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Low medication-adherence and persistence may reduce the effectiveness of ADHD-medication. This preregistered systematic review (PROSPERO CRD42020218654) on medication-adherence and persistence in children and adolescents with ADHD focuses on clinically relevant questions and extends previous reviews by including additional studies. We included a total of n = 66 studies. There was a lack of consistency in the measurement of adherence/persistence between studies. Pooling the medication possession ratios (MPR) and using the most common adherence definition (MPR ≥ 80%) indicated that only 22.9% of participants had good adherence at 12-month follow-up. Treatment persistence on medication measured by treatment duration during a 12-month follow-up averaged 170 days (5.6 months). Our findings indicate that medication-adherence and persistence among youth with ADHD are generally poor and have not changed in recent years. Clinicians need to be aware that various factors may contribute to poor adherence/persistence and that long-acting stimulants and psychoeducational programs may help to improve adherence/persistence. However, the evidence to whether better adherence/persistence contributes to better long-term outcomes is limited and requires further research.
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Disruptive behavior disorders [including conduct disorder (CD) and oppositional defiant disorder (ODD)] are common childhood and adolescent psychiatric conditions often linked to altered arousal. The recommended first-line treatment is multi-modal therapy and includes psychosocial and behavioral interventions. Their modest effect sizes along with clinically and biologically heterogeneous phenotypes emphasize the need for innovative personalized treatment targeting impaired functions such as arousal dysregulation. A total of 37 children aged 8-14 years diagnosed with ODD/CD were randomized to 20 sessions of individualized arousal biofeedback using skin conductance levels (SCL-BF) or active treatment as usual (TAU) including psychoeducation and cognitive-behavioral elements. The primary outcome was the change in parents´ ratings of aggressive behavior measured by the Modified Overt Aggression Scale. Secondary outcome measures were subscales from the Child Behavior Checklist, the Inventory of Callous-Unemotional traits, and the Reactive-Proactive Aggression Questionnaire. The SCL-BF treatment was neither superior nor inferior to the active TAU. Both groups showed reduced aggression after treatment with small effects for the primary outcome and large effects for some secondary outcomes. Importantly, successful learning of SCL self-regulation was related to reduced aggression at post-assessment. Individualized SCL-BF was not inferior to active TAU for any treatment outcome with improvements in aggression. Further, participants were on average able to self-regulate their SCL, and those who best learned self-regulation showed the highest clinical improvement, pointing to specificity of SCL-BF regulation for improving aggression. Further studies with larger samples and improved methods, for example by developing BF for mobile use in ecologically more valid settings are warranted.
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There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63-2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06-1.56), guanfacine (OR = 1.43, 95% CI = 1.12-1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09-1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Metilfenidato , Niño , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Clorhidrato de Atomoxetina/efectos adversos , Guanfacina/efectos adversos , Estimulantes del Sistema Nervioso Central/efectos adversos , Metilfenidato/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Comorbilidad , Cefalea/inducido químicamente , Cefalea/epidemiología , Cefalea/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Neurofeedback is considered a promising intervention for the treatment of attention-deficit hyperactivity disorder (ADHD). NEWROFEED is a prospective, multicentre, randomized (3:2), reference drug-controlled trial in children with ADHD aged between 7 and 13 years. The main objective of NEWROFEED was to demonstrate the noninferiority of personalized at-home neurofeedback (NF) training versus methylphenidate in the treatment of children with ADHD. METHODS: The NF group (n = 111) underwent eight visits and two treatment phases of 16 to 20 at-home sessions with down-training of the theta/beta ratio (TBR) for children with high TBR and enhancing the sensorimotor rhythm (SMR) for the others. The control group (n = 67) received optimally titrated long-acting methylphenidate. The primary endpoint was the change between baseline and endpoint in the Clinician ADHD-RS-IV total score in the per-protocol population (90 NF/59 controls). TRIAL REGISTRATION: US National Institute of Health, ClinicalTrials.gov #NCT02778360. RESULTS: Our study failed to demonstrate noninferiority of NF versus methylphenidate (mean between-group difference 8.09 90% CI [8.09; 10.56]). However, both treatment groups showed significant pre-post improvements in core ADHD symptoms and in a broader range of problems. Reduction in the Clinician ADHD-RS-IV total score between baseline and final visit (D90) was 26.7% (SMD = 0.89) in the NF and 46.9% (SMD = 2.03) in the control group. NF effects increased whereas those of methylphenidate were stable between intermediate and final visit. CONCLUSIONS: Based on clinicians' reports, the effects of at-home NF were inferior to those of methylphenidate as a stand-alone treatment.