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1.
J Child Psychol Psychiatry ; 61(3): 312-332, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32020643

RESUMO

BACKGROUND: Adolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk factor for suicide, which is now the second leading cause of death in young people. Up to twenty per cent of adolescents will experience MDD before adulthood, and while a substantial proportion will improve with standard-of-care treatments (psychotherapy and medication), roughly one third will not. METHODS: Here, we have reviewed the literature in order to discuss the concept of treatment-resistant depression (TRD) in adolescence, examine risk factors, diagnostic difficulties, and challenges in evaluating symptom improvement, and providing guidance on how to define adequate medication and psychotherapy treatment trials. RESULTS: We propose a staging model for adolescent TRD and review the treatment literature. The evidence base for first- and second-line treatments primarily derives from four large pediatric clinical trials (TADS, TORDIA, ADAPT, and IMPACT). After two medications and a trial of evidence-based psychotherapy have failed to alleviate depressive symptoms, the evidence becomes quite thin for subsequent treatments. Here, we review the evidence for the effectiveness of medication switches, medication augmentation, psychotherapy augmentation, and interventional treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, and ketamine) for adolescent TRD. Comparisons are drawn to the adult TRD literature, and areas for future pediatric depression research are highlighted. CONCLUSIONS: As evidence is limited for treatments in this population, a careful consideration of the known risks and side effects of escalated treatments (e.g., mood stabilizers and atypical antipsychotics) is warranted and weighed against potential, but often untested, benefits.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31697973

RESUMO

BACKGROUND: Minimizing dropouts across antidepressant, placebo-controlled trials remains a major opportunity to improve the efficiency of trials. This meta-analysis investigated placebo dropout rate and its predictors in second generation antidepressant (SGA) for anxiety, depression and obsessive-compulsive disorder (OCD). METHODS: A random-effects meta-analysis was performed to examine placebo group dropout rate in SGA trials for depression, anxiety and OCD using Freeman - Tukey transformation. Stratified subgroup analysis by diagnostic indication was performed to examine the dropout rate across disorders. Meta-regression was performed to identify correlates between placebo dropout rate and trial and subject characteristics. RESULTS: Meta-analysis included 148 trials with 18,016 participants receiving placebo. Across antidepressant trials the overall placebo dropout rate was 25% (dropout rate ±â€¯standard error (SE) = 0.25 ±â€¯0.01, 95% CI: 0.23-0.27, z = 23.95, p < .001) and was similar across disorders (χ2 = 1.09, df = 2, p = .58). The placebo group dropout rate was 26% in depressive disorders, 25% in anxiety disorders and 22% in OCD. Across all diagnostic indications, earlier publication year, placebo lead-in, studies conducted in a single country (instead of internationally), longer trial duration, fewer study sites, more study visits and less baseline illness severity were associated with higher placebo dropout rate. Significant predictors of placebo dropout did not replicate across disorders. CONCLUSION: No significant difference was found in placebo dropout rate between internalizing disorders with overall dropout rate for placebo groups in antidepressant trials being around 25%. Placebo dropouts in trials can be minimized by reducing subject burden in trials, enrolling more severely affected subjects and foregoing placebo lead-in periods.

3.
J Child Adolesc Psychopharmacol ; 30(1): 32-37, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31800306

RESUMO

Background: Many children and adults with Obsessive-Compulsive Disorder (OCD) fail to respond to first-line pharmacological and behavioral treatments. Glutamate dysfunction may contribute to the development of OCD. N-acetylcysteine (NAC), a glutamate modulating drug, has shown to be a promising agent in adults with OCD. Methods: We conducted a double-blind, placebo-controlled clinical trial from July 2012 to January 2017. Children ages 8 to 17 years with OCD were assigned to receive NAC (up to 2700 mg/day) or the matching placebo for a period of 12 weeks. Children were required to be on stable psychiatric treatment (both medication and therapy) but were not required to be treatment-refractory. The primary outcome was OCD symptom severity as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We used linear mixed models to analyze the effect of NAC compared to placebo. Results: Due to poor recruitment and eventual expiration of the study medication, enrollment was stopped at 11 children out of a planned sample size of 40. Nonetheless, NAC was associated with significant reduction in CY-BOCS total score compared to placebo (Satterthwaite's test: t (37) = 2.36, p = 0.024) with effects separating from placebo beginning at week 8. Mean CY-BOCS total score decreased in the NAC group from 21.4 ± 4.65 at baseline to 14.4 ± 5.55 at week 12. In the placebo group, mean CY-BOCS total score remained unchanged (21.3 ± 4.65). In the NAC group, 1 out of 5 participants achieved >35% improvement in CY-BOCS total score, while none of the six patients in placebo group reached this improvement level. NAC and placebo were well tolerated. One mild adverse event was reported in each group. Conclusions: Our trial suggests that there may be some initial improvement in OCD symptom severity with NAC treatment. NAC was well tolerated in the study population. Future trials should employ multiple sites and have a larger study population to further confirm any benefits of NAC.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31794677

