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1.
Artigo em Inglês | MEDLINE | ID: mdl-31682918

RESUMO

OBJECTIVE: To compare antidepressant-related adverse events (AEs), suicidality and AE-related discontinuation in double-blind, placebo-controlled trials of pediatric patients with OCD and anxiety disorders treated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). METHOD: MEDLINE, PubMed, Web of Science, PsycINFO and Embase were searched for peer-reviewed, English-language articles from inception through March 1, 2019. We identified prospective, randomized, SSRI and SNRI studies in patients <18 years of age with OCD, generalized, separation or social anxiety disorders. AE rates were extracted and antidepressant-placebo differences examined using Bayesian hierarchical models (BHM) then posterior estimates of relative risk (RR) was determined for each AE by medication class and disorder. RESULTS: Data were included from 18 trials (2631 patients) and 7 medications (16 SSRI and 4 SNRI trials). Compared to placebo, SSRIs were associated with a greater likelihood of AE-related discontinuation (RR: 3.59, CrI: 0.019 to 0.067, p=0.0003), activation (RR: 2.39, CrI: 0.048 to 0.125, p=0.003), sedation (RR: 1.94, CrI: 0.035 to 0.157, p=0.002), insomnia (RR: 1.93, CrI: 0.040 to 0.149, p=0.001), abdominal pain (RR: 1.53, Credible Interval [CrI]: 0.032 to 0.164, p=0.005) and headache (RR: 1.24, CrI: 0.003 to 0.139, p=0.04). Activation was more common with SSRI (vs. SNRIs, RR: 1.32, CrI: 0.018 to 0.114, p=0.007). Neither SSRIs nor SNRIs were associated with treatment-emergent suicidality. CONCLUSION: In pediatric OCD and anxiety disorders, SSRIs (compared to placebo) are associated with distinct adverse events (AEs) and greater AE-related discontinuation, although their tolerability does not differ between anxiety disorders and OCD. Compared to SNRIs, SSRIs are more likely to produce activation. Class-related AEs are important for clinicians to consider, particularly in light of data suggesting differences in class-related efficacy. While SSRIs are superior to SNRIs and the treatment of choice for anxiety, for youth who become activated on SSRIs, SNRIs might represent a good second choice given their reported efficacy and lower risk of activation.

2.
Pharmacopsychiatry ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31509860

RESUMO

INTRODUCTION: The use of pharmacogenomic (PGx) testing to guide decisions and improve patient outcomes has increased in recent years. PGx testing represents a decision support tool that may inform dosing, increase the likelihood of treatment response, and identify patients at risk for medication side effects. METHODS: This is a narrative review of utilization of PGx testing in psychiatry from stakeholders including, pharmacists, genetic counselors, implementation scientists, industry, and clinicians. RESULTS: While many limitations exist to streamline use of PGx testing in psychiatry, various stakeholders are crucial to clinical implementation. DISCUSSION: PGx testing can assist in medication selection and improve patient outcomes; however, more data are needed to understand when and how to incorporate PGx testing into psychiatric practice.

3.
Environ Health Perspect ; 127(9): 97006, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31553231

RESUMO

BACKGROUND: Acute exposure to ambient particulate matter <2.5µm in aerodynamic diameter (PM2.5) has been associated with adult psychiatric exacerbations but has not been studied in children. OBJECTIVES: Our objectives were to estimate the association between acute exposures to ambient PM2.5 and psychiatric emergency department (ED) utilization and to determine if it is modified by community deprivation. METHODS: We used a time-stratified case-crossover design to analyze all pediatric, psychiatric ED encounters at Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio, from 2011 to 2015 (n=13,176). Conditional logistic regression models adjusted for temperature, humidity, and holiday effects were used to estimate the odds ratio (OR) for a psychiatric ED visit 0-3 d after ambient PM2.5 exposures, estimated at residential addresses using a spatiotemporal model. RESULTS: A 10-µg/m3 increase in PM2.5 was associated with a significant increase in any psychiatric ED utilization 1 [OR=1.07 (95% CI: 1.02, 1.12)] and 2 [OR=1.05 (95% CI: 1.00, 1.10)] d later. When stratified by visit reason, associations were significant for ED visits related to adjustment disorder {e.g., 1-d lag [OR=1.24 (95% CI: 1.02, 1.52)] and suicidality 1-d lag [OR=1.44 (95% CI: 1.03, 2.02)]}. There were significant differences according to community deprivation, with some lags showing stronger associations among children in high versus low deprivation areas for ED visits for anxiety {1-d lag [OR=1.39 (95% CI: 0.96, 2.01) vs. 0.85 (95% CI: 0.62, 1.17)] and suicidality same day [OR=1.98 (95% CI: 1.22, 3.23) vs. 0.93 (95% CI: 0.60, 1.45)]}. In contrast, for some lags, associations with ED visits for adjustment disorder were weaker for children in high-deprivation areas {1-d lag [OR=1.00 (95% CI: 0.76, 1.33) vs. 1.50 (95% CI: 1.16, 1.93)]}. DISCUSSION: These findings warrant additional research to confirm the associations in other populations. https://doi.org/10.1289/EHP4815.

