- Email: [email protected]
TOSCA: No Longer Just an Opera
EDITORIAL
TOSCA: No Longer Just an Opera Peter S. Jensen,
T
he Puccini opera Tosca, beloved by many for more than a century, may finally be upstaged by a project of the same name—at least in the minds of child mental health aficionados waiting for research findings to advance their care for children. The upstart? The Treatment of Severe Child Aggression study (TOSCA). Like the opera, TOSCA is best appreciated in 3 acts, although the stage and the players differ for each act of our new TOSCA. The first act must open with a brief review of the history of randomized controlled trials (RCTs) and their role in improving public health. Arguably, one area where we have seen the greatest advances in children’s health during the past 50 years has been in the treatment of children’s cancers, specifically acute lymphoblastic leukemia. Before that time, nearly all children developing this form of leukemia succumbed to the illness. In contrast, current 5-year survival rates have reached 90%, with just a fraction of afflicted children ultimately dying of pediatric leukemia.1 How have these advances been accomplished? In the late 1960s and early 1970s, children benefited from a systematic “war on cancer” supported by legislation and a massive influx of funds into research at the National Cancer Institute.2 In the pediatric oncology area, many multisite, placebo-controlled RCTs were launched, comparing various medications and medication combinations on children’s leukemia outcomes (e.g., survival rates). Most children who developed leukemia were enrolled in these clinical trials, such that every child with leukemia had the benefit of receiving treatment within a highquality RCT that offered the best available chemotherapeutic treatment at the time or another experimental treatment that one hoped would be even better.1 Most importantly, the information obtained from the careful study of each child’s treatment responses during that era benefited future generations of children, as new knowledge of the most efficacious interventions was gradually distilled from these studies.
938
www.jaacap.org
MD
Still within Act I, in 1990, under then-Director Lewis Judd, the National Institute of Mental Health launched a major new initiative, in essence, a “war on children’s mental disorders.”3 Since then, dozens of multisite RCTs have been launched, with results transforming our understanding of effective treatments for children’s mental disorders. Despite this influx of new trials supported by the National Institute of Mental Health and by legislation that incentivized pharmaceutical companies to conduct pediatric trials, there have only been a handful of studies comparing 1 medication with 2 medications for childhood psychiatric illnesses to date. As a consequence, robustly efficacious treatments for the most severe psychiatric disorders afflicting children have remained only a partial reality, and often more than 50% of children with mental disorders, despite receiving the most rigorous treatments within recent clinical trials, are not sufficiently benefitted such that they return to normal function within 1 year.4,5 One area where efficacious treatments have been most urgently needed has been the area of pediatric aggression, which complicates many childhood mental disorders and results in the lion’s share of impairment, hospitalization, and out-of-home placements. Just as pain or fever constitutes symptoms that accompany many illnesses, pediatric aggression is a severe symptom complicating the presentation and degree of impairment for most childhood mental disorders, including attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant disorder, conduct disorder, Tourette’s syndrome, depressive and bipolar disorders, and even anxiety disorders. Even after rigorous treatment and with a relatively common condition such as ADHD, as many as 50% of children with ADHD will manifest significant aggressive symptoms that constitute the most impairing component of their overall clinical picture. Given the degree of
JOURNAL
OF THE
AMERICAN ACADEMY OF C HILD & ADOLESCENT PSYCHIATRY VOLUME 53 NUMBER 9 SEPTEMBER 2014
EDITORIAL
clinical morbidity attributable to pediatric aggression when it accompanies and complicates the outcomes of pediatric mental health disorders, a consensus conference involving key stakeholders (scientists, ethicists, policymakers, child and family advocates, Food and Drug Administration representatives, etc.) readily reached agreement that the impulsive, “hot” aggression accompanying pediatric mental health disorders is in fact a viable, even critical, treatment target for pediatric RCTs, and that such research studies must be encouraged.6 The preferred designs for such an RCT, as recommended by conference attendees, bore a great deal of similarity to the generations of studies for pediatric leukemia: first, within a rigorously conducted RCT, ensure that efficacious, high-quality treatment is provided for the primary underlying disorder (such as ADHD) to all children; and second, once the optimal