Clinical Guidelines on Antidepressant Withdrawal Urgently Need Updating.
In February 2018 the international debate on antidepressant withdrawal was reignited.[1][2][3][4] In response to a letter published in The Times by Davies et al on the benefits and harms of antidepressants,[1] the Royal College of Psychiatrists publicly stated that “[for] the vast majority of patients, any unpleasant symptoms experienced on discontinuing antidepressants have resolved within two weeks of stopping treatment.”[2]
To support this claim, the college referred to the guidelines from the National Institute for Health and Care Excellence (NICE), which state that “[withdrawal] symptoms are usually mild and self-limiting over about 1 week.”[5]
When Davies et al issued a freedom of information request to NICE asking for the evidence for its 1 week claim, NICE was able to provide only two short review articles, neither of which support the 1 week claim while both cite numerous sources that contradict it.[6]
We think that NICE's current position on antidepressant withdrawal (first established in 2004) not only was advanced on insufficient evidence but is now widely countered by subsequent research. Several studies, using a range of methods, show that many people experience withdrawal for longer than 1 week—for example, for over 2 weeks in 55% of patients,[7] at least 6 weeks in 40%,[8] at least 12 weeks in 25%, [9] and between 1 and 13 weeks in 58%[10]—with other studies finding mean durations of 11 days[11] and 43 days.[12]
Examples of longer durations, more than a year, are reported in two recent, community samples of people experiencing difficulties with withdrawal—that is, by 38.6% (n=185)[13] and for a mean duration of 90.5 weeks (n=97).[14]
Systematic reviews of withdrawal also concur, with one of the largest concluding that withdrawal symptoms “typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well.”[15] Another stated, “[withdrawal reactions] typically occur within a few days from drug discontinuation and last a few weeks . . . many variations are possible, including late onset and/or longer persistence of disturbances.”[16] The most recent systematic review, by Davies and Read, also concluded, on the basis of 14 studies of varied methods, that around half of users experience withdrawal when trying to stop or reduce antidepressant treatment, that nearly half of those experiencing withdrawal (46%) report it as severe, and that reports of symptoms lasting several months are common across many recent studies (see examples of duration above).[17]
That the evidence base contradicts NICE’s official position on antidepressant withdrawal raises concerns for the substantial number of antidepressant users who will experience withdrawal for a longer duration than current guidelines recognise. Assuming doctors abide by such guidelines, we believe that many people may have their antidepressant withdrawal misdiagnosed—for example, as relapse or as a failure to respond to treatment—with antidepressants being reinstated, switched, or doses increased as a result. These practices, if routinely enacted, would help partly explain why the average time a person spends taking antidepressants has doubled in the UK since the guidelines were introduced in 2004,[18] [19] why antidepressant prescriptions are rising overall, and why patients regularly report that their withdrawal is not properly acknowledged, understood, and managed by doctors.[20] [21] In addition, the pooled results of two recent surveys showed that fewer than 2% of around 3000 patients were able to recall being told anything about withdrawal effects, dependence, or potential difficulties in discontinuing treatment.[22] [23]
It is concerning that antidepressants are causing withdrawal effects that can be long lasting and severe and that this is not being sufficiently recognised by current clinical guidelines and, by extension, many prescribers. NICE is now in the process of updating its depression guidelines, and we call on it and the royal colleges to revise their practice guidelines and recommendations to bring them in line with the scientific evidence base.
Competing interests: None declared.
1 Davies J, Moncrieff J, Kinderman P, et al, Council for Evidence-based Psychiatry. Stigma and efficacy of taking antidepressants. Letter to the editor. Times 2018 Feb 23. https://www.thetimes.co.uk/article/stigma-and-efficacy-of-taking-antidep...
2 Baldwin D, Burns W. Pills for depression. Letter to the editor. Times 2018 Feb 24. https://www.thetimes.co.uk/article/86afb2fc-18c7-11e8-a427-78e8af199a96
3 Hengartner MP. Rapid response to: Adlington K, Pop a million happy pills? Antidepressants, nuance, and the media. BMJ 2018. https://www.bmj.com/content/360/bmj.k1069/rr-1
4 Davies J, Read J, Hengartner M, et al. Rapid response to: Iacobucci G, NHS prescribed record number of antidepressants last year. BMJ 2019.
5 National Institute for Health and Care Excellence. Depression in adults: recognition and management. 2009. https://www.nice.org.uk/guidance/cg90/resources/depression-in-adults-rec...