4.
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.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31264800

RESUMO

AIM: Previous studies suggest that Mindfulness-Based Cognitive Therapy for Children (MBCT-C) is feasible and may improve anxiety and emotion regulation in youth with anxiety disorders at-risk for bipolar disorder. However, controlled studies are warranted to replicate and extend these findings. METHODS: In the current study, 24 youth with anxiety disorders who have at least one parent with bipolar disorder participated in a MBCT-C treatment period (n = 24; Mage = 13.6, 75% girls, 79% White) with a subset also participating in a prior psychoeducation waitlist control period (n = 19 Mage = 13.8, 68% girls, 84% White). Participants in both the waitlist and MBCT-C periods completed independently-rated symptom scales at each time point. Participants in the waitlist period received educational materials 12 weeks prior to the beginning of MBCT-C. RESULTS: There were significantly greater improvements in overall clinical severity in the MBCT-C period compared to the waitlist period, but not in clinician- and child-rated anxiety, emotion regulation or mindfulness. However, increases in mindfulness were associated with improvements in anxiety and emotion regulation in the MBCT-C period, but not the waitlist period. CONCLUSIONS: Findings suggest that MBCT-C may be effective for improving overall clinical severity in youth with anxiety disorders who are at-risk for bipolar disorder. However, waitlist controlled designs may inflate effect sizes so interpret with caution. Larger studies utilizing prospective randomized controlled designs are warranted.

7.
J Child Adolesc Psychopharmacol ; 29(5): 348-361, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31066578

RESUMO

Objective: To determine whether genetic variants in a pharmacokinetic gene (the number of CYP2C19 reduced function alleles [RFAs]), and in pharmacodynamic genes (HTR2A, SLC6A4, and GRIK4) influence sertraline tolerability and response in a cohort of pediatric patients with anxiety and depressive disorders. Methods: A retrospective analysis was performed using the electronic medical record data of 352 patients <19 years of age being treated for anxiety and/or depressive disorders with sertraline and who underwent routine clinical CYP2C19 genotyping. Additional genotyping and analysis of variants in HTR2A, SLC6A4, and GRIK4 were conducted for 249 patients. Multivariate regression models testing for associations with CYP2C19 were adjusted for concomitant use of interacting medications. Combinatorial classification and regression tree (CART) analyses containing all pharmacokinetic and pharmacodynamic genes and clinical factors were performed. Results: The maximum sertraline dose during the initial titration period of sertraline was inversely associated with the number of CYP2C19 RFAs and sertraline dose at 60 (p = 0.025) and 90 days (p = 0.025). HTR2A rs6313 was associated with sertraline dose (p = 0.011) and time to the average maximum sertraline dose (p = 0.039). Regarding efficacy, the number of CYP2C19 RFAs was not associated with the sertraline dose at the time of response (p = 0.22), whereas for the pharmacodynamic genes, only HTR2A rs6313 was associated with response dose (p = 0.022). An association was observed between predicted expression levels of SLC6A4 and the duration on sertraline (p = 0.025). Combinatorial CART and multivariate regression analyses implicated that pharmacodynamic genes and clinical factors influence the maximum sertraline dose and response dose. The total number of side effects was not associated with any of the variants tested. Conclusion: Both pharmacokinetic and pharmacodynamic factors, in addition to clinical and demographic components, influence sertraline dose, response, and tolerability, thereby necessitating further research to assess for the validity of these pharmacogenetic associations in children and adolescents.

8.
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.

