Agomelatine in pediatric patients with moderate to severe major depressive disorder: an open-label extension study.

Major depressive disorder (MDD) in young people is a common psychiatric disorder, but treatment options are limited. Agomelatine has demonstrated short-term efficacy and safety in pediatric patients. We report here the results of a 92-week open-label extension (OLE). The international, multicenter, double-blind, study randomized 400 patients (80 children, 320 adolescents) with moderate-to-severe MDD to one of four treatment groups: agomelatine 10 mg (n = 102), agomelatine 25 mg (n = 95), placebo (n = 103), and fluoxetine 10-20 mg (n = 100). After 12 weeks, patients who could benefit from treatment continuation were offered entry into an optional OLE during which they received agomelatine 10 or 25 mg for a further 92 weeks. A total of 339 patients (271 adolescents) entered the OLE. Treatment groups considered for the OLE analysis reflected those received in the double-blind and OLE periods: agomelatine (10 or 25 mg) in both (ago/ago, n = 170); placebo then agomelatine 10-25 mg (pcb/ago, n = 85); or fluoxetine then agomelatine 10-25 mg (fluox/ago, n = 84). Mean age (± SD) at entry into the double-blind phase (Week 0) was 13.6 ± 2.7 years and 61.9% were female. Mean changes in Children's Depression Rating Scale revised (CDRS-R) raw total score from Week 12 to last post-Week 12 value in the three groups were - 16.3 ± 12.2 (ago/ago), - 18.9 ± 16.1 (pcb/ago), and - 16.1 ± 15.5 (fluox/ago), reflecting the difference in efficacy between treatments during the double-blind period, and heterogeneity at W12 between the treatment groups. Adverse events considered related to treatment occurred in 14.5% of patients: 15.3% ago/ago, 16.5% pcb/ago, and 10.7% fluox/ago. Three patients (all adolescents) experienced treatment-related severe adverse events: two treated with ago/ago and one treated with pcb/ago. Among the adolescents, one treatment-related severe adverse event in a patient in the pcb/ago group led to study withdrawal. Agomelatine was associated with continuous improvement in depressive symptoms without unexpected safety signals. These findings support the safe use of agomelatine in a pediatric population with moderate-to-severe MDD for up to 104 weeks.Trial registration No: EUDRACT No. 2015-002181-23.

Pilot Study: Cut the Cut-A Treatment Program for Adolescent Inpatients with Nonsuicidal Self-Injury.

Non-suicidal-self-injury (NSSI) in adolescents needing inpatient treatment is a serious health risk behaviour. NSSI-specific treatment programs for inpatients hardly exist. "Cut the Cut" (CTC) is a new treatment program in intervals, addressing this problem. Aim of this pilot-study was to evaluate acceptability and feasibility of CTC. 23 female inpatients (12 CTC, 11 control, aged 15-17; mean = 16.80, SD.70) engaging in NSSI were evaluated for service user satisfaction, frequency, and severity of NSSI at T1 (admission), T2 (discharge after interval 1, CTC-group) and T3 (discharge). A qualitative interview was performed at T3. Significant improvement in NSSI-frequency was given (T1-T3: CTC p = 0.010; control p = 0.038). Severity of NSSI reduced slightly (mild NSSI: CTC p = 0.022, control p = 0.087; severe NSSI: CTC p = 0.111, control p = 0.066). Satisfaction of parents (T3 mean 28.38) and adolescents (T3 mean 26.11) in CTC was rated high. CTC is a feasible treatment option for inpatients engaging in NSSI. Further studies over time are needed.Trial registration Number DRKS00016762, 05.03.2019, retrospectively registered.

Debate: Quantity of impatient beds and quality of child psychiatric and psychotherapeutic care provision - a German perspective.

Provision of care for children with mental health disorders or behavioural difficulties differs from country to country. Historically, Germany has the highest number of inpatient beds throughout Europe (64 inpatient beds per 100,000 young people). In addition, nearly 146 departments for child and adolescent psychiatry offer day-care beds as well as ambulatory care. A high number of resident child and adolescent psychiatrists/psychotherapists (more than 12,000 professionals) complement provision of care in the different regions of Germany. Yet, only 50% of children and adolescents with mental health problems receive the treatment they need. Barriers to care - for example lack of transportation, fear of stigmatization, long distances in rural regions or fear of long hospital inpatient stays - keep families from presenting their child/adolescent to the relevant institutions. Recently, a new treatment module: StäB, an intensive daily home treatment, delivered by a multiprofessional team, has been added to the portfolio of treatment options in Germany. This closes the gap between highly intensive inpatient care and low-frequency outpatient treatment, allowing a continuum of care in intensity and frequency within the treatment alternatives.

