The use of antipsychotic (AP) and other psychotropic medications in children and adolescents is a complex phenomenon with many aspects yet to be satisfactorily characterized. Several studies have demonstrated a dramatic rise in the use of second generation antipsychotics (SGAs) in young people, which has intensified concerns regarding their overall safety and effectiveness profile in this age group [1–22].

We suspected from our clinical and literature-based knowledge that AP use in youth, particularly in those with lower incomes, was increasing in Nova Scotia. We conducted a mixed methods study with an initial quantitative phase followed by a qualitative phase. Using a retrospective population database design, we aimed to characterize AP prescribing by prevalence, drug, dose, duration, indication/diagnoses, prescriber type, psychotropic co-prescribing, morbidity, and mortality in a population of low income youth.

Although some improvements in building knowledge and capacity in child and youth mental healthcare have been made in the face of formal policies (e.g., the US Best Pharmaceuticals for Children Act and Pediatric Research Equity Act), and frameworks [27], many aspects (e.g., appropriate starting and target dose, duration, etc.,) of pharmacotherapy in children and adolescents are relatively disadvantaged by a lack of reliable, empirically derived data [28]. This is particularly concerning given the disparities that can occur in health services among various subgroups (e.g., low income, visible minority, mental illness) within child and adolescent populations.

Antipsychotics have not been substantially or systematically evaluated prospectively in children and adolescents, but their diffusion of use continues to increase in this population. The prevalent use of SGAs in younger age strata in our study is similar to others [2, 14, 29]. The causes are likely to be multi-factorial and include, but are not limited to, changes in societal attitudes about medication use, changes in health care system delivery in which resources serving as alternatives to medications are not available, changes in service delivery such that more severe cases of mental problems are managed in the community, putative effectiveness of these compounds, prescriber expectations of therapeutic results, and marketing pressures.

Young people with mental illness may experience inequalities in health service access and delivery and experience suboptimal treatment and health-related outcomes [25, 30–41]. Children and adolescents similar to those in our database could experience increased burden of illness related to poorer health as they age due to these inequalities in care. These considerations must also be placed in context of uncertainties and a general lack of understanding regarding the long-term consequences (e.g., cardiometabolic effects) of AP use in this group. Given the enormous direct and indirect cost implications of managing chronic diseases, the implication of the expanded use of APs and other psychotropics in youth needs to be explored more thoroughly. The direct AP costs in our cohort are similar to the results of others [42–45], but we do not know if these added costs were offset by benefits (e.g., fewer hospitalizations, improved clinical or functional outcomes) or were compounded by trade-offs (e.g., managing cardiometabolic side effects). It is apparent that the profile of adverse consequences of these agents are the impetus for changes in some settings of mental health care service delivery in which specific metabolic monitoring programs are in place for children and adolescents [46, 47].

We identified several diagnoses in AP users that are concerning from a chronic disease perspective. In the 1270 long-term users aged 0 to 25 years, 64 had non-mental health diagnoses temporally related to APs including sexual and reproductive, cardiometabolic disorders, and movement disorders. With the limitations of claims data in mind [48], these findings of morbidity that are potentially treatment related are notable. Antipsychotic users in the community services database had a significantly higher mortality than the age matched general population of Nova Scotia and neared significance compared to other community services recipients. It cannot be inferred that the higher mortality rate is associated with AP use due to numerous limitations of our methods. Other Canadian researchers have found that children in welfare systems are at higher risk for suicide and suicide attempts [49]. We do not know from our data what, if any (for example, protective, neutral or negative), impact of AP use had on such behaviors but this is an important issue for further study.

Risperidone was the most commonly prescribed SGA in our cohort. There was a rapid rise in risperidone use towards the final quarter of 2003 and later, which followed a change in formulary status of risperidone. On December 1, 2003, Pharmacare changed the benefit status of both risperidone and quetiapine from medications that required specific criteria for use (i.e., restricted use) to an open benefit. Other researchers have shown significant increases in usage and costs occurring with changes in AP formulary reimbursement strategies [42–45]. By contrast, quetiapine did not show a similar increase with the same change in policy. This agent was relatively new to prescribers and, unlike risperidone, had no US FDA pediatric indications [50]. ADHD, a non-Health Canada approved indication, was the most common diagnosis for the use of risperidone in approximately 31% of AP users based on our diagnostic algorithm. Other research has shown similar trends with SGAs used for ADHD and conduct disorder [14, 29]. Most AP use in our study was off-label; all use in youth under 18 was off-label as was use in young adults with diagnoses other than psychoses or bipolar disorder (Figure 5).

Co-prescribing of other psychotropic medications was prevalent in our cohort and rates found by other researchers vary [51]. The rationale for co-prescribing likely depends on a host of factors (e.g., physician preference, diagnosis, etc.). The use of mood stabilizers in the 0 to 15 year old group was more prevalent than expected. The presence of co-prescribing in 0 to 5 year olds requires further detailed characterization especially given the lack of prospective evaluation of psychotropic polypharmacy in younger age groups.

