Atypical antipsychotic prescribing patterns amongst Child and Adolescent Mental Health Services clinicians in a defined National Health Service Trust

Abstract

Background

In the last decade, the prescription of atypical antipsychotics in minors, by all specialists, has increased. The use has been both licensed and ‘off-label’, with the aim of targeting different symptoms and clinical conditions. However, most research around safety and efficacy of these pharmacological agents has been conducted in adults and with repeated calls for such research in minors in vain.

Objectives

This survey aims to describe current prescribing practices in a ‘real-world’ scenario and to compare the results with existing research to evaluate lessons learnt.

Methods

The survey consisted of a semi-structured questionnaire that aimed to evaluate the current practices of Child and Adolescent Mental Health Services (CAMHS) prescribers. A total of 31 questionnaires sent out yielded 24 completed returns (77.41%). A literature search yielded articles that described prescribing trends over the last decade. The results from the survey were compared with the existing literature.

Results

The commonest indication for using atypical antipsychotics in minors was psychosis (75%). Other indications included reduced behavioural control (50%), tic disorders (37.5%), ADHD and anxiety disorders. Atypical antipsychotics were the commonest first-line medications for managing behavioural control with Risperidone (54%) being the most preferred agent. Second-line medications included Quetiapine (7%) and Olanzapine (15%). Doses were lower for managing behavioural control, and atypical antipsychotics were trialled for up to 8 weeks, and with duration of treatment extending up to 9 months. When such medications were used for non-psychotic presentations, most common target symptoms were aggression (85%), agitation (54%) and anxiety (54%). Most prescribers reported peer/expert opinion and their own clinical experience as evidence base for their use and clinical practice.

Conclusions

In the investigated sample, atypical antipsychotics continue to be used as first-line medications for psychotic and non-psychotic psychiatric presentations in minors, despite an absence of clear evidence comparable to the adult literature, and also despite repeated calls for in-depth research in this particular population. Although the present survey was conducted amongst psychiatrists, this has implications for all prescribers in children and adolescents, regardless of their specialty.

• atypical antipsychotics
• second-generation antipsychotics
• off-label use
• prescribing patterns Responsible Editor: Daniel Mueller, Centre for Addiction and Mental Health, Toronto, Canada.

To access the supplementary material to this article, please see Supplementary files under ‘Article Tools’.

With schizophrenia often showing first onset in adolescence (1), the use of antipsychotic pharmacological agents is a central component of the treatment (2) of psychotic symptoms. Much of the evidence for such treatments in minors is extrapolated from studies conducted in adult patients with schizophrenia. Although Clark and Lewis have reviewed the use of antipsychotics in children and adolescents, their analysis only included English language literature, and this analysis was conducted approximately 15 years ago (2). There has been a plethora of new classes of antipsychotics introduced since this particular article was written. However, remarkably, there have not been many new recommendations for the use of antipsychotic agents in minors. Moreover, the recent National Institute of health and Clinical Excellence (NICE) guidelines (3) on the treatment of schizophrenia bases its recommendations on studies conducted in adult patients.

The American Academy of Child and Adolescent Psychiatry (AACAP) has issued practice parameters (4) that acknowledge an increase in controlled trials of atypical antipsychotic agents for early onset schizophrenia and recommend antipsychotic medication as the primary treatment for schizophrenia spectrum disorders in minors. However, they state that all studies have limitations and that more studies are needed. They also acknowledge the presence of some studies comparing the safety and efficacy of different antipsychotics in minors (TEOSS Study) but conclude that none of the agents in that study worked ‘sufficiently well’ and ‘all had potential problems with side effects’. The guidelines also state that ‘safety and effectiveness data addressing the use of antipsychotic medications for early onset schizophrenia remain limited’, and this is postulated to reflect short-term use and a lack of comparative trials. In sum, there is a paucity of evidence for the use of antipsychotics in minors when compared to the existing literature for adults.

