Antipsychotics for aggressive adolescents: barriers to

Review

Antipsychotics for aggressive adolescents: barriers to best practice Elizabeth A Pappadopulos†, Sonja E Siennick and Peter S Jensen

Adolescents, aggression & antipsychotics Optimal therapy: what we know about treating aggressive youths with antipsychotics Treatment recommendations for antipsychotics use in aggressive youths

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CONTENTS

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In adolescents, antipsychotics are most often used to treat complex, comorbid conditions with core disruptive features. However, the literature guiding such practices is limited. Best practice guidelines bridging the gap between the evidence and clinical practice have been developed to promote the appropriate and safe use of antipsychotics in aggressive youths. Due to complex barriers that exist at the level of the physician, patient/family and organization, merely disseminating these guidelines will not likely change antipsychotic prescribing practices. Negative attitudes, time constraints, lack of staff training and resources, or adolescent/family nonadherence can impede the translation of best practice guidelines into routine practices. Efforts to implement best practice guidelines must address these barriers if changes in prescribing practices are to occur and be sustained.

Expert Rev. Neurotherapeutics 3(1), (2003)

Aggressive and dangerous behaviors are major criteria for the psychiatric hospitalization of youth [2,4]. Aggression often occurs within the context of disorders, such as conduct disorder (CD), oppositional defiant disorder (ODD) and attention deficit–hyperactivity disorder (ADHD) [5,6]. These ‘disruptive behavior disorders’ are among the most common diagnoses of youths with psychiatric hospitalization [3]. Inspection of Medicaid databases reveals that antipsychotic prescribing rates have increased in recent years. In a Midwestern US Medicaid population, antipsychotic prescription rates for youths increased by 63% between 1990 and 1996, primarily due to a substantial increase in the use of atypical antipsychotics [7]. In Texas, USA, the corresponding figure for 1996–2000 was 160% [8]. These rates are in fact so high that they surpass the prescription rates which would be expected for psychotic disorders, confirming that these drugs are frequently used for nonpsychotic cases. Clinical studies confirm that antipsychotics are prescribed to aggressive youths outside of the diagnostic indications for antipsychotic use, suggesting a symptom-chasing

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Implementing clinical practice guidelines Expert opinion Five-year view Information resources

References Affiliations

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Key issues

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KEYWORDS: adolescents, aggression, antipsychotic medications, barriers, best practice guidelines, dissemination and implementation of practice guidelines

It is widely accepted that despite the astounding progress made in child and adolescent psychiatry over the past few decades, many of these proven treatments either fail to reach the youth who need them or are delivered inappropriately [1]. A popular solution to this dilemma has been the development of ‘best practices’ or clinical practice guidelines (CPGs), which combine empirical evidence and expert consensus to provide a clinical decision-making tool [2]. However, despite these CPGs, there still exist large gaps between proven treatments and actual practice [3]. This gap between recommended and ‘realworld’ practices exists largely because patients, parents and doctors encounter barriers that prevent them from implementing evidencebased practices effectively (FIGURE 1). Each of these stakeholders plays an essential role in executing successful treatment and barriers can undermine the process at any point from the initial consultation to the final encounter. Identifying and addressing potential barriers at the provider, patient, or family level may help ensure that evidence-based treatments are effectively implemented and adolescent mental health outcomes are maximized.

†Author for correspondence

Columbia University College of Physicians and Surgeons, & Director, Medication Best Practices Project, Center for the Advancement of Children’s Mental Health at Columbia University Tel.: +1 212 543 6085 Fax: +1 212 543 5260 [email protected]

Adolescents, aggression & antipsychotics

Pappadopulos, Siennick & Jensen

Barriers to best practice Provider level • Lack of knowledge/training • Time pressure • Negative attitudes/beliefs • Lack of self-efficacy • Social norms

Ideal treatment: application of antipsychotic best practice guidelines

Organizational level • Staff resistance • Lack of staff training • Fiscal pressure

"Real world" treatment and outcome

treatment inertia may not represent the most beneficial treatment approach for the child. In fact, concerns have been raised that such practices are ineffective and even worse, potentially dangerous because of elevated side-effect risks [14]. Furthermore, polypharmacy makes it difficult to determine the primary diagnosis and to evaluate the efficacy of individual agents. Other problems associated with combined pharmacotherapy include increased costs without increased benefits and the fact that noncompliance is more likely with complex medication regimes [15].

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pharmacotherapy approach to aggressive youths which ignores the underlying primary diagnosis [9]. Indeed, when adolescents are prescribed antipsychotic medications, it is often for complex, comorbid conditions with core disruptive or aggressive features, characterized as ‘impulsive, unplanned, unprofitable and poorly controlled’ [10]. Studies show that antipsychotics are administered to youths in structured psychiatric settings in high proportions to address aggressive behavior problems. Similarly, these studies reveal that 45– 85% of all inpatient children and adolescents receiving psychotropic medications are prescribed antipsychotics, regardless of the type of facility (private, county university, or public facility [3,9,11–13]. However, there has been limited guidance from the literature for such off-label use of antipsychotics. Psychiatric treatment of aggressive adolescents is complicated further by the frequent use of polypharmacy. Studies have shown that inpatient youths are admitted and maintained on multiple medications during their inpatient stays and that antipsychotics are the most frequently combined class of medications [9,11–13]. Pappadopulos and colleagues reported that among inpatient children and adolescents receiving antipsychotics, 40% received adjunctive mood stabilizers, 30% received adjunctive selective serotonin reuptake inhibitors, 16% received all three classes of medication simultaneously and 14% received two antipsychotics simultaneously [3]. Similar findings have been reported in other studies [9,11–13]. Despite the common use of combined pharmacotherapy to treat youths in structured psychiatric settings, there is little evidence supporting this practice. Polypharmacy usually occurs when previously prescribed medications are maintained and new medications are introduced, as the child moves between the different levels of care, as is usually the case for youths with serious psychiatric conditions involving aggression [3]. The resulting

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Figure 1. Barriers to antipsychotic ‘best practices’ for adolescents.