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Neurorretroalimentación , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/farmacología , Niño , Humanos , Metilfenidato/farmacología , Metilfenidato/uso terapéutico , Neurorretroalimentación/métodos , Estudios Prospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Despite the growing evidence base for psychotropic drug treatment in pediatric patients, knowledge about the benefit-risk ratio in clinical practice remains limited. The 'Therapeutic Drug Monitoring (TDM)-VIGIL' study aimed to evaluate serious adverse drug reactions (ADRs) in children and adolescents treated with antidepressants and/or antipsychotics in approved ('on-label'), and off-label use in clinical practice. METHODS: Psychiatric pediatric patients aged 6-18 years treated with antidepressants and/or antipsychotics either on-label or off-label were prospectively followed between October 2014 and December 2018 within a multicenter trial. Follow-up included standardized assessments of response, serious ADRs and therapeutic drug monitoring. RESULTS: 710 youth (age=14.6±2.2 years, female=66.6%) were observed for 5.5 months on average; 76.3% received antidepressants, 47.5% antipsychotics, and 25.2% both. Altogether, 55.2% of the treatment episodes with antidepressants and 80.7% with antipsychotics were off-label. Serious ADRs occurred in 8.3% (95%CI=6.4-10.6%) of patients, mainly being psychiatric adverse reactions (77.4%), predominantly suicidal ideation and behavior. The risk of serious ADRs was not significantly different between patients using psychotropics off-label and on-label (antidepressants: 8.1% vs. 11.3%, p=0.16; antipsychotics: 8.7% vs 7.5%, p=0.67). Serious ADRs occurred in 16.6% of patients who were suicidal at enrollment versus 5.6% of patients who were not suicidal (relative risk 3.0, 95%CI=1.9-4.9). CONCLUSION: Off-label use of antidepressants and antipsychotics in youth was not a risk factor for the occurrence of serious ADRs in a closely monitored clinical setting. Results from large naturalistic trials like ours can contribute to bridging the gap between knowledge from randomized controlled trials and real-world clinical settings.
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Antipsicóticos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Adolescente , Antidepresivos/efectos adversos , Antipsicóticos/efectos adversos , Niño , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Humanos , Uso Fuera de lo Indicado , Psicotrópicos/uso terapéuticoRESUMEN
The Genetic Basis of ADHD - An Update Abstract. Genetic risks play an important role in the etiology of attention-deficit/hyperactivity disorder (ADHD). This review presents the current state of knowledge concerning the genetic basis of the disorder. It discusses the results of twin- and family-based studies, linkage and association studies as well as recent findings resulting from Genome Wide Association Studies (GWAS). Furthermore, it elaborates on the relevance of polygenic risk scores, rare variants, and epigenetic alterations, especially in light of findings on genetic pleiotropy in the context of frequent psychiatric comorbidities in patients with ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Estudio de Asociación del Genoma Completo , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/genética , Comorbilidad , Predisposición Genética a la Enfermedad/genética , Humanos , Herencia Multifactorial/genéticaRESUMEN
Therapeutic drug monitoring to optimize psychopharmacotherapy in children and adolescents - Update and guidelines for practice Abstract. Despite the improved evidence base, many uncertainties remain in child and adolescent psychiatric pharmacotherapy about the efficacy and tolerability of drugs, which are often prescribed off-label or in combination therapy in this age group. Because medium- to long-term use is unavoidable in many cases, clinicians should minimize adverse drug reactions as far as possible and tailor an effective dosage to the individual characteristics of the patient. Not only are children and adolescents particularly vulnerable to certain adverse drug effects, they are also exposed to iatrogenic risks from dosing or application errors, which can lead to under- or overdosing with correspondingly negative effects on the success of the therapy. In addition to determining a strict indication, it is therefore essential to establish precise dosage and systematic monitoring of the safety of the psychopharmacotherapy. This article introduces therapeutic drug monitoring as a useful clinical tool and describes how its correct application in practice can improve the efficacy as well as the safety and tolerability of psychotropic therapy in children and adolescents for the immediate benefit of patients. Keywords: Psychopharmacotherapy, adverse drug reactions, pharmacovigilance, therapeutic drug monitoring, quality assurance.