treatment has been delivered, randomly assign children to receive an additional potentially therapeutic agent versus placebo under doubleblinded conditions. Happily, we are just beginning to see more of precisely this type of urgently needed study and must see more if we are to achieve optimal outcomes for children with complicated psychiatric disorders.7 Act II of our modern-day TOSCA opens with a new team of players, all seasoned investigators who fully anticipated the need for the type of study outlined above: Gadow et al.8 designed a 4site RCT for children with ADHD and severe aggression that tested optimal stimulant medication plus parent behavior training augmented with risperidone or placebo. Although previous research had shown that medication plus intensive parent and teacher training achieved excellent outcomes for up to two thirds of children with ADHD, a subgroup of children within the Multimodal Treatment Study of Children with ADHD remained substantially impaired by the end of treatment, even after 14 months of intensive medication treatment, medical care, and behavioral training. How we can better address these children’s needs has lingered as an important question, now addressed by the TOSCA investigators. For TOSCA, children were randomly assigned at baseline to 1 of 2 groups: a “basic” condition, i.e., open treatment with a high-quality intervention consisting of individualized titration and optimization of medication (OROS methylphenidate) plus 9 sessions of parent management
training, followed by double-blinded placebo if children continued to show clinically significant impairment owing to aggressive symptoms after the third week; or an “augmented” condition, consisting of the same open therapy and medication treatments but augmented after 3 weeks with double-blinded risperidone if they showed continued impairment owing to aggression. Placebo or risperidone were individually titrated and administered for an additional 6 weeks until the end of 9 weeks, at which point overall outcomes were compared based on parents’ subscores and teachers’ rating scales for oppositional-defiant disorder symptoms, conduct symptoms, and peer aggression. In their previous report,9 these investigators reported that children in the augmented condition showed significantly greater decreases in parent-reported aggression when using the Disruptive-Total subscale score from the Nisonger Child Behavior Rating Form and lower levels of “hot,” impulsive aggression. Surprisingly, clinicians’ ratings of improvement using the Clinical Global Impression Improvement and Severity scales did not show significant differences. In this report, the investigators sought to extend their previous findings, reporting here on ADHD, oppositional-defiant disorder, and conduct disorder symptoms, symptom-related impairment, and peer aggression, by examining these outcomes in home and school settings using parent and teacher reports. Results indicated that children receiving the augmented intervention showed significantly greater improvements than those receiving placebo for parent-rated oppositionality and peer aggressive symptoms. In contrast, few differences were found for teacher-rated oppositionality and aggression. Instead, teachers of children in the augmented condition reported significant decreases in ADHD symptoms (especially inattentive and impulsive symptoms) compared with teachers of children in the basic (placebo) condition. As the investigators note, the most dramatic differences are those seen from before to after treatment (baseline through 9 weeks), found virtually on all outcomes. When statistically significant differences were found between groups, they were modest, comparatively speaking, as were the effect sizes (except for teachers’ ratings of ADHD symptoms: effect size ¼ 0.61). Act III now opens on the stage of children’s mental health and on all of us who are players on this stage. For us, given TOSCA’s dramatic
JOURNAL OF THE AMERICAN ACADEMY OF C HILD & ADOLESCENT PSYCHIATRY VOLUME 53 NUMBER 9 SEPTEMBER 2014
www.jaacap.org
939
JENSEN
pre-post changes and the more modest changes as a function of risperidone augmentation, the study’s results raise new questions that we must now struggle to answer. First, why are more improvements in children’s oppositional and aggressive behavior seen at home than at school? When such discrepancies exist clinically, how do we determine whether the nature of “the problem” lies in some characteristics of the child, features of his or her environment, or in an interaction between children and their differing environments? Understandably, Gadow et al. anticipated and skirted this question, but only somewhat, by providing a proven pharmacologic intervention for the child and behavioral management and skills training for the parents. As clinicians, we cannot dodge quite so easily. To wit, and second, given the common discrepancies in children’s behavior and outcomes across settings, how should our interventions for children differ if the aggression is seen only within 1 setting versus multiple settings? Should