants was long, with a mean of 252.2 weeks (SD 250.8).CONCLUSIONS: People accessing antidepressant withdrawal websites report experiencing protracted withdrawal symp­toms. There are some differences in the characteristics of withdrawal associated with different classes of antidepressants.

Tom Stockmann"-", Dolapo Odegbaro", Sarni Timimi? and Joanna Moncrieff"aNELFT NHS Foundation Trust, Division of Psychiatry, University College London, UKbNorthampton Healthcare NHS Foundation Trust, Northampton, UKCFaculty of Health and Social Sciences, University of Lincoln, Lincoln, UKdDivision of Psychiatry, University College London, UK

SSRI and SNRI withdrawal symptomsreported on an internet forum

175International Journal of Risk & Safety in Medicine 29 (2018) 175-180DOl 10.3233/JRS-180018lOS Press

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The data suggest that somepeople experience protracted withdrawal symptoms followingboth SSRIandSNRI withdrawal.The averageduration of withdrawal symptoms amongSSRI users was almost 21months, and for SNRI users it was nearly 12months. Among SSRI users, 50% experienced symptomslasting 7.8 months or more, and for 25% symptoms lasted at least 2 years. For 50% of SNRI users,symptoms lasted at least 6.4 months, and for 25% they lasted for 14.4months or more.Reported time before onset of withdrawal symptoms was also longer than previously documented

for people withdrawingfrom SSRIs/SNRls. For 50%of SSRI users this was almost 9 days or more, andfor 25% of users it exceeded 6 weeks. For those taking SNRIs it was closer to the duration previouslyreported, which likely reflects the short action of venlafaxine, the most commonly used agent in thisgroup.The positive correlation between duration of symptoms and length of taper is likely to indicate that

people experiencing difficult and protracted withdrawal symptoms reduce their antidepressants moreslowly.The prominence of psychological, neurological and gastrointestinal symptoms is consistent with the

previous literature on SSRI and SNRI withdrawal [4], and lends this study face validity.The findings

4. Discussion

escitalopram (N=35), sertraline (N=23), paroxetine (N=24) and citalopram (N=I9). 63 peoplereported withdrawal symptoms following SNRI use, specifically venlafaxine (N= 50) and duloxetine(N= 13).There was no statistically significant difference between mean durations of prior treatment or mean

lengths of taper in the SSRI and SNRI groups. The combined mean length of prior treatment was252.2 weeks (standard deviation, SD, 250.8; N = 146); the median was 156.0 (interquartile range,IQR, 50-416). Combined mean length of taper was 16.6 weeks (SD 25.9; median 4.0, IQR 0-20.0;N=79).The mean time to onset of withdrawal symptoms following SSRI discontinuation or reduction (4.5

weeks, SD 13.0;median 1.3, IQR 0-6.0; N =66) appeared longer than for SNRls (1.5 weeks, SD 3.0;median 0.3, IQR 0-1.3; N =46), however this differencedid not reach statistical significance (t = 1.51;P =0.13). The combined mean time to onset was 3.3 weeks (SD 10.2; median 1.0, IQR 0-3.4).Withdrawal symptoms lasted significantly longer for those taking SSRIs than SNRIs. The mean

duration of withdrawal symptoms in the SSRI group was 90.5 weeks (SD 150.0; median 34.0, IQR8.0-104.0; N =97), and in the SNRI group 50.8 weeks (SD76.0; median 28.0, IQR 4.5-62.8; N =40);t= 2.05, P =0.043.The duration of symptoms positively correlated with length of taper (R2 = 0.258, p =0.038;N =65),

but not with duration of previous treatment. Time to onset of symptoms was not associated with either.Table 1 shows numbers and proportions of users experiencing at least one symptom in each class of

withdrawal symptoms. The most common types of symptom in both the SSRI and SNRI groups werepsychological, followed in descending frequency by neurological, gastrointestinal, musculoskeletal,and cardiovascular symptoms. Neurological effects were significantly more common among peoplewho had withdrawn from SNRls. There was a trend towards sexual and genitourinary effects beingmore frequent in people withdrawing from SSRIs; however, this difference did not reach statisticalsignificance.Users' descriptions of neurological and psychological symptoms indicate experiences that are hard

to classify using standard medical technology. Some, such as 'brain zaps' and electric shock-likesensations, havebeen noted before, but some are less familiar, such as 'brain sloshing,' 'vision laggingbehind eye movements' and 'head like cotton balls stuffed in' .

177T. Stockmann et at. / SSRI and SNRI withdrawal symptoms reported on an internetforum

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ST and JM had the original idea for the research. ST and DO developed the methodology andperformed data collection. TS and JM carried out the analysis and wrote the first draft of the paper.All authors have approved the final article.

Author contributions

Whilst its limitations should be borne in mind, this analysis of self-reported symptoms of SSRIand SNRI withdrawal highlights some important issues for clinical practice. The reported maximumduration of withdrawal symptoms was far in excess of the upper limit that is commonly quoted topatients, with both drug classes but particularly with SSRIs. Clinicians and patients need to be awareof this possibility when considering starting or stopping antidepressants.The study illustrates some differences between antidepressant classes in the nature of subjective

symptoms of SSRI and SNRI withdrawal, and the sometimes idiosyncratic ways in which they aredescribed by individual patients. Knowledge of such descriptors may aid clinicians in understandingunusual presentations after antidepressant discontinuation.Given the high and increasing rate of prescribing of antidepressants across western countries, this

study suggests that further research into ways to alleviate prolonged adverse experiences followingantidepressant withdrawal would be beneficial.

s. Conclusion

This study has a number of limitations.Most importantly,the website used was specificallydesignedto help people withdrawfromantidepressants, and as such is likely to attract users whohavehad partic­ular difficultieswith the process ofwithdrawal. Moreover, the users of the site had used antidepressantsfor long periods, and results are likely to reflect this long duration of prior use.The study does not, therefore, represent a prevalence study of occurrence of withdrawal symptoms,

and does Dotdescribe the characteristics of antidepressant withdrawal among all users. Nevertheless,given the frequency of antidepressant prescribing. it is important that these adverse experiences aredescribed and that differences between commonly used agents are recognised. This is especiallyimportant in view of evidence that people are raking antidepressants for longer [12, 13]. In 2011, 60%of antidepressant users in the US reported using them for more than 2 years [14].It is also possible that symptoms were misanributed, exaggerated or influenced by reports by other

people, and that they might be associated with confounding factors such as use of other medicationor the presence medical conditions. However, other research suggests that internet data can be usedto provide reliable accounts of users' experiences of drug-induced adverse effects that are consistentwith academic and professional literature [15].

)

4.1. Limitations

of higher rates of neurological symptoms with SNRI withdrawal, as well as the trend towards higherrates of psychosexual/genitourinary symptoms with SSRIs, havenot been documented before and arelikely to reflect the differentpbarmacological profiles of the different classes of antidepressant.The verbatimdescription of symptoms revealedsomeunusual examples, not previously documented

in the literature. The language used vividly illustrates tbe sometimes bizarre and highly distressingexperiences that can follow SSRI and S1\'RIwithdrawal.

E:..:acted)

179T. Stockmann et al. / SSRI and SNRJ withdrawal symptoms reported on an internet forum

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