9.
J Child Adolesc Psychopharmacol ; 29(5): 340-347, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30817183

RESUMO

Objective: Cytochrome P4502C19 (CYP2C19) is a highly polymorphic gene that encodes an enzyme that metabolizes escitalopram and sertraline, two selective serotonin reuptake inhibitors (SSRIs) that are FDA approved for pediatric use and commonly used to treat anxiety and depressive disorders in youth. Using pharmacokinetic (PK) models in adolescents, we sought to (1) model SSRI dosing across CYP2C19 phenotypes to compare SSRI exposure (area under curve, AUC) and maximum concentration (Cmax), (2) evaluate the impact of b.i.d. dosing (in rapid metabolizers [RM] and ultrarapid metabolizers [UM]) on SSRI exposure and Cmax, and (3) determine pharmacogenomically-informed dosing strategies to provide similar exposure across CYP2C19 phenotypes in adolescents. Methods: Using PK parameters in CYP2C19 phenotype groups and previously reported pediatric PK data for escitalopram and sertraline, we modeled exposure (AUC0-24) and Cmax and determined CYP2C19-guided dosing strategies. Results: Compared with normal CYP2C19 metabolizers treated with either escitalopram or sertraline, Cmax and AUC0-24 were higher in slower metabolizers and lower in patients with increased CYP2C19 activity, although the magnitude of these differences was more pronounced for escitalopram than for sertraline. For escitalopram, poor metabolizers (PMs) require 10 mg/day and UMs require 30 mg/day to achieve an exposure that is equivalent to 20 mg/day in a normal metabolizer (NM). For sertraline, to achieve AUC0-24 and Cmax similar to NMs receiving 150 mg/day, PMs require 100 mg/day, whereas a dose of 200 mg/day was required in rapid and UMs. For UMs, b.i.d. escitalopram dosing was necessary to achieve comparable trough levels and exposure to NMs. Conclusions: This simulation study raises the possibility that achieving similar escitalopram and sertraline plasma concentrations could require dose adjustments in CYP2C19 poor metabolizers and UMs, although the magnitude of these differences were more pronounced for escitalopram than for sertraline. However, prospective trials of pharmacogenomically guided dosing in the pediatric population are needed to extend the findings of these modeling studies.

10.
J Child Adolesc Psychopharmacol ; 29(4): 250-255, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30810350

RESUMO

Objective: To guide clinicians in selecting the "next line" selective serotonin reuptake inhibitor (SSRI) for adolescents with treatment-resistant major depressive disorder, we sought to compare response rates among SSRIs in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study and to jointly model tolerability and efficacy for the specific SSRI comparisons. Methods: Efficacy and tolerability data for paroxetine, citalopram, and fluoxetine were extracted from the TORDIA study. Using a joint bivariate normal likelihood for response and tolerability (based on the maximum implied variance from the 95% credible intervals previously reported for the three SSRIs), a Monte Carlo pseudorandom sample (100,000 draws) was obtained, from which credible intervals, means, posterior tail probabilities, etc. were determined. Joint null hypotheses of no difference in efficacy and tolerability were then evaluated with regard to superiority of each SSRI over the others. Results: No significant differences in response were observed for citalopram compared with fluoxetine (p = 0.247) or for fluoxetine compared with paroxetine (p = 0.110), although citalopram trended toward being superior to paroxetine (mean difference: 0.2, p = 0.055). For efficacy-tolerability models, citalopram and fluoxetine were superior to paroxetine (p = 0.029 and p = 0.022, respectively) but did not differ between each other (p = 0.146). Conclusions: Joint efficacy-tolerability models suggest that citalopram and fluoxetine were statistically significantly superior to paroxetine while citalopram trended toward superiority over paroxetine in the efficacy model. These findings provide a more granular and practical evidence base for clinicians faced with treatment sequencing decisions in adolescents with SSRI-resistant depression.

