New generation antidepressants for depression in children and adolescents: a network meta-analysis

Hetrick, Sarah; Meader, Nick; Bailey, Alan P; Badcock, Paul B.; Moller, Carl I.; Cox, Georgina; Merry, Sally; McKenzie, Joanne E.

doi:10.1002/14651858.cd013674.pub2

Cited by 67 publications

(76 citation statements)

References 186 publications

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“…23 A recent Cochrane review found no antidepressant had a clinically significant effect compared with placebo, leading the authors to question 'whether they should be used at all', especially considering some antidepressants increased suicide risk compared with placebo in this population. 24 Re-analysis of original clinical study reports from adolescent trials suggests that the published accounts of studies exaggerated benefits (for example, by switching reporting to outcomes not specified in the protocol) and under-reported risks (for example, by coding suicide attempts in the antidepressant group as 'emotional lability'). 23 25 The number of 12-to 17-year-olds prescribed antidepressants more than doubled between 2005 and 2017.…”

Section: Questions Relating To Efficacymentioning

confidence: 99%

Newer generation antidepressants and withdrawal effects: reconsidering the role of antidepressants and helping patients to stop

Horowitz

Wilcock

2021

DTB

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In England, the prescribing of antidepressants, primarily the newer generation antidepressant classes, has steadily increased over recent years. There is ongoing debate about how the efficacy of these drugs is viewed, their place in therapy and the harms associated with stopping them. Much of the evidence of their efficacy comes from short-term placebo-controlled trials which tend not to include outcomes that are of greatest relevance to patients, such as social functioning or quality of life, but rather restrict outcomes narrowly to symptom measures. On such measures these studies do not demonstrate clinically significant differences from placebo for depression. A range of adverse effects are also recognised, often greater in naturalistic studies of long-term antidepressants users than those measured in short-term efficacy studies, including emotional numbing, sexual difficulties, fatigue and weight gain. There is increasing recognition that withdrawal symptoms from antidepressants are common and that these symptoms can be severe and long-lasting in some patients. Recent guidance on how to stop antidepressants in a tolerable way has been presented by the Royal College of Psychiatrists. We believe that increasing awareness about the difficulty that some patients have in stopping antidepressants should lead to more cautious prescribing practice, with antidepressants given to fewer patients and for shorter periods of time. This article discusses the perceived benefits and harms of antidepressant use.

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Section: Questions Relating To Efficacymentioning

confidence: 99%

Newer generation antidepressants and withdrawal effects: reconsidering the role of antidepressants and helping patients to stop

Horowitz

Wilcock

2021

DTB

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“…It was found that antidepressants were associated with a greater risk of suicide-related events than placebo (OR 1.58, 95%CI 1.02-2.45; 17 studies; n=3229; low quality of evidence). In 2021 the same author published a new review concerning children and adolescents with major depressive disorder in which the effect of different types of antidepressants was analysed separately 22 . Statistically significant differences were only found for venlafaxine, which showed an increase in suicide-related events: OR 13.84, 95%CI (1.79-106.90) (low quality of evidence).…”

Section: Suicidalitymentioning

confidence: 99%

“…A higher risk of serious adverse events was fond with SSRIs (RR 1.71 95%CI 1. 22 Atomoxetine is indicated for the treatment of attentiondeficit hyperactivity disorder (ADHD) in patients aged 6 years and older. However, it was initially developed as an antidepressant, and suicidal behaviours (suicide attempts and suicidal ideation) have also been reported immediately, symptoms that might be subsequently interpreted as side effects should be monitored for 7 days before prescribing.…”

Section: Serious Adverse Eventsmentioning

confidence: 99%

Suicidality associated with the use of antidepressants in children and adolescents

