Antipsychotic prescribing patterns in children and adolescents attending Australian general practice in 2011 and 2017.

Background: Antipsychotics are increasingly prescribed to children and adolescents worldwide, but little is known about reasons for prescribing. We aimed to examine patterns of paediatric antipsychotic prescribing in Australian primary care services in 2011 and 2017, including diagnoses, sociodemographic characteristics, off-label prescribing, and psychotropic co-prescribing. Methods: Retrospective analysis of electronic health records (EHRs) using a large Australian general practice database (MedicineInsight). Diagnoses of mental disorders were extracted from EHRs and associated with antipsychotic prescriptions within the same calendar year for three age-groups: 0-9, 10-14, and 15-18-year-olds. Results: In 2017, children/adolescents with mental health diagnoses were more likely to be prescribed antipsychotics (2.9% of 27,412 patients) than in 2011 (2.0% of 8418 patients; absolute difference +0.9, 95% CI + 0.5, +1.4). The likelihood was greater for patients with bipolar disorders (21.6% vs. 41.5%), eating disorders (1.1% vs. 7.2%), and autism without behavioural problems (3.7% vs. 6.1%). Depression/anxiety (adjusted 26.8% of patients 2011; 30.8% 2017) was the most common diagnosis associated with antipsychotics in both years. Most antipsychotics were prescribed off-label (69.8% 2011; 79.7% 2017; absolute difference +9.8, 95% CI + 1.54, +18.4). Off-label prescribing increased most among those aged 15-18-years, females, and patients living in outer regional/remote/very remote communities and the most disadvantaged areas. The three most frequently prescribed antipsychotics in both years were risperidone, quetiapine, and olanzapine. Psychotropic co-prescribing among patients receiving antipsychotic prescriptions was approximately 69% in both years. Conclusions: Prescribing antipsychotics for mental health diagnoses to children/adolescents attending Australian general practices was more frequent in 2017 than 2011, and most commonly associated with depression/anxiety diagnoses. In both years, most prescribing was off-label. The majority of patients were co-prescribed other classes of psychotropics along with antipsychotics.

Treatment guesses in the Treatment for Adolescents with Depression Study: Accuracy, unblinding and influence on outcomes.

OBJECTIVE: We evaluated the presence and impact of unblinding during the influential Treatment for Adolescents with Depression Study (ClinicalTrials.gov Identifier: NCT00006286). METHOD: Our analysis was part of a Restoring Invisible and Abandoned Trials reanalysis. Treatment for Adolescents with Depression Study trialled fluoxetine, placebo, cognitive behaviour therapy or their combination, in treating adolescents with major depressive disorder. We analysed the accuracy of guesses of fluoxetine or placebo allocation, and their effects on change in Children's Depression Rating Scale-Revised at 12 weeks. RESULTS: Of 221 participants allocated to fluoxetine or placebo, 151 adolescents (68%) had their guess about pill-treatment-arm allocation recorded at week 6, and guesses were recorded for 154 independent evaluators, 159 parents and 164 pharmacotherapists. All of these groups guessed treatment allocation more accurately than would be expected by chance (60-66% accuracy; all p-values ⩽ 0.004). Guesses did not become more accurate between 6 and 12 weeks and were not predicted by adverse events, though event documentation was poor. Treatment guess had a substantial and statistically significant effect on outcome (Children's Depression Rating Scale-Revised change mean difference 9.12 [4.69; 13.55], ß = 0.334, p < 0.001), but actual treatment arm did not (1.53 [-2.83; 5.89], ß = 0.056, p = 0.489). Removing guess from the analysis increased the apparent effect of treatment arm, making it almost statistically significant at the conventional alpha-level of 0.05 (p = 0.06). CONCLUSIONS: For Treatment for Adolescents with Depression Study, treatment guesses strongly predicted outcomes and may have led to the exaggeration of drug effectiveness in the absence of actual effects. The integrity of double-blinding in trials should be routinely assessed and reported.

Trends in prescription of psychotropic medications to children and adolescents in Australian primary care from 2011 to 2018.

OBJECTIVE: To examine trends in prescribing psychotropic medications to children and adolescents in Australian primary care from 2011 to 2018. METHOD: A retrospective cohort study examined prescriptions written by general practitioners using MedicineInsight, a large Australian primary care database, covering approximately 9% of all general practitioner practices. Numbers of patients receiving prescriptions for five main classes of psychotropics (antipsychotics, antidepressants, attention deficit hyperactivity disorder medications, anxiolytics, and hypnotics/sedatives [including benzodiazepines and Z-drugs, but excluding melatonin]) were examined annually by age-group (0-4, 5-9, 10-14, 15-18 years). Melatonin was analysed separately. RESULTS: The number of patients prescribed any psychotropic increased from 25.6 to 36.2 per 1000 individuals from 2011 to 2018 (average annual increase +4.5%, 95% confidence interval [4.1%, 4.9%]; overall +41.4%). Among the five main classes, the largest annual increase was for attention deficit hyperactivity disorder medications (+9.6%, 95% confidence interval [8.8%, 10.5%]; overall +95.8%), followed by antipsychotics (+6.2%, 95% confidence interval [5.0%, 7.3%]; overall +62.8%) and antidepressants (+4.5%, 95% confidence interval [4.0%, 5.0%]; overall +42.8%). Hypnotic/sedative prescribing decreased on average 6.5% per year (95% confidence interval [-8.0%, -5.0%]; overall -40.2%). Anxiolytic prescribing remained steady. Melatonin prescriptions showed the highest increase of all (+24.7%, 95% confidence interval [23.7%, 25.8%]; overall +606.7%). The largest annual increase in antipsychotic, antidepressant or attention deficit hyperactivity disorder medication prescribing occurred in 10- to 14-year-olds (+7.5%, +6.5% and +10.4%, respectively). The largest point prevalence occurred in 2018 among 15- to 18-year-olds, with 98.5 per 1000 prescribed antidepressants. Antidepressants were more frequently prescribed to females; antipsychotics, attention deficit hyperactivity disorder medications and melatonin more often to males. The most prescribed antipsychotics were risperidone (<15 years) and quetiapine (15- to 18-year-olds). Fluoxetine was the most prescribed antidepressant in those aged 5+ years and amitriptyline in 0- to 4-year-olds. CONCLUSION: General practitioner prescribing of melatonin, antipsychotics, antidepressants and attention deficit hyperactivity disorder medications to under-19-year-olds increased markedly from 2011 to 2018. Although benzodiazepine and Z-drug prescriptions declined, this was offset by a substantial increase in melatonin prescribing.