The Science and Ethics of Antipsychotic Use in Children

By Judy Illes

The Science and Ethics of Antipsychotic Use in Children reviews the latest findings for the safety and efficacy of the rapidly rising incidence of antipsychotic use in children and examines tensions that are created by off-label use, both in clinical psychiatric practice and research.In the past ten years, the number of antipsychotics prescribed to children with psychiatric disorders has skyrocketed. Despite this rapid growth, most medications have been inadequately studied in children for safety or efficacy and many have serious adverse health. Measures are needed to ensure that the health and safety of children are being protected, and debates have emerged over whether or not clinical trials in this population should be conducted.

• Offers coverage of efficacy, prevalence, and adverse impacts of the use of antipsychotics in children
• Explores ethics challenges of clinical research in this patient population
• Serves as a platform for future discussions designed to increase the safety of children taking antipsychotics
• Edited work with chapters authored by leading neuroethicists in the field around the globe – the broadest, most expert coverage available

• Language: English
• Publisher: Academic Press
• Release date: Apr 25, 2015
• ISBN: 9780128004814

Book preview

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Introduction: A Call for Partnership

Nina Di Pietro; Judy Illes

There are more than 60 years of clinical evidence demonstrating the benefits of antipsychotic medications for improving the lives of individuals affected by serious mental illnesses such as schizophrenia and bipolar disorder. The benefits of these medicines, however, are not without potential risk, ranging from mild unwanted side effects such as drowsiness to serious complications such as diabetes. For children and youth,¹ the risks are compounded by therapeutic uncertainties about their effectiveness for treatment of mental health conditions in this group. Nonetheless, antipsychotics are increasingly being applied to treat a wide range of emotional and behavioral problems in children, a trend that is causing many to wonder about how these medications are being used and prescribed. In this book, we explore the tension between the risk of treatment and the risk of illness within the context of off-label antipsychotic prescribing practices. Using a pragmatic neuroethics framework, we build on empirical research to inform best practices for prescribing antipsychotic medications to young people. This approach allows for the integration of a variety of medical, ethical, and sociological perspectives, which are ultimately needed to guide clinical practice (Racine et al., 2011).

The book is a direct product of the workshop Deliberations on the Ethical Use of Antipsychotic Medications in Children that we held in September 2013 at the University of British Columbia, with the support of the Peter Wall Institute for Advanced Studies and NeuroDevNet, Inc. The workshop brought together research and clinical leaders in child psychiatry, ethics, and neuroscience in a think tank setting to consider the state of the science and ethics of prescribing antipsychotic medicines for children. From it, we identified critical unanswered questions and formed the Canadian Working Group on Antipsychotics for Children to address them.

The Working Group weighed in on three key questions:

1. What phenomena account for the increase in prescribing antipsychotics for children and adolescents?

2. What gaps in knowledge need to be filled in order to begin to address concerns about safety and efficacy?

3. What are the ethical, legal, and social consequences of increased off-label use of antipsychotic medications in young people, and where do we go from here?

The group deliberations under each question are summarized below:

(1) What phenomena account for the increase in prescribing antipsychotics for children and adolescents?

The Working Group recognized that the reason for the burgeoning off-label use of antipsychotics in children and youth is likely multifactorial—a phenomenon that situates itself within political, sociocultural, and economic arenas (Di Pietro & Illes, 2014). To date, there has been little attempt to study how or to what extent any of these arenas may influence prescribing practices within the context of antipsychotics for children. Evidence is mostly anecdotal and in the form of news reports in the popular media. The proposed factors that account for the increase in second-generation antipsychotic prescription use, as derived from our group discussions and supplemented by the scientific literature, are as follows:

i. Wider availability of new antipsychotics on the market in the last 15 years.

Throughout the 1970s and 1980s, the term atypical was synonymous with clozapine. At the turn of the millennium, however, several new atypical antipsychotics were developed and made available on the North American market: risperidone (1993), olanzapine (1997), quetiapine (1997), ziprasidone HCl (2001), aripiprazole (2002), and paliperidone (2006). Soon after the introduction of these atypical drugs, they quickly became the most studied treatments for schizophrenia and other indications (Meltzer, 2013). As a result, second-generation antipsychotic (SGA) use also increased during this time period. For instance, prescriptions in the province of Manitoba for SGAs went from 1.9 per 1000 in 1999 to 7.4 per 1000 in 2008 (Alessi-Severini et al., 2012). Prior to the 1990s, the level of antipsychotic use among children was relatively constant (Olfson et al., 2002).

ii. Approval of antipsychotics to treat indications in adolescents.

In 2011, Health Canada approved Abilify® (aripiprazole) for the treatment of schizophrenia and bipolar disorder in adolescents, making it the first atypical antipsychotic to be specifically approved for use in children and youth. In the United States, the FDA approved it for the treatment of irritability in children with autism as young as age 6. Growing approval for use in minors may contribute to perceptions that antipsychotics are generally safe and effective, even if evidence for this is limited to older adolescents with serious mental health conditions.

iii. Emerging clinical trial data supporting antipsychotic use for youths outside of approved Health Canada indications.

The empirical basis for the use of SGAs outside of approved Health Canada indications is supported by a growing number of studies that show that they may be effective for treating a variety of different mental health problems in children and adolescents. According to the Cochrane Database of Systematic Reviews, there is some evidence of the efficacy of antipsychotics in reducing aggression and conduct problems in children with disruptive behavior disorders in the short term and for treating the symptoms of Tourrette’s syndrome (Loy et al., 2012; Pringsheim & Marras, 2009). Results of double-blind randomized controlled studies have also demonstrated the efficacy of risperidone for the short-term treatment of disruptive behavioral symptoms in children with autism, pervasive developmental disorders, or sub-average intelligence (Olfson et al., 2006). Although still limited, these positive early results may sway prescribers to adopt antipsychotic treatments for these conditions.

iv. Increasing diagnoses of bipolar disorder and autism spectrum disorders in young people.