Gutiérrez-Valencia¹,

Leache²,

Saiz³

2021

Bol Inf Farmacoter Navar

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INTRODUCTION Suicide is a public health problem in the infant and adolescent population and is one of the leading causes of death in that age range. Since the introduction of new classes of antidepressants in the early 1990s, concerns about the risk of suicidality associated with the use of these drugs in children and adolescents began to appear. Since then, numerous studies have been published in this regard, and several regulatory agencies have issued warnings concerning this possible increased risk. Despite this, the use of antidepressants in this population continues to increase. OBJECTIVE To analyse the evidence for the relationship between antidepressant use in children and adolescents and the risk of suicidality. In addition, to determine the relationship between this use and the onset of serious adverse events, as well as the treatment discontinuation due to such events. METHODS A literature search was carried out in MedLine and the Cochrane Library. Reviews were prioritised and, if necessary, the search was broadened to include randomised clinical trials. Studies concerning treatment with any antidepressant, irrespective of the diagnosis, compared with placebo, any non-pharmacological treatment or no treatment were analysed. Additionally, position papers from scientific societies and healthcare institutions were also identified. The prescriptions database of the Navarre Health Service was used to obtained information regarding antidepressant use in children and adolescents in Navarre, and the BIFAP (www.bifap.org) database was used to obtain this information for Navarre and Spain as a whole. CONCLUSIONS Current evidence indicates that antidepressants increase the risk of suicidality in children and adolescents. Therefore the use in this population should be restricted and they should only be used for the authorised indications. This risk is closely related to an increase in suicidal ideation. Indirect evidence suggests that the risk of suicidality may be higher with venlafaxine. There is insufficient evidence that any antidepressant reduces this risk. There is a large body of evidence that antidepressants increase the risk of serious adverse events and discontinuations due to adverse events under any indication in comparison with placebo. In the studies available, the safety is analysed when treatment starts and, in general, these are short-term studies, therefore the risk of this type of adverse event in the long term cannot be ruled out.

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“… 6 Also, Hetrick et al defined ‘suicide-related behaviour’ as a collection of suicide, suicide attempt and suicidal ideation when exploring new generation antidepressants for depression in children and adolescents, with suicidal ideation rated with standardised, validated and reliable rating scales. 7 Normally, suicide-related scales were used to detect suicidal ideation, suicide attempt and suicide behaviour in many previous studies. However, several recent studies cast doubts on the validity of these scales.…”

Section: Introductionmentioning

confidence: 99%

Observing time effect of SSRIs on suicide risk and suicide-related behaviour: a network meta-analysis protocol

Chen

et al. 2021

BMJ Open

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IntroductionSuicide is a serious problem worldwide and 90% cases are associated with pre-existing or underlying mental illness. As a common treatment for depressive symptoms that suicidal people may receive, selective serotonin reuptake inhibitors (SSRIs) have been linked to a possible increase in suicide rates. Studies focusing on SSRIs and suicide have produced inconsistent results, suggesting that use of SSRIs decreases, increases, has no effect on suicide rates, or that the effect of SSRIs on suicide is age-dependent. This protocol of network meta-analysis aims to precisely evaluate the time effects of SSRIs by observing weekly changes of suicidality in the first 2 months of the treatment, and consequently, to explore whether the effect of the SSRIs on suicide varies depending on the stages of the treatment; if so, we will identify the turning point.Methods and analysisWe will search in the following databases: PubMed, Web of science, China National Knowledge Infrastructure and Wanfang Data, from dates of inception to 9 July 2021, with language restricted to English and Chinese. Studies focusing on the time effect of SSRIs on suicide will be retrieved. Then, the study selection process will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, and the quality assessment will be conducted with Cochrane Collaboration’s tool. Two researchers will work independently on data extraction using a standardised data extraction spreadsheet. Any disagreement between two researchers will be discussed and determined by a third researcher.Ethics and disseminationThis work does not require ethics approval as it will be based on published studies. This review will be published in peer-reviewed journals.PROSPERO registration numberCRD42021244779.

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New generation antidepressants for depression in children and adolescents: a network meta-analysis

Abstract: Trusted evidence. Informed decisions. Better health.

Cited by 67 publications

References 186 publications

Newer generation antidepressants and withdrawal effects: reconsidering the role of antidepressants and helping patients to stop

Newer generation antidepressants and withdrawal effects: reconsidering the role of antidepressants and helping patients to stop

Suicidality associated with the use of antidepressants in children and adolescents

Observing time effect of SSRIs on suicide risk and suicide-related behaviour: a network meta-analysis protocol

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