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Adolescent & family level • Negative attitudes • Nonadherance • Poor engagement • Social/developmental factors • Patient safety

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Optimal therapy: what we know about treating aggressive youths with antipsychotics

A recent review of the available literature and an expert consensus survey and workshop combined the available evidence on the effectiveness of antipsychotic medications for aggression with expert consensus to develop clinical treatment guidelines [3,16,17]. Below, we present a brief review of the empirical literature. It is important to note that aggression, occurring as part of the clinical profile of a primary psychiatric condition, should be addressed by using first-line pharmacological treatments for the underlying condition, before using antipsychotic agents. See Connor for a review of the literature on the use of different psychotropic medications to treat comorbid aggression [18]. Typical antipsychotics

There is some empirical evidence on the use of typical antipsychotic medications (e.g., haloperidol, chlorpromazine) to treat aggression in youths [19,20]. Currently, these medications are often used intermittently for acute aggressive episodes rather than at standing therapeutic doses [3]. Safety concerns about the development of tardive dyskinesia and the introduction of the relatively safer atypical antipsychotics are probably responsible for their declining use in youths.


Antipsychotics for aggressive adolescents

Atypical antipsychotics Risperidone

gain (e.g., [29]). Some data indicate that the rate of agranulocytosis (a potentially fatal disruption of white cell production) may be higher among younger patients [31].

Among the atypicals, risperidone has the most empirical support for the treatment of aggression in youth. Several double-blind studies have demonstrated risperidone’s effectiveness in treating aggression in children with subaverage to low normal intelligence [5,21]. In a study of 118 children with behavioral problems and mental retardation, risperidone was associated with significant improvements in behavioral problems and this effect appeared to persist for subjects who were continued on risperidone for 48 weeks [22,23]. Uncontrolled research has also demonstrated that risperidone may help reduce aggression in complex comorbid disorders, including those involving psychosis and among youths with normal intelligence (e.g., [7]). With regard to side effects, weight gain, extrapyramidal symptoms (EPS) and elevated prolactin levels have emerged as the most serious [24–26]. In one study of 16 psychotic youths treated blindly with risperidone, patients gained a mean of 0.68 kg (1.5 pounds) per week [25]. The only study directly comparing weight gain associated with risperidone and olanzapine treatment of youths found no significant difference in the rate of weight gain associated with these two medications [25]. Weight gain associated with antipsychotic treatment is particularly disconcerting to children and adolescents because of the social ramifications. Although typical antipsychotics are more strongly associated with EPS, risperidone can also cause EPS, especially at higher doses [25]. In the majority of studies where aggression was treated with lower doses of risperidone, acute EPS was mild and disappeared with time. Risperidone has also been associated with the development of tardive dyskinesia [27]. Elevations in prolactin, which may cause galactorrhea, may also be greater with risperidone than with either haloperidol or olanzapine [24,25]. However, recent data in children suggests that prolactin levels may return to normal with long-term use (12 months) [28].

To date, there are no controlled trials of quetiapine for the treatment of aggression in youths. Weight gain and new-onset diabetes have been reported in adults [35]. One open-label study reported tachycardia in nine out of ten young patients treated with quetiapine [39]. Preliminary epidemiological data in adults also suggests an increased risk of Type 2 diabetes compared with typical antipsychotics [40].

Clozapine

Aripiprazole

Olanzapine

There are little controlled data on the use of olanzapine for the reduction of aggression in children or adolescents. However, in one open-label trial of children, adolescents and adults, olanzapine was associated with reductions in self-injurious behavior and aggression against people and property [36]. With regard to side effects, weight gain and the development of diabetes have been reported in studies of olanzapine treatment of youths with a variety of diagnoses [37,38].

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Quetiapine

Ziprasidone

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Given its relatively recent introduction, we are unaware of any published trials of ziprasidone for aggression. There is only one controlled study thus far of ziprasidone in youths. In this double-blind study, 28 children with Tourette’s syndrome or chronic tic disorder were given ziprasidone for 28 days [41]. The most common side effect was transient mild sedation and weight gain was not a serious problem. However, in adults, ziprasidone may cause cardiac conduction abnormalities, an effect that in rare cases has been associated with potentially fatal ventricular arrhythmias, especially when delivered in conjunction with other medications that prolong the QTc interval [42].

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The literature indicates that clozapine may reduce aggression in youth, but its safety profile, marked by its rare, but serious association with agranulocytosis and by its association with seizures, significant weight gain and tachycardia, limits its use in children and youths [29–31]. Reduced aggression with clozapine has been reported for ten youths with bipolar disorder, schizophrenia, or psychotic disorder not otherwise specified [29]. In a study of 331 schizophrenic adults, clozapine’s association with decreased aggression was independent of its antipsychotic and sedative effects [30]. In adults, clozapine has been associated with cardiovascular side effects (e.g., [32]), electroencephalogram changes, white blood cell abnormalities, elevated blood sugar, seizures (e.g., [33]) and new onset diabetes (e.g., [34]). Studies comparing the atypicals’ respective weight-gain liabilities in adults have found that clozapine results in the greatest and most enduring weight gain [26,35]. Clozapine use in pediatric populations shows a sideeffect profile that includes sedation, hypersalivation and weight


Aripiprazole is the most recent atypical antipsychotic to be released and is considered a ‘next-generation’ atypical antipsychotic with a mechanism of action that differs from previous antipsychotic agents. Therefore, there are no published data on the use of this agent with children and adolescents. An initial report comparing aripiprazole to haloperidol and placebo in adults with schizophrenia shows that it is efficacious and well-tolerated. There is little if any incidence of EPS, increased prolactin, weight gain, or QTc interval lengthening [43]. Treatment recommendations for antipsychotics use in aggressive youths