we intervene with the child, such as using medication, or should we intervene with the environment, such as more intensive coaching or training of parents or teachers? If we always assume that we should first “fix” the child, it is likely that a good number of children will receive medication when other interventions might be more appropriate, such as teacher support and training, a change of the child’s classroom, assistance to parents in developing their skills in working with a hard-to-manage child, or even anger control psychotherapy. Third, how much initial “pretreatment” should we provide before we augment our intervention with an atypical antipsychotic medication? For example, should children be tested with one stimulant and then tested with another stimulant if the first one does not decrease the child’s aggression before augmenting the treatment with an atypical agent? More crucially, how long should therapy be carried out and with what intensity? Gadow et al. had to make critical choices during Act II. They did not test 2 different stimulants REFERENCES 1. Kersey JH. Fifty years of studies of the biology and therapy of childhood leukemia. Blood. 1997;90:4243-4251. 2. National Cancer Institute. Developmental therapeutics. Milestone: National Cancer Act of 1971. http://dtp.nci.nih.gov/timeline/ noflash/milestones/M4_Nixon.htm. Accessed June 9, 2014. 3. National Advisory Mental Health Council. National Plan for Research on Child and Adolescent Mental Disorders: A Report Requested by the U.S. Congress. Rockville, MD: US Department of Health and Human Services, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health; 1990.
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before turning to the augmentation strategy, and they chose to limit the length of therapy provided to 3 weeks before augmentation—which are understandable choices within a complex RCT. What will we do? When we consider the relevance and application of Act II’s findings to Act III’s real-world patients and families, most of us as clinicians have discovered that the hard-to-learn, specialized skills that parents need to manage a hard-to-manage child are not easily learned in a few weeks. How long does it take a parent to acquire these skills? If Gadow et al. had required 6 to 9 months of intensive parent and/or teacher training (as in the Multimodal Treatment Study of Children with ADHD), this study would have been nearly impossible to execute, given its focus on severely aggressive children with ADHD. However, in a child with aggression seen principally at home and not at school, unless there is severe and immediate physical danger to the child or others or other adverse consequences (e.g., school expulsion), aggression treatment guidelines as applied to ADHD generally suggest a more intensive and lengthier period of psychotherapy, and testing of alternative stimulant preparations.10,11 As Act III unfolds, let us hope that we, as current players on this stage, can craft adequate solutions to these thorny challenges, and that the roles we play in this real-life drama lead to healthier outcomes for our children and families. & Accepted July 9, 2014. Dr. Jensen is with The REACH Institute, New York City. Disclosure: Dr. Jensen holds stock in CATCH Services, Inc., and has received book royalties from American Psychiatric Publishing, Guilford Press, Civic Research Institute, and Random House/Ballantine Books. In addition, he has received charitable donations from Shire, Inc., through the Mayo Clinic and the REACH Institute. Correspondence to Peter S. Jensen, MD, The REACH Institute, 224 West 35th Street, Suite 1304-B, New York, NY 10001; e-mail: [email protected] 0890-8567/$36.00/ª2014 American Academy of Child and Adolescent Psychiatry http://dx.doi.org/10.1016/j.jaac.2014.06.008
4. Kennard B, Silva S, Vitiello B, TADS Team, et al. Remission and residual symptoms after short-term treatment in the Treatment of Adolescents With Depression Study (TADS). J Am Acad Child Adolesc Psychiatry. 2006;45:1404-1411. 5. Swanson JM, Kraemer HC, Hinshaw SP, et al. Clinical relevance of the primary findings of the MTA: success rates based on severity of symptoms at the end of treatment. J Am Acad Child Adolesc Psychiatry. 2001;40S:168-179. 6. Jensen PS, Youngstrom E, Steiner H, et al. Consensus report: impulsive aggression as a symptom across diagnostic categories in child psychiatry: implications for medication
JOURNAL
OF THE
AMERICAN ACADEMY OF C HILD & ADOLESCENT PSYCHIATRY VOLUME 53 NUMBER 9 SEPTEMBER 2014
EDITORIAL
studies. J Am Acad Child Adolesc Psychiatry. 2007;46: 309-322. 7. Blader JC, Schooler NR, Jensen PS, Pliszka SR, Kafantaris V. Adjunctive divalproex sodium vs. placebo for children with ADHD and aggression refractory to stimulant monotherapy. Am J Psychiatry. 2009;166:1392-1401. 8. Gadow K, Arnold LE, Molina B, et al. Risperidone added to parent training and stimulant medication: effects on attention-deficit/ hyperactivity disorder, oppositional defiant disorder, conduct disorder, and peer aggression. J Am Acad Child Adolesc Psychiatry. 2014;53:948-959.