The impact of child maltreatment on non-suicidal self-injury: data from a representative sample of the general population.

BACKGROUND: Child maltreatment is an identified risk factor for Non-Suicidal Self-Injury (NSSI). The aim of the current study was to investigate effects of different types of maltreatment, and mediating effects of depression and anxiety on NSSI in the general population. METHODS: A representative sample of the German population, comprising N = 2498 participants (mean age = 48.4 years (SD = 18.2), 53.3% female) participated in this study. Child maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ),NSSI was assessed with a question on lifetime engagement in NSSI, depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-2) and anxiety symptoms by the General Anxiety Disorder questionnaire (GAD-2). RESULTS: Lifetime prevalence of NSSI in this sample was 3.3, and 30.8% reported at least one type of child maltreatment. Participants in the NSSI group reported significantly more experiences of child maltreatment. Emotional abuse was endorsed by 72% of all participants with NSSI. A path analytic model demonstrated an unmediated direct effect of emotional neglect, a partially mediated effect of emotional abuse, and a fully mediated effect of sexual abuse and physical neglect by depression and anxiety on NSSI. CONCLUSIONS: Especially emotional neglect and abuse seem to play a role in the etiology of NSSI above and beyond depression and anxiety, while sexual and physical abuse seem to have a rather indirect effect.

[Home treatment - especially effective among boys with externalizing disorders? Age- and sex-specific effectiveness of home treatment for internalizing and externalizing disorders]. / Home treatment - insbesondere für expansive Jungen? Alters- und geschlechtsspezifische Wirksamkeit von Home treatment bei internalisierenden vs. externalisierenden Störungen.

OBJECTIVE: Indications for home treatment for specific diagnoses in child and adolescent psychiatry have not yet been evaluated. METHOD: In a recent intervention study (primary outcome: length of stay), 92 patients aged 5 to 17 years were randomized into an intervention group (early discharge followed by home treatment in combination with inpatient treatment, where needed) and a control group (regular length inpatient treatment). The aim of this explorative analysis was to retrieve additional information on "what works for whom." Outcome parameters were as follows: Children's Global Assessment Scale (CGAS), Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA), Strengths and Difficulties Questionnaire (SDQ) and Columbia Impairment Scale (CIS) at T1 (within 14 days after intake), T2 (end of treatment) and T3 (∅ 8.4-month follow-up). Multiple regression was used to investigate the association between diagnoses, treatment setting, age, sex, and improvement in both groups. RESULTS: In children externalizing disorders were predominant, whereas in adolescents internalizing disorders were prominent. Patients improved equally under both types of treatment. Home treatment, however, was rated by the patients to be significantly more effective in adolescents (SDQ p = .017), boys (CIS p = .009, SDQ p < .001), and with externalizing disorders (SDQ p = .005). CONCLUSIONS: Home treatment may be considered an alternative to inpatient treatment, especially in boys with externalizing disorders.

Developmental trauma disorder: pros and cons of including formal criteria in the psychiatric diagnostic systems.

BACKGROUND: This article reviews the current debate on developmental trauma disorder (DTD) with respect to formalizing its diagnostic criteria. Victims of abuse, neglect, and maltreatment in childhood often develop a wide range of age-dependent psychopathologies with various mental comorbidities. The supporters of a formal DTD diagnosis argue that post-traumatic stress disorder (PTSD) does not cover all consequences of severe and complex traumatization in childhood. DISCUSSION: Traumatized individuals are difficult to treat, but clinical experience has shown that they tend to benefit from specific trauma therapy. A main argument against inclusion of formal DTD criteria into existing diagnostic systems is that emphasis on the etiology of the disorder might force current diagnostic systems to deviate from their purely descriptive nature. Furthermore, comorbidities and biological aspects of the disorder may be underdiagnosed using the DTD criteria. SUMMARY: Here, we discuss arguments for and against the proposal of DTD criteria and address implications and consequences for the clinical practice.

Health-related quality of life after child maltreatment in institutions: Results from a representative population-based sample in Germany.

