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1.
Bipolar Disord ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479581

RESUMO

OBJECTIVES: To clarify the clinical features preceding the onset of bipolar disorder (BD) has become a public health priority for the prevention of high morbidity and mortality. BD remains frequently under- or misdiagnosed, and under- or mistreated, often for years. METHODS: We assessed the predictive value of precursors and prodromes of BD. We assessed precursors of first-lifetime manic or hypomanic episodes with/without mixed features in retrospective and prospective studies. The task force evaluated and summarized separately assessments of familial risk, premorbid personality traits, retrospective, and prospective studies. RESULTS: Cyclothymic features, a family history of BD, retrospectively reported attenuated manic symptoms, prospectively identified subthreshold symptoms of hypomania, recurrence of depression, panic anxiety and psychotic features, have been identified as clinical precursors of BD. The prodromal symptoms like [hypo]mania often appears to be long enough to encourage early identification and timely intervention. CONCLUSIONS: The predictive value of any risk factor identified remains largely unknown. Prospective controlled studies are urgently needed for prevention and effective treatment.

2.
J Clin Psychiatry ; 80(5)2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31390496

RESUMO

OBJECTIVE: To determine the prevalence of abnormal thyroid-stimulating hormone (TSH) measures in youth with severe mood and anxiety disorders and to examine clinical and demographic predictors of abnormal TSH measures. METHODS: We retrospectively examined screening TSH concentrations in psychiatrically hospitalized children and adolescents (3-19 years) with mood/anxiety disorders (DSM-IV and DSM-5 criteria) at a large, urban, pediatric hospital between September 2013 and April 2017. Symptoms were extracted from the medical record using adaptive natural language processing algorithms, and the utility of demographic, clinical, and treatment variables as predictors of abnormal TSH measures was evaluated using logistic regression. RESULTS: In this sample (N = 1,017, mean ± SD age = 14.7 ± 2.24 years), 62 patients had a TSH concentration > 3.74 µIU/mL (5.3% [n = 6] of patients < 12 years of age and 6.2% [n = 56] of patients ≥ 12 years of age), and 7 patients had a TSH concentration < 0.36 µIU/mL. Elevated TSH concentrations were associated with a recent weight gain (odds ratio [OR] = 3.60; 95% CI, 1.13-9.61; P = .017), a history of thyroid disease (OR = 6.88; 95% CI, 2.37-10.7; P ≤ .0001), abnormal menstrual bleeding/menometrorrhagia (OR = 2.03; CI, 1.04-3.63; P = .024), and benzodiazepine treatment (OR = 2.29; 95% CI, 1.07-4.52; P = .02). No association was observed for sex, age, or body mass index z score. Among patients with elevated TSH measures, 12.9% (n = 8, mean ± SD age = 16.5 ± 1.5 years, 87.5% female) had an abnormal free/total thyroxine (T4) level or other biochemical findings consistent with thyroid disease. Patients with thyroid disease (compared to those patients with elevated TSH and normal active thyroid hormone concentrations) were older (16.5 ± 1.5 vs 14.6 ± 2.3 years, P = .020) but did not differ in sex distribution (87.5% vs 63.6% female, P = .444). CONCLUSIONS: TSH concentrations are abnormal in approximately 6% of psychiatrically hospitalized youth, although thyroid disease was present in < 1% of the total sample. Targeted screening should focus on patients with recent weight gain, those treated with benzodiazepines, and girls with a history of abnormal uterine bleeding/menometrorrhagia.

3.
Bipolar Disord ; 21(6): 503-513, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31025452

RESUMO

OBJECTIVES: Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first- and multi-episode bipolar individuals. We hypothesized that the latter would demonstrate evidence of neurophysiological differences consistent with a model of progressive functional degradation of these networks. METHODS: First- and multi-episode manic bipolar subjects participated in functional magnetic resonance imaging (fMRI) including a continuous performance task with emotional distractors, and in single-voxel (1 H) magnetic resonance spectroscopy (MRS). A priori fMRI regions-of-interest (ROI) included structures comprising prefrontal-striatal-amygdala networks; (1 H)MRS voxels were placed within bilateral ventrolateral prefrontal (VLPFC) and anterior cingulate cortex (ACC). Both ROI and voxel-based brain activation in response to emotional stimuli, and neurochemical concentrations derived from (1 H)MRS were compared across bipolar groups. RESULTS: Multi-episode bipolar subjects showed relatively lower regional activation across prefrontal-striatal-amygdala networks, including bilateral VLPFC, orbitofrontal cortex, ACC, putamen, caudate, and amygdala. Exploratory whole-brain, voxel-based analysis suggested additional areas of lower activation extending into Brodmann area 22, posterior parietal regions, and right thalamus. Glutamate and N-acetylaspartate (NAA) concentrations were also relatively lower in the ACC of multi-episode subjects. CONCLUSIONS: Disease burden, exemplified by multiple affective episodes is associated with evidence of widespread decrements in affective network activity. Lower ACC NAA concentration is similarly consistent with a model of progressive functional deficits. These findings support the functional significance of previously observed progressive structural changes throughout these regions.