9. Aman MG, Bukstein OG, Gadow KD, et al. What does risperidone add to parent training and stimulant for severe aggression in child attention-deficit/hyperactivity disorder? J Am Acad Child Adolesc Psychiatry. 2014;53:47-60. 10. Pappadopulos E, MacIntyre JC II, Crismon ML, et al. Treatment Recommendations for the use of Antipsychotics for Aggressive Youth (TRAAY): part two. J Am Acad Child Adolesc Psychiatry. 2003;42:145-161. 11. Scotto Rosato N, Correll CU, T-MAY Steering Group, et al. Treatment of Maladaptive Aggression in Youth (T-MAY). CERT guidelines II. Psychosocial interventions, medication treatments, and side effects management. Pediatrics. 2012;129:e1577-e1586.
JOURNAL OF THE AMERICAN ACADEMY OF C HILD & ADOLESCENT PSYCHIATRY VOLUME 53 NUMBER 9 SEPTEMBER 2014
www.jaacap.org
941
TOSCA: No Longer Just an Opera Peter S. Jensen,
T
he Puccini opera Tosca, beloved by many for more than a century, may finally be upstaged by a project of the same name—at least in the minds of child mental health aficionados waiting for research findings to advance their care for children. The upstart? The Treatment of Severe Child Aggression study (TOSCA). Like the opera, TOSCA is best appreciated in 3 acts, although the stage and the players differ for each act of our new TOSCA. The first act must open with a brief review of the history of randomized controlled trials (RCTs) and their role in improving public health. Arguably, one area where we have seen the greatest advances in children’s health during the past 50 years has been in the treatment of children’s cancers, specifically acute lymphoblastic leukemia. Before that time, nearly all children developing this form of leukemia succumbed to the illness. In contrast, current 5-year survival rates have reached 90%, with just a fraction of afflicted children ultimately dying of pediatric leukemia.1 How have these advances been accomplished? In the late 1960s and early 1970s, children benefited from a systematic “war on cancer” supported by legislation and a massive influx of funds into research at the National Cancer Institute.2 In the pediatric oncology area, many multisite, placebo-controlled RCTs were launched, comparing various medications and medication combinations on children’s leukemia outcomes (e.g., survival rates). Most children who developed leukemia were enrolled in these clinical trials, such that every child with leukemia had the benefit of receiving treatment within a highquality RCT that offered the best available chemotherapeutic treatment at the time or another experimental treatment that one hoped would be even better.1 Most importantly, the information obtained from the careful study of each child’s treatment responses during that era benefited future generations of children, as new knowledge of the most efficacious interventions was gradually distilled from these studies.