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Monitoreo de Drogas , Trastornos Mentales , Adolescente , Niño , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/tratamiento farmacológico , Psicotrópicos/efectos adversosRESUMEN
Objective: This study investigates whether adolescents' adherence to psychotropic medication is associated with demographic and socioeconomic factors, and to what extent parents' assessments of their offspring's attitudes toward treatment correspond with the adolescents' self-report. Methods: This study is part of the multicenter SEMA study (Subjective Experience and Medication Adherence in Adolescents with Psychiatric Disorders). Adolescents' subjective attitudes toward medication and their adherence were assessed using the patient and parent versions of the QATT (Questionnaire on Attitudes Toward Treatment) and the MARS (Medication Adherence Rating Scale). Furthermore, we collected socioeconomic and demographic data. Results: Of the n = 75 adolescents included in the study, n = 45 (60 %) were classified as completely adherent. Patients receiving monotherapy were more often completely adherent than those receiving a combination of different medications. There was no statistically significant association between adherence and demographic or socioeconomic factors. Consensus between adolescents and their parents regarding adolescents' attitudes toward treatment ranged from slight (κ = 0.157) to fair (κ = 0.205). Conclusion: Incomplete medication adherence in adolescents with psychiatric disorders is a common phenomenon and still poorly understood. Demographic and socioeconomic factors do not seem to be relevant in this respect. However, adolescents' subjective attitudes towards medication, which parents are presumably unable to adequately assess, warrant more careful consideration in future research.
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Trastornos Mentales , Adolescente , Humanos , Cumplimiento de la Medicación , Trastornos Mentales/tratamiento farmacológico , Padres , Psicotrópicos/efectos adversos , Encuestas y CuestionariosRESUMEN
ADHD often affects multiple generations in a family. Previous studies suggested that children with ADHD benefit less from therapy if parents are also affected, since ADHD symptoms interfere with treatment implementation. This two-group randomised controlled trial examined whether targeting maternal ADHD boosts the efficacy of parent-child training (PCT) for the child's ADHD. Here, we report follow-up results 2 years from baseline. Mothers of 144 mother-child dyads (ADHD according to DSM-IV) were examined for eligibility (T1) and randomised to 12 weeks of intensive multimodal treatment comprising pharmacotherapy and DBT-based cognitive behavioural group psychotherapy (TG, n = 77) or clinical management comprising non-specific counselling (CG, n = 67) for Step 1 (concluded by T2). Subsequently, all dyads participated in 12 weekly PCT sessions for Step 2 (concluded by T3). In Step 3, participants received maintenance treatments for 6 months (concluded by T4). At 24 months after baseline (T5), we performed follow-up assessments. The primary endpoint was child ADHD/ODD score (observer blind rating). Outcomes at T5 were evaluated using ANCOVA. Assessments from 101 children and 95 mothers were available at T5. Adjusted means (m) of ADHD/ODD symptoms (range 0-26) in children did not differ between TG and CG (mean difference = 1.0; 95% CI 1.2-3.1). The maternal advantage of TG over CG on the CAARS-O:L ADHD index (range 0-36) disappeared at T5 (mean difference = 0.2; 95% CI - 2.3 to 2.6). Sensitivity analyses controlling for medication and significant predictors of follow-up participation showed unchanged outcomes. Within-group outcomes remained improved from baseline. At the 24-month follow-up, TG and CG converged. The superiority of intensive treatment regarding maternal symptoms disappeared. In general, cross-generational treatment seems to be effective in the long term. (BMBF grant 01GV0605; registration ISRCTN73911400).