4.
Bipolar Disord ; 21(4): 330-341, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30864200

RESUMO

OBJECTIVES: To investigate neurochemical abnormalities in the left and right ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) of youth at risk for bipolar disorder using proton magnetic resonance spectroscopy before and after their first mood episode. METHODS: Children and adolescents offspring of parents with bipolar I disorder (at-risk group, n = 117) and matched healthy controls (HC group, n = 61) were recruited at the University of Cincinnati. At-risk subjects had no lifetime major mood and psychotic disorders at baseline, and were followed up every 4 months to monitor for development of a major depressive, manic, hypomanic, or mixed mood episode. Levels of N-acetyl-aspartate (NAA), phosphocreatine plus creatine (PCr + Cr), choline-containing compounds, myo-inositol, and glutamate were determined using LCModel and corrected for partial volume effects. RESULTS: There were no baseline differences in metabolite levels for any of the brain regions between at-risk and HC youth. Nineteen at-risk subjects developed a first mood episode during follow-up. Survival analyses showed that baseline PCr + Cr levels in the left VLPFC significantly predicted a mood episode during follow-up in the at-risk group (HR: 0.47, 95% CI: 0.27-0.82, P = 0.008). There were no longitudinal changes in metabolites levels in the VLPFC and ACC before and after a mood episode in at-risk subjects. CONCLUSIONS: We found no evidence for abnormal proton spectroscopy metabolite levels in the VLPFC and ACC of at-risk youth, prior and after the development of their first mood episode. Preliminary findings of association between baseline PCr + Cr levels in the left VLPFC and risk to develop a mood episode warrant further investigation.

5.
J Clin Psychiatry ; 80(1)2019.
Artigo em Inglês | MEDLINE | ID: mdl-30865789

RESUMO

Despite the availability of effective treatments for MDD, many individuals have difficulty achieving remission. Residual symptoms can be difficult to differentiate from treatment side effects. Through 2 comic-based case presentations, this CME activity depicts common clinical scenarios and provides evidence-based strategies for effectively identifying and managing residual symptoms of MDD.


Assuntos
Transtorno Bipolar , Educação em Saúde/métodos , Pais/educação , Educação de Pacientes como Assunto/métodos , Reabilitação Psiquiátrica/métodos , Psicotrópicos/uso terapêutico , Adulto , Transtorno Bipolar/psicologia , Transtorno Bipolar/terapia , Criança , Saúde da Família , Humanos , Pais/psicologia
6.
Psychiatry Res Neuroimaging ; 286: 53-59, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30903953

RESUMO

We examined the effects of lisdexamfetamine (LDX) treatment on ventral prefrontal cortex (VPFC) and striatal brain activation in binge eating disorder (BED). We hypothesized that participants with BED have an abnormal brain response to palatable food cues, and that VPFC and striatal regions would respond to such cues after LDX treatment. Twenty women with moderate to severe BED consented to a 12-week, open-label trial of LDX with fMRI before and after treatment. Twenty obese women without BED served as healthy controls and received one fMRI. LDX was started at 30 mg/d with a target of 70 mg/d at week 12. At baseline, women with BED showed greater activation in ventrolateral prefrontal cortex (VLPFC), striatum, and globus pallidus to food pictures and brain activation to food pictures predicted clinical outcome at 12 weeks. After 12 weeks of LDX treatment, BED women showed significant reductions in globus pallidus activation. Reductions in ventromedial prefrontal cortex (VMPFC) and thalamus activation specifically correlated with binge eating and obsessive-compulsive symptom reductions, respectively. Results suggest that BED is characterized by an abnormally large VPFC-subcortical brain response to palatable foods that LDX treatment helps modify. Moreover, VPFC-subcortical activation at baseline is a potential biomarker of LDX response.

