Suicide related events and attention deficit hyperactivity disorder treatments in children and adolescents: a meta-analysis of atomoxetine and methylphenidate comparator clinical trials

Abstract

Background: Attention Deficit Hyperactivity Disorder (ADHD) is becoming an increasingly commonly diagnosed and treated childhood illness. Untreated ADHD is recognised as an independent risk factor for suicide-related events and deliberate self-harm and is reported more commonly in these populations. With the treatment of ADHD it is thus crucial to understand further any associations between pharmacological treatments and suicide-related events. Specific data for suicide-related events with stimulants have not been publically reported. Suicidal tendencies are, however, a contraindication to the treatment of patients with methylphenidate. Clinicians and patients may be helped by a meta-analytic comparison of suicide-related events in comparative randomised double-blind atomoxetine and methylphenidate clinical trials.

Methods: Suicide-related events retrospectively mapped to the suicide-related event assessment instrument recommended by the FDA, the Columbia Classification Algorithm for Suicide Assessment (C-CASA), were evaluated in five double-blind placebo controlled comparative studies of atomoxetine and methylphenidate (n = 1024) of 6 to 9 weeks duration. The Mantel-Haenszel risk ratio and Mantel-Haenszel incidence differences have been calculated.

Results: In total there were 5 suicide-related events, atomoxetine (ATX) 3/559 and methylphenidate (MPH) 2/465. There were no suicide attempts nor completed suicides. Meta-analysis finds no difference of a difference in risk between ATX and MPH with a Mantel-Haenszel risk ratio of 0.52 (95% CI; 0.06, 4.54).

Conclusion: In the only reported meta-analysis of comparative suicide-related events between atomoxetine and methylphenidate, no significant evidence of a difference in risk has been found. These data may be informative to clinicians and patients when developing clinical guidelines.

Keywords: ADHD; Atomoxetine; Methylphenidate; Suicide-related events; Summary of product characteristics; Systematic review.

Figure 1

Paediatric, active comparator-controlled studies meta-analysis for FDA codes 1, 2, 3, or 4, which include all events related to either suicidal behaviour or ideation.