Withdrawal, dependence and adverse events of antidepressants: lessons from patients and data

Tomlinson, Anneka; Boaden, Katharine; Cipriani, Andrea

doi:10.1136/ebmental-2019-300121

Cited by 4 publications

(3 citation statements)

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“…The fact that all psychotherapies can be efficacious means that, when choosing a therapy, patient's preferences can have a prominent role. Mental health professionals need to facilitate access to evidence‐based updated information about the effects of treatment interventions and to involve patients more in their day‐to‐day care, with a focus on carefully acknowledging the risk and outlining potential effects while managing expectations 29 . It is possible that a more detailed characterization of each patient with a diagnosis of depression may lead to a more precise matching between individual patients and individual psychotherapies 30 .…”

Section: Discussionmentioning

confidence: 99%

Psychotherapies for depression: a network meta‐analysis covering efficacy, acceptability and long‐term outcomes of all main treatment types

et al. 2021

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The effects of psychotherapies for depression have been examined in several hundreds of randomized trials, but no recent network meta‐analysis (NMA) has integrated the results of these studies. We conducted an NMA of trials comparing cognitive behavioural, interpersonal, psychodynamic, problem‐solving, behavioural activation, life‐review and “third wave” therapies and non‐directive supportive counseling with each other and with care‐as‐usual, waiting list and pill placebo control conditions. Response (50% reduction in symptoms) was the primary outcome, but we also assessed remission, standardized mean difference, and acceptability (all‐cause dropout rate). Random‐effects pairwise and network meta‐analyses were conducted on 331 randomized trials with 34,285 patients. All therapies were more efficacious than care‐as‐usual and waiting list control conditions, and all therapies – except non‐directive supportive counseling and psychodynamic therapy – were more efficacious than pill placebo. Standardized mean differences compared with care‐as‐usual ranged from –0.81 for life‐review therapy to –0.32 for non‐directive supportive counseling. Individual psychotherapies did not differ significantly from each other, with the only exception of non‐directive supportive counseling, which was less efficacious than all other therapies. The results were similar when only studies with low risk of bias were included. Most therapies still had significant effects at 12‐month follow‐up compared to care‐as‐usual, and problem‐solving therapy was found to have a somewhat higher long‐term efficacy than some other therapies. No consistent differences in acceptability were found. Our conclusion is that the most important types of psychotherapy are efficacious and acceptable in the acute treatment of adult depression, with few significant differences between them. Patient preference and availability of each treatment type may play a larger role in the choice between types of psychotherapy, although it is possible that a more detailed characterization of patients with a diagnosis of depression may lead to a more precise matching between individual patients and individual psychotherapies.

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Section: Discussionmentioning

confidence: 99%

Psychotherapies for depression: a network meta‐analysis covering efficacy, acceptability and long‐term outcomes of all main treatment types

et al. 2021

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“…Moreover, specific adverse events—no matter how severe they are—are important for patients and for the shared decision-making process ( 48 ). Tolerability, withdrawal effects and dependence on antidepressants is also topical in the current scientific debate, as highlighted by the recent report published on September 2019 by Public Health England ( 49 ). We aim to cover this issue in future evidence synthesis projects.…”