6 Davies J, Read J. A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based? Addictive Behaviors 2018. https://doi.org/10.1016/j.addbeh.2018.08.027 4 Sep 2018 [epub ahead of print]
7 Perahia DG, Kajdasz DK, Desaiah D, Haddad PM. Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder. J Affect Disord 2005;89:207-12. Epub 2005 Nov 2.
8 Zajecka J, Fawcett J, Amsterdam F, et al. Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled study. J Clin Psychopharmacol 1998;18:193-7.
9 Royal College of Psychiatrists. Coming off antidepressants. 2012. http://www.rcpsych.ac.uk/healthadvice/treatmentswellbeing/antidepressant... [Accessed Feb 2018.]
10 Black K, Shea C, Dursun S, Kutcher S. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. Revue de Psychiatrie et de Neuroscience 2000;25:256-60.
11 Price J, Waller P, Wood S, MacKay A. A comparison of the post-marketing safety of four selective serotonin re-uptake inhibitors including the investigation of symptoms occurring on withdrawal Br J Clin Pharmacol 1996;42:757-63.
12 Naryan V, Haddad PH. Antidepressant discontinuation manic states: a critical review of the literature and suggested diagnostic criteria. J Psychopharmacol 2011;25:306-13.
13 Davies J, Pauli R, Montagu L. Antidepressant withdrawal: a survey of patients’ experience by the All-Party Parliamentary Group for Prescribed Drug Dependence. 2018. http://prescribeddrug.org/wp-content/uploads/2018/10/APPG-PDD-Survey-of-...
14 Stockmann T, Odegbaro D, Timimi D, Moncrieff M. SSRI and SNRI withdrawal symptoms reported on an internet forum. Int J Risk Saf Med 2018;29:175-80. doi: 10.3233/JRS-180018
15 Fava GA, Benasi G, Lucente M, Offidani E, Cosci F, Guidi J. Withdrawal symptoms after serotonin-noradrenaline reuptake Inhibitor discontinuation: systematic review. Psychotherapy and Psychosomatics 2018;87:195-203.
16 Fava GA, Gatti A, Belaise C, Guidi J, Offidani E. Withdrawal symptoms after selective serotonin reuptake inhibitor discontinuation: a systematic review. Psychotherapy and Psychosomatics 2015;84:72-81.
17 Davies J, Read J. A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based? Addictive Behaviors 2018 4 Sep. https://doi.org/10.1016/j.addbeh.2018.08.027 [epub ahead of print]
18 NHS Digital. Prescriptions dispensed in the community—Statistics for England, 2006-2016. https://digital.nhs.uk/data-and-information/publications/statistical/pre...
19 Kendrick T. Long-term antidepressant treatment: Time for a review? Prescriber2015;26(19):7-8.
20 Davies J, Pauli G, Montagu L. A survey of antidepressant withdrawal reactions and their management in primary care. Report from the All Party Parliamentary Group for Prescribed Drug Dependence. 2018. http://prescribeddrug.org/wp-content/uploads/2018/10/APPG-PDD-Survey-of-...
21 Cartwright C, Gibson K, Read J, Cowan O, Dehar T. Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient Preferences and Adherence 2016;28:1401-7.
22 Read J, Cartwright C, Gibson K. How many of 1,829 antidepressant users report withdrawal symptoms or addiction? International Journal of Mental Health Nursing 2018 Jun 5. https://doi.org/10.1111/inm.12488
23 Read J, Williams J. Adverse effects of antidepressants reported by a large international cohort: emotional blunting, suicidality, and withdrawal effects. Current Drug Safety 2018;13:1-11.
