Polypharmacy in children and adolescents initiating antipsychotic drug in 2008-2016 : a nationwide register study

Objective The use of antipsychotics in children and adolescents has increased rapidly. Little is known about psychotropic polypharmacy in children and adolescent initiating an antipsychotic drug. Thus, we investigated the frequency and predictors of polypharmacy during the first year of antipsychotic use in Finnish children and adolescents. Methods Between 2008 and 2016, 14 848 individuals aged 1-17 years initiating risperidone, quetiapine, aripiprazole, or olanzapine treatment were identified from Finnish Prescription Registry. Data on psychotropic drug prescriptions prior to and during antipsychotic treatment were collected. Associations between predictors and polypharmacy were analyzed with regression models. Results During the study period polypharmacy occurred in 44.9% of the new antipsychotic users, being more frequent in girls (55.5%) than in boys (44.5%, p < 0.001). The two most frequent concomitant psychotropic drug classes were antidepressants (66.2%) and psychostimulants/atomoxetine (30.8%). Adolescents aged 13-15 and 16-17 years, and girls showed an increased risk of polypharmacy during antipsychotic treatment (OR 2.37 [95% CI 1.91-2.92], OR 2.39 [95% CI 1.92-2.98], and OR 1.64 [95% CI 1.51-1.78], respectively). The use of psychostimulants/atomoxetine or antidepressants prior to initiation of antipsychotic treatment was strongly associated with polypharmacy during antipsychotic treatment (OR 8.39 [95% CI 7.49-9.41], OR 3.02 [95% CI 2.75-3.31]). Conclusions Polypharmacy was common in children and adolescents initiating antipsychotic treatment. Prior use of psychostimulants/atomoxetine and antidepressants increased the risk of polypharmacy. The use of antipsychotics was mainly off-label, thus, the risks of concomitant use of antipsychotics with other psychotropic drugs should be carefully weighed.Peer reviewe

New Users of Antipsychotics Among Children and Adolescents in 2008–2017: A Nationwide Register Study

IntroductionRecently, prescribing antipsychotics for children and adolescents has been increasing in many countries. These drugs are often prescribed off-label, although antipsychotics have been associated with adverse effects. We determined the recent incidence of antipsychotic use among children and adolescents in Finland.MethodsFinnish National Prescription Register including all Finnish inhabitants receiving reimbursement for pharmaceuticals was searched for subjects of 1 to 17 years of age who had started an antipsychotic drug between January 1, 2008, and December 31, 2017 (n = 26,353). Between 2008 and 2017, the range of number of Finnish children and adolescents aged 1 to 17 years was 1.01 to 1.03 million/year. The incidence was calculated by dividing the number of new users by all age- and sex-matched Finnish inhabitants in the year.ResultsBetween 2008 and 2017, the incidence of antipsychotic use among children and adolescents increased from 2.1 to 3.8 per 1000 individuals, respectively. In children aged 7 to 12 years, the incidence of antipsychotic use 1.4-folded (from 1.9 (95% CI: 1.8–2.0) to 2.7 (95% CI: 2.5–2.9) per 1000) with a cumulative increase of 0.2% per year (χ2 = 51.0, p <0.0001). In adolescents aged 13 to 17 years, the incidence 2.2-folded (from 4.3 (95% CI: 4.1–4.5) to 9.4 (95% CI: 9.1–9.8) per 1000) with a cumulative increase of 0.6% per year (χ2 = 590.3, p <0.0001). The increase in the incidence of use was steeper in girls (2.3-fold) than in boys (1.4-fold) (χ2 = 85.6, p <0.0001), especially between 2015 and 2017 (1.6-fold and 1.2-fold, respectively) (χ2 = 151.7, p <0.0001). The year 2011 was the turning point when the incidence in girls exceeded the incidence in boys, and the incidence of quetiapine use exceeded that of risperidone use.ConclusionsThe incidence of antipsychotic use increased between 2008 and 2017, especially in adolescent girls. The use of quetiapine increased, although it has few official indications in children and adolescents. Future studies should investigate the reasons for increasing use of antipsychotics, especially quetiapine, in children and adolescents.Peer reviewe

Anti-Müllerian hormone and letrozole levels in boys with constitutional delay of growth and puberty treated with letrozole or testosterone

STUDY QUESTION: Does treatment of constitutional delay of growth and puberty (CDGP) in boys with aromatase inhibitor letrozole (Lz) or conventional low-dose testosterone (T) have differing effects on developing seminiferous epithelium?SUMMARY ANSWER: Anti-Mullerian hormone (AMH) declined similarly in both treatment groups, and the two Sertoli cell-derived markers (AMH and inhibin B (iB)) exhibited differing responses to changes in gonadotrophin milieu.WHAT IS KNOWN ALREADY: Boys with CDGP may benefit from puberty-inducing medication. Peroral Lz activates gonadotrophin secretion, whereas intramuscular low-dose T may transiently suppress gonadotrophins and iB.STUDY DESIGN, SIZE, DURATION: Sera of 28 boys with CDGP who participated in a randomised, controlled, open-label trial at four paediatric centres in Finland between August 2013 and January 2017 were analysed. The patients were randomly assigned to receive either Lz (2.5 mg/day) (n = 15) or T (I mg/kg/month) (n = 13) for 6 months.PARTICIPANTS/MATERIALS, SETTING, METHODS: The 28 patients were at least 14 years of age, showed first signs of puberty, wanted medical attention for CDGP and were evaluated at 0, 3, 6 and 12 months of visits. AMH levels were measured with an electrochemiluminescence immunoassay and L2 levels with liquid chromatography coupled with tandem mass spectrometry.MAIN RESULTS AND THE ROLE OF CHANCE: AMH levels decreased in both treatment groups during the 12-month follow-up (P LIMITATIONS, REASONS FOR CAUTION: The original trial was not blinded for practical reasons and included a limited number of participants.WIDER IMPLICATIONS OF THE FINDINGS: In early puberty, treatment-induced gonadotrophin stimulus was unable to counteract the androgen-mediated decrease in AMH, while changes in iB levels were associated with changes in gonadotrophin levels. AMH decreased similarly in both groups during the treatment, reassuring safety of developing seminiferous epithelium in both treatment approaches. Since a fixed dose of Li induced variable serum Lz levels with a desired puberty-promoting effect in all boys, more research is needed to aim at a minimal efficient dose per weight.</div