RESUMO
OBJECTIVE: To evaluate the efficacy, safety, and tolerability of the selective serotonin norepinephrine inhibitor duloxetine in children and adolescents with generalized anxiety disorder (GAD). METHOD: Youth aged 7 through 17 years with a primary diagnosis of GAD were treated with flexibly dosed duloxetine (30-120 mg daily, n = 135) or placebo (n = 137) for 10 weeks, followed by open-label duloxetine (30-120mg daily) for 18 weeks. Efficacy measures included the Pediatric Anxiety Rating Scale (PARS), Clinical Global Impression-Severity (CGI-Severity) scale, and Children's Global Assessment Scale (CGAS). Safety measures included the Columbia-Suicide Severity Rating Scale (C-SSRS) as well as vital signs and electrocardiographic and laboratory monitoring. RESULTS: On the primary efficacy measure (PARS severity for GAD), mean improvement from baseline to 10 weeks was statistically significantly greater for duloxetine (-9.7) compared with placebo (-7.1, p ≤ .001, Cohen's d: 0.5). Symptomatic response (50% improvement on the PARS severity for GAD), remission (PARS severity for GAD ≤8), and functional remission (CGAS >70) rates for the duloxetine group (59%, 50%, 37%, respectively) were statistically significantly greater than for the placebo group (42%, 34%, 24%, respectively, p ≤ .05) during acute treatment. Changes in systolic and diastolic blood pressure and discontinuation because of adverse events did not statistically differ between the duloxetine and placebo groups, although gastrointestinal-related adverse events, oropharyngeal pain, dizziness, cough, and palpitations were reported with a statistically significantly greater incidence for the duloxetine group compared with the placebo group. Mean changes in pulse and weight for the duloxetine group (+6.5 beats/min, -0.1 kg, respectively) were statistically different from the placebo group (+2.0 beats/min, +1.1 kg, respectively, p ≤ .01). CONCLUSION: In this study, duloxetine was superior to placebo on the primary efficacy analysis of mean change from baseline to week 10 on the PARS severity for GAD score, and safety results were consistent with the known safety profile of duloxetine in pediatric and adult patients. Clinical trial registration information-A Study in Pediatric Participants With Generalized Anxiety Disorder; http://clinicaltrials.gov; NCT01226511.
Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Cloridrato de Duloxetina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Ideação Suicida , Adolescente , Criança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Cloridrato de Duloxetina/efeitos adversos , Feminino , Humanos , Masculino , México , Escalas de Graduação Psiquiátrica , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Índice de Gravidade de Doença , África do Sul , Resultado do Tratamento , Estados UnidosRESUMO
Family history of mental illness provides important information when evaluating pediatric bipolar disorder (PBD). However, such information is often challenging to gather within clinical settings. This study investigates the feasibility and utility of gathering family history information using an inexpensive method practical for outpatient settings. Families (N=273) completed family history, rating scales, and the Mini-International Neuropsychiatric Interview (Sheehan et al., 1998) and the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (Kaufman et al., 1997) about youths 5-18 (median=11) years of age presenting to an outpatient clinic. Primary caregivers completed a half-page Family Index of Risk for Mood issues (FIRM). All families completed the FIRM quickly and easily. Most (78%) reported 1+ relatives having a history of mood or substance issues (M=3.7, SD=3.3). A simple sum of familial mood issues discriminated cases with PBD from all other cases (area under receiver operating characteristic [AUROC]=.63, p=.006). FIRM scores were specific to youth mood disorder and not attention-deficit/hyperactivity disorder or disruptive behavior disorder. FIRM scores significantly improved the detection of PBD even controlling for rating scales. No subset of family risk items performed better than the total. Family history information showed clinically meaningful discrimination of PBD. Two different approaches to clinical interpretation showed validity in these clinically realistic data. Inexpensive and clinically practical methods of gathering family history can help to improve the detection of PBD.
Assuntos
Transtorno Bipolar/diagnóstico , Saúde da Família , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Masculino , Transtornos do Humor/diagnóstico , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Transtornos Relacionados ao Uso de Substâncias/diagnósticoRESUMO
OBJECTIVE: Pediatric bipolar disorder (PBD) involves a potent combination of mood dysregulation and interpersonal processes, placing these youth at significantly greater risk of suicide. We examined the relationship between suicidal behavior, mood symptom presentation, family functioning, and quality of life (QoL) in youth with PBD. METHODS: Participants were 138 youths aged 5-18 years presenting to outpatient clinics with DSM-IV diagnoses of bipolar I disorder (n=27), bipolar II disorder (n=18), cyclothymic disorder (n=48), and bipolar disorder not otherwise specified (n=45). RESULTS: Twenty PBD patients had lifetime suicide attempts, 63 had past or current suicide ideation, and 55 were free of suicide ideation and attempts. Attempters were older than nonattempters. Suicide ideation and attempts were linked to higher depressive symptoms, and rates were even higher in youths meeting criteria for the mixed specifier proposed for DSM-5. Both suicide ideation and attempts were associated with lower youth QoL and poorer family functioning. Parent effects (with suicidality treated as outcome) and child effects (where suicide was the predictor of poor family functioning) showed equally strong evidence in regression models, even after adjusting for demographics. CONCLUSIONS: These findings underscore the strong association between mixed features and suicidality in PBD, as well as the association between QoL, family functioning, and suicidality. It is possible that youths are not just a passive recipient of family processes, and their illness may play an active role in disrupting family functioning. Replication with longitudinal data and qualitative methods should investigate both child and parent effect models.
Assuntos
Afeto , Transtorno Bipolar/psicologia , Depressão/psicologia , Família , Qualidade de Vida/psicologia , Suicídio/psicologia , Adolescente , Distribuição por Idade , Transtorno Bipolar/diagnóstico , Criança , Pré-Escolar , Estudos Transversais , Relações Familiares , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento , Prevenção do SuicídioRESUMO
OBJECTIVE: To assess the short- and long-term cardiovascular effects of once-daily treatment with a mixed amphetamine salts extended-release formulation (MAS XR; Adderall XR(R)) in children age 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD). STUDY DESIGN: Short-term cardiovascular effects were assessed during a 4-week, double-blind, randomized, placebo-controlled, forced-dose-titration study of once-daily 10, 20, and 30 mg MAS XR (n = 580). Long-term cardiovascular effects were assessed in 568 subjects during a 2-year, open-label extension study of MAS XR (10 to 30 mg/day). Resting sitting blood pressure and pulse were measured at baseline and weekly during the short-term study, then monthly during long-term treatment. RESULTS: Changes in blood pressure, pulse, and QT interval corrected by Bazett's formula (QTcB) in children receiving MAS XR were not statistically significantly different than those changes seen in children receiving placebo during short-term treatment. Mean increases in blood pressure after 2 years of MAS XR treatment (systolic, 3.5 mm Hg; diastolic, 2.6 mm Hg) and pulse (3.4 bpm) were clinically insignificant, and there was no apparent dose-response relationship. CONCLUSIONS: Cardiovascular effects of short- and long-term MAS XR were minimal during short- and long-term MAS XR treatment at doses of