Competing interests:
No competing interests
16 May 2019
James Davies
Academic
John Read, professor, School of Psychology, University of East London, London, UK. Michael P. Hengartner, senior lecturer, School of Applied Psychology, Zurich University of Applied Sciences, Zurich, Switzerland. Fiammetta Cosci, associate professor, Department of Health Sciences, University of Florence, Italy. Giovanni Fava, professor, School of Medicine and Biomedical Sciences, University at Buffalo, USA. Guy Chouinard, professor, Psychiatry Department, University of Montreal, Canada. Jim van Os, professor, Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, Netherlands. Antonio Nardi, professor, Institute of Psychiatry, Federal Univ Rio de Janeiro, Brazil. Peter Gøtzsche, professor, Institute for Scientific Freedom, Copenhagen, Denmark. Peter Groot, researcher, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, Netherlands. Emanuela Offidani, assistant professor, Department of Psychology, Pennsylvania State University, USA. Sami Timimi, visiting professor, School of Health and Social Care, University of Lincoln, Lincolnshire, UK. Joanna Moncrieff, reader, Division of Psychiatry, University College London, London, UK. Marcantonio Spada, professor, School of Applied Sciences, London South Bank University, London, UK. Anne Guy, researcher, All-Party Parliamentary Group for Prescribed Drug Dependence, Houses of Parliament, Westminster
Rapid Response:
Clinical Guidelines on Antidepressant Withdrawal Urgently Need Updating.
In February 2018 the international debate on antidepressant withdrawal was reignited.[1][2][3][4] In response to a letter published in The Times by Davies et al on the benefits and harms of antidepressants,[1] the Royal College of Psychiatrists publicly stated that “[for] the vast majority of patients, any unpleasant symptoms experienced on discontinuing antidepressants have resolved within two weeks of stopping treatment.”[2]
To support this claim, the college referred to the guidelines from the National Institute for Health and Care Excellence (NICE), which state that “[withdrawal] symptoms are usually mild and self-limiting over about 1 week.”[5]
When Davies et al issued a freedom of information request to NICE asking for the evidence for its 1 week claim, NICE was able to provide only two short review articles, neither of which support the 1 week claim while both cite numerous sources that contradict it.[6]
We think that NICE's current position on antidepressant withdrawal (first established in 2004) not only was advanced on insufficient evidence but is now widely countered by subsequent research. Several studies, using a range of methods, show that many people experience withdrawal for longer than 1 week—for example, for over 2 weeks in 55% of patients,[7] at least 6 weeks in 40%,[8] at least 12 weeks in 25%, [9] and between 1 and 13 weeks in 58%[10]—with other studies finding mean durations of 11 days[11] and 43 days.[12]
Examples of longer durations, more than a year, are reported in two recent, community samples of people experiencing difficulties with withdrawal—that is, by 38.6% (n=185)[13] and for a mean duration of 90.5 weeks (n=97).[14]
Systematic reviews of withdrawal also concur, with one of the largest concluding that withdrawal symptoms “typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well.”[15] Another stated, “[withdrawal reactions] typically occur within a few days from drug discontinuation and last a few weeks . . . many variations are possible, including late onset and/or longer persistence of disturbances.”[16] The most recent systematic review, by Davies and Read, also concluded, on the basis of 14 studies of varied methods, that around half of users experience withdrawal when trying to stop or reduce antidepressant treatment, that nearly half of those experiencing withdrawal (46%) report it as severe, and that reports of symptoms lasting several months are common across many recent studies (see examples of duration above).[17]
That the evidence base contradicts NICE’s official position on antidepressant withdrawal raises concerns for the substantial number of antidepressant users who will experience withdrawal for a longer duration than current guidelines recognise. Assuming doctors abide by such guidelines, we believe that many people may have their antidepressant withdrawal misdiagnosed—for example, as relapse or as a failure to respond to treatment—with antidepressants being reinstated, switched, or doses increased as a result. These practices, if routinely enacted, would help partly explain why the average time a person spends taking antidepressants has doubled in the UK since the guidelines were introduced in 2004,[18] [19] why antidepressant prescriptions are rising overall, and why patients regularly report that their withdrawal is not properly acknowledged, understood, and managed by doctors.[20] [21] In addition, the pooled results of two recent surveys showed that fewer than 2% of around 3000 patients were able to recall being told anything about withdrawal effects, dependence, or potential difficulties in discontinuing treatment.[22] [23]
It is concerning that antidepressants are causing withdrawal effects that can be long lasting and severe and that this is not being sufficiently recognised by current clinical guidelines and, by extension, many prescribers. NICE is now in the process of updating its depression guidelines, and we call on it and the royal colleges to revise their practice guidelines and recommendations to bring them in line with the scientific evidence base.
Competing interests: None declared.
1 Davies J, Moncrieff J, Kinderman P, et al, Council for Evidence-based Psychiatry. Stigma and efficacy of taking antidepressants. Letter to the editor. Times 2018 Feb 23. https://www.thetimes.co.uk/article/stigma-and-efficacy-of-taking-antidep...
