Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review

Abstract

Background: Selective serotonin reuptake inhibitors (SSRI) are widely used in medical practice. They have been associated with a broad range of symptoms, whose clinical meaning has not been fully appreciated. Methods: The PRISMA guidelines were followed to conduct a systematic review of the literature. Titles, abstracts, and topics were searched using the following terms: ‘withdrawal symptoms' OR ‘withdrawal syndrome' OR ‘discontinuation syndrome' OR ‘discontinuation symptoms', AND ‘SSRI' OR ‘serotonin' OR ‘antidepressant' OR ‘paroxetine' OR ‘fluoxetine' OR ‘sertraline' OR ‘fluvoxamine' OR ‘citalopram' OR ‘escitalopram'. The electronic research literature databases included CINAHL, the Cochrane Library, PubMed and Web-of-Science from inception of each database to July 2014. Results: There were 15 randomized controlled studies, 4 open trials, 4 retrospective investigations, and 38 case reports. The prevalence of the syndrome was variable, and its estimation was hindered by a lack of case identification in many studies. Symptoms typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering. However, many variations are possible, including late onset and/or longer persistence of disturbances. Symptoms may be easily misidentified as signs of impending relapse. Conclusions: Clinicians need to add SSRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs. The term ‘discontinuation syndrome' that is currently used minimizes the potential vulnerabilities induced by SSRI and should be replaced by ‘withdrawal syndrome'.

Research on a ‘drug-centred’ approach to psychiatric drug treatment: assessing the impact of mental and behavioural alterations produced by psychiatric drugs

“…It is also important to establish the course of changes following withdrawal. Some patients report protracted symptoms following withdrawal of benzodiazepines and antidepressants, for example (Fava, Gatti, Belaise, Guidi & Offidani, 2015), and so far we are unable to clarify whether withdrawal-related changes normalise over time in everyone or not.…”

Recognition and management of antidepressant discontinuation syndrome

“…1 ADDS is often seen during taper or after missed doses with short half-life agents, such as paroxetine and venlafaxine. [2][3][4] Up to 70% of patients prescribed anti depressants occasionally skip doses. 5 For diagnosis, ADDS symptoms should not be present before dose reduction and should not be better explained by another psychiatric disorder.…”

“…1 Symptoms that fit the FINISH mnemonic (flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, hyperarousal), can be experienced by up to 40% of patients upon abrupt antidepressant discontinuation. 2,[6][7][8] The Discontinuation Emergent Signs and Symptoms Scale (DESS) can be used to quantify symptoms.…”

“…1,2 In addition, misdiagnosing the physical symptoms of ADDS can lead to unnecessary medical and laboratory workup. 9 Patients must be informed of ADDS when starting treatment and of the differences between ADDS and withdrawal associated with addiction.…”

“…9 Patients must be informed of ADDS when starting treatment and of the differences between ADDS and withdrawal associated with addiction. 10 Although withdrawal symptoms and ADDS could have neurobiological similarities, such as a "receptor rebound" phenomenon upon sudden discontinuation, 2,7,11,12 there are important differences. Unlike antidepressants, use of drugs of abuse include reinforcing/ euphoric effects of the drug and associated drug-seeking behaviour.…”