7.
J Affect Disord ; 242: 1-4, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30153563

RESUMO

BACKGROUND: Identifying correlates of capacity to provide informed consent among individuals with bipolar disorder is essential for patient protection. As part of a clinical trial involving approved, standard treatments, we investigated relationships between clinical characteristics and capacity to provide informed consent in adults with bipolar disorder using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). After administering the MacCAT-CR, continuing participants in the trial were capable of and provided informed consent. METHODS: Trained, board-certified psychiatrists administered the MacCAT-CR to potential study participants (N = 50) after they provided informed consent, but prior to initiation of study procedures. RESULTS: Higher Schedule for Assessment of Positive Symptoms (SAPS) scores were significantly correlated with worse MacCAT-CR Understanding and Appreciation (p < 0.04) subscale scores; lower Hamilton Depression Rating Scale (HDRS) scores and higher Clinical Global Impression-Severity (CGI-S) scores were significantly correlated with worse Reasoning and Understanding subscale scores (p < 0.03); and patients with comorbid substance use disorders (SUD) had better Appreciation and Reasoning subscale scores (p < 0.05). LIMITATIONS: The MacCAT-CR identifies areas where participants need explanation. However, there is not a predetermined score to indicate understanding of study procedures and therefore input from a trained clinician is needed to determine capacity to provide informed consent. CONCLUSIONS: Our findings suggest that certain measures of illness severity are associated with lower levels of capacity to provide informed consent among adults with bipolar disorder. This study provides important information for clinicians and researchers to consider when obtaining informed consent in this population.


Assuntos
Transtorno Bipolar/psicologia , Consentimento Livre e Esclarecido/psicologia , Competência Mental/psicologia , Adulto , Tomada de Decisões , Feminino , Humanos , Testes de Inteligência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resolução de Problemas
8.
J Am Acad Child Adolesc Psychiatry ; 57(10): 725-727, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30274645

RESUMO

There have been many longitudinal studies examining biological and environmental risk factors for developing bipolar disorder in youth. Specifically, well-established risk factors for bipolar disorder in children and adolescents include having a family history of bipolar disorder, depression, disruptive behavior disorders, psychosis, antidepressant-induced manic symptoms, anxiety, and subsyndromal symptoms of mania and depression.1 In an effort to identify individuals at highest risk for developing bipolar disorder, several investigators have attempted to characterize a bipolar prodrome. A recent meta-analysis of early manifestations of bipolar disorder in youth found that the most common prodromal symptoms were increased energy, diminished ability to think, indecision, pressured speech, talkativeness, elated mood, academic or work difficulties, insomnia, depressed mood, and increased goal-directed activities.2 The authors concluded that despite many of the participants having symptoms prior to their illness onset, there was significant heterogeneity in symptom presentation, making it difficult to define a consistent bipolar prodrome. Although it is important to explore risk factors and rates of early symptoms of incipient bipolar disorder, to date, most studies have examined risk within an entire group rather than quantified an individual's risk of having bipolar disorder, which is essential to advance personalized monitoring and treatment strategies.

9.
J Am Acad Child Adolesc Psychiatry ; 57(10): 792-793, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30274654

RESUMO

Substantial numbers of children and adolescents are treated with second-generation antipsychotic medications (SGAs), and the cardiometabolic adverse effects of this medication class have raised concerns.1 In the October 2017 issue of the Journal, Handen et al.2 published a 16-week open-label extension study of youth 6 to 17 years of age with autism spectrum disorder treated with liquid metformin after a 16-week double-blinded, placebo-controlled clinical efficacy trial. The acute-phase and open-label extension trials demonstrated that liquid metformin was well tolerated, and significant improvements in body mass index z-scores were observed in the metformin-metformin and placebo-metformin groups.2 Handen et al.2 concluded that metformin can be effective for decreasing weight gain associated with SGA use and maintaining prior improvement in children and adolescents with autism spectrum disorder.