938
www.jaacap.org
MD
Still within Act I, in 1990, under then-Director Lewis Judd, the National Institute of Mental Health launched a major new initiative, in essence, a “war on children’s mental disorders.”3 Since then, dozens of multisite RCTs have been launched, with results transforming our understanding of effective treatments for children’s mental disorders. Despite this influx of new trials supported by the National Institute of Mental Health and by legislation that incentivized pharmaceutical companies to conduct pediatric trials, there have only been a handful of studies comparing 1 medication with 2 medications for childhood psychiatric illnesses to date. As a consequence, robustly efficacious treatments for the most severe psychiatric disorders afflicting children have remained only a partial reality, and often more than 50% of children with mental disorders, despite receiving the most rigorous treatments within recent clinical trials, are not sufficiently benefitted such that they return to normal function within 1 year.4,5 One area where efficacious treatments have been most urgently needed has been the area of pediatric aggression, which complicates many childhood mental disorders and results in the lion’s share of impairment, hospitalization, and out-of-home placements. Just as pain or fever constitutes symptoms that accompany many illnesses, pediatric aggression is a severe symptom complicating the presentation and degree of impairment for most childhood mental disorders, including attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant disorder, conduct disorder, Tourette’s syndrome, depressive and bipolar disorders, and even anxiety disorders. Even after rigorous treatment and with a relatively common condition such as ADHD, as many as 50% of children with ADHD will manifest significant aggressive symptoms that constitute the most impairing component of their overall clinical picture. Given the degree of
JOURNAL
OF THE
AMERICAN ACADEMY OF C HILD & ADOLESCENT PSYCHIATRY VOLUME 53 NUMBER 9 SEPTEMBER 2014
EDITORIAL
clinical morbidity attributable to pediatric aggression when it accompanies and complicates the outcomes of pediatric mental health disorders, a consensus conference involving key stakeholders (scientists, ethicists, policymakers, child and family advocates, Food and Drug Administration representatives, etc.) readily reached agreement that the impulsive, “hot” aggression accompanying pediatric mental health disorders is in fact a viable, even critical, treatment target for pediatric RCTs, and that such research studies must be encouraged.6 The preferred designs for such an RCT, as recommended by conference attendees, bore a great deal of similarity to the generations of studies for pediatric leukemia: first, within a rigorously conducted RCT, ensure that efficacious, high-quality treatment is provided for the primary underlying disorder (such as ADHD) to all children; and second, once the optimal treatment has been delivered, randomly assign children to receive an additional potentially therapeutic agent versus placebo under doubleblinded conditions. Happily, we are just beginning to see more of precisely this type of urgently needed study and must see more if we are to achieve optimal outcomes for children with complicated psychiatric disorders.7 Act II of our modern-day TOSCA opens with a new team of players, all seasoned investigators who fully anticipated the need for the type of study outlined above: Gadow et al.8 designed a 4site RCT for children with ADHD and severe aggression that tested optimal stimulant medication plus parent behavior training augmented with risperidone or placebo. Although previous research had shown that medication plus intensive parent and teacher training achieved excellent outcomes for up to two thirds of children with ADHD, a subgroup of children within the Multimodal Treatment Study of Children with ADHD remained substantially impaired by the end of treatment, even after 14 months of intensive medication treatment, medical care, and behavioral training. How we can better address these children’s needs has lingered as an important question, now addressed by the TOSCA investigators. For TOSCA, children were randomly assigned at baseline to 1 of 2 groups: a “basic” condition, i.e., open treatment with a high-quality intervention consisting of individualized titration and optimization of medication (OROS methylphenidate) plus 9 sessions of parent management
