Psychiatric adverse drug reactions reported during a 10‐year period in the Swedish pediatric population

Abstract

Psychiatric ADRs in the pediatric population have been reported for a wide range of reactions and drugs and display age and sex differences including a higher number of suicidal reactions in boys. An association was seen between serious reactions and off-label drug use. Further studies are needed to elucidate safety aspects of unlicensed drugs and drugs used off-label and whether there are differences in children's susceptibility to develop ADRs.

Neuropsychiatric adverse drug reactions in children initiated on montelukast in real-life practice

“…In montelukast-associated ADR reports, children were markedly overrepresented compared to adults, with more reports of depressive and psychotic symptoms, sleep disorders and suicidal behaviour, suggesting increased susceptibility compared to adults [17]. In our study, where 75% of children were aged ⩽8 years, the most frequent ADRs were irritability, aggressiveness and sleep disturbances, in line with pharmacovigilance reports, where the main symptoms in toddlers were sleep disorders, in those aged 2-11 years the main symptoms were anxiety and depression, and in adolescents the main symptoms were suicidal behaviour, depression and anxiety [16][17][18].…”

“…It remained large, at six-fold, when replicated in several post hoc analyses exploring the potential impact of cohort selection and co-interventions, due to a doubling of events to 2% in the larger ICS group, in the face of stable incidence in the montelukast group. The observed risk is consistent with the disproportionally high proportion (60%) of neuropsychiatric ADRs reported with montelukast compared to ICS (7%) or β 2 -agonists (7%) in several pharmacovigilance databases [17,18,31]. In montelukast-associated ADR reports, children were markedly overrepresented compared to adults, with more reports of depressive and psychotic symptoms, sleep disorders and suicidal behaviour, suggesting increased susceptibility compared to adults [17].…”

“…anxiety is to be expected. Similar to diverging findings observed between efficacy versus effectiveness trials [9,10], it is thus likely that the exclusion criteria used in clinical trials to increase internal validity may have introduced a bias in the assessment of the safety profile, resulting in lower generalisability to that observed in the real-world setting [18].…”

“…In fact, in a Swedish postmarketing paediatric surveillance study, montelukast was one of five drug classes most frequently associated with neuropsychiatric adverse drug reactions (ADRs), representing 10% of all reports, closely followed by inhaled budesonide (6.5%) [18]. Yet postmarketing safety information remains quite limited in children [6], and importantly, such studies usually lack a denominator.…”

Classification and pharmacological treatment of preschool wheezing: changes since 2008

“…Recent evidence suggests significant behavioural problems as a side-effect of montelukast in a small proportion of young children with wheeze [32]. This has also been described in case reports of children using ICS [33] but this side-effect appears to be very rare in preschool children [34].…”