10.
Neuropsychopharmacology ; 43(11): 2256-2263, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29946107

RESUMO

The need for treatment response predictive biomarkers is being increasingly recognized in children and adolescents with psychiatric disorders. Structural gray matter abnormalities as a predictor of treatment outcome in pediatric bipolar disorder have not been systematically investigated, especially early in the illness course. With a prospective longitudinal study design, the present study enrolled 52 bipolar adolescents with no history of treatment with mood stabilizers or a therapeutic dose of antipsychotic drugs and 31 healthy controls. Patients were randomly assigned to treatment with quetiapine or lithium after pretreatment data collection. A hierarchical cluster analysis was performed using pretreatment cortical thickness data that identified two discrete patient subgroups. Compared to healthy subjects, patients in subgroup 1 (n = 16) showed widespread greater cortical thickness mainly across heteromodal cortex but also involving some regions of unimodal cortex, while those in subgroup 2 (n = 36) showed regional cortical thinning mainly in superior temporal and superior parietal regions. Patients within subgroup 1 showed a significantly higher response rate to quetiapine than those in subgroup 2 (100% vs 53%). No statistically significant difference was found in lithium response rate between the patient subgroups (63% vs 53%). Pretreatment clinical ratings and neuropsychological data did not differ across subgroups. Our findings suggest the existence of distinct and clinically relevant subgroups of pediatric bipolar patients, as defined by pattern of cortical thickness. These groups appear to differentially respond to antipsychotic treatment-notably with greater cortical thickness relative to controls predicting better treatment response.

11.
J Am Acad Child Adolesc Psychiatry ; 57(5): 353-354, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29706167

RESUMO

We would like to respond to some concerns raised by Dr. McClellan in his editorial comment1 on our article that reported the results of a placebo-controlled study of lurasidone for the treatment of children and adolescents with bipolar I depression.2.

12.
J Affect Disord ; 234: 14-19, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29522938

RESUMO

BACKGROUND: The neurophysiological substrates of cognition and emotion, as seen with fMRI, are generally explained using modular structures. The present study was designed to probe the modular structure of cognitive-emotional processing in bipolar and healthy individuals using factor analysis and compare the results with current conceptions of the neurophysiology of bipolar disorder. METHODS: Exploratory factor analysis was used to assess patterns of covariation among brain regions-of-interest activated during the Continuous Performance Task with Emotional and Neutral Distractors in healthy and bipolar individuals without a priori constraints on the number or composition of latent factors. RESULTS: Results indicated a common cognitive-emotional network consisting of prefrontal, medial temporal, limbic, parietal, anterior cingulate and posterior cingulate modules. However, reduced brain activation to emotional stimuli in the frontal, medial temporal and limbic modules was apparent in the bipolar relative to the healthy group, potentially accounting for emotional dysregulation in bipolar disorder. LIMITATIONS: This study is limited by a relatively small sample size recruited at a single site. The results have yet to be validated on a larger independent sample. CONCLUSIONS: Although the modular structure of cognitive-emotional processing is similar in bipolar and healthy individuals, activation in response to emotional/neutral cues varies. These findings are not only consistent with recent conceptions of mood regulation in bipolar disorder, but also suggest that regional activation can be considered within tighter modular structures without compromising data interpretation. This demonstration may serve as a template for data reduction in future region-of-interest analyses to increase statistical power.


Assuntos
Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Emoções/fisiologia , Adulto , Afeto , Mapeamento Encefálico , Análise Fatorial , Feminino , Voluntários Saudáveis , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
13.
Bipolar Disord ; 20(7): 658-665, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29479787

RESUMO

OBJECTIVES: The aims of the present study were to characterize cardiometabolic risk factors in a cohort of bipolar disorder patients with limited exposure to psychotropic medications, and to evaluate their associations with mood symptoms and omega-3 polyunsaturated fatty acid (PUFA) blood levels. METHODS: Cardiometabolic risk assessments were compared in individuals with bipolar I disorder experiencing a first manic or mixed episode or an early depressive episode (n=117) and healthy subjects (n=56). Patients were medication free at assessment and had no or limited exposure to mood-stabilizer or antipsychotic medications prior to the current admission. Associations among cardiometabolic parameters and Clinical Global Impression-Severity scale (CGI-S), manic (Young Mania Rating Scale [YMRS]), and depressive (Hamilton Depression Rating Scale [HDRS]) symptom ratings were evaluated within the bipolar group. RESULTS: Following adjustment for demographic variables (i.e., age, gender, and parental education), significantly higher fasting triglyceride levels were observed in the bipolar group compared to the healthy group (121.7 mg/dL vs 87.0 mg/dL; P<.01). There were no clear trends for other metabolic indicators, including blood pressure, body mass index, and fasting glucose. Nineteen percent of the bipolar group and 6% of the healthy group met the criteria for metabolic syndrome (P=.23). The omega-3 index was lower in the bipolar group (3.4% vs 3.9%; P<.01). Within the bipolar group, no associations were found between the cardiometabolic parameters and CGI-S, YMRS, and HDRS symptom ratings. CONCLUSIONS: Recent-onset medication-free bipolar disorder is associated with higher triglyceride levels. These findings are suggestive of early metabolic dysregulation prior to long-term psychotropic medication exposure. Lower omega-3 PUFA levels in individuals with bipolar I disorder represent a potential therapeutic target for additional investigation.