RESUMO

Objectives: In clinical trials of pediatric trichotillomania (TTM), three instruments are typically employed to rate TTM severity: (1) the Massachusetts General Hospital Hair Pulling Scale (MGH-HPS), (2) the National Institute of Mental Health Trichotillomania Severity Scale (NIMH-TSS), and (3) the Trichotillomania Scale for Children (TSC). These instruments lack standardized definitions of treatment response, which lead researchers to determine their own definitions of response post hoc and potentially inflate results. We performed a meta-analysis to provide empirically determined accuracy measures for percentage reduction cut points in these three instruments. Methods: MEDLINE was searched for TTM clinical trials. A total of 67 studies were initially identified, but only 5 were clinical trials focused on TTM in pediatric populations and therefore were included in this meta-analysis (n = 180). A Clinical Global Impressions Improvement score ≤2 was used to define clinical response. Receiver operating characteristic principles were employed to determine accuracy measures for percentage reduction cut points on each one of the instruments. Meta-DiSc software was employed to provide pooled accuracy measures for each cut point for each instrument. The Youden Index and the distance to corner methods were used to determine the optimal cut point. Results: The optimal cut points to determine treatment response were a 45% reduction on the MGH-HPS (Youden Index 0.40, distance to corner 0.20), a 35% reduction on the NIMH-TSS (Youden Index 0.42, distance to corner 0.17), a 25% reduction on the TSC child version (TSC-C; Youden Index 0.40, distance to corner 0.18), and a 45% (distance to corner 0.30) or 50% reduction (Youden Index 0.33) on the TSC parent version (TSC-P). The TSC-C had less discriminative ability at determining response in younger children in comparison to older children; no age-related differences were observed on the TSC-P. Conclusions: This study provides empirically determined cut points of treatment response on three instruments that rate TTM severity. These data-driven cut points will benefit future research on pediatric TTM.

5.
Biol Psychiatry ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31668476

RESUMO

BACKGROUND: Activity in the supplementary motor area (SMA) has been associated with tics in Tourette syndrome (TS). The aim of this study was to test a novel intervention-real-time functional magnetic resonance imaging neurofeedback from the SMA-for reduction of tics in adolescents with TS. METHODS: Twenty-one adolescents with TS were enrolled in a double-blind, randomized, sham-controlled, crossover study involving two sessions of neurofeedback from their SMA. The primary outcome measure of tic severity was the Yale Global Tic Severity Scale administered by an independent evaluator before and after each arm. The secondary outcome was control over the SMA assessed in neuroimaging scans, in which subjects were cued to increase/decrease activity in SMA without receiving feedback. RESULTS: All 21 subjects completed both arms of the study and all assessments. Participants had significantly greater reduction of tics on the Yale Global Tic Severity Scale after real neurofeedback as compared with the sham control (p < .05). Mean Yale Global Tic Severity Scale Total Tic score decreased from 25.2 ± 4.6 at baseline to 19.9 ± 5.7 at end point in the neurofeedback condition and from 24.8 ± 8.1 to 23.3 ± 8.5 in the sham control condition. The 3.8-point difference is clinically meaningful and corresponds to an effect size of 0.59. However, there were no differences in changes on the secondary measure of control over the SMA. CONCLUSIONS: This first randomized controlled trial of real-time functional magnetic resonance imaging neurofeedback in adolescents with TS suggests that this neurofeedback intervention may be helpful for improving tic symptoms. However, no effects were found in terms of change in control over the SMA, the hypothesized mechanism of action.