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BACKGROUND: Attention deficit hyperactivity disorder (ADHD), defined by the core symptoms impulsiveness, inattention and motor hyperactivity, is one of the most common neurodevelopmental disorders beginning in early childhood. OBJECTIVE: This article reviews the current state of research on the epidemiology, etiology, diagnostics and therapeutic interventions for ADHD in children and adolescents. METHODS: A selective literature search was carried out in PubMed with reference to the German S3 clinical guidelines on ADHD in children, adolescents and adults. RESULTS AND CONCLUSION: The epidemiological prevalence of ADHD in children is estimated to be 5.3%. The etiology is complex and heterogeneous and a high percentage of the phenotypic variance can be explained by genetic influences. The challenge of ADHD diagnostics is to exclude differential diagnoses while simultaneously identifying common coexisting psychiatric conditions. Treatment recommendations depend on the severity of symptoms. In severe ADHD pharmacotherapy should be considered as the first line intervention. Psychostimulants (various methylphenidate and amphetamine preparations) and the non-stimulants atomoxetine and guanfacine are approved in Germany for treatment of ADHD in children and adolescents. In milder cases as well as in preschool children, psychosocial interventions (including behavioral psychotherapy) are often sufficient.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Adolescente , Adulto , Clorhidrato de Atomoxetina/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/terapia , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Preescolar , Alemania/epidemiología , Humanos , Metilfenidato/uso terapéuticoRESUMEN
The more recent term "adherence" is now taking the place of the earlier notion of "compliance," as it emphasizes the physician-patient partnership. To date, however, it has not been clearly defined. There are many limitations to measuring adherence, and presently no standard methods have been established. Even in clinical trials throughout medicine, the reported rates for adherence range only between 43 % and 78 %. Particularly medication adherence is highly relevant to the treatment of mentally ill adolescents, as they make up a population especially vulnerable to nonadherence - and high rates thereof have been reported. Factors influencing adherence are poorly understood and researched, especially in adolescents with mental illness. Physicians can currently rely only on concepts from other populations and expert recommendations. Concepts for children or adults should not directly be transferred to adolescent patients. Results from the current "SEMA" study should contribute to guiding future research in the development of interventions to improve medication adherence, in particular for this juvenile population.
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Cumplimiento de la Medicación/psicología , Cumplimiento de la Medicación/estadística & datos numéricos , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/psicología , Adolescente , Adulto , Niño , Humanos , Relaciones Médico-Paciente , Resultado del TratamientoRESUMEN
OBJECTIVE: We examined predictors and moderators of treatment outcome in mothers and children diagnosed with ADHD in a large multicentre RCT. METHOD: In total, 144 mother-child dyads with ADHD were randomly assigned to either a maternal ADHD treatment (group psychotherapy and open methylphenidate medication, TG) or to a control treatment (individual counselling without psycho- or pharmacotherapy, CG). After maternal ADHD treatment, parent-child training (PCT) for all mother-child dyads was added. The final analysis set was based on 123 dyads with completed primary outcome assessments (TG: n = 67, CG: n = 56). The primary outcome was the change in each child's externalizing symptoms. Multiple linear regression analyses were performed. RESULTS: The severity of the child's externalizing problem behaviour in the family at baseline predicted more externalizing symptoms in the child after PCT, independent of maternal treatment. When mothers had a comorbid depression, TG children showed more externalizing symptoms after PCT than CG children of depressive mothers. No differences between the treatment arms were seen in the mothers without comorbid depression. CONCLUSIONS: Severely impaired mothers with ADHD and depressive disorder are likely to need additional disorder-specific treatment for their comorbid psychiatric disorders to effectively transfer the contents of the PCT to the home situation (CCTISRCTN73911400).