14.
Artigo em Inglês | MEDLINE | ID: mdl-29358037

RESUMO

The tolerability of antidepressants is poorly characterized in children and adolescents with depressive and anxiety disorders. Among adverse events that affect the tolerability of antidepressants in youth is activation, a cluster of symptoms that represent a hyperarousal event characterized by impulsivity, restlessness, and/or insomnia. This cluster of symptoms was first identified as a side effect of selective serotonin and selective serotonin norepinephrine inhibitors (SSRIs and SSNRIs) in the early 1990s; however, activation remains poorly characterized in terms of prevalence, risk factors, and pathophysiology. This article describes the pathophysiology of antidepressant-related activation, predictors of activation and its clinical management in youth with depressive and anxiety disorders who are treated with antidepressant medications.

15.
Clin J Sport Med ; 28(2): 100-105, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-27755011

RESUMO

OBJECTIVE: To examine effects of participating in collegiate football on neural health several years after retirement. We hypothesized that relative cortical thinning and loss of white matter integrity would be observed in former players. DESIGN: Former NCAA Division I football players were compared with demographically similar track-and-field athletes with regard to cortical thickness and white matter integrity. SETTING: Participants participated in MRI scans at the Center for Imaging Research at the University of Cincinnati. PARTICIPANTS: Eleven former football players and 10 demographically similar track-and-field athletes. MAIN OUTCOME MEASURES: Normalized cortical thickness was compared between groups using 2-tailed Student t test. As a secondary analysis, Spearman correlation coefficient was calculated between cortical thickness and number of concussions. Fractional anisotropy for regions-of-interest placed in frontal white matter tracts and internal capsule were compared between groups using 2-tailed Student t test. RESULTS: Football players showed significantly lower cortical thickness within portions of both the frontal and temporal cortex. Affected frontal regions included left frontal pole and right superior frontal gyrus. Affected temporal regions included portions of the superior temporal gyrus, left inferior temporal gyrus, and right middle and superior temporal gyri. Cortical thickness inversely correlated with number of reported concussions over most of these regions. In addition, fractional anisotropy was lower in the right internal capsule of former football players, relative to controls. CONCLUSIONS: These findings suggest that at least some consequences of high-level collegiate football play persist even after the cessation of regular head blows. Longer-term studies are warranted to examine potential cognitive and functional implications of sustained cortical atrophy.


Assuntos
Concussão Encefálica/patologia , Futebol Americano/lesões , Córtex Pré-Frontal/patologia , Lobo Temporal/patologia , Substância Branca/patologia , Adulto , Atletas , Imagem de Tensor de Difusão , Humanos , Imagem por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto Jovem
16.
J Child Adolesc Psychopharmacol ; 28(1): 47-54, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29035574

