The current evidence suggests that antidepressant withdrawal reactions are widespread and nearly half of them are severe. Hence, the U.K.'s current National Institute for Health and Care Excellence and the American Psychiatric Association's depression guidelines need to be updated immediately. The review had significant methodological weaknesses, so the findings should be interpreted with caution. Further, well-designed studies focused on the dependency-forming nature of antidepressants are needed.
Overall summary High risk of bias in the review
Eligibility criteria were not explicitly defined. Only English language studies published in peer-reviewed journals were considered for inclusion in the review. A limited range of databases was searched for study selection process. Search terms were provided but a full search strategy was not reported. No information was provided on the number of reviewers involved in the study selection process and data extraction process. Relevant study results appear to have been extracted. There was no formal assessment of the methodological quality of the included studies. The method of analysis was not explained clearly in the methodology section.
|A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4?||No|
|B. Was the relevance of identified studies to the review's research question appropriately considered?||Probably yes|
|C. Did the reviewers avoid emphasizing results on the basis of their statistical significance?||Probably yes|
|Risk of bias in the review||High|
|Number of studies||24 papers (31 findings)|
|Number of participants||NR|
|Last search date||NR|
|Objective||To evaluate the accuracy and helpfulness of the U.K.'s current National Institute for Health and Care Excellence and the American Psychiatric Association's depression guidelines on the incidence, duration and severity of antidepressant withdrawal.|
|Population||Patients with antidepressant withdrawal of any condition.|
|Interventions||Withdrawal of antidepressants.|
|Outcome||Incidence, duration and severity of antidepressant withdrawal effects.|
|Study design||Not specified, surveys, cohorts and others.|
Fourteen methodologically diverse studies produced incidence rates of antidepressant withdrawal ranged from 27% to 86%, with a weighted average of 56.4% (2991/5299). Four large studies reported that the severity of antidepressant withdrawal ranged from 43% to 51%, with a weighted average of 45.7% (1157/2529).
Ten studies reported on the duration of antidepressant withdrawal. These do not permit a weighted average, because of the variety of methodologies and ways duration. Seven of the ten studies contradict the UK and USA withdrawal Guidelines and found that a significant proportion of people experiencing withdrawal do so for more than 2 weeks. One study found withdrawal lasting at least 6 weeks in 40% of people and another found it lasting at least 12 weeks in 25% of people. Four studies calculating mean duration were 5 days, 10 days, 43 days and 79 weeks with a heterogeneous population.
The research objective was clearly stated. Eligibility criteria were not explicitly defined. No restrictions were applied based on study characteristics. Only English language studies published in peer-reviewed journals were considered for inclusion in the review.
|1.1 Did the review adhere to pre-defined objectives and eligibility criteria?||Probably yes|
|1.2 Were the eligibility criteria appropriate for the review question?||Probably yes|
|1.3 Were eligibility criteria unambiguous?||Probably no|
|1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)?||Probably yes|
|1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)?||No|
|Concerns regarding specification of study eligibility criteria||High|
Articles were searched in MEDLINE/PubMed, PsycINFO and Google Scholar. In addition, bibliographies of included studies were searched for additional findings. Search terms were provided but a full search strategy was not reported. No restrictions were reported based on date, publication format, or language. No information was provided on the number of reviewers involved in the study selection process.
|2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports?||Probably no|
|2.2 Were methods additional to database searching used to identify relevant reports?||Yes|
|2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible?||Probably no|
|2.4 Were restrictions based on date, publication format, or language appropriate?||Probably yes|
|2.5 Were efforts made to minimise error in selection of studies?||No information|
|Concerns regarding methods used to identify and/or select studies||High|
No information was provided on the number of reviewers involved in the data extraction process. Relevant study results appear to have been extracted. There was no formal assessment of the methodological quality of the included studies.
|3.1 Were efforts made to minimise error in data collection?||No information|
|3.2 Were sufficient study characteristics considered for both review authors and readers to be able to interpret the results?||Probably no|
|3.3 Were all relevant study results collected for use in the synthesis?||Probably yes|
|3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria?||No|
|3.5 Were efforts made to minimise error in risk of bias assessment?||Probably no|
|Concerns regarding methods used to collect data and appraise studies||High|
The synthesis appeared to have included all relevant studies. The method of analysis was not explained clearly in the methodology section. A narrative synthesis was performed to summarise the findings, complemented with calculations of weighted means. The risk of bias in primary studies was not addressed in the synthesis.
|4.1 Did the synthesis include all studies that it should?||Probably yes|
|4.2 Were all pre-defined analyses reported or departures explained?||Probably no|
|4.3 Was the synthesis appropriate given the degree of similarity in the research questions, study designs and outcomes across included studies?||Probably yes|
|4.4 Was between-study variation minimal or addressed in the synthesis?||Probably no|
|4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses?||Probably no|
|4.6 Were biases in primary studies minimal or addressed in the synthesis?||Probably no|
|Concerns regarding synthesis and findings||High|
Introduction: The U.K.'s current National Institute for Health and Care Excellence and the American Psychiatric Association's depression guidelines state that withdrawal reactions from antidepressants are 'self-limiting' (i.e. typically resolving between 1 and 2 weeks). This systematic review assesses that claim. Methods: A systematic literature review was undertaken to ascertain the incidence, severity and duration of antidepressant withdrawal reactions. We identified 24 relevant studies, with diverse methodologies and sample sizes. Results: Withdrawal incidence rates from 14 studies ranged from 27% to 86% with a weighted average of 56%. Four large studies of severity produced a weighted average of 46% of those experiencing antidepressant withdrawal effects endorsing the most extreme severity rating on offer. Seven of the ten very diverse studies providing data on duration contradict the UK and USA withdrawal Guidelines in that they found that a significant proportion of people who experience withdrawal do so for more than two weeks, and that it is not uncommon for people to experience withdrawal for several months. The findings of the only four studies calculating mean duration were, for quite heterogeneous populations, 5 days, 10 days, 43 days and 79 weeks. Conclusions: We recommend that U.K. and U.S.A. guidelines on antidepressant withdrawal be urgently updated as they are clearly at variance with the evidence on the incidence, severity and duration of antidepressant withdrawal, and are probably leading to the widespread misdiagnosing of withdrawal, the consequent lengthening of antidepressant use, much unnecessary antidepressant prescribing and higher rates of antidepressant prescriptions overall. We also recommend that prescribers fully inform patients about the possibility of withdrawal effects.