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Trastorno por Déficit de Atención con Hiperactividad/terapia , Hijo de Padres Discapacitados/psicología , Metilfenidato/uso terapéutico , Madres/psicología , Psicoterapia de Grupo , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Niño , Femenino , Humanos , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Concerns have been raised over the safety of methylphenidate (MPH), with regard to adverse effects on growth and blood pressure. Our study investigates whether, and to what extent, methylphenidate use in boys with ADHD is associated with having low body mass index (BMI), having low height, and increased systolic and diastolic blood pressure. METHODS: Data used for this study stem from the German KiGGS dataset. Three different groups of boys aged 6-15 years were included in the analysis: ADHD patients who used MPH for less than 12 months; ADHD patients who used MPH for 12 months or more; and ADHD patients without current MPH treatment. Each of these three groups was compared to a non-ADHD control group regarding low weight (BMI ≤ 3rd percentile), low height (≤3rd percentile) and raised systolic and diastolic blood pressure. For growth outcomes, boys were categorized according to age (< 11 years/≥11 years, to account for pubertal maturation). Multivariable logistic regression was conducted to test for associations. RESULTS: 4244 boys were included in the study; MPH < 12 months: n = 65 (n = 36 < 11 years), MPH ≥ 12 months: n = 53 (n = 22 < 11 years), ADHD controls: n = 320 (n = 132 < 11 years), non-ADHD controls: n = 3806 (n = 2003 < 11 years). Pre-pubertal boys with MPH use less than 12 months and pubertal/postpubertal boys with MPH use of 12 months or greater were significantly more likely to have a BMI ≤ 3rd percentile compared to non-ADHD controls. Boys from the ADHD control group were significantly less likely to have a raised systolic blood pressure compared to non-ADHD controls. Beyond that, no significant between group differences were observed for any other growth and BP parameter. CONCLUSION: The analyses of the KiGGS dataset showed that MPH use in boys with ADHD is associated with low BMI. However, this effect was only observed in certain groups. Furthermore, our analysis was unable to confirm that MPH use is also associated with low height (≤3rd percentile) and changes in blood pressure.
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Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Presión Sanguínea/efectos de los fármacos , Estatura/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/administración & dosificación , Encuestas Epidemiológicas/métodos , Metilfenidato/administración & dosificación , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Presión Sanguínea/fisiología , Estatura/fisiología , Índice de Masa Corporal , Niño , Estudios de Cohortes , Estudios Transversales , Esquema de Medicación , Alemania/epidemiología , Humanos , Masculino , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacos , Pérdida de Peso/fisiologíaRESUMEN
BACKGROUND: The efficacy of parent-child training (PCT) regarding child symptoms may be reduced if the mother has attention-deficit/hyperactivity disorder (ADHD). The AIMAC study (ADHD in Mothers and Children) aimed to compensate for the deteriorating effect of parental psychopathology by treating the mother (Step 1) before the beginning of PCT (Step 2). This secondary analysis was particularly concerned with the additional effect of the Step 2 PCT on child symptoms after the Step 1 treatment. METHODS: The analysis included 143 mothers and children (aged 6-12 years) both diagnosed with ADHD. The study design was a two-stage, two-arm parallel group trial (Step 1 treatment group [TG]: intensive treatment of the mother including psychotherapy and pharmacotherapy; Step 1 control group [CG]: supportive counseling only for mother; Step 2 TG and CG: PCT). Single- and multi-group analyses with piecewise linear latent growth curve models were applied to test for the effects of group and phase. Child symptoms (e.g., ADHD symptoms, disruptive behavior) were rated by three informants (blinded clinician, mother, teacher). RESULTS: Children in the TG showed a stronger improvement of their disruptive behavior as rated by mothers than those in the CG during Step 1 (Step 1: TG vs. CG). In the CG, according to reports of the blinded clinician and the mother, the reduction of children's disruptive behavior was stronger during Step 2 than during Step 1 (CG: Step 1 vs. Step 2). In the TG, improvement of child outcome did not differ across treatment steps (TG: Step 1 vs. Step 2). CONCLUSIONS: Intensive treatment of the mother including pharmacotherapy and psychotherapy may have small positive effects on the child's disruptive behavior. PCT may be a valid treatment option for children with ADHD regarding disruptive behavior, even if mothers are not intensively treated beforehand. TRIAL REGISTRATION: ISRCTN registry ISRCTN73911400 . Registered 29 March 2007.