RESUMO

OBJECTIVES: In this 6-month open-label extension (OLE) of NCT01491035 (a 14-day, open-label, pharmacokinetic/safety lead-in study), the long-term safety and tolerability of vortioxetine (5-20 mg/day) were investigated in children and adolescents with a DSM-IV-TR™ diagnosis of depressive or anxiety disorder in the United States or Germany. The study also was designed to provide data to inform dose selection and titration in future pediatric studies with vortioxetine. METHODS: Safety evaluations included spontaneously reported adverse events (AEs), the Columbia Suicide Severity Rating Scale (C-SSRS), and the Pediatric Adverse Events Rating Scale (PAERS; clinician administered). Clinical effectiveness was determined by Clinical Global Impressions. Comorbid attention-deficit/hyperactivity disorder was permitted, including concomitant use of stimulant medication (US sites only). RESULTS: Of the 47 patients who completed the lead-in period, 41 continued into the OLE. Most patients (n = 39 [95%]) continued their previous dose regimen. Twenty-one patients (51%) withdrew during the OLE; the most common primary reasons were administrative [n = 8], AEs [n = 4], and lack of efficacy [n = 3]. Thirty-five patients (85%) had ≥1 AE, 86% of which were mild or moderate in severity. Five patients (12%) reported a severe AE, none of which was considered related to study medication. The most common AEs (≥10%) were headache (27%), nausea (20%), dysmenorrhea (females; 19%), and vomiting (15%), with no relationship between AE intensity and age or dose. Five patients reported instances of suicidal ideation during the OLE, one of whom also reported this during the lead-in period. Two patients had nonsuicidal self-injurious behavior; one had a nonfatal suicide attempt. Throughout the study, there was a decrease over time in the incidence and intensity of AEs collected using the PAERS. Effectiveness assessment indicated a trend toward improvement based on numeric results. CONCLUSION: This OLE confirms the findings from the lead-in study, which concluded that a dosing strategy of 5-20 mg/day is safe, well tolerated, and suitable for future clinical studies of vortioxetine in pediatric patients.

17.
J Am Acad Child Adolesc Psychiatry ; 56(12): 1015-1025, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29173735

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of lurasidone in children and adolescents with bipolar depression. METHOD: Patients 10 to 17 years old with a DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double-blind treatment with flexible doses of lurasidone 20 to 80 mg/day. The primary endpoint was change from baseline to week 6 in the Children's Depression Rating Scale-Revised (CDRS-R) total score, evaluated by a mixed-model repeated-measures analysis. RESULTS: A total of 347 patients were randomized and received at least 1 dose of lurasidone (n = 175; mean age 14.2 years; mean dose 33.6 mg/day) or placebo (n = 172; mean age 14.3 years). At week 6, treatment with lurasidone was associated with statistically significant improvement compared with placebo in CDRS-R total score (-21.0 versus -15.3; p < .0001; effect size 0.45). Lurasidone also was associated with statistically significant improvement in the Clinical Global Impression-Bipolar Severity depression score (key secondary measure) and in measures of anxiety, quality of life, and global functioning. Study completion rates were 92.0% in the lurasidone group and 89.7% in the placebo group; discontinuation rates due to adverse events were the same for the 2 groups (1.7%). The 2 most common adverse events on lurasidone were nausea and somnolence. Treatment with lurasidone was associated with few effects on weight and metabolic parameters. CONCLUSION: In this placebo-controlled study, monotherapy with lurasidone, in the dose range of 20 to 80 mg/day, significantly decreased depressive symptoms in children and adolescents with bipolar depression. Lurasidone was well tolerated, with minimal effects on weight and metabolic parameters. Clinical trial registration information-Lurasidone Pediatric Bipolar Study; http://Clinicaltrials.gov; NCT02046369.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Cloridrato de Lurasidona/uso terapêutico , Adolescente , Transtorno Bipolar/diagnóstico , Criança , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
18.
Ann Clin Psychiatry ; 29(4): 227-234A, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29069107

RESUMO

BACKGROUND: In pediatric patients with anxiety disorders, existing symptom inventories are either not freely available or require extensive time and effort to administer. We sought to evaluate a brief self-report scale-the Generalized Anxiety Disorder 7-item scale (GAD-7)-in adolescents with generalized anxiety disorder (GAD). METHODS: The Pediatric Anxiety Rating Scale (PARS) and the GAD-7 were administered to youth with GAD (confirmed by structured interview). Relationships between the measures were assessed, and sensitivity and specificity was determined with regard to a global symptom severity measure (Clinical Global Impression-Severity). RESULTS: In adolescents with GAD (N = 40; mean age, 14.8 ± 2.8), PARS and GAD-7 scores strongly correlated (R = 0.65, P ≤ .001) and a main effect for symptom severity was observed (P ≤ .001). GAD-7 scores ≥11 and ≥17 represented the optimum specificity and sensitivity for detecting moderate and severe anxiety, respectively. CONCLUSIONS: The PARS and GAD-7 similarly reflect symptom severity. The GAD-7 is associated with acceptable specificity and sensitivity for detecting clinically significant anxiety symptoms. GAD-7 scores may be used to assess anxiety symptoms and to differentiate between mild and moderate GAD in adolescents, and may be more efficient than the PARS.