BACKGROUND: Child maltreatment (CM) is a major public health problem associated with enormous consequences, including impaired health-related quality of life (HRQOL). While the consequences of CM that occurs in the family context have been studied numerous times, studies on the consequences of institutional CM are lacking. This is of particular importance because cases of CM in churches, sport clubs and school, educational and medical settings have become increasingly apparent in Germany. OBJECTIVE: Thus, the objective of this study was to assess the association of CM in various institutions with HRQOL in adulthood. PARTICIPANTS AND SETTING: In a cross-sectional observational approach, a representative sample of the German population (N = 2516) was identified via a random-route. METHODS: Socioeconomic information, HRQOL and CM experiences in school, medical and educational institutions were obtained and statistically evaluated. RESULTS: Of the 2516 participants, 834 (33.14 %) reported CM in institutions and 1194 (47.46 %) reported impaired HRQOL. Participants who reported CM in institutions were more likely to have HRQOL impairments than participants who had been in the respective institution in childhood but had not reported having experienced CM there. In the case of CM in medical institutions, HRQOL impairments increased 2.2-3.9-fold. If CM in school was reported, HRQOL impairments increased 1.6-2.0-fold. If CM in educational institutions was reported, HRQOL impairments increased 2.1-2.7-fold. CONCLUSIONS: CM in institutions is associated with an increased likelihood of HRQOL impairments in Germany. Institutions need to be aware of the risk of CM and safeguarding measures should be implemented.

Ethics in child and adolescent psychiatric care: An international perspective.

In the treatment of children with psychiatric disorders as a vulnerable population, ethical issues arise that seldom come into play with adults. The UN Conventions on the Rights of the Child and the Rights of Persons with Disabilities set out rights to be respected in child and adolescent psychiatric treatment. Rights of participation and inclusion (minimizing of barriers to the involvement of disabled people) can create complex problems in cases of restraint or deprivation of liberty. This paper analyses the consequences of these conventions and other ethics guidelines on child and adolescent psychiatric treatment and research. Beneficence, justice and autonomy are core principles that are mirrored in the problems of inclusion and protection, confidentiality, and the safety of psychopharmacological interventions. Factors of inclusion are involved in the areas of availability of care, participation in best evidence-based treatment, and research. The right of the child to protection, the right of inclusion, and parents' rights and duties to safeguard their child's wellbeing form a triangle. National laws to regulate the treatment of psychiatrically ill children should be created and implemented and these should be non-discriminatory but at the same time safeguard the developing human being.

Maternal separation and contact to a stranger more than reunion affect the autonomic nervous system in the mother-child dyad: ANS measurements during Strange Situation Procedure in mother-child dyad.

BACKGROUND: The autonomic nervous system (ANS) processes underlying attachment-related mother-child interactions are not well understood. We aimed to describe and compare the responsivity of the ANS for mothers and their infants during the different phases of the Strange Situation Procedure (SSP). METHODS: Continuous measurements of the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS were obtained simultaneously in 91 mothers and their infants (range 10-15 months). Heart rate (HR), respiratory sinus arrhythmia (RSA), pre-ejection period (PEP) and left ventricular ejection time (LVET), were calculated for the baseline period (e1) and seven subsequent episodes (e2-e8) of the SSP. RESULTS: The largest difference between the mother and infant was during e7, when the stranger went into the room where the infant was while the mother waited outside the room. Mothers showed reduced SNS-activity or stress reduction while the child showed PNS withdrawal or increased stress response. Additionally, LVET was found to be a marker for SNS changes in the one-year-old infant during SSP. CONCLUSION: Mothers and infants showed different stress-related ANS responses during e7. Since this study showed that simultaneous measurement of ANS responses in mother-child dyads during the SSP is feasible, future studies can assess both mother and child stress responses in different contexts. The measure of LVET may be a valid SNS-reactivity measure in the one-year-olds. Since the separation episode e7 led to the strongest ANS responses, future studies might assess stress responses in more normative circumstances, such as child care programs.

Intensified testing for attention-deficit hyperactivity disorder (ADHD) in girls should reduce depression and smoking in adult females and the prevalence of ADHD in the longterm.