Section: Discussionmentioning

confidence: 99%

Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment

et al. 2020

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Antidepressants are prescribed for the treatment of a number of psychiatric disorders in children and adolescents, however there is still controversy about whether they should be used in this population. This meta-review aimed to assess the effects of antidepressants for the acute treatment of attention-deficit/hyperactivity disorder (ADHD), anxiety disorders (ADs), autistic spectrum disorder (ASD), enuresis, major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) in children and adolescents. Efficacy was measured as response to treatment (either as mean overall change in symptoms or as a dichotomous outcome) and tolerability was measured as the proportion of patients discontinuing treatment due to adverse events. Suicidality was measured as suicidal ideation, behavior (including suicide attempts) and completed suicide. PubMed, EMBASE, and Web of Science were systematically searched (until 31 October 2019) for existing systematic reviews and/or meta-analyses of double-blind randomized controlled trials. The quality of the included reviews was appraised using AMSTAR-2. Our meta-review included nine systematic reviews/meta-analyses (2 on ADHD; 1 on AD; 2 on ASD; 1 on enuresis; 1 on MDD, 1 on OCD and 1 on PTSD). In terms of efficacy this review found that, compared to placebo: fluoxetine was more efficacious in the treatment of MDD, fluvoxamine and paroxetine were better in the treatment of AD; fluoxetine and sertraline were more efficacious in the treatment of OCD; bupropion and desipramine improved clinician and teacher-rated ADHD symptoms; clomipramine and tianeptine were superior on some of the core symptoms of ASD; and no antidepressant was more efficacious for PTSD and enuresis. With regard to tolerability: imipramine, venlafaxine, and duloxetine were less well tolerated in MDD; no differences were found for any of the antidepressants in the treatment of anxiety disorders (ADs), ADHD, and PTSD; tianeptine and citalopram, but not clomipramine, were less well tolerated in children and adolescents with ASD. For suicidal behavior/ideation, venlafaxine (in MDD) and paroxetine (in AD) were associated with a significantly increased risk; by contrast, sertraline (in AD) was associated with a reduced risk. The majority of included systematic reviews/meta-analyses were rated as being of high or moderate in quality by the AMSTAR-2 critical appraisal tool (one and five, respectively). One included study was of low quality and two were of critically low quality. Compared to placebo, selected antidepressants can be efficacious in the acute treatment of some common psychiatric disorders, although statistically significant differences do not always translate into clinically significant results. Little information was available about tolerability of antidepressants in RCTs of OCD and in the treatment of ADHD, ASD, MDD, and PTSD. There is a paucity of data on suicidal ideation/behavior, but paroxetine may increase the risk of suicidality in the treatment of AD and ven...

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“…In recent decades, the number of prescriptions has been steadily increasing around the world (Mikulic, 2021). Between 2017 and 2018, 7.3 million adults (17% of the adult population) were prescribed and dispensed antidepressants in the UK (Davies & Read, 2019;Public Health England, 2019;Tomlinson et al, 2019). Long-term antidepressant medication is only indicated for a minority of patients; therefore, antidepressants will eventually need to be ceased in most.…”

Section: Introductionmentioning

confidence: 99%

Do discontinuation symptoms predict depression relapse after antidepressant cessation?

Volkmann¹,

Abulikemu²,

Isabel³

et al. 2023

Preprint

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Background: Discontinuing antidepressants after recovering from a depressive episode is associated with a risk for two events: discontinuation symptoms and relapse. Little is known about who can discontinue safely and whether discontinuation symptoms constitute a risk factor for relapse. This study investigated risk factors for experiencing discontinuation symptoms and whether discontinuation symptoms are associated with depression relapse.Methods: 103 patients with a currently remitted major depressive disorder were randomized to continuation or discontinuation of antidepressants. Discontinuation symptoms were assessed with the Discontinuation Emergent Signs and Symptoms (DESS) scale. The discontinuation syndrome (ADS) was defined as experiencing at least 4 DESS symptoms. We investigated the association of clinical factors with the number of discontinuation symptoms in Bayesian linear regressions. After the randomization phase, all patients discontinued their antidepressant and were followed up over 6 months. We investigated the association of discontinuation symptoms and clinical factors with relapse risk in logistic regressions and a cox proportional hazards model. Results: An ADS was experienced by 29% (95% PI [8.3%, 72%]) of patients. Women reported more discontinuation symptoms than men (factor 1.67 (95% interval [1.06, 2.56])). None of the other prespecified predictors were associated with the risk or severity of ADS. Trait anxiety (Slope = 0.42, 95% PI [-0.01, 0.90]), ADS severity (0.58, 95% PI [0.07, 1.16]) and early depressive symptoms (0.63, 95% PI [0.16, 1.17]) were associated with a higher relapse risk. Conclusion: Antidepressant discontinuation symptoms were relatively common and experienced mainly by women. Experiencing discontinuation symptoms may adversely impact relapse risk.

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Withdrawal, dependence and adverse events of antidepressants: lessons from patients and data

Cited by 4 publications

References 7 publications

Psychotherapies for depression: a network meta‐analysis covering efficacy, acceptability and long‐term outcomes of all main treatment types

Psychotherapies for depression: a network meta‐analysis covering efficacy, acceptability and long‐term outcomes of all main treatment types

Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment

Do discontinuation symptoms predict depression relapse after antidepressant cessation?

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