Most of the recommendations from studies (2) and guidelines (3) are based on expert consensus. While some individual antipsychotics have been shown to be effective for (behavioural) symptoms (5), there are no clear recommendations in therapeutic guidelines on the use of an individual antipsychotic for either psychotic disorders (3) or developmental/behavioural disorders (6). A number of factors such as purported efficacy of the medication, adverse effects profile and patient preference are stated as being important when making a clinical decision when it comes to the use of such pharmacological agents in minors. However, there is no clear weight assigned to these particular factors, and it is up to the prescribing physician to make an individual clinical decision. NICE guidelines (3) recommend that this decision should be made giving consideration to adverse effect profiles and patient choice, but there is little elaboration on the relative weight of factors that should be considered when making that choice. Currently, the evidence on comparative benefits, safety and potential harms of the use of antipsychotics in minors is limited (4) when compared to the use of such agents in adults (7).

Overall, currently clinicians do not appear to have a clear theoretical framework for their choice of antipsychotic pharmacological agents when aiming to treat psychotic symptoms/schizophrenia in minors. The efficacy and effectiveness data on such pharmacological agents are largely based on the adult literature, and there is no existing theoretical framework in determining the choice of an antipsychotic when prescribing it to minors. Reports from the United States (8) suggest that the bestselling antipsychotics are Aripiprazole and Quetiapine. However, when psychiatrists were quizzed about which drugs they would prefer being prescribed if they were to experience a psychotic episode, the top two choices were Risperidone and Olanzapine (9). Thus, it appears that there is a mismatch between what psychiatrists would like to prescribe and what they actually prescribe, although it must be noted that the data are not directly comparable as they are from two different countries.

The current situation can be summarised as follows:

1. Current guidelines do not recommend using individual antipsychotic medications in any particular order in minors, mostly due to lack of high-quality comparative studies.

2. The decision on the choice of antipsychotic is left to the physician in charge of treatment ‘in consultation’ with the patient. In this context, it is difficult to imagine how patients will have enough high-quality information to make an informed choice if this information is not available to the prescribing physicians. Therefore, there is potential for a wide variation in prescribing practices in the absence of a clear and evidence-based template for clinical decision-making when using antipsychotics in minors. Antipsychotics are medications that are potentially prescribed for a long period of time (i.e. many years), and the use of such medications can be associated with diverse and long-lasting adverse effects.

3. Currently, evidence is of variable quality and physician's preferences also seem to show considerable variability.

4. There is a distinct lack of research in this area in minors when compared to the adult literature.

A recent analysis (10) of diagnostic practices of child and adolescent psychiatrists indicated a number of factors distinct from clinical signs and symptoms, such as clinician training and attitudes, patient and family expectations, perceived stigma and economic drivers that influence diagnoses. A similar question could potentially be asked about factors potentially influencing prescribing practices.

The use of antipsychotics for managing non-psychotic symptoms and aspects of behavioural control in minors is even less clear. A systematic review (11) found that while there was a potential favourable risk to benefit profile for the use of atypical antipsychotics for managing behavioural disorders, long-term data on the safety and efficacy with respect to these particular indications did not exist and additional studies are warranted. This particular article also identified the lack of controlled clinical data to guide practice for the use of atypical antipsychotics for treating psychotic symptoms and bipolar disorder in minors. A recent Cochrane review (12) concluded that while there was some limited evidence of efficacy of particular antipsychotics (most notably Risperidone for treating aggressive behaviours) reducing behavioural problems in the short term, caution was required due to limitations of the evidence and the small number of high-quality studies. They identified factors such as inadequate power of studies, heterogeneity of the population, methodological issues with individual studies amongst others as factors that limited generalisability to real-life clinical practice.

Given the above, there is a need to explore what the current prescribing practices are when it comes to the use of antipsychotic medications in minors, and how psychiatrists currently make clinical decisions with regard to the choice of a specific antipsychotic for administration in children and adolescents. The survey conducted and outlined in this publication aims to understand the use of antipsychotics in minors, and to identify the various clinical conditions that are managed with antipsychotics in that age group, and the guidance relied upon to support clinical practice.