Mental healthcare resources for young people in North America have increased rapidly in the last 20 years and have coincided with increased psychotropic medication use (Olfson et al., 2014). According to national data, approximately 10-20% of Canadian children and adolescents have a diagnosable mental illness (Canadian Mental Health Association, n.d.). However, numerous studies have shown that rates of diagnosis for mental health conditions such as ADHD and autism are increasing (Boyle et al., 2011). Increased awareness and improved diagnostic tools for developmental disorders in children may contribute to the observed increases in mental health conditions and subsequent increases in antipsychotic use. In addition, the number of antipsychotic prescriptions ordered by non-psychiatrist physicians has grown. Several Canadian studies have shown that general practitioners (GPs) initiate the majority of prescriptions for antipsychotics in children and adolescents (Alessi-Severini et al., 2012; Murphy et al., 2013; Patten et al., 2012). This finding has led some to suggest that more consultations with psychiatrists and other mental health specialists may be needed to ensure that appropriate diagnostic assessments are being made by GPs (Olfson et al., 2014). Further research is needed to assess the extent to which GPs consult with mental health specialists when making diagnoses and when considering antipsychotic treatment.

v. Lower rates of acute and chronic extrapyramidal adverse effects with SGAs.

The defining characteristic of atypical agents that sets them apart from first-generation antipsychotics is their ability to produce minimal extrapyramidal symptoms (EPS) at clinically effective doses. Thus, the perception that SGAs are safer may mitigate safety concerns and increased the willingness of prescribers to use them in children and adolescents.

vi. Lack of access to and availability of effective non-pharmacological interventions, particularly for people living in remote or rural areas or with limited income.

Health administrators argue that access to effective psychosocial programs and services remains limited because excessive dollars are spent on government coverage of medications instead (Latimer, Bond, & Drake, 2011). Often, parents of children with complex mental health needs must rely upon a poorly coordinated network of psychosocial services for interventions that are chronically underfunded (Madsen, 2009). A misallocation of resources has also been blamed for inadequate community supports, contributing to an overreliance on medications (Latimer et al., 2011). Accessing mental health care for children is especially challenging in rural communities. Geographic and professional isolation make smaller, rural communities less attractive to mental health workers, who tend to concentrate in larger urban areas (Dyck & Hardy, 2013). Patients and families often have to travel great distances, resulting in lost work and wages and other financial burdens related to the costs of travel, such as gas, parking, meals, and hotel accommodation (Boydell et al., 2006). In contrast, treatment with antipsychotic medication may be less expensive for families who are covered under government-sponsored drug plans that pay for most of the costs of antipsychotic medications (Alessi-Severini et al., 2008).

vii. Cultural factors, including greater public acceptance of psychotropic medications.

Data suggest that North American attitudes toward psychiatric medications have changed. Over the last 10 years, people have become more willing to take psychotropic medications for a wide variety of conditions, including relatively minor concerns such as coping with daily stress (Mojtabai, 2007). The decreasing stigma associated with seeking treatment for mental health problems, which has been especially pronounced among younger individuals, may have further contributed to the increasing number of prescriptions for antipsychotic medications for young people (Mojtabai, 2007, 2009). Public willingness to give psychiatric medications to children has been shown to be highest in instances where suicidal behavior is present or when a child displays oppositional behaviors and behaviors associated with ADHD (Mcleod et al., 2004).

viii. Pharmaceutical marketing, including the promotion of off-label use.

Pharmaceutical marketing tactics such as direct-to-consumer advertising and distribution of product samples and token gifts that increase physician interactions with representatives have been shown to influence prescribing practices in favor of the marketed drug (Rhee, 2008). Since 2008, the U.S. Department of Justice has ordered a number of pharmaceutical companies to pay substantial fines for fraudulent marketing practices. Practices deemed fraudulent include the promotion of antipsychotics to physicians and pharmacists for off-label purposes in children, and the use of misleading information that overstates their efficacy and downplays their risks.

ix. Social pressures, including pressure from schools, law enforcement, and the foster care system to ensure that kids stay in school and do not get in trouble.

Experts note that parents often seek pharmacological treatment for their children in order to avoid potentially negative social outcomes from problem behaviors. Unfortunately, almost no research has been conducted to examine the extent to which social, academic, and legal pressures influence prescribing practices. One study, however, suggests that hyperactivity and hallucinations or delusions are the most frequent problems for teachers in the classroom that lead to the use of pharmaceutical treatment (Epstein et al., 1991). Another study reports that physicians feel social pressure to prescribe antipsychotic medications when staff members complain of dangerous or particularly disruptive patient behavior (Pappadopulos et al., 2002). Other research indicates that incarcerated youth suffer disproportionally from mood and anxiety disorders that can lead to aggressive behavior. A meta-analysis of the research literature on the prevalence of mental disorders in juvenile detention and correctional facilities reveals that adolescents are about 10 times more likely to suffer from psychosis than the general adolescent population. The most common diagnoses found in this population are conduct disorder, ADHD, depression, and psychotic illness (Fazel et al., 2008). In a recent study, aggression was also linked with a greater likelihood of psychiatrists recommending off-label antipsychotic treatment (Rodday et al.,