Risk of Suicidal Behaviors and Antidepressant Exposure Among Children and Adolescents: A Meta-Analysis of Observational Studies

Abstract

ObjectivesAlthough several studies have reviewed the suicidal risk of antidepressants, the conclusions remain inconsistent. We, therefore, performed a meta-analysis of observational studies to address the association between exposure to antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) and the risk of suicide and suicide attempt in children and adolescents.MethodsMEDLINE and Embase were searched from January 1990 to April 2021. Seventeen cohort and case-control studies were identified that reported suicide or suicide attempt in children and young adults (aged 5–25 years) who were exposed to any antidepressants. We extracted the estimates and corresponding 95% confidence intervals (CIs) from each publication.ResultsThe results showed that antidepressant exposure significantly increased the risk of suicide and suicide attempt when compared with no antidepressant usage among children and adolescents. The pooled relative risk (RR) was 1.38 (95% CI: 1.16–1.64; I2 = 83.1%). Among the antidepressants, SSRI use was associated with an increased risk of suicide and suicide attempt, and the pooled RR was 1.28 (95% CI: 1.09–1.51; I2 = 68.8%). In subgroup analysis, the attempted suicidal risk of antidepressant and SSRI was significantly increased (RR = 1.35, 95% CI: 1.13–1.61; I2 = 86.2% for all antidepressants; and RR = 1.26, 95% CI: 1.06–1.48; I2 = 73.8% for SSRIs), while the completed suicidal risk of antidepressant and SSRI was not statistically significant (RR = 2.32, 95% CI: 0.82–6.53; I2 = 6.28% for all antidepressants; and RR = 1.88, 95% CI: 0.74–4.79; I2 = 52.0% for SSRIs). In addition, the risk of suicide and suicide attempt between SSRIs and other antidepressants was similar (RR 1.13, 95% CI: 0.87–1.46, I2 = 32.4%).ConclusionThe main findings of this meta-analysis provide some evidence that antidepressant exposure seems to have an increased suicidal risk among children and young adults. Since untreated depression remains one of the largest risk factors for suicide and the efficacy of antidepressants is proven, clinicians should evaluate carefully their patients and be cautious with patients at risk to have treatment emergence or worsening of suicidal ideation (TESI/TWOSI) when prescribing antidepressants to children and young patients.

Increasing Adiponectin Signaling by Sub-Chronic AdipoRon Treatment Elicits Antidepressant- and Anxiolytic-Like Effects Independent of Changes in Hippocampal Plasticity

“…Antidepressants have a delayed therapeutic onset [55], which contributes to the disease burden and vulnerability to suicidal behavior [56]. Here, we demonstrated that 7 days of AdipoRon treatment at a dosage of 20 mg/kg effectively modulate behaviors indicative of antidepressant-and anxiolytic-like properties in naïve mice, which is a shorter onset of antidepressant response compared to conventional antidepressants [40], whereas our molecular and electrophysiological results suggest that the hippocampus is not a key structure mediating such responses.…”

Clinical practice guidelines for management of suicidal behaviour

“…Steps like prescription of very short duration, supervised medications, and keeping medicines under lock (wherever feasible) should be discussed. [ 16 ] Antidepressants - Antidepressant treatment is generally recommended in treatment of suicidal behavior in cases with unipolar depression. The efficacy of fluoxetine and venlafaxine has been proved in reducing depression and suicidality in adult and geriatric population.…”

“…Ketamine is usually administered as an iv infusion. Though the Va/DOD Clinical Practice Guidelines[ 16 ] recommend its use, the major issue concerning ketamine is that the benefits have been found to be short term and the trials have been carried out on small patient groups. Hence, the use of ketamine infusion in suicidal behavior still remains off-label.…”

Aumento del riesgo suicida asociado a farmacoterapia en pacientes con trastornos psiquiátricos.

“…En relación con lo anterior, el papel de los antidepresivos ha sido ampliamente discutido. Si bien su efecto protector ha sido largamente demostrado, hay evidencias de incremento del riesgo de conductas suicidas en niños y adolescentes con inhibidores de la recaptura de serotonina [5,[8][9][10]. Respecto a los estabilizadores del ánimo, es claro el beneficio en el tratamiento de los trastornos bipolares, además de la eficacia del litio como antisuicidal; sin embargo, existe controversia sobre el aumento del riesgo de suicido con algunos estabilizadores anticonvulsivantes [3,11].…”