In our study, GPs initiated prescriptions for incident APs most of the time, which is consistent with the findings of some [2, 29] but not all researchers including those in Canada [14]. This finding requires further ex-plication of GPs’ roles in the care of children and adolescents with mental illness given our findings related to AP indication, dosing and duration. Because of the limited income criteria for eligibility to be in the cohort, AP users were likely only able to receive care from a psychiatrist if referred by a GP. Accessing psychiatrist services through private or uninsured mechanisms would be unexpected because it would be cost-prohibitive. Whether the GPs in our study initiated these prescriptions in consultation or collaboration with, or based on the recommendation of a psychiatrist or pediatrician, is unknown. Some Canadian data have shown that family physicians can operate autonomously in their care of adolescents with mental health problems [52]. We are also unable to determine the characteristics of the prescribing GPs and whether these physicians work in groups, individually, or have formal collaborative arrangements with specialist mental health professionals. Canadian researchers in Quebec developed typologies for GPs or groups of GPs generally involved in caring for those with chronic or serious mental disorders [53]. Characterizing GP prescribers by typology or some other methods could be useful for enhancing capacity and networks, determining efficient models of care, and developing and targeting education and training programs.

The dosing of APs in our study was highly variable. These findings warrant further investigation to determine appropriateness of these doses given the age, diagnoses, and available evidence. Olanzapine dosing appeared higher than dosing of other SGAs perhaps due to its preferential use for the treatment of psychosis. The median duration of AP use was similar across age groups. This finding is noteworthy, as we could have anticipated that the median duration would be shorter in younger children and increase with increasing age as with the findings of others [14]. One explanation is that longer treatment was associated with chronic conditions such as pervasive developmental disorder or learning disability.

We are currently conducting a qualitative study with data analyses nearing completion (to be reported elsewhere). We will use the information from the lived experiences of youth, parents or caregivers, and prescribers vis a vis APs and the results presented in this work to inform healthcare decision and policy making, future research, and clinical practice.

Antipsychotic prescribing was high in a low income cohort of youth. The majority of the prescribing was initiated by GPs and would be considered off-label. Co-prescribing of psychotropics was prevalent. The change in the formulary status of risperidone was associated with an increase in prescribing. This study raises questions about the appropriateness of prescribing given the wide range of diagnoses, doses, duration and combinations of treatments for all ages, especially those less than 5 years old. The cumulative body of research regarding AP use in youth demonstrates that there are gaps in knowledge regarding safe and effective use of these agents. Translation and implementation of knowledge to inform policy and practice towards appropriate use is needed.

ALM is an Associate Professor with the College of Pharmacy and Department of Psychiatry at Dalhousie University. She worked as a clinical pharmacist in mental health with inpatient and outpatient youth and is a team member of the Sun Life Financial Chair in Adolescent Mental Health. DMG is a Professor with Dalhousie University Department of Psychiatry and works clinically as a pharmacist with the Nova Scotia Early Psychosis Program. DMG also volunteers extensively making contributions regarding medication and condition-related knowledge for support groups of those with lived experiences of mental illness. He was a member of the Science Advisory Committee for the Mental Health Commission of Canada and currently Chairs the Awards Committee on Research for the Commission. CC is a Masters prepared (Community Health and Epidemiology) practicing community pharmacist with extensive training and expertise in health related databases. She conducts pharmacoepidemiology and related epidemiology health services research. She has been a member of the Drug Evaluation Alliance of Nova Scotia (DEANS) since 2006. At the time of the research, CC was employed at the Population Health Research Unit. SK is trained in addiction, public health medicine and psychiatry. He is currently practicing in Australia as a Professor and the Director of Health LinQ at the University of Queensland while maintaining an adjunct appointment with Dalhousie University's Departments of Psychiatry, Community Health and Epidemiology. His work as a clinician and scholar inform one another and he has focused on researching mental health services delivery, epidemiology/pharmacoepidemiology, and psychiatric co-morbidity. JH is a Professor in the School of Nursing at Dalhousie University and a Research Scientist with the Department of Psychiatry at the IWK Health Centre. She is also Senior Editor for the Canadian Journal of Community Mental Health. Her research and publications concentrate on marginalized populations (high inequalities, homeless) of children and youth with a focus on mental health issues. She is closely linked to her advocacy work at the provincial and national levels with professional regulatory boards, the Canadian Mental Health Association, Laing House, and a number of other community organizations. SPK holds the Sun Life Financial Chair in Adolescent Mental Health and directs the World Health Organization Collaborating Center in Mental Health at Dalhousie University. He holds numerous awards and honors locally, nationally and internationally for his work including: Best Doctor in Canada; Dr. John Savage Memorial Award for outstanding humanitarian contributions to global health; Canadian College of Neuropsychopharmacolgy Gold Medal; membership in the Canadian Academy of Health Sciences; and the Lifetime Achievement Award of the Canadian Psychiatric Research Foundation. He has been appointed a Fellow of the Canadian Psychiatric Association. He is a member of the Institute of Neuroscience, Mental Health and Addictions of the Canadian Institutes for Health Research; Interhealth Canada; Mental Health Commission of Canada (Child and Youth Advisory Committee); the Canadian Society for International Health; and the Canadian Coalition for Global Health Research. He is leading the development of a Canadian child and youth mental health framework: Evergreen. His current focus is on knowledge translation pertaining to youth mental health as it is applied in schools and primary care.