11.
J Clin Psychiatry ; 80(1)2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30753760

RESUMO

OBJECTIVE: To evaluate the efficacy and tolerability of pharmacotherapy in pediatric anxiety disorders using network meta-analysis. DATA SOURCES: PubMed, Cochrane Database, Web of Science, PsycNET, and ClinicalTrials.gov were searched for double-blind, controlled pharmacotherapy trials in youth with anxiety disorders from 1966 to September 2017. DATA SELECTION: All double-blind, placebo-controlled trials of pharmacotherapy in the treatment of pediatric patients with generalized, social, and/or separation anxiety disorders were included. DATA EXTRACTION: We extracted demographic, symptom severity, global improvement, discontinuation, and suicidality data. Risk of bias was assessed with the Cochrane risk-of-bias tool, and a network meta-analysis comparing the efficacy and tolerability of medications and medication classes was performed using the gemtc package (R). RESULTS: We identified 20 citations (22 RCTs, 24 treatment arms) with 2,623 patients. Selective serotonin reuptake inhibitors (SSRIs) were the only class that was superior in reducing anxiety (standardized mean difference: 5.2; credible interval [CrI]: [2.8 to 8.8]) and in likelihood of treatment response compared to placebo (odds ratio [OR]: 4.6; CrI: [3.1 to 7.5]). Serotonin-norepinephrine reuptake inhibitor (SNRI) and α2 agonist treatment were associated with more frequent treatment response compared to placebo. The likelihood of treatment response was greater for SSRIs compared to SNRIs (OR: 1.9; CrI: [1.1 to 3.5]). All-cause discontinuation and treatment-emergent suicidality significantly differed among medications but not medication class. CONCLUSIONS: Although multiple medications reduce anxiety in children and adolescents, treatment response, tolerability, and treatment-emergent suicidality differ among these medications and medication classes. Determining whether efficacy and tolerability differences represent true differences (or reflect differences in trial design) requires additional head-to-head medication trials and-to exclude the impact of missing treatment interventions-requires trials of medications that successfully treat anxiety in adults but that have not been evaluated in youth.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Inibidores da Captação de Neurotransmissores/farmacologia , Criança , Humanos , Meta-Análise em Rede , Resultado do Tratamento
13.
Neuroscience ; 396: 108-118, 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30439538

RESUMO

Panic disorder (PD), a prevalent anxiety disorder, is characterized by unexpected panic attacks, persistent anxiety and avoidance of panic contexts. Selective serotonin reuptake inhibitors (SSRIs) are effective in treating PD; however, the mechanisms underlying SSRI efficacy are poorly understood. Using CO2-inhalation, a PD-relevant translational paradigm, we examined the effect of chronic SSRI (fluoxetine) treatment on unconditioned and context-conditioned defensive behaviors, as well as respiratory responses, in mice. In addition, cFos expression was evaluated as a measure of the functional activity and interregional correlation matrices were used to explore the neurocircuitry recruited in CO2-conditioned behavior and SSRI treatment response. Chronic fluoxetine attenuated CO2-induced passive (freezing) behavior during inhalation and active (rearing) behavior on re-exposure to context, in addition to reducing CO2-evoked respiratory responses. Brain mapping in CO2-context-conditioned mice revealed altered regional neuronal activation within and correlations across midbrain regions subserving defensive behaviors (periaqueductal gray (PAG) and raphe nuclei) and forebrain emotional and contextual processing loci (medial prefrontal cortex, insular cortex and hippocampus). Importantly, fluoxetine treatment normalized these alterations. Collectively, our results provide novel information on fluoxetine modulation of panic-relevant defensive behaviors and neurocircuitry, facilitating increased understanding of panic neurobiology in the context of treatment response.

14.
Expert Opin Pharmacother ; 19(10): 1057-1070, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30056792

RESUMO

INTRODUCTION: Generalized anxiety disorder (GAD) often begins during adolescence or early adulthood and persists throughout the lifespan. Randomized controlled trials support the efficacy of selective serotonin and selective serotonin norepinephrine reuptake inhibitors (SSRIs and SNRIs, respectively), as well as benzodiazepines, azapirones, anti-adrenergic medications, melatonin analogs, second-generation antipsychotics, kava, and lavender oil in GAD. However, psychopharmacologic treatment selection requires clinicians to consider multiple factors, including age, co-morbidity, and prior treatment. Areas covered: The authors review the literature concerning pharmacotherapy for pediatric and adult patients with GAD with specific commentary on the efficacy and tolerability of selected agents in these age groups. The authors describe an algorithmic approach to the pediatric and adult patient with GAD and highlight considerations for the use of selected medications in these patients. Expert opinion: In adults with GAD, SSRIs and SNRIs represent the first-line psychopharmacologic treatment while second-line pharmacotherapies include buspirone, benzodiazepines, SGAs, and pregabalin. In pediatric patients with GAD, SSRIs should be considered the first line pharmacotherapy and psychotherapy enhances antidepressant response.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Adulto , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtornos de Ansiedade/patologia , Criança , Prática Clínica Baseada em Evidências , Humanos , Inibidores da Monoaminoxidase/uso terapêutico
15.
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.