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Hijo de Padres Discapacitados/psicología , Madres/psicología , Psicoterapia/métodos , Psicotrópicos/administración & dosificación , Adulto , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno por Déficit de Atención con Hiperactividad/terapia , Niño , Terapia Combinada/métodos , Femenino , Humanos , Masculino , Problema de Conducta , Escalas de Valoración Psiquiátrica , Resultado del TratamientoRESUMEN
Multimodal treatment of children with ADHD often includes parent-child training (PCT). However, due to the high heritability, parents of children with ADHD are frequently also affected by the disorder, which is likely to constitute a significant barrier to successful treatment of the child. This secondary analysis of our randomized controlled multicentre AIMAC trial (ADHD in mothers and children) investigates whether children's outcomes following parent-child training in combination with maternal ADHD treatment depend on maternal symptom improvement. In a first step focusing on treatment of maternal ADHD, 144 mothers of mother-child dyads were randomized to multimodal ADHD treatment (group psychotherapy plus methylphenidate) or clinical management (mainly supportive counselling). After 12 weeks (T2), a 12-week PCT program (T2-T3) for all mother-child dyads was added to treat children's ADHD. Maternal symptomatology (CAARS-O:L; SCL-90-R) and children's externalizing symptoms (ADHD-ODD Scale, SDQ) were repeatedly assessed (T1 = baseline, T2, T3). Effects of changes in maternal symptomatology (T1-T2) on the change in children's symptom scores (T1-T3) were analysed using a general linear model, controlling for baseline scores, study centre, and maternal treatment group. 125 mother-child dyads were analysed. Mothers showed significant improvements in ADHD symptoms and overall psychopathology [CAARS-O:L ADHD index: mean - 3.54, SE 0.74 p < 0.0001; SCL-90-R Global Severity (GS): mean - 11.03, SE 3.90, p = 0.0056]. Although children's externalizing symptoms improved significantly (ADHD-ODD Scale: mean - 4.46, SE 0.58, p < 0.0001), maternal improvement had no effect on children's outcomes after Bonferroni-Holm correction for multiple testing. The findings do not support our hypothesis that children's outcomes following PCT for ADHD depend on maternal symptom improvements.Trial register CCT-ISRCTN73911400.
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Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Madres/psicología , Psicoterapia/métodos , Trastorno por Déficit de Atención con Hiperactividad/genética , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
Introduction: Whether patients take their medication as prescribed is of increasing importance in adolescent psychiatry since both the number of efficacious pharmaceutical treatments and the rate of prescriptions of psychotropic compounds are on the rise. Previous research showed high rates of medication nonadherence among both adolescents with medical disorders and adult patients with psychiatric disorders. Methods: The present review was performed according to PRISMA guidelines and evaluates existing scientific literature concerning adherence to psychotropic medication among adolescents. The goal was to determine rates of nonadherence in this age group as well as the factors associated with it. Therefore, we conducted a comprehensive literature search of PubMed from its inception until 15 September 2015 using the keywords "adherence," "compliance," "adolescent," and "psychotropic medication." Results: A total of 607 pertinent articles were collected and screened; 15 publications were selected for detailed review. The studies differed, among other things, regarding sample characteristics, medication type, and indications. Furthermore, the definitions of what constitutes nonadherence and the methods used to assess it varied widely. Nonadherence rates ranged from 6 % to 62 % (median 33 %). Conclusions: Nonadherence to psychotropic medication is a clinically relevant problem among adolescents. Because of the methodological heterogeneity across studies and partially contradictory results, no conclusions could be drawn concerning the influence of factors such as psychopathology, medication type, side effects, the effectiveness of treatment, or family-related factors. Well-designed long-term studies of large patient samples and a consensus regarding definitions are therefore warranted. Such research would facilitate the design of tailored strategies to improve adherence in these patients.