training, followed by double-blinded placebo if children continued to show clinically significant impairment owing to aggressive symptoms after the third week; or an “augmented” condition, consisting of the same open therapy and medication treatments but augmented after 3 weeks with double-blinded risperidone if they showed continued impairment owing to aggression. Placebo or risperidone were individually titrated and administered for an additional 6 weeks until the end of 9 weeks, at which point overall outcomes were compared based on parents’ subscores and teachers’ rating scales for oppositional-defiant disorder symptoms, conduct symptoms, and peer aggression. In their previous report,9 these investigators reported that children in the augmented condition showed significantly greater decreases in parent-reported aggression when using the Disruptive-Total subscale score from the Nisonger Child Behavior Rating Form and lower levels of “hot,” impulsive aggression. Surprisingly, clinicians’ ratings of improvement using the Clinical Global Impression Improvement and Severity scales did not show significant differences. In this report, the investigators sought to extend their previous findings, reporting here on ADHD, oppositional-defiant disorder, and conduct disorder symptoms, symptom-related impairment, and peer aggression, by examining these outcomes in home and school settings using parent and teacher reports. Results indicated that children receiving the augmented intervention showed significantly greater improvements than those receiving placebo for parent-rated oppositionality and peer aggressive symptoms. In contrast, few differences were found for teacher-rated oppositionality and aggression. Instead, teachers of children in the augmented condition reported significant decreases in ADHD symptoms (especially inattentive and impulsive symptoms) compared with teachers of children in the basic (placebo) condition. As the investigators note, the most dramatic differences are those seen from before to after treatment (baseline through 9 weeks), found virtually on all outcomes. When statistically significant differences were found between groups, they were modest, comparatively speaking, as were the effect sizes (except for teachers’ ratings of ADHD symptoms: effect size ¼ 0.61). Act III now opens on the stage of children’s mental health and on all of us who are players on this stage. For us, given TOSCA’s dramatic
JOURNAL OF THE AMERICAN ACADEMY OF C HILD & ADOLESCENT PSYCHIATRY VOLUME 53 NUMBER 9 SEPTEMBER 2014
www.jaacap.org
939
JENSEN
pre-post changes and the more modest changes as a function of risperidone augmentation, the study’s results raise new questions that we must now struggle to answer. First, why are more improvements in children’s oppositional and aggressive behavior seen at home than at school? When such discrepancies exist clinically, how do we determine whether the nature of “the problem” lies in some characteristics of the child, features of his or her environment, or in an interaction between children and their differing environments? Understandably, Gadow et al. anticipated and skirted this question, but only somewhat, by providing a proven pharmacologic intervention for the child and behavioral management and skills training for the parents. As clinicians, we cannot dodge quite so easily. To wit, and second, given the common discrepancies in children’s behavior and outcomes across settings, how should our interventions for children differ if the aggression is seen only within 1 setting versus multiple settings? Should we intervene with the child, such as using medication, or should we intervene with the environment, such as more intensive coaching or training of parents or teachers? If we always assume that we should first “fix” the child, it is likely that a good number of children will receive medication when other interventions might be more appropriate, such as teacher support and training, a change of the child’s classroom, assistance to parents in developing their skills in working with a hard-to-manage child, or even anger control psychotherapy. Third, how much initial “pretreatment” should we provide before we augment our intervention with an atypical antipsychotic medication? For example, should children be tested with one stimulant and then tested with another stimulant if the first one does not decrease the child’s aggression before augmenting the treatment with an atypical agent? More crucially, how long should therapy be carried out and with what intensity? Gadow et al. had to make critical choices during Act II. They did not test 2 different stimulants REFERENCES 1. Kersey JH. Fifty years of studies of the biology and therapy of childhood leukemia. Blood. 1997;90:4243-4251. 2. National Cancer Institute. Developmental therapeutics. Milestone: National Cancer Act of 1971. http://dtp.nci.nih.gov/timeline/ noflash/milestones/M4_Nixon.htm. Accessed June 9, 2014. 3. National Advisory Mental Health Council. National Plan for Research on Child and Adolescent Mental Disorders: A Report Requested by the U.S. Congress. Rockville, MD: US Department of Health and Human Services, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health; 1990.