2 Baldwin D, Burns W. Pills for depression. Letter to the editor. Times 2018 Feb 24. https://www.thetimes.co.uk/article/86afb2fc-18c7-11e8-a427-78e8af199a96
3 Hengartner MP. Rapid response to: Adlington K, Pop a million happy pills? Antidepressants, nuance, and the media. BMJ 2018. https://www.bmj.com/content/360/bmj.k1069/rr-1
4 Davies J, Read J, Hengartner M, et al. Rapid response to: Iacobucci G, NHS prescribed record number of antidepressants last year. BMJ 2019.
5 National Institute for Health and Care Excellence. Depression in adults: recognition and management. 2009. https://www.nice.org.uk/guidance/cg90/resources/depression-in-adults-rec...
6 Davies J, Read J. A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based? Addictive Behaviors 2018. https://doi.org/10.1016/j.addbeh.2018.08.027 4 Sep 2018 [epub ahead of print]
7 Perahia DG, Kajdasz DK, Desaiah D, Haddad PM. Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder. J Affect Disord 2005;89:207-12. Epub 2005 Nov 2.
8 Zajecka J, Fawcett J, Amsterdam F, et al. Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled study. J Clin Psychopharmacol 1998;18:193-7.
9 Royal College of Psychiatrists. Coming off antidepressants. 2012. http://www.rcpsych.ac.uk/healthadvice/treatmentswellbeing/antidepressant... [Accessed Feb 2018.]
10 Black K, Shea C, Dursun S, Kutcher S. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. Revue de Psychiatrie et de Neuroscience 2000;25:256-60.
11 Price J, Waller P, Wood S, MacKay A. A comparison of the post-marketing safety of four selective serotonin re-uptake inhibitors including the investigation of symptoms occurring on withdrawal Br J Clin Pharmacol 1996;42:757-63.
12 Naryan V, Haddad PH. Antidepressant discontinuation manic states: a critical review of the literature and suggested diagnostic criteria. J Psychopharmacol 2011;25:306-13.
13 Davies J, Pauli R, Montagu L. Antidepressant withdrawal: a survey of patients’ experience by the All-Party Parliamentary Group for Prescribed Drug Dependence. 2018. http://prescribeddrug.org/wp-content/uploads/2018/10/APPG-PDD-Survey-of-...
14 Stockmann T, Odegbaro D, Timimi D, Moncrieff M. SSRI and SNRI withdrawal symptoms reported on an internet forum. Int J Risk Saf Med 2018;29:175-80. doi: 10.3233/JRS-180018
15 Fava GA, Benasi G, Lucente M, Offidani E, Cosci F, Guidi J. Withdrawal symptoms after serotonin-noradrenaline reuptake Inhibitor discontinuation: systematic review. Psychotherapy and Psychosomatics 2018;87:195-203.
16 Fava GA, Gatti A, Belaise C, Guidi J, Offidani E. Withdrawal symptoms after selective serotonin reuptake inhibitor discontinuation: a systematic review. Psychotherapy and Psychosomatics 2015;84:72-81.
17 Davies J, Read J. A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based? Addictive Behaviors 2018 4 Sep. https://doi.org/10.1016/j.addbeh.2018.08.027 [epub ahead of print]
18 NHS Digital. Prescriptions dispensed in the community—Statistics for England, 2006-2016. https://digital.nhs.uk/data-and-information/publications/statistical/pre...
19 Kendrick T. Long-term antidepressant treatment: Time for a review? Prescriber2015;26(19):7-8.
20 Davies J, Pauli G, Montagu L. A survey of antidepressant withdrawal reactions and their management in primary care. Report from the All Party Parliamentary Group for Prescribed Drug Dependence. 2018. http://prescribeddrug.org/wp-content/uploads/2018/10/APPG-PDD-Survey-of-...
21 Cartwright C, Gibson K, Read J, Cowan O, Dehar T. Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient Preferences and Adherence 2016;28:1401-7.
22 Read J, Cartwright C, Gibson K. How many of 1,829 antidepressant users report withdrawal symptoms or addiction? International Journal of Mental Health Nursing 2018 Jun 5. https://doi.org/10.1111/inm.12488
23 Read J, Williams J. Adverse effects of antidepressants reported by a large international cohort: emotional blunting, suicidality, and withdrawal effects. Current Drug Safety 2018;13:1-11.
Competing interests: No competing interests