As indicated earlier in this paper, the use of antipsychotics to treat aggression in children and adolescents is a common clinical practice that has developed primarily through clinical experience rather than through rigorous research. In an effort to promote the safe and appropriate use of antipsychotics for this population of youngsters, our group collaborated with concerned New

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Implementing clinical practice guidelines

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Several studies show that practice guidelines alone are insufficient to change physicians’ prescribing practices. Barriers to implementing evidence-based treatments have been addressed in other domains of medicine [44–46]. These studies highlight how barriers to best practice implementation operate by examining issues specific to the treatment setting, targeted professional group and patient population. They also emphasize the importance of the information being delivered, how and to whom. At the organizational level, policies and cultural factors can either promote or impede the translation of treatment guidelines into actual practice in mental health settings for adolescents [47,48]. Emphasis must also be placed on the use of an evaluative process to assess the results of implementation efforts [49]. The empirical literature and our experience and data show that guidelines on the use of powerful and potentially toxic medications, such as antipsychotics, in growing adolescents may have unique barriers and may be particularly difficult to implement (BOX 1 and TABLE 1). Specifically:

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• In the first stage, 12 focus groups were conducted with multidisciplinary treatment providers from psychiatric inpatient settings for children and adolescents to identify salient medication and treatment issues [3] • We completed a extensive review of the literature of the use of antipsychotics to treat aggression [17] • In an effort to address gaps in the literature, we surveyed physicians and researchers with significant experience treating aggressive youth on their preferred treatment and prescribing practices [3] • Treatment practices that were strongly supported by survey responders as ‘extremely appropriate’ served as candidate ‘treatment recommendations’ and were used to guide the agenda of a consensus workshop attended by stakeholders in the project and national experts on the topic [16] • Next, 100 inpatient records were reviewed to determine the extent to which proposed treatment recommendations corresponded with actual inpatient prescribing practices • Treatment recommendations were revised and finalized, based on feedback from research and clinical experts [16]

standing medications statim, or both), 42% of in-patient records revealed evidence that psychotropic medications were abruptly discontinued and there was no evidence that standardized rating scales were used to track target symptoms or treatment effects. Despite good intentions to apply ‘best practices,’ physicians encounter barriers that obstruct their ability to change.

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York State Office of Mental Health clinicians and experts across the USA to develop best practice guidelines [16,17]. These Treatment Recommendations for the Use of Antipsychotics for Aggressive Youth (TRAAY) were developed in seven stages:

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Thus, the TRAAY recommendations are based on multiple sources of information and address sensitive treatment issues that may not be addressed by the literature. In addition to encouraging the use of psychosocial and behavioral interventions and comprehensive diagnostic assessment before emergency or standing antipsychotics are prescribed, the TRAAY recommend that doctors:

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• Monitor symptoms and side effects for patients taking antipsychotics • Use a first-line atypical antipsychotic for aggressive youths, switching to a different atypical for nonresponse and augmenting with a mood stabilizer for partial response • Use conservative dosing strategy with low starting doses and cautious titration and tapering • Ensure that adequate trials of antipsychotics are completed before changes to the medication regime are made • Avoid frequent emergency medication administration and extreme polypharmacy (more than three concurrent medications) • Discontinue antipsychotics in youth taking antipsychotics for aggression who have displayed no aggressive symptoms in 6 months (see [16] for the complete TRAAY and treatment rationale) Unfortunately, an examination of 100 patient records in New York State’s public psychiatric facilities for youth reveal that physicians have difficulty implementing the guidelines that they themselves endorse as highly appropriate [3]. For example, 34% of youth received two antipsychotics simultaneously (either as

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• Previous studies have identified many clinician and organizational barriers to the use of CPGs, both generally and with specific sets of guidelines • Particularly with an adolescent population, many patient and family factors may impede the implementation of CPGs The aggressive behavior for which antipsychotics are prescribed may itself make clinicians, families, schools and other stakeholders reluctant to use conservative medication strategies. FIGURE 1 illustrates how real-world barriers hamper the efficacy of ideal practices, resulting in insufficient treatment outcomes. Barriers to the implementation of CPGs: provider level

The first step in the implementation of CPGs in practice settings is dissemination. Clinicians are simply uninformed about some existing best practices [47]. This is not surprising given the recent dramatic increase in guideline development [50]. Even when providers know about specific sets of CPGs, however, this awareness does not mean that they remember the guidelines’ content [50]. Additionally, even when physicians complete a formal continuing education class on sets of CPGs and receive later booster materials, they are not necessarily any more likely to follow the guidelines [51]. Even when successful dissemination protocols are followed, another major obstacle to ensuring adherence to practice guidelines is the fact that many clinicians do not agree with CPGs in general or with specific sets of practice guidelines. If clinicians are unconvinced of the utility or applicability of practice guidelines, they will be unwilling to use them. For example, doctors



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Physician attitudes toward practice guidelines on the use of antipsychotic medications to treat aggressive behavior. Objective: To examine child psychiatrists’ attitudes toward and perceived barriers to the implementation of clinical practice guidelines on the use of antipsychotic medications for aggressive youth (TRAAY; [16]). Method: First, 33 child psychiatrists were asked to rate the appropriateness or desirability of applying each of the clinical practice guidelines (CPGs) on a 9-point likert-type scale (1 = highly inappropriate, 9 = highly appropriate, standard of care). Then, using a semistructured interview, 14 child psychiatrists employed in psychiatric inpatient settings for children and adolescents were asked to generate the advantages, disadvantages and obstacles they associated with implementing each CPG. Results: Overall, subjects considered the CPGs to be highly appropriate practices. Means for four CPGs were as follows: use rating scales to track target symptoms (8.57) and side effects (8.58), conservative dosing strategy (8.14) and limit use of emergency medications (8.62). Interview data using a coding system based on categories gleaned from respondents’ most salient advantages, disadvantages and obstacles. TABLE 1 presents the frequencies with which subjects mentioned these categories. Conclusions: Physicians view CPGs on the use of antipsychotic medications for aggressive youth as highly appropriate practices whose implementation would likely result in clear advantages for patients. However, physician perceptions of practices guidelines are complex because they also simultaneously weigh the perceived disadvantages of each practice. Simply agreeing with a prescribing ‘best practices’ may not be enough to ensure their translation into routine clinical practice. Frequently mentioned barriers may limit their actual implementation.

