Using marginal structural models to identify the cardiovascular adverse effects of second generation antipsychotics in children and adolescents

In pediatric patients, we examined the association between exposure to five second generation antipsychotics (SGAs) and incidentcardiovascular events (arrhythmic or ischemic/myocardial) over time using marginal structural models (MSM), while controllingfor salient comorbid conditions and co-prescribed psychotropic medications. A retrospective cohort, longitudinal/ observationalstudy design was used to evaluate Medicaid medical and pharmacy claims in 4140 children and adolescents prescribed SGAsfrom South Carolina USA’s Medicaid program covering outpatient and inpatient medical services and medication prescriptionsbetween January, 1996 and December, 2005. Exposure to multiple SGAs (Risk Ratio [RR]=2.37; 95% CI=1.17-4.83), coprescribedpsychostimulants (RR=1.37; CI=1.03-1.81), and comorbid hypertension (RR=2.23; CI=1.28-3.89) were associatedwith a significantly increased risk of arrhythmias compared to those not exposed, whereas exposure to co-prescribed serotoninnorepinephrine reuptake inhibitor/heterocyclic compounds was associated with a significantly decreased risk of arrhythmias(RR=0.59; CI=0.35-0.99). The risk of incident ischemic/myocardial events was significantly associated with the co-prescription ofmood stabilizers (RR=1.68; CI=1.06-2.68) or selective serotonin reuptake inhibitors (RR=1.91; CI=1.18-3.09), and the presenceof comorbid hypertension (RR=3.97; CI=1.96-8.07) and obesity (RR=2.21; CI=1.34-3.67). MSM analyses comparing multipletreatments while controlling for confounding variables in an observational, longitudinal data set provide important, differentialestimates of outcome, when randomized, controlled trials estimating low-incidence outcomes such as cardiovascular adverseevents in large pediatric patient populations are not feasible.

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Children and adolescents with major depressive disorders: are some second generation antidepressants better than others?

European Psychiatry ◽

10.1016/s0924-9338(11)72956-x ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1251-1251

Author(s):

A. Kaminski ◽

G. Gartlehner

Keyword(s):

Children And Adolescents ◽

Comparative Effectiveness ◽

Selective Serotonin Reuptake Inhibitors ◽

Depressive Disorders ◽

Second Generation ◽

Young Patients ◽

Antidepressant Drugs ◽

Cochrane Library ◽

Major Depressive ◽

Increased Risk

IntroductionSince the black box warning of the FDA (Food and Drug Administration) regarding an increased risk of suicidality in children and adolescents treated with antidepressants, cautious prescription of antidepressant drugs in young patients became even more important. In the light of potentially severe side effects the comparative effectiveness and harms of antidepressants should be known to clinicians to provide optimal treatment.ObjectivesTo compare the benefits and harms of second-generation antidepressants for the treatment of Major Depressive Disorder (MDD) in children and adolescents.AimsTo provide an evidence base for clinicians and policymakers when making informed decisions regarding the prescription of Selective Serotonin Reuptake Inhibitors and other newer antidepressants.MethodsWe updated a comparative effectiveness report of the Oregon Drug Effectiveness Review Project searching MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to August 2010. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias.ResultsWe could not identify any head-to-head trials. There is insufficient evidence to compare one second-generation antidepressant to another in pediatric outpatients with MDD. Evidence from a systematic review of published and unpublished data indicates, that in children and adolescents only fluoxetine shows a good risk-benefit ratio.ConclusionsTo date, the evidence is insufficient to make any clear inferences about the comparative benefits and harms of second-generation antidepressants for the treatment of MDD in children. Clinicians must be aware of the small benefits and the high potential risks when prescribing antidepressant medications to children and adolescents.

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