6.
CNS Drugs ; 33(10): 971-980, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31573058

RESUMO

BACKGROUND: Roughly 80% of the symptom improvement experienced on antidepressants in clinical trials is also observed in the placebo comparison group. Understanding the correlates of placebo improvement and response is important to designing efficient and successful trials of future antidepressants. OBJECTIVE: The objective of this meta-analysis was to investigate the magnitude of placebo symptom improvement and placebo response rates in second-generation antidepressant trials of depression, anxiety, and obsessive-compulsive disorder. METHODS: We searched PubMed on 10 June, 2016, with no date or language limits, to identify randomized placebo-controlled trials of second-generation antidepressants in adults with depression, anxiety, or obsessive-compulsive disorder. We used a random-effects meta-analysis to examine the magnitude of placebo symptom improvement using standardized mean difference and placebo response rate. Stratified subgroup analysis and meta-regression were utilized to examine the effect of diagnostic indication and correlates of placebo symptom improvement. RESULTS: The meta-analysis included 164 trials involving 19,591 participants. Magnitude of placebo improvement and placebo response rates varied significantly between diagnostic indications. The magnitude of placebo improvement was much lower in obsessive-compulsive disorder (standardized mean difference = 0.58, 95% confidence interval 0.36-0.79) than in depression (standardized mean difference = 1.22, 95% confidence interval 1.12-1.32) or anxiety (standardized mean difference = 1.01, 95% confidence interval 0.90-1.12) trials. There was a large amount of heterogeneity in placebo improvement between studies (Q = 899, df = 110, p < 0.001, I2 = 88%). A greater number of study sites and a later publication year were associated with a greater magnitude of placebo improvement and response rate. Presence of a placebo lead-in and absence of non-US sites were associated with a reduced magnitude of placebo improvement. Trial duration was positively associated with the magnitude of placebo improvement in depression trials but negatively associated with the magnitude of placebo improvement in anxiety and obsessive-compulsive disorder trials. CONCLUSIONS: Magnitude of placebo symptom improvement differed significantly based on diagnostic indication with improvement being significantly less in obsessive-compulsive disorder than anxiety and depression. Some trial characteristics were associated with a greater magnitude of placebo improvement in trials across disorders but others were disorder specific.

8.
Curr Psychiatr ; 18(9): 26-42F, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31511767
9.
Ther Adv Psychopharmacol ; 9: 2045125319869791, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489174

RESUMO

The American Psychiatric Association (APA) currently recommends the use of omega-3 fatty acid supplementation for depressive disorders, impulse-control disorders, and psychotic disorders in treatment guidelines. This review examines the evidence for efficacy of omega-3 fatty acids in depressive disorders, bipolar disorder, anxiety disorders, post-traumatic stress disorder (PTSD), and psychosis. Meta-analysis of randomized-controlled trials of omega-3 fatty acids for depression are inconclusive, with strong evidence of publication bias, sizable heterogeneity between included studies, and substantial methodological shortcomings in included trials. The large amount of heterogeneity in findings of RCTs of omega-3 fatty acids for unipolar depression is likely attributable to highly heterogeneous sample populations that are given different omega-3 supplements [which differ widely in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content, ratio, and dosage] as either adjunctive or monotherapy of other existing treatments, and then measure several different outcomes of depression symptomatology with likely incomplete blinding. Evidence of efficacy of omega-3 supplementation in treating psychosis, PTSD, anxiety, and bipolar mania is minimal. The current guidelines recommending the use of omega-3 fatty acids in adulthood psychiatric conditions should be revisited, especially given several recent negative studies examining the effects of omega-3 fatty acids for cardiovascular disease. Recommending likely ineffective treatment to patients, no matter how benign the side-effect profile, has opportunity cost (e.g. other more effective medications or therapies not being utilized) and likely affects patient compliance with other evidence-based treatments.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31220521

RESUMO

BACKGROUND: Tourette syndrome (TS) is estimated to have a prevalence of 0.30-0.77% in school aged children. Longitudinal studies suggest that roughly half-to-two-thirds of children with TS experience a substantial improvement in tic symptoms during adolescence. By contrast, few studies have examined adulthood prevalence of TS. Accurate prevalence estimates across the lifespan are needed to support regulatory and public health decisions. METHODS: We searched PubMED and EMBASE for studies that examined the prevalence of TS in adults. We conducted a random-effects meta-analysis of logit event rates to estimate prevalence of TS across studies. Too few studies are available to conduct moderator analysis or examine publication bias. We also examined the risk ratio of TS prevalence in adults for males compared to females. RESULTS: Three studies involving 2,356,485 participants were included. There were significant differences in TS adulthood prevalence estimates between studies ranging from 49 to 657 cases of TS per million adults. Overall prevalence of TS in adulthood was estimated to be 118 cases of TS per million adults (95%CI: 19-751 cases per million adults). There was a large amount of heterogeneity between studies (I2 = 99%) that was likely related to differences in their methods of identification of TS cases. By contrast, the male:female ratio of risk of adulthood TS was similar between studies with a Risk Ratio = 2.33 (95% CI: 1.72-3.16). CONCLUSION: Estimates of adulthood prevalence of TS are sparse and likely highly affected by differences in method of case identification. Diagnosis and diagnostic estimates of TS could be aided by including a requirement for impairment as well as potential remission criteria similar to other psychiatric conditions.

11.
Depress Anxiety ; 36(6): 533-542, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30990937

RESUMO

BACKGROUND: Recent findings suggest an association between attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Thus, we evaluated the clinical associated features of ADHD in a large sample of adult OCD patients. METHODS: A cross-sectional study including 955 adult patients with