However, physicians report that they feel unable to carry out some specific CPGs, whether because of inadequate training or skill – this may be particularly true for preventative guidelines [47]. Furthermore, if clinicians are expected to deliver psychoeducation about best practices to patients and families, they must feel confident that they can do this effectively as well. Unfortunately, attempting to teach patients about best practices is seen as time-consuming and difficult [54]. Clinicians’ past behavior predicts their future behavior and CPGs that deviate from a doctor’s normal procedure may not be adhered to [47]. Walker et al. found that past behavior predicted 15% of the variance in general practitioners’ intentions to prescribe antibiotics for sore throats [56]. Torrey et al. suggest that best practices that would require major changes to the status quo will not be warmly received [48]. A major barrier, particularly to the implementation of complex or long-term CPGs, is the amount of time required to use a guideline. In our experience with physicians to date, time is listed as the main obstacle to most of the TRAAY (conducting diagnostic evaluations, using standardized measures to track treatment effects and side effects, using behavioral treatments, slowly tapering medication levels and ensuring adequate trials of medication) (see BOX 1 and TABLE 1). However, while clearly the concern over time sometimes reflected the physician’s own reluctance to ‘waste’ their time on these new best practices, equally as often, the time pressure was reported as coming from above – as pressure from hospital administration or insurance companies to titrate faster, sedate faster, discharge faster.

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Box 1.

report that, in general, CPGs are too rigid and leave no room for clinical judgment [47]. In addition, specific guidelines may be seen as irrelevant to a patient population or particular case [47,52,53]. Furthermore, even when clinicians feel generally favorable toward a specific CPG, they see patients individually and make decisions on a case-by-case basis. For example, Butler et al. found that general practitioners were aware that antibiotics were generally not effective treatments for sore throats, but cited characteristics of individual patients, such as expectations and the possibility of response in certain patients as reasons to continue this prescribing practice [54]. Convincing clinicians of the utility of CPGs is a particularly crucial step, as provider intentions to follow CPGs may have a greater impact on actual adherence to practice guidelines than any aspect of dissemination [52]. Self-efficacy, or one’s belief that they can perform a behavior, may also be a vital factor in adherence to best practices [55].


Barriers to the implementation of CPGs: organizational level

The atmosphere and resources of the organization in which a clinician works can have profound effects on the degree to which CPGs are implemented. Physician perceptions of CPGs may vary by setting [57]. The type of setting in which a provider operates affects climate, caseload, staffing, patient population and financial and physical resources, which in turn affect attitudes and self-efficacy beliefs about CPGs [51]. For example, independent general practitioners feel less favorably toward CPGs than do those affiliated with practices [58]. Administrative support is critical [48]. Our research demonstrates that uncooperative staff and pressure from high-level administrators or managed-care companies are barriers to physician use of the TRAAY recommendations. For example, pressure to discharge patients and to produce immediate clinical improvement was cited as a barrier to ensuring adequate trials of antipsychotic medications (TABLE 1). The degree to which other actors in a provider’s setting support CPGs can also enhance or decrease adherence. Pathman et al. revealed that physicians who learned about best vaccination practices from their colleagues had higher rates of awareness about and agreement with specific guidelines than did physicians who learned about CPGs from other sources [53]. Additionally, the structural resources needed to use certain CPGs may not be available [47]. This is particularly true for CPGs that require additional investments of money or time

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Table 1. Child psychiatrists’ attitudes toward selective CPGs from the TRAAY (n = 13). Reported barriers to implementation (% represent proportion of Frequency total responses generated and coded) (%)

Assess and track symptoms with a rating scales

Time pressure Scales unavailable Scales not applicable Inconvenience Takes control away from doctor Staff resistance Physician not trained to use them

22.5 18.4 18.4 10.5 10.5 7.9 7.9

Use conservative dosing strategy (start low, go slow)

Time pressure Increased risk to patient and staff Staff resistance Patient resistance

45.5 31.8 13.6 9.1

Limit the frequent use of statim or pro re nata medications

Safety Staff resistance Patient too aggressive, risk to patient/staff Limited staff recourses to monitor patient No effective alternatives available

33.3 16.7 16.7 12.5 20.8

Assess side effects routinely using standardized measure

Time pressures Physician not trained to use them Scales unavailable Administrative issues Laziness/clinician resistance Patient uncooperative

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beyond what is typically exerted by an organization, for example, the obtainment and completion of standardized outcome measures [48]. Furthermore, the cost and time devoted to staff training can be a disadvantage [48]. Variation in staff ability at different times of the day and month can preclude the development of uniformity in the use of CPGs. For example, Bernard and Littlejohn report that at one hospital, pro re nata medications were administered more frequently at night [59]. Turnover can also pose a major problem to organizations that invest limited resources in training staff to implement best practices [48]. Solutions for providers & organizations

