Medline ® Abstracts for References 1-3
of 'Effect of antidepressants on suicide risk in children and adolescents'
Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors.
Psychother Psychosom. 2003;72(2):71.
BACKGROUND: There has been a long-standing controversy about the possibility that selective serotonin reuptake inhibitor (SSRI) antidepressants might induce suicidality in some patients.
METHODS: Starting from the clinical studies that gave rise to this issue, this paper reviews an unselected cohort of randomized clinical trials (RCTs), a series of meta-analyses undertaken to investigate aspects of the problem, studies in recurrent brief depressive disorders, epidemiological studies and healthy volunteer studies using SSRIs to shed light on this issue.
RESULTS: The original clinical studies produced evidence of a dose-dependent link, present on a challenge, dechallenge and rechallenge basis, between SSRIs and both agitation and suicidality. Meta-analyses of RCTs conducted around this time indicate that SSRIs may reduce suicidal ideation in some patients. These same RCTs, however, yield an excess of suicides and suicide attempts on active treatments compared with placebos. This excess also appears in the best-controlled epidemiological studies. Finally, healthy volunteer studies give indications that SSRIs may induce agitation and suicidality in some individuals.
CONCLUSIONS: The data reviewed here, which indicate a possible doubling of the relative risk of both suicides and suicide attempts on SSRIs compared with older antidepressants or non-treatment, make it difficult to sustain a null hypothesis, i.e. that SSRIs do not cause problems in some individuals to whom they are given. Further studies or further access to data are indicated to establish the magnitude of any risk and the characteristics of patients who may be most at risk.
North Wales Department of Psychological Medicine, University of Wales College of Medicine, Bangor, UK. firstname.lastname@example.org
Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data.
Whittington CJ, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington E
BACKGROUND: Questions concerning the safety of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression in children led us to compare and contrast published and unpublished data on the risks and benefits of these drugs.
METHODS: We did a meta-analysis of data from randomised controlled trials that evaluated an SSRI versus placebo in participants aged 5-18 years and that were published in a peer-reviewed journal or were unpublished and included in a review by the Committee on Safety of Medicines. The following outcomes were included: remission, response to treatment, depressive symptom scores, serious adverse events, suicide-related behaviours, and discontinuation of treatment because of adverse events.
FINDINGS: Data for two published trials suggest that fluoxetine has a favourable risk-benefit profile, and unpublished data lend support to this finding. Published results from one trial of paroxetine and two trials of sertraline suggest equivocal or weak positive risk-benefit profiles. However, in both cases, addition of unpublished data indicates that risks outweigh benefits. Data from unpublished trials of citalopram and venlafaxine show unfavourable risk-benefit profiles.
INTERPRETATION: Published data suggest a favourable risk-benefit profile for some SSRIs; however, addition of unpublished data indicates that risks could outweigh benefits of these drugs (except fluoxetine) to treat depression in children and young people. Clinical guideline development and clinical decisions about treatment are largely dependent on an evidence base published in peer-reviewed journals. Non-publication of trials, for whatever reason, or the omission of important data from published trials, can lead to erroneous recommendations for treatment. Greater openness and transparency with respect to all intervention studies is needed.
Centre for Outcomes Research and Effectiveness, Subdepartment of Clinical Health Psychology, University College London, 1-19 Torrington Place, London WC1E 7HB, UK. email@example.com
Efficacy and safety of antidepressants for children and adolescents.
Jureidini JN, Doecke CJ, Mansfield PR, Haby MM, Menkes DB, Tonkin AL
Department of Psychological Medicine, Women's and Children's Hospital, North Adelaide, 5006 SA, Australia. firstname.lastname@example.org