Attention-deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in youth. About a third to one-half of the affected subjects continue to have symptoms in adulthood. Remarkably, the prevalence numbers published for adult females are higher than for girls. The differences in the epidemiological data between the age groups clearly point to underdiagnosed ADHD in girls. Major depression, the most frequent psychiatric condition worldwide in adulthood, is twice as common in female as in male adults. Anxiety and depression are also among the most common comorbidities in adults with ADHD. Therefore, an undiagnosed ADHD may often underlie the psychopathology in depressive women. Another possibly associated phenomenon is the increased frequency of smoking in adult females. Since nicotine indirectly enhances the intrasynaptic dopamine level which presumably is too low both in ADHD and in depression, smoking might be used as a self-medication in women with untreated ADHD and consecutive depression. Furthermore, smoking during pregnancy is a major risk factor for ADHD in the offspring, so the vicious circle is complete. Depression in mothers of children with ADHD is associated with a higher rate of comorbidity in the children. Improved screening for ADHD in girls and treatment in childhood might thus reduce the rate of depression and smoking in adult females. We hypothesize that earlier identification and interventions might not only improve the lives of millions of girls and women but might also reduce the prevalence rates in future generations or at least moderate the deviant behaviour in this highly heritable disorder in which the development and severity of symptoms and the functional impairment depend to a high degree on epigenetic factors.

Covariation, co-occurrence and epiphenomenal correlation of empirically based syndromes in children and adolescents.

BACKGROUND: This paper determines the co-occurrence and correlations of different problem behaviours in children and adolescents in German clinical and general population samples. SAMPLING AND METHODS: The 2 samples were matched by age and gender (each sample n = 1,760). Including both categorical and dimensional models, rates of co-occurrence, relative risks, odds ratios and Pearson correlations were calculated. RESULTS: The bidirectional comorbidity rates ranged from 7.3 to 34.3% (epidemiological sample) and from 22.5 to 54.8% (clinical sample). Most correlations between syndrome scales show medium or large effects. Many can be identified as 'epiphenomenal'; partial correlations from each pair, excluding influences of other syndromes, are much lower. CONCLUSIONS: This study shows the cross-cultural generalizability of comorbidity rates. The epiphenomenal nature of some comorbidities warrants future attention.

Trauma-focused group intervention for unaccompanied young refugees: "Mein Weg"-predictors of treatment outcomes and sustainability of treatment effects.

BACKGROUND: Current research on treatment predictors and long-term effects of trauma-focused interventions for (unaccompanied) refugee minors is limited. This secondary analysis of a recent randomised controlled trial (RCT), evaluating the trauma-focused group intervention "Mein Weg" (English "My Way") compared to usual care, investigated several refugee-specific factors such as treatment predictors and sustainability of treatment gains. METHODS: In total N = 50 participants (M age = 17.00, 94% male) were included in this analysis. Evaluation of 3-month follow-up data included: posttraumatic stress symptoms [(PTSS) CATS-Self, CATS-Care], depression (PHQ-8), and dysfunctional posttraumatic cognitions (CPTCI-S). Baseline symptom severity of the above-mentioned measures, trauma load and socio-demographic factors were investigated as the treatment predictors. RESULTS: Intention-to-treat-analyses (ITT) revealed the sustainability of treatment effects in self-reported PTSS (pre to post change: 6.48 ± 1.60, d = 0.62, p < 0.001; post to 3-month follow-up change: 1.41 ± 1.96, d = 0.11, p = 0.47) and depression (pre to post change: 7.82 ± 2.09, d = 0.64, p < 0.001; post to 3-month follow-up change: 1.35 ± 2.17, d = 0.05, p = 0.54). Country of origin alone was a significant predictor of the change in PTSS (b = - 8.22 ± 3.53, t(30) = - 2.33, p = 0.027), and baseline levels of depression were a significant predictor of the change in depression (b = 0.83 ± 0.19, t(33) = 4.46, p < 0.001). CONCLUSION: This group intervention can serve as a valuable component in a stepped care approach with promising long-term effects for young refugees.Trial registration DRKS, #DRKS00010915. Registered 15 September 2016, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00010915.

The effects of childhood maltreatment on epigenetic regulation of stress-response associated genes: an intergenerational approach.