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Fortunately, many of the barriers to provider adherence to best practices are modifiable or surmountable. See TABLE 2 for strategies to overcome provider and organizational barriers to the implementation of best practices. Providers may be more receptive to CPGs if they are formatted to be consistent with their perceptions of the needs of their patients – tailoring dissemination strategies to physicians’ needs or presenting CPGs in a more palatable way may prevent some provider resistance from ever arising [51,52]. Similarly, guidelines that are reasonably consistent with a provider’s current practice will be more readily accepted and used, if coincidentally [51]. The rationale behind CPGs may be disseminated with the guidelines and illustrations or examples pertaining to different patient groups can be included. Clinicians like video tapes and other materials that provide real-world examples of implementation [48]. It is also important to stress that CPGs are intended as aids and should be used as supplements to clinical judgment, rather than rigid prescriptions for action. 94

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CPGs

25.0 18.7 15.6 9.4 15.6 15.6

Tools that allow clinicians to explore CPGs without feeling that they are completely committing themselves to these new behaviors will encourage at least initial use of the guidelines. Providers more readily adopt CPGs that may be first used on a trial basis [51]. Furthermore, toolkits have been shown to be helpful to clinicians in the initial phases of guideline use [60–62]. For example, the developers of the Texas Implementation of Medication Algorithms project offer fill-in flow charts and checklists for clinicians and patients, the rationale behind each step of their algorithm and other materials, available at [101]. In addition, there is some evidence that adoption of CPGs is enhanced by role play [52] and that clinicians appreciate opportunities to observe guidelines’ implementation and consequences [48]. Interventions, such as academic detailing, offer intensive support to providers and allow the chance to explore the relevance and practical implementation of CPGs [51]. Academic detailing is usually an industry-sponsored physician education strategy where knowledge about medication prescribing practices is conveyed in face-to-face meetings with experts [51]. In addition, helping clinicians incorporate aspects of CPGs into their current routines will make the guidelines more convenient to use and partially overcome time-related barriers. Creating climates that encourage clinicians’ use of CPGs may be a more daunting task. Administrative support for CPGs may be enhanced by focus groups which will reveal the specific concerns of treatment setting management and staff – these concerns should guide the implementation plan. Guideline developers may offer training sessions or consultations with staff members, as not only will the convenience of these implementation techniques encourage adoption of Expert Rev. Neurotherapeutics 3(1), (2003)


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Consistent with research with other populations and in other arenas, adolescent medication compliance and health-related behaviors cannot be changed by dissemination of information alone [63]. Rather, the health-related views and experiences of adolescent consumers of mental health services are linked to health-seeking behaviors, medication compliance and engagement in treatment [64]. This is consistent with cognitive and interpersonal theories of behavior, such as the Health Beliefs Model [65,66] and the Theory of Reasoned Action [67,68]. Collectively, these theories propose that patient attitudes toward medication (based on perceived costs and benefits), in combination with the attitudes and support of significant others, including the psychiatrist, largely determine medication adherence [69]. Adolescents’ perceptions of doctor–patient communication, staff availability, side effects and whether the treatments received match their mental health needs all play a role in the perceived benefits of treatment [64]. However, physicians do not always take the special needs of youth into account and while the clinicians that we interviewed cited patient resistance as a major barrier to use of the TRAAY, research shows that factors, such as demographic characteristics (e.g., type of insurance) affect agreement with and adherence to certain best practices [53]. Mental health professionals require an understanding of the challenges that adolescents negotiate as they develop (i.e., maturing social and romantic relationships, independence, academic/professional achievement [70]) and how these developmental priorities interface with and potentially obstruct mental health treatment [71]. Unfortunately, a high proportion of adolescents with psychiatric difficulties criticize their prior mental health treatment as ‘lack[ing] of psychological help’ or ‘information on how to cope’ with their illness [64]. Adolescents also feel that psychiatrists share far too little information about the medications they are taking, especially with regard to the expected benefits, side effects and treatment effects. Addressing these issues may help improve patient–doctor communication and therapeutic alliance, thereby making adolescents less reluctant to seek and adhere to recommended treatments (TABLE 2). Research shows that understanding parent and patient attitudinal barriers to the implementation of evidence-based psychiatric treatments is essential to improving outcomes [72–75]. However, the importance of recognizing and treating adolescents as autonomous individuals who control their own behavior is reinforced by

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Adolescent developmental challenges & attitudes about mental health treatment

literature showing a decline in parental influence on youths’ health behaviors during the teenage years. Bastiaens found that parental knowledge, beliefs and attitudes all failed to predict adolescents’ medication compliance – in contrast, adolescents’ own pre-existing beliefs and attitudes toward pharmacotherapy did predict compliance [63]. While interventions addressing belief/attitudinal factors have the potential to mitigate the problem of noncompliance, they must target the adolescents, rather than parents, particularly because adolescents’ attitudes toward antipsychotic medications may be very different than adults’. An understanding of developmental processes during adolescence is necessary for the understanding of attitude formation and other determinants of treatment compliance. The major developmental tasks of adolescence are to strengthen peer relations and to establish independence from parents [76]. As a result, the adolescent may perceive any request to change his or her behavior as a control issue. Issues of confidentiality and the degree of involvement by parents can be problematic to the alliance between the patient and the provider. The clinician must walk a delicate line between privileged information and the responsibility to keep the patient safe. In addition, having parents monitor compliance can also lead to unintended conflicts over independence and privacy. While adolescent medication noncompliance is difficult to remedy, some evidence from the literature suggests that medication compliance issues are a significant impediment to appropriate treatment in adolescent psychopathology. While most studies on adherence focus on stimulants, they show that compliance in youths ranges from 56 to 76% [77]. It should be noted that these rates are likely to be underestimates because they are based on parental reports, which tend to minimize noncompliance. Regarding noncompliance with antipsychotic medications, in adult psychiatric populations, antipsychotic nonadherence is high (in some reports >50%) and is associated with increased recidivism and poorer outcomes [78,79]. Adolescents who are prescribed antipsychotics may be particularly vulnerable to medication nonadherence because of age-specific developmental challenges related to independence, social stigma, poor family support, intolerance of side effects and lack of insight into their difficulties.