Assuntos
Transtornos de Ansiedade/diagnóstico , Escalas de Graduação Psiquiátrica , Autorrelato , Adolescente , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes
19.
Ann Clin Psychiatry ; 29(4): 258-265, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29069111

RESUMO

BACKGROUND: Despite the high prevalence of suicidality in psychiatrically hospitalized youth, its risk factors and impact on inpatient psychopharmacologic treatment are unknown. We identified characteristics associated with suicidality in psychiatrically hospitalized youth and determined the association of suicidality with subsequent psychopharmacologic interventions. METHODS: Medical records from consecutive psychiatric admissions to a large, acute care, urban, pediatric hospital were analyzed retrospectively (N = 1,309). Demographic, clinical, and treatment-related features of suicidal and nonsuicidal youth were characterized. Logistic regression identified predictors of suicidality, and multiple comparison analyses evaluated the association between suicidality and changes to antidepressant prescribing during inpatient course. RESULTS: Compared with nonsuicidal patients, inpatients who were suicidal were more likely to have a mood disorder or posttraumatic stress disorder, as well as Cannabis and alcohol use, were more commonly girls, and at least 13 years of age (all P ≤ .05). Hospitalization was shorter for suicidal patients, was more likely to be associated with antidepressant treatment (P ≤ .001), and among suicidal patients prescribed antidepressants at the time of admission, was associated with a greater likelihood of changing antidepressant treatment compared with nonsuicidal inpatients (P ≤ .05). CONCLUSIONS: These findings reveal differences between suicidal and nonsuicidal psychiatrically hospitalized youth and suggest that suicidality is associated with specific pharmacologic treatment approaches within this population.


Assuntos
Antidepressivos/uso terapêutico , Demografia/estatística & dados numéricos , Hospitais Psiquiátricos , Suicídio , Adolescente , Criança , Feminino , Humanos , Masculino , Transtornos do Humor , Estudos Retrospectivos , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos
20.
J Clin Psychiatry ; 78(9): e1158-e1166, 2017 Nov/Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28922591

RESUMO

BACKGROUND: Early predictors of response and remission in pediatric mania are lacking, requiring further study. METHODS: This was a post hoc analysis of a 3-week, randomized, placebo-controlled trial of olanzapine conducted between November 2002 and May 2005 in 161 adolescents aged 13-17 years who were diagnosed with a DSM-IV acute manic or mixed episode of bipolar I disorder. Data from the olanzapine arm were analyzed to investigate the predictive power of early response or early nonresponse (≥25% or < 25% reduction in Young Mania Rating Scale [YMRS] score, respectively) at week 1 for ultimate response or nonresponse (≥ 50% or < 50% reduction in YMRS score, respectively) and for remission (YMRS total score ≤ 12 [standard definition] or ≤ 8 [stringent definition]) at week 3. Correlates of early response and ultimate response were examined in multivariable regression models. RESULTS: By week 1, 69.2% of olanzapine-treated adolescents (n = 104, 2.5-20.0 mg/d) achieved early response, and 49.0% reached ultimate response at week 3. Patients with early response and early nonresponse were similar regarding baseline variables except higher scores for sleep and thought content were found with early response (P < .05) and higher olanzapine doses with early nonresponse (P < .01). At week 3, early response was associated with significantly greater improvements in YMRS, Clinical Global Impressions-Severity of Illness scale (both P < .001), and Overt Aggression Scale scores (P = .024). Adverse events were similar in patients with early response and early nonresponse, except for higher AIMS scores for patients with early nonresponse (P = .036). Early response significantly predicted ultimate response (OR = 5.61, P < .001; sensitivity = 86.3, specificity = 47.2, positive predictive value = 61.1, negative predictive value = 78.1). Significantly more early response than early nonresponse patients achieved ultimate response (61.1% vs 21.9%, P < .001) and remission defined by YMRS score ≤ 12 (45.8% vs 12.5%, P < .001) and YMRS score ≤ 8 (33.3% vs 3.1%, P < .001). In multivariable analyses, among other variables, early response remained an independent correlate of ultimate response and remission. CONCLUSIONS: In acute pediatric manic or mixed episodes, early response to olanzapine at week 1 was strongly associated with ultimate response and remission at week 3, while absence of early response predicted the unlikely success of further treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00050206.

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