While biological alterations associated with childhood maltreatment (CM) have been found in affected individuals, it remains unknown to what degree these alterations are biologically transmitted to the next generation. We investigated intergenerational effects of maternal CM on DNA methylation and gene expression in N = 113 mother-infant dyads shortly after parturition, additionally accounting for the role of the FKBP5 rs1360780 genotype. Using mass array spectrometry, we assessed the DNA methylation of selected stress-response-associated genes (FK506 binding protein 51 [FKBP5], glucocorticoid receptor [NR3C1], corticotropin-releasing hormone receptor 1 [CRHR1]) in isolated immune cells from maternal blood and neonatal umbilical cord blood. In mothers, CM was associated with decreased levels of DNA methylation of FKBP5 and CRHR1 and increased NR3C1 methylation, but not with changes in gene expression profiles. Rs1360780 moderated the FKBP5 epigenetic CM-associated regulation profiles in a gene × environment interaction. In newborns, we found no evidence for any intergenerational transmission of CM-related methylation profiles for any of the investigated epigenetic sites. These findings support the hypothesis of a long-lasting impact of CM on the biological epigenetic regulation of stress-response mediators and suggest for the first time that these specific epigenetic patterns might not be directly transmitted to the next generation.

Knowledge transfer: a worldwide challenge in child mental health: a recommendation to the readership of CAPMH concerning the revised version of the IACAPAP Textbook of Child and Adolescent Mental Health.

BACKGROUND: Transfer of knowledge is an important issue throughout all scientific disciplines, especially in the medical and psycho-social field. The issue of worldwide knowledge transfer in child mental health is one of the aims and goals of the journal Child and Adolescent Psychiatry and Mental Health (CAPMH). The demand for mental health training is high worldwide, and especially in low- to lower-middle income countries, where inadequate access to knowledge resources in the field of child and adolescent mental health (CAMH) is prevalent. At the same time, many of these countries are showing an increased risk for mental health issues in children and adolescents. The International Association for Child and Adolescent Psychiatry and Allied Professions (IACAPAP) Textbook of Child and Adolescent Mental Health counters this problem. It is an open-access e-textbook aiming to provide an overview of current and established treatment and practical approaches for child and adolescent psychiatrists, psychotherapists and allied (mental health) professionals worldwide. First published in 2012, the updated and revised version was launched in 2015. The aim of this commentary is to review and disseminate the usefulness and practicability of content and further material included in the new version of the textbook. REVIEW: Overall, the textbook contains ten sections divided into 59 chapters, with a total of 1435 pages. The original version of the textbook was written in English. The revised version contains translations of 49 chapters into different languages (to date French, Spanish, Hebrew, Arabic, Portuguese, Russian, Norwegian and/or Japanese), with additional material for knowledge dissemination and self-directed learning (e.g. videos and quizzes) for several chapters. The textbook and the add-on materials for dissemination are of high quality and convey a great introduction to important topics concerning mental health. Apart from knowledge transfer, there is a pragmatic focus on clinical practice and on regional and cultural differences. CONCLUSION: The textbook is a new and unique opportunity for professionals all over the world to improve their knowledge, skills and expertise in CAMH. High-quality, up-to-date and freely accessible materials in the field of CAMH are combined with the opportunity to share insights with colleagues.

Associations of adverse childhood experiences and bullying on physical pain in the general population of Germany.

BACKGROUND: Chronic pain is a frequent burden in the general population. Child maltreatment and bullying are risk factors for the development of chronic pain. Aim of this cross-sectional study was to investigate the association of child maltreatment and bullying and pain experiences in a representative sample of the general population. MATERIALS AND METHODS: A total of N=2,491 people from the general population of Germany participated in the study (Mage=48.3 years [SD=18.2], 53.2 % female). Child maltreatment was assessed with the Childhood Trauma Questionnaire (CTQ), pain was rated with the Polytrauma Outcome (POLO)-physical state domain, depression scores were assessed with the Patient Health Questionnaire, and anxiety scores via the General Anxiety Disorder Questionnaire. Regression analyses were calculated to investigate the effect of bullying and child maltreatment, as well as depression, anxiety, and gender on pain experiences. RESULTS: A significant correlation between increasing pain levels and number of adverse childhood experiences was found. With regard to specific types of maltreatment, largest effect sizes were found for emotional abuse. Bullying was significantly, but overall rather moderately, related to pain suffering. In women, all forms of maltreatment were associated with pain, while in men only sexual and physical abuse revealed significant effects. Although depression and anxiety scores were significantly associated with the experience of current pain, they did not change the effect of child maltreatment on pain significantly. CONCLUSION: In this sample of the general population, adverse childhood experiences were significantly associated with pain and showed cumulative effects, over and above depressive and anxiety symptoms.

[Therapeutic drug monitoring in child and adolescent psychiatry--practical recommendations]. / Therapeutisches Drug-Monitoring in der Kinder- und Jugendpsychiatrie--Grundlagen und praktische Empfehlungen.