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CPGs, but also having experts on the guidelines available during the initial implementation phase will likely increase fidelity to the guidelines. Conversely, if administrations are receptive to CPGs, new policies may change the behavior of even the most resistant individual clinicians. Organizations may also consider easing time restrictions on staff members during the initial phase of implementation – as clinicians become more familiar with the CPGs and their use, the time necessary to use them will decrease.


Clinical symptoms as a barrier to medication adherence

Adolescents who are prescribed antipsychotic medications for disruptive behavior problems may have oppositional–defiant traits that prevent them from taking medications as prescribed [3]. Independent thought emerging in adolescents may question the need for antipsychotics to help manage symptoms or control behavior. On the other hand, children and adolescents with disruptive behavior disorders may lack the cognitive ability and/or ‘insight’ to acknowledge the usefulness of antipsychotic agents in improving their clinical status and functioning. The link between antipsychotic medication compliance and insight has been demonstrated in schizophrenia, but similar studies have yet to be undertaken with adolescents with complex comorbid conditions involving aggression [80,81]. The

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Table 2. Possible strategies to overcome barriers. Barrier

Strategy

Intended outcome

Providers Provider lack of knowledge, Role play training or feelings of poor Training videotapes & materials self-efficacy Portable reference materials Academic detailing Intensive support or technical assistance Format guidelines so they are applicable to provider’s current practices

Enhance adoption of CPGs Increase intentions to use CPGs Increase physicians’ self-efficacy on the application of CPG

Organizations Focus groups with stakeholders Demonstrate clear commitment to applying CPGs Policy changes

Ensure buy-in from setting Make changes in policy that will enable physicians to implement CPGs more readily

Time pressures

Incorporate guidelines into routine paperwork (i.e., symptom rating scales included in intake package) Ease time constraints when first implementing CPGs

Increase feasibility of implementing CPGs Alter clinicians’ views of implementing guidelines as burdensome

Staff resistance & lack of training

Staff training Supervision Policy changes Focus groups

Improve staff knowledge and self-efficacy Increase staff adherence to CPGs Emphasize team role in implementation of CPGs

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Adolescents/families Negative attitudes

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Lack of commitment

Address negative attitudes and preconceived ideas about Improve attitudes and increase compliance with mental illness and treatment treatment Take the mental health needs of youth into account (do not rely on parent and teacher reports alone) Increase engagement and compliance Improve parenting skills Improve parental involvement in the treatment Establish consumer demand for best practice

Poor adolescent–doctor communication

Increase engagement and compliance

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Adolescent/family lack of Provide adolescents with materials and information on knowledge and resistance their treatment and medication toward implementing CPGs Provide parents with materials and information on treatment and information on adolescent development Encourage family participation in advocacy groups Educate about medication, treatment rationale, time needed to realize benefits and possible side effects

Target areas of concern to the adolescent Discuss concerns about peers and stigma with regard to mental illness and psychotropic medications

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CPG: Clinical practice guideline; TRAAY: Treatment Recommendations for the Use of Antipsychotics for Aggressive Youth.

available studies do show that individuals with little insight do not acknowledge the need for medication or the symptoms they exhibit [82]. Antipsychotic agents are associated with a host of side effects that can deter optimal compliance with the treatment regime. In adults, atypical antipsychotics have replaced conventional neuroleptics as first-line treatments for schizophrenia and related disorders largely because of the safer side-effect profile. A similar trend has been observed in child and adolescent psychiatry, although aggression and not psychosis is the primary target symptom [3,12]. Although atypicals are associated with fewer side effects than conventional agents, (fewer EPSs etc.), treatment adherence is nonetheless influenced by the severity and perceived drawback of the experienced side effects, including the significant safety risks of even the atypicals [17]. For example, in adolescents, weight gain and decreased libido may 96

be especially problematic side effects associated with atypical agents because of the negative impact on social functioning. Such side effects may easily be seen as outweighing the positive effects of antipsychotic treatment. Parents

As the dissemination of best practices often targets providers (e.g., in medical journals, continuing medical education), patients and families may be unaware that best practices exist for their conditions. Educating patients and families about treatment alternatives has been shown to increase patient engagement in and compliance with treatment [51,52] (TABLE 2). Education alone, however, is insufficient to ensure that parents and adolescent patients participate in treatment, as negative parental attitudes and beliefs about mental illness and psychiatric treatment can be deterrents to initiating and sustaining treatment [83]. Expert Rev. Neurotherapeutics 3(1), (2003)


then they are unlikely to adhere to CPGs. Additionally, these beliefs may prevent or delay parental referrals of youths to mental health services or maintenance of engagement with services. As beliefs and attitudes toward treatment are factors in parental delivery of prescribed treatments for youths, attempts to implement CPGs for adolescent mental healthcare must take these into account. Once initial contact with services is made, the provider may play an important role in modifying these beliefs and attitudes to be more consistent with best practices. Solutions for adolescents & parents