940
www.jaacap.org
before turning to the augmentation strategy, and they chose to limit the length of therapy provided to 3 weeks before augmentation—which are understandable choices within a complex RCT. What will we do? When we consider the relevance and application of Act II’s findings to Act III’s real-world patients and families, most of us as clinicians have discovered that the hard-to-learn, specialized skills that parents need to manage a hard-to-manage child are not easily learned in a few weeks. How long does it take a parent to acquire these skills? If Gadow et al. had required 6 to 9 months of intensive parent and/or teacher training (as in the Multimodal Treatment Study of Children with ADHD), this study would have been nearly impossible to execute, given its focus on severely aggressive children with ADHD. However, in a child with aggression seen principally at home and not at school, unless there is severe and immediate physical danger to the child or others or other adverse consequences (e.g., school expulsion), aggression treatment guidelines as applied to ADHD generally suggest a more intensive and lengthier period of psychotherapy, and testing of alternative stimulant preparations.10,11 As Act III unfolds, let us hope that we, as current players on this stage, can craft adequate solutions to these thorny challenges, and that the roles we play in this real-life drama lead to healthier outcomes for our children and families. & Accepted July 9, 2014. Dr. Jensen is with The REACH Institute, New York City. Disclosure: Dr. Jensen holds stock in CATCH Services, Inc., and has received book royalties from American Psychiatric Publishing, Guilford Press, Civic Research Institute, and Random House/Ballantine Books. In addition, he has received charitable donations from Shire, Inc., through the Mayo Clinic and the REACH Institute. Correspondence to Peter S. Jensen, MD, The REACH Institute, 224 West 35th Street, Suite 1304-B, New York, NY 10001; e-mail: [email protected] 0890-8567/$36.00/ª2014 American Academy of Child and Adolescent Psychiatry http://dx.doi.org/10.1016/j.jaac.2014.06.008
4. Kennard B, Silva S, Vitiello B, TADS Team, et al. Remission and residual symptoms after short-term treatment in the Treatment of Adolescents With Depression Study (TADS). J Am Acad Child Adolesc Psychiatry. 2006;45:1404-1411. 5. Swanson JM, Kraemer HC, Hinshaw SP, et al. Clinical relevance of the primary findings of the MTA: success rates based on severity of symptoms at the end of treatment. J Am Acad Child Adolesc Psychiatry. 2001;40S:168-179. 6. Jensen PS, Youngstrom E, Steiner H, et al. Consensus report: impulsive aggression as a symptom across diagnostic categories in child psychiatry: implications for medication
JOURNAL
OF THE
AMERICAN ACADEMY OF C HILD & ADOLESCENT PSYCHIATRY VOLUME 53 NUMBER 9 SEPTEMBER 2014
EDITORIAL
studies. J Am Acad Child Adolesc Psychiatry. 2007;46: 309-322. 7. Blader JC, Schooler NR, Jensen PS, Pliszka SR, Kafantaris V. Adjunctive divalproex sodium vs. placebo for children with ADHD and aggression refractory to stimulant monotherapy. Am J Psychiatry. 2009;166:1392-1401. 8. Gadow K, Arnold LE, Molina B, et al. Risperidone added to parent training and stimulant medication: effects on attention-deficit/ hyperactivity disorder, oppositional defiant disorder, conduct disorder, and peer aggression. J Am Acad Child Adolesc Psychiatry. 2014;53:948-959.
9. Aman MG, Bukstein OG, Gadow KD, et al. What does risperidone add to parent training and stimulant for severe aggression in child attention-deficit/hyperactivity disorder? J Am Acad Child Adolesc Psychiatry. 2014;53:47-60. 10. Pappadopulos E, MacIntyre JC II, Crismon ML, et al. Treatment Recommendations for the use of Antipsychotics for Aggressive Youth (TRAAY): part two. J Am Acad Child Adolesc Psychiatry. 2003;42:145-161. 11. Scotto Rosato N, Correll CU, T-MAY Steering Group, et al. Treatment of Maladaptive Aggression in Youth (T-MAY). CERT guidelines II. Psychosocial interventions, medication treatments, and side effects management. Pediatrics. 2012;129:e1577-e1586.
JOURNAL OF THE AMERICAN ACADEMY OF C HILD & ADOLESCENT PSYCHIATRY VOLUME 53 NUMBER 9 SEPTEMBER 2014
www.jaacap.org
941