17.
J Am Acad Child Adolesc Psychiatry ; 57(4): 235-244.e2, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29588049

RESUMO

OBJECTIVE: To determine the trajectory and magnitude of antidepressant response as well as the effect of antidepressant class and dose on symptomatic improvement in pediatric anxiety disorders. METHOD: Weekly symptom severity data were extracted from randomized, parallel group, placebo-controlled trials of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) in pediatric anxiety disorders. Treatment response was modeled for the standardized change in continuous measures of anxiety using Bayesian updating. Posterior distributions for each study served as informative conjugate prior to distributions update subsequent study posteriors. Change in symptom severity was evaluated as a function of time, class and, for SSRIs, standardized dose. RESULTS: Data from 9 trials (SSRIs: n = 5; SNRIs, n = 4) evaluating 7 medications in 1,673 youth were included. In the logarithmic model of treatment response, statistically, but not clinically, significant treatment effects emerged within 2 weeks of beginning treatment (standardized medication-placebo difference = -0.054, credible interval [CI] = -0.076 to -0.032, p = .005, approximate Cohen's d ≤ 0.2) and by week 6, clinically significant differences emerged (standardized medication-placebo difference = -0.120, CI = -0.142 to -0.097, p = .001, approximate Cohen's d = 0.44). Compared to SNRIs, SSRIs resulted in significantly greater improvement by the second week of treatment (p = .0268), and this advantage remained statistically significant through week 12 (all p values <.03). Improvement occurred earlier with high-dose SSRI treatment (week 2, p = .002) compared to low-dose treatment (week 10, p = .025), but SSRI dose did not have an impact on overall response trajectory (p > .18 for weeks 1-12). CONCLUSIONS: In pediatric patients with generalized, separation, and/or social anxiety disorders, antidepressant-related improvement occurred early in the course of treatment, and SSRIs were associated with more rapid and greater improvement compared to SNRIs.

18.
Neurology ; 90(11): e963-e970, 2018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29444968

RESUMO

OBJECTIVE: To evaluate the effect of a stress-reduction intervention in participants with medication-resistant epilepsy. METHODS: Adults with medication-resistant focal epilepsy (n = 66) were recruited from 3 centers and randomized to 1 of 2 interventions: (1) progressive muscle relaxation (PMR) with diaphragmatic breathing, or (2) control focused-attention activity with extremity movements. Following an 8-week baseline period, participants began 12 weeks of double-blind treatment. Daily self-reported mood and stress ratings plus seizure counts were completed by participants using an electronic diary, and no medication adjustments were permitted. The primary outcome was percent reduction in seizure frequency per 28 days comparing baseline and treatment; secondary outcomes included stress reduction and stress-seizure interaction. RESULTS: In the 66 participants in the intention-to-treat analysis, seizure frequency was reduced from baseline in both treatment groups (PMR: 29%, p < 0.05; focused attention: 25%, p < 0.05). PMR and focused attention did not differ in seizure reduction (p = 0.38), although PMR was associated with stress reduction relative to focused attention (p < 0.05). Daily stress was not a predictor of seizures. CONCLUSIONS: Both PMR and the focused-attention groups showed reduced seizure frequency compared to baseline in participants with medication-resistant focal seizures, although the 2 treatments did not differ. PMR was more effective than focused attention in reducing self-reported stress. CLINICALTRIALSGOV IDENTIFIER: NCT01444183.

19.
Artigo em Inglês | MEDLINE | ID: mdl-29337001

RESUMO

Anxiety and depressive disorders are common in the pediatric primary care setting, and respond to both psychotherapeutic and psychopharmacologic treatment. However, there are limited data regarding the optimal treatment duration. This article systematically reviews guidelines and clinical trial data related to antidepressant treatment duration in pediatric patients with depressive and anxiety disorders. The extant literature suggests 9-12 months of antidepressant treatment for youth with major depressive disorder. For generalized, separation and social anxiety disorders, 6-9 months of antidepressant treatment may be sufficient, though many clinicians extend treatment to 12 months based on extrapolation of data from adults with anxiety disorders. Such extended treatment periods may decrease the risk of long-term morbidity and recurrence; however, the goal of treatment is ultimately remission, rather than duration of antidepressant pharmacotherapy. Moreover, while evidence-based guidelines represent a starting point, appropriate treatment duration varies and patient-specific response, psychological factors, and timing of discontinuation must be considered for individual pediatric patients.

20.
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.

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