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It has been noted that patient perceptions of antipsychotic side effects often differ from clinicians’ – those that clinicians notice are not always noticed by patients and those that are not viewed as medically significant can be quite distressing to patients (e.g., [90]). Psychoeducation may be a critical adjunct to medication treatment, as it enhances communication as well as patient and family trust in the prescribing clinician [90]. Psychoeducation for patients and families about treatment effects may also be valuable, as parental perceptions may differ from patients’ subjective experiences [91]. Weiss and colleagues suggest that clinicians question adolescents using a forced choice question format (e.g., asking which of two feelings about treatment is stronger) to help teenagers express their feelings about treatment and to establish a hierarchy of the adolescent’s concerns [91]. The teenage processes of developing identities and negotiating social environments must also be considered if treatment adherence is to be maximized. Clinicians must be sensitive to any generalization of the need for medication to the adolescent’s selfimage (e.g., incorporating ‘mental’ into their identities) and encourage a realistic self-perception [91]. Arranging medication prescriptions and doses so that they may be taken in private in the morning and evening, rather than during the day at school or work, may prevent social stigma or busy mid-day routines from becoming obstacles to compliance (e.g., [92]). Psychoeducation programs may also be effective in heightening patient and family intentions to follow through with prescribed treatment. However, these must include behavior change components. Studies of antipsychotic compliance in adults have revealed that psychoeducational interventions that do not aim to change attitudes and behavior will not increase compliance – effective interventions will explicitly address medication compliance [93]. Furthermore, parental participation in advocacy groups may not only increase knowledge of available treatments and best practices, but can also provide valuable social support networks. See TABLE 2 for strategies to overcome patient and family barriers to implementing best practices.

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Since mental health treatments, such as medication, require the active and continual involvement of caretakers, poor working relations between parents and providers can obstruct the appropriate delivery of pharmacological treatments. These relationships can be fraught with psychological, interpersonal and practical impediments that can derail the treatment process. For example, caregivers may feel that their child’s behavior does not warrant the use of antipsychotic agents. Therefore, in order to be effective, implementation strategies for interventions aimed at increasing adherence to CPGs must target actors at all levels of the mental health service delivery system [84]. Unfortunately, although parental involvement in youths’ mental healthcare decisions is critical, when dealing with mental health professionals, parents report feeling excluded, marginalized and confused by medical terminology [85]. This perception of the psychiatric world as a family-unfriendly environment no doubt adds to the difficulty that caregivers already have in adhering to best mental health treatment practices for youths. Alternatively, research also shows that consumer demand also influences provider behavior, making physicians more likely to deliver evidence-based treatments [48]. Physicians report greater adherence to best pediatric vaccination practices if they believe that parents request recommended practices [53]. Cockburn and Pitt demonstrated that while patients who expected their doctors to prescribe them medication were three times more likely to receive prescriptions than were patients who did not have such expectations, when general practitioners perceived that patients expected these treatments, they were ten times more likely to deliver them [86]. However, patient expectations and doctor perceptions were significantly related [86]. A large literature on compliance with treatments for ADHD reveals large gaps between best practices and parental practices. Bussing and Gary found that parents only implement the portions of provider-recommended treatments that are consistent with the parents’ own ideas of appropriate treatment [87]. For example, while stimulant medications are effective for ADHD symptoms, parents are resistant to administering prescribed stimulants to their children [87]. Instead, parents implemented dietary changes for their children to manage symptoms, despite the lack of scientific evidence to support this practice [87]. These findings suggest that it is important to ensure that caregivers feel positively toward prescribed best practices for adolescents. Recent efforts in Texas to disseminate and implement treatment best practices do involve patients and families as major stakeholders to help promote the acceptance, support and use of treatment guidelines in clinical settings [88]. However, even when parents believe that best practices are appropriate treatments for psychiatric disorders, they may fail to link their children’s behavior with mental illness. A study of parental attitudes toward stimulant medication for ADHD revealed that parents did not understand the link between medication and their children’s behavior and made incorrect attributions for good and bad behaviors [89]. If parents do not connect adherence to psychiatric best practices and youths’ behavior,


Safety

Aggressive behavior is highly disruptive, visible and increasingly dangerous as physical strength increases over the course of adolescence. Our interviews with physicians in combination with the available literature indicate that managing aggression is a priority for the staff of inpatient units, even at the expense of the safe and appropriate use of psychiatric medications. In fact,

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facility administration. Again, policy changes regarding the balance of psychosocial treatments and emergency medications can ensure the cooperation of staff members. In sum, factors inherent to the treatment of aggression in adolescents with powerful and potentially harmful antipsychotics (e.g., safety, lack of insight) make applying CPGs a difficult undertaking. In addition, barriers nested within and between patients, caregivers, providers and organizations further complicate efforts to improve antipsychotic prescribing practices. Lack of awareness, negative attitudes and time pressures, are examples of common barriers that exist across treatment stakeholders. Efforts to improve the quality of care through the application of CPGs should proactively address such barriers with the use of the possible strategies presented in TABLE 2.

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There is mounting evidence from clinical trials that atypical antipsychotics are an effective treatment for adolescents with complex emotional and behavioral difficulties. However, these same agents often have disappointing outcomes when delivered in ‘real-world’ treatment settings because of unnecessary and sometimes inappropriate treatment variability (e.g., excessive use of statim medications or subtherapeutic administration of antipsychotic agents). The use of CPGs for atypical antipsychotic use in youths is one way to enhance optimal prescribing practices and outcomes. To be effective, these efforts must be accompanied by multilayered interventions that address barriers nested within and between providers, patients and caregivers.

