In this register based cohort study, we followed 37 936 patients with a diagnosis of ADHD for 150 721 person years to study the association between the use of drug treatment for ADHD and the risk of suicidal behaviour. At the population level, the use of ADHD drug treatment seemed to be associated with an increased rate of concomitant suicide related events in patients of both sexes. However, these associations were not evident in within patient comparisons in which the point estimates suggested no evidence for a harmful effect of ADHD drug treatment on suicidal behaviour irrespective of whether the drug was stimulant or non-stimulant. In fact, the results suggested that ADHD drug treatment was associated with a reduction in concomitant suicide related events. Any protective effect is probably mediated by the improvement of ADHD symptoms, particularly impulsivity.

Strengths and limitations of study

To the best of our knowledge, this is the first nationwide longitudinal study investigating ADHD drug treatment in relation to suicidal behaviour. By linking Swedish national registers, we identified a total of 7019 validated suicide related events for analysis. Furthermore, the study used within patient comparisons to control for both measured time varying confounding and unmeasured time fixed confounding during the follow-up. The attenuation of the within patient estimates suggests that the increased rate of suicide related events associated with the use of drug treatment at the population level might be due to unmeasured confounding factors, such as baseline severity of ADHD or familial susceptibility to ADHD, rather than the use of ADHD drug treatment. Nevertheless, although we did not find an increased rate of suicide related events in the within patient analyses of non-stimulant drugs, the upper limit of the 95% confidence interval of the hazard ratio was estimated to be 1.30, so an elevated rate of suicide related events associated with the use of ADHD drug treatment cannot be excluded.

Depressive disorder frequently co-occurs with ADHD and represents a major risk factor for suicidal behaviour.29 30 In October 2004 the Food and Drug Administration issued a black box warning on an increased risk of suicidality associated with antidepressants in the treatment of major depressive disorder among children and adolescents.31 In our sample, a large proportion of the ADHD patients also had a diagnosis of depressive disorder and used antidepressants during the follow-up. We accordingly did sensitivity analyses among ADHD patients with a lifetime diagnosis of depressive disorder while adjusting for the use of antidepressants during the follow-up. In the within patient comparisons, we observed a protective effect of ADHD drug treatment on suicidal behaviour, both before and after adjustment for antidepressant treatment status. However, the effect of drug combinations in real life is more complex. Future research needs to use more stringent definitions of depressive episodes and antidepressant treatment status to disentangle the effect of ADHD drug treatment on suicidal behaviour. On the other hand, other psychotropic drugs such as antidepressants have very different patterns of use, as well as onset and end of effect. Thus, the use of psychotropic or other drugs would be unlikely to have the potential to explain the association between ADHD drug treatment and suicidal behaviour.

The results should be interpreted in the context of several limitations. Firstly, the ascertainment of treatment period was based on a sequence of dispensed prescriptions that might inaccurately reflect the actual consumption of drugs by patients, because other family members or healthcare staff could also pick up the drug. This might give rise to misclassification of exposure time. Such a problem is similar to the potential non-adherence to protocol in clinical trials, which can rarely be overcome by the intention to treat analysis used in most randomised controlled trials. In our study, the within patient estimates, based on different definitions of treatment status, did not invalidate the results from the main analyses, indicating that exposure time misclassification is unlikely to account for the results.

Secondly, confounding by time varying factors, such as sporadic onset of comorbid conditions that are associated with both drug treatment and suicide related events, are not taken into account in within patient comparisons. However, we did stratified analyses in a subgroup of ADHD patients without the main psychiatric comorbidities and observed no increased rate of suicide related events associated with the use of ADHD drug treatment.

The validity of diagnosis of ADHD in adults has been considered controversial.32 33 Nevertheless, studies have consistently reported that ADHD is a relatively stable condition that persists from childhood into adulthood in a large number of cases and is associated with impairments in both clinical and psychosocial functioning.34 The Swedish prescribed drug register contains mainly patients with severe ADHD who received drug treatment when non-drug interventions alone had failed. Therefore, we consider overdiagnosis of ADHD in adults to be unlikely in this study, even though generalisations of the results to patients with mild to moderate ADHD should be made with caution.