Meta-Analysis of Suicide-Related Behavior or Ideation in Child, Adolescent, and Adult Patients Treated with Atomoxetine

Abstract

http://www.clinicaltrials.gov . The data reported are from an analysis of 23 pediatric and 9 adult clinical trials completed between 1998 and 2011. Ten pediatric (Studies HFBD, HFBK, LYAC, LYAS, LYAT, LYAW, LYAX, LYBG, LYBI, and LYBP) and two adult trials (Studies LYAA and LYAO) were conducted before the requirement to post trials at initiation (ongoing as of July 1, 2005) and, therefore, do not have a registration number. The registration numbers for the 13 pediatric trials meeting this requirement are: NCT00191698 (LYBX), NCT00486122 (LYCC), NCT00386581 (LYCZ), NCT00485459 (S010), NCT00191542 (LY15), NCT00191295 (LYBC), NCT00191906 (LYCK), NCT00192023 (LYCY), NCT00191945 (LYDM), NCT00546910 (LYDV), NCT00406354 (LYDW), NCT00380692 (S017), and NCT00607919 (LYEB). For the seven adult trials, the registration numbers are: NCT00190931 (LYBV), NCT00190957 (LYBY), NCT00190736 (LYCU), NCT00190775 (LYCW), NCT00190879 (LYDQ), NCT00510276 (LYDZ), and NCT00962104 (LYEE).

The Safety of Atomoxetine for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Comprehensive Review of Over a Decade of Research

“…As in the meta-analysis reported in 2008 by Bangs et al [29], no completed suicides were reported in the more recent and larger meta-analysis by Bangs et al [26], which involved 3883 pediatric patients from 23 double-blind, placebo-controlled clinical trials with short treatment durations (5-15 weeks). One (0.04 %) of 2445 atomoxetine-treated patients and none of 1438 placebo-treated patients were classified as showing suicidal behavior (MHRR = 1.19, p = 0.91) [26].…”

“…In our predefined literature search, we identified 13 studies and two case reports related to suicidality or self-harm [17,18,[25][26][27][28][29][30][31][32][33][34][35][36][37]. The nine studies with the largest atomoxetine-treated patient populations (range 421-6818) were four meta-analyses and one pooled analysis of data from atomoxetine pediatric clinical trials, two national register-based studies, and two clinical trials [17, 25-27, 29, 30, 32, 33, 36].…”

“…Moreover, in the two studies of suicidality with the largest atomoxetine-treated patient populations identified in our search, and which are also the most recent studies (published in 2014), the data suggest that the risk of suicidality does not increase during treatment with atomoxetine. These studies are a register-based study in Sweden [25], in which 37,936 adult and pediatric patients (6818 [26.1 %] received atomoxetine) were followed for up to 4 years; another meta-analysis by Bangs et al [26], reporting suicide-related events in 3883 pediatric patients (aged 6.0-17.9 years; 2445 patients received atomoxetine) from 23 double-blind, placebo-controlled, Eli Lilly-sponsored clinical trials of atomoxetine (5-15 weeks in duration).…”

“…As well as the large patient population and 4-year duration, a further strength of the Swedish registry-based study was a within-subject design whereby patients acted as their own matched controls, with ''non-treatment periods'' (i.e., ADHD medication-free periods) compared with ''treatment periods'' (i.e., with ADHD medication) [25], rather than the more traditional between-subject design used in the clinical trials in the two meta-analyses by Bangs et al [26,29]. This reduces the effects of factors such as baseline severity of ADHD or familial susceptibility to ADHD.…”

Risk of Suicidal Events With Atomoxetine Compared to Stimulant Treatment: A Cohort Study

“…Two additional meta-analyses were published that were likewise compromised by sample size, resulting in limited inferences for rare events. 8,9 Also, there is some evidence of increased rates of suicide in nontrial populations. 10 In summary, available evidence lacks inferences for nonclinical trial populations, older adolescents, risk after 3 months of treatment, and, importantly, whether suicidal ideation indeed manifests in risk of suicide.…”