The therapy of children and adolescents with psychotropic drugs differs from that of adults. Due to the differences in the pharmacokinetic behaviour of the drugs used that are dependent on a child's, respectively an adolescent's stage of development, the same dosages as recommended for adults cannot be used. Moreover, many of the drugs used have not been approved for use in children and adolescents. Thus the criteria which guarantee their efficacy and safety for use in adults do not apply for their use in children and adolescents. Therefore therapeutic drug monitoring (TDM) is a general indication for the administration of psychotropic drugs in children and adolescents. TDM enables the clinician to adjust the dosage of a drug according to the characteristics of the individual patient. It is also a valid tool to increase the safety of therapy and optimise therapy with psychotropic drugs. However, standardized studies are also needed to find therapeutic ranges of plasma concentrations for children and adolescents. Such studies will deliver new insights into the pharmacokinetic and pharmacodynamic behaviour of drugs used in child and adolescent psychiatry. The present contribution begins with a brief description of the strategy of TDM in psychiatry, followed by a discussion of the characteristics of pharmacotherapy in child and adolescent psychiatry and the reasons for the general indication of TDM in children and adolescents. Finally, recommendations are given for the routine performance of TDM. For a detailed treatment of TDM in psychiatry, the interested reader is referred to the AG-NP-TDM Expert Group Consensus Guidelines published earlier (Baumann et al., 2004).

A German e-learning-training in the context of early preventive intervention and child protection: preliminary findings of a pre-post evaluation.

BACKGROUND: In recent years, a number of government-sponsored initiatives have been implemented in Germany that are focused on early preventive intervention in child protection. In response to the need for interdisciplinary training in this area, the internet-based e-learning program "Early Preventive Intervention and Child Protection" was developed for professionals in the child welfare and health care systems working with families with infants and toddlers. The program is currently undergoing evaluation for effectiveness and user satisfaction. METHODS: In a pre-post design, users are requested to complete questionnaires that assess three measures of expertise: theoretical knowledge of relevant fields, the ability to correctly identify subtle signals of infant communication, and the ability to assess maternal sensitivity. This article presents the contents of the program and the pre-training results (N = 1.294 participants). Descriptive analyses as well as Pearson correlations and Bonferroni corrections of error were conducted using the statistical program SPSS v. 21.0. RESULTS: The findings show that a wide range of professionals are making use of the program, and that their existing theoretical knowledge about early preventive intervention, as well as their ability to identify subtle signals of infant communication, is relatively good. However, their ability to assess maternal sensitivity, which is considered a crucial indicator for the risk of child abuse, was low. CONCLUSIONS: The outcome of the pre-training results indicates that professionals working in the area of child protection need to develop more capability in recognizing maternal sensitivity, in order to ensure early detection of families who are at risk and thus in need of support. Finally, the number of years of professional experience did not correlate with the scores on any of the three measures, which emphasizes the importance of providing interdisciplinary training in this area for all those working in child and family services, regardless of background.

Risperidone in children with disruptive behavior disorders and subaverage intelligence: a 1-year, open-label study of 504 patients.

OBJECTIVE: To determine the long-term safety and effectiveness of risperidone for severe disruptive behaviors in children. METHOD: A multisite, 1-year, open-label study of patients aged 5 to 14 years with disruptive behaviors and subaverage intelligence was conducted. RESULTS: Seventy-three percent of the 504 patients enrolled completed the study. The mean +/- SE dose of risperidone was 1.6 +/- 0.0 mg/day. The most common adverse events were somnolence (30%), rhinitis (27%), and headache (22%). The incidence of movement disorders was low, and mean Extrapyramidal Symptom Rating Scale scores decreased during risperidone treatment. No clinically significant changes in mean laboratory values were noted, except for a transient increase in serum prolactin levels. Scores on the Nisonger Child Behavior Rating Form Conduct Problem Scale improved significantly as early as week 1, and improvement was maintained throughout the trial (p < .001 at each time point). Significant improvements were noted on positive social behavior and other Nisonger Child Behavior Rating Form subscales, Aberrant Behavior Checklist, Clinical Global Impressions scale, and tests of patients' cognitive function (each p < .001). CONCLUSIONS: Risperidone was well tolerated and effective in the long-term treatment of disruptive behavior disorders in children with subaverage intelligence.