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Cumplimiento de la Medicación/psicología , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/psicología , Psicotrópicos/uso terapéutico , Adolescente , Terapia Conductista , Humanos , Cuidados a Largo Plazo , Psicopatología , Psicotrópicos/efectos adversos , Estadística como AsuntoRESUMEN
OBJECTIVE: Research has implicated glutamatergic projections between the various frontal subregions in the pathogenesis of compulsivity and impulsivity. Reducing striatal glutamate release, or antagonising the action of glutamate at its receptors, may therefore represent viable treatment strategies. Several glutamatergic agents with regulatory approval for other indications are available and may be of potential benefit in the treatment of compulsivity/impulsivity in psychiatric disorders in paediatric patients. METHOD: This review was performed according to PRISMA guidelines and evaluates available scientific literature concerning the use of glutamatergic agents in these patients, in order to determine their reported effectiveness/efficacy and tolerability/safety. RESULTS: Out of a total of 1,426 publications, 21 trials examining six glutamatergic substances in patients with obsessive-compulsive disorder, autism spectrum disorders, and attention deficit/hyperactivity disorder were included. CONCLUSIONS: Trial designs as well as results were heterogeneous and thus comparability was limited. Available data support the hypothesis that glutamatergic agents are of potential value in the treatment of compulsivity/impulsivity in children and adolescents. Based on the data reviewed, memantine and N-acetylcysteine suggest the best risk-benefit profile for future trials. Riluzole should primarily be further investigated in adults. Clinical research of this nature is a key element of the TACTICS Consortium project funded by the European Union (FP7).
Asunto(s)
Encéfalo/efectos de los fármacos , Fármacos actuantes sobre Aminoácidos Excitadores/uso terapéutico , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Acetilcisteína/efectos adversos , Acetilcisteína/uso terapéutico , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno del Espectro Autista/tratamiento farmacológico , Niño , Cuerpo Estriado/efectos de los fármacos , Fármacos actuantes sobre Aminoácidos Excitadores/efectos adversos , Ácido Glutámico/metabolismo , Humanos , Memantina/efectos adversos , Memantina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores de Glutamato/efectos de los fármacos , Medición de Riesgo , Resultado del TratamientoRESUMEN
Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in multiple domains of patients' lives. A secondary objective of this randomized, active-controlled, head-to-head, double-blind, dose-optimized clinical trial was to compare the effects of lisdexamfetamine dimesylate (LDX) and atomoxetine (ATX) on functional impairment in children and adolescents with ADHD. Patients aged 6-17 years with an ADHD Rating Scale IV total score ≥ 28 and an inadequate response to methylphenidate treatment (judged by investigators) were randomized (1:1) to once-daily LDX or ATX for 9 weeks. Parents/guardians completed the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at baseline and at week 9 or early termination. p values were nominal and not corrected for multiple comparisons. Of 267 randomized patients, 200 completed the study (LDX 99, ATX 101). At baseline, mean WFIRS-P total score in the LDX group was 0.95 [standard deviation (SD) 0.474; 95% confidence interval (CI) 0.87, 1.03] and in the ATX group was 0.91 (0.513; 0.82, 1.00). Scores in all WFIRS-P domains improved from baseline to endpoint in both groups, with least-squares mean changes in total score of -0.35 (95% CI -0.42, -0.29) for LDX and -0.27 (-0.33, -0.20) for ATX. The difference between LDX and ATX was statistically significant (p < 0.05) for the Learning and School (effect size of LDX vs ATX, 0.43) and Social Activities (0.34) domains and for total score (0.27). Both treatments reduced functional impairment in children and adolescents with ADHD; LDX was statistically significantly more effective than ATX in two of six domains and in total score.
Asunto(s)
Clorhidrato de Atomoxetina/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Dimesilato de Lisdexanfetamina/uso terapéutico , Metilfenidato/uso terapéutico , Adolescente , Atención , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
OBJECTIVE: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age. METHOD: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age. RESULTS: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable. CONCLUSION: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.