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the literature suggests that pro re nata and statim medications are quite common – Kaplan and Busner report that 78% of medicated youth at a state hospital and 86% of medicated youth at a university hospital received at least one administration of a statim or pro re nata medication during their stay [12]. The vast majority of these administrations were for agitation [12]. Furthermore, most youths who received statim or pro re nata antipsychotics were already taking standing doses of antipsychotics [12]. In some cases, statim administrations are actually preferred to standing prescriptions for antipsychotics because of the belief that standing doses will lead youths to think that they do not have control over their behavior [59]. Clinicians may direct treatment at alleviating the symptoms rather than the underlying disorder that is responsible for the symptoms [94]. This may be particularly true of physicians prescribing antipsychotics for youths, as these medications have such immediate effects on aggressive behavior that they may be preferred to lengthy diagnostic exams or management of primary diagnoses. In fact, in our interviews with physicians, the need for quick reduction of aggressive behavior in a behavioral emergency was the third most frequently cited barrier to conducting an initial diagnostic examination for aggressive youth and the single most frequently named obstacle to treating primary disorders before prescribing antipsychotics for aggression (see BOX 1 and TABLE 1). The clinicians also indicated that conservative dosing strategies and the use of behavioral interventions before medication pose risks to staff and other patients. This confirms the impression that managing youths’ aggression by whatever means necessary is a unit priority, even when these tactics may not be the best course of action for an individual adolescent. In addition to a general apprehension about reducing the use of emergency medications in favor of behavioral interventions or standing doses of antipsychotics, the fact that pro re nata and statim administrations depend on the judgment of multiple clinicians poses another obstacle to the implementation of the TRAAY recommendations and optimal prescribing methods. That is, while the order is written by a physician, nurses must decide when to fill the order, within the parameters of the physician’s prescription [12]. In our experience, physicians cite staff resistance as a major barrier to using more conservative interventions in place of emergency medications and share a feeling that as the nurses are on the front lines, it is unfair to take away the statim medication safety net. Thus, the successful implementation of CPGs on antipsychotics will require the cooperation of professionals besides the prescribing physician and interventions may also need to target nursing staff and technicians. Solutions for unit safety

CPGs may be presented within treatment algorithms, both to reduce the time required to process them and to show in detail how they may be applied in emergency situations or incorporated into post-crisis treatment [61]. Unit staff may be trained in psychosocial interventions that can prevent agitation from escalating and requiring emergency administrations of antipsychotics. Supervision and training should be an ongoing priority of 98

Five-year view

The real utility of implementing best practice guidelines may be realized in the next 5 years, as CPGs become a greater part of clinical practice. Simultaneously, as the next generation of better-tolerated and more effective atypical antipsychotics enters the marketplace, administering antipsychotics to adolescents is likely to become safer and easier. In the meantime, CPGs can help ensure that providers administer antipsychotics appropriately and cautiously. In addition, increased public awareness of mental illness and ‘best practice’ treatments will likely lead to a more sophisticated and demanding consumer. Information resources

The website for the Center for the Advancement of Children’s Mental Health can be found at: www.kidsmentalhealth.org. The website for the New York University Child Study Center can be found at: www.aboutourkids.org. These sites provide information for caregivers and organizations on best practices in child and adolescent mental healthcare. The website for the Children’s Medication Algorithm Project can be found at: • www.mhmr.state.tx.us/centraloffice/medicaldirector/cmap.html This site provides information on treatment algorithms for children with ADHD and major depressive disorder. The website for the Practice Parameters of the American Academy of Child and Adolescent Psychiatry can be found at: www.aacap.org/clinical/parameters.htm. Expert Rev. Neurotherapeutics 3(1), (2003)


Key issues

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Papers of special note have been highlighted as: • of interest •• of considerable interest 1 Jensen PS, Bhatara V, Vitiello B, Hoagwood K, Feil M, Burke L. Psychoactive medication prescribing practices for US children: Gaps between research and clinical practice. J. Am. Acad. Child Adolesc. Psychiatry 38, 557–565 (1999). • Excellent review of psychopharmacological prescribing trends in youth highlighting the gaps between research and clinical practice. 2 American Academy of Child and Adolescent Psychiatry. Practice parameters for the assessment and treatment of children and adolescents with bipolar disorder. J. Am. Acad. Child Adolesc. Psychiatry 36, 157–176 (1997).

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• Atypical antipsychotics appear effective for the treatment of adolescents with complex comorbid conditions involving persistent aggressive behavior. • Although atypical antipsychotics are considered safer than typical agents, side effects, such as weight gain, elevated prolactin and cardiac abnormalities, make medication management an issue of paramount importance. • Despite such cautions, evidence indicates that there are wide variations in antipsychotic prescribing practices in adolescents. • The application of best practice guidelines based on the literature and expert consensus is needed to promote the appropriate and safe use of antipsychotics for aggressive youth. Examples of guidelines include: use psychosocial strategies and treat primary disorders before using antipsychotics for aggression; use atypicals over typicals when antipsychotics are indicated for aggression; minimize the use of stats for behavior management; monitor target symptoms, treatment effects and side effects using standardized rating scales. • Simple dissemination of clinical practice guidelines (CPGs) is insufficient to change: physicians’ prescribing practices, organizational policies that result in treatment inertia and treatment nonadherence in adolescent consumers. • Provider barriers to implementing CPGs include lack of knowledge, training and feelings of low self-efficacy. • Organizational barriers to implementing CPGs include lack of organizational buy-in, time pressure, costs and staff resistance or lack of training. • Consideration of the perspectives of young people with mental health problems, as well as the perspectives of their caregivers, is vital in maximizing adherence to CPGs for antipsychotics. • To make the greatest impact, efforts to implement CPGs must be accompanied by multilayered interventions that address barriers nested within and between organizations, providers, patients and caregivers.

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www.mhmr.state.tx.us/centraloffice/ medicaldirector/timasczman.pdf

Affiliations •

Elizabeth A Pappadopulos, PhD, Assistant Professor of Clinical Psychology, (In Psychiatry), Columbia University College of Physicians and Surgeons, & Director, Medication Best Practices Project, Center for the Advancement of Children’s Mental Health at Columbia University, Tel.: +1 212 543 6085, Fax: +1 212 543 5260, [email protected] Sonja E Siennick, BA, Research Associate, Center for the Advancement of Children’s Mental Health at Columbia University. Tel.: +1 212 543 2533, Fax: +1 212 543 5260, [email protected] Peter S Jensen, MD, Ruane Professor of Child Psychiatry, Columbia University, College of Physicians and Surgeons, & Director, Center for the Advancement of Children’s Mental Health at Columbia University. Tel.: +1 212 543 5334, Fax: +1 212 543 5260, [email protected]

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