Methodology

The present survey was conducted amongst a group of Child and Adolescent Psychiatrists in a defined National Health Service (NHS) Trust in England.

A questionnaire was developed that aimed to understand the following (based on physicians’ reports):

1. To identify commonly used antipsychotics in minors

2. To identify indications for the use of antipsychotics in this particular age group

3. To gain information on dose range and target symptoms

4. To assess the duration of treatment in minors with such medications

5. To identify the evidence considered when clinicians make a decision to prescribe such pharmacological agents to children and adolescents

The questionnaire can be found in the Supplementary file related to this publication. The questionnaire was developed with the above aims in mind. We divided the questions into three categories: 1) Information about the individual prescribers, 2) Their use of atypical antipsychotics – this part of the questionnaire attempted to gain information on what the practitioners said they would prescribe antipsychotics for and how they went about making decisions regarding dose range, length of treatment and so on and 3) Their opinions based upon their clinical experience. A draft version of the questionnaire was sent for an opinion to a senior Professor of Psychiatry, University of Leicester, UK, and after some modifications, was administered to a colleague to check for acceptability and ease of use.

Following this process, the questionnaire was sent by internal mail to all prescribers whose contact details were obtained from the organisation's pharmacy. Ethical approval for the study was obtained from the Trust's audit and research committee. The survey consisted of a semi-structured questionnaire that aimed to evaluate the current practices of CAMHS prescribers. A total of 31 questionnaires were sent out yielding 24 completed returns (77.41%).

Data analysis

The data were analysed in a descriptive manner using simple arithmetic sums and percentages with regard to the prescribers’ information and the above-mentioned factors and variables.

Results

Indications and preferred medications

Most of the prescribers (67%) were from general child and adolescent community outpatient clinics, with the remainder coming from inpatient or specialised services. About 77% of the prescribers had prescribed atypical antipsychotics for a variety of disorders, and 14% only for treating psychotic disorders with the remainder having never had prescribed any atypical antipsychotics to minors.

Figure 1 shows common indications reported for the use of atypical antipsychotics in minors.

Fig. 1. Indications for the use of atypical antipsychotics amongst respondents.

An overwhelming majority (95%) of clinicians who responded preferred to prescribe atypical antipsychotics as first-line medications for the treatment of schizophrenia and related psychotic symptoms, and 75% preferred these medications as first-line treatment of bipolar disorder and psychotic depression. The results for first-line management of behavioural control differed as depicted in Fig. 2.

Fig. 2. First-line choice of treatment for behavioural control amongst respondents.

Figure 3a and b shows the preferred antipsychotics (first line and second line) of the respondents.

Fig. 3. The (a) first- and (b) second-line choices of antipsychotics for psychotic disorders and behavioural symptoms amongst respondents.

Dose and target symptoms

Figure 4 shows the doses of the medications when atypical antipsychotics were used for managing behavioural control in minors. Target symptoms for behavioural control included aggression, agitation and self-harm (Fig. 5).

Fig. 4. Doses of antipsychotic medications used for behavioural control.

Fig. 5. Target symptoms when using antipsychotics for behavioural control.

Duration of treatment

Clinicians prescribed atypical antipsychotics for up to 12 weeks for treating psychotic symptoms and up to 8 weeks for managing behavioural control before switching/terminating medications.

Variables considered for treating behavioural control

Clinicians were asked to outline factors and variables that they considered when aiming to manage behavioural control in minors by prescribing atypical antipsychotics. The results are given in Fig. 6.

Fig. 6. Variables considered by respondents when prescribing antipsychotics –for behavioural control.

Consideration of evidence

Figure 7 provides the evidence that clinicians considered when prescribing atypical antipsychotics in children and adolescents.

Fig. 7. Evidence considered by respondents when prescribing antipsychotics for behavioural control.

Discussion

The present survey aimed to assess current clinical prescribing practices with regard to using atypical antipsychotic medications in minors in a ‘real-world’ scenario and to compare the results with existing research. Overall, the results indicate that within the respondent group, atypical antipsychotics were prescribed for the treatment of a variety of conditions other than psychotic disorders in minors. They were preferred by most prescribers as first-line treatments for treating psychotic conditions and were also used extensively for targeting behavioural control in patients with non-psychotic disorders such as autism spectrum disorders. Common target symptoms included aggression and agitation.

Recent trends across the world indicate a high rate of use of antipsychotics in children and adolescents. For instance, in the United States, Harrison et al. in 2012 (13) reported a 2–5-fold increase in use of atypical antipsychotics in preschool children. Pathak et al. (14) reported a doubling in prescriptions between 2001 and 2005, and with 41% of the prescriptions being tendered in situations where there was no diagnosis for which antipsychotic medications as a treatment were supported in any published study. A Canadian study (15) in 2007 reported a similar increase in prescriptions of antipsychotics to children, and with 12% of all prescriptions being made to children of less than 9 years of age. Similar reports of an increased use of atypical antipsychotics in children have also been reported from Europe (16) and Australia (17).

Some of the possible reasons for an increased use of antipsychotics in children and adolescents may include (13) greater acceptability of psychotropic use, limited access to non-pharmacological treatments (in particular for behavioural disorders), a demand for quick and affordable treatments, inadequate time and resources for managing behavioural problems and limited options for alternate psychological treatments in some vulnerable groups such as minors in the care system, or even in the juvenile justice system. Implications for prescribers of antipsychotic pharmacological agents in minors could include an acknowledgement that based on existing literature (13, 18) antipsychotics, in some situations, could perhaps be considered as a second-line treatment after behavioural treatments, where indicated.

Some of the concerns in relation to the increasing use of antipsychotics in children and adolescents relate to the paucity of high-quality evidence-based standards to guide their use, significant long-term adverse effects of these medications but also limited knowledge of their long-term effects in minors, and the necessity of close monitoring of adverse effects. These data also raise concerns about the openness of communication in relation to the choices made available to patients and their families.

Limitations of the study

The present survey is subject to limitations as it was conducted in a defined organisation. Moreover, although the survey was conducted anonymously and participants could not be linked to responses, all participants were colleagues working together in one organisation with close clinical ties. The number of participants is rather small and was limited by the fact that the survey was limited to one organisation. These factors limit the generalisability of the study, and which should be addressed by future studies.

Conclusions

The results of the present survey are largely in line with similar trends observed across the world. Atypical antipsychotics continue to be used in children and adolescents as first-line medications for a variety of disorders. Currently available guidelines do not clearly recommend the use of any particular antipsychotic medications for the treatment of psychotic symptoms, and there is even less clarity on their use with regard to using antipsychotics for treating other behavioural conditions. There is no clear framework that professionals or patients and families can rely upon, with regard to existing evidence, on which to base such a crucial decision when it comes to available treatment options. It is imperative that future studies should focus on building up an evidence base for the safety and efficacy of antipsychotic use in minors. Another area for future studies includes the possible use of qualitative methods (such as Grounded Theory (19)) to find out more about the currently used processes and factors related to prescribers. This can potentially build a theoretical framework for the use of antipsychotics in children within the constraints of the current (lack of) evidence base.

Conflict of interest and funding

In the past 6 years, F D Zepf was the recipient of an unrestricted award donated by the American Psychiatric Association (APA), the American Psychiatric Institute for Research and Education (APIRE), and AstraZeneca (Young Minds in Psychiatry Award). He has also received research support from the German Federal Ministry for Economics and Technology, the German Society for Social Pediatrics and Adolescent Medicine, the Paul and Ursula Klein Foundation, the Dr. August Scheidel Foundation and the IZKF of RWTH Aachen University and a travel stipend donated by the GlaxoSmithKline Foundation. He is the recipient of an unrestricted educational grant, travel support and speaker honoraria by Shire Pharmaceuticals, Germany, as well as editorial fees from Co-Action Publishing (Sweden). In addition, he has received support from the Raine Foundation for Medical Research (Raine Visiting Professorship). The other authors have nothing to disclose or report.

Notes

To access the supplementary material to this article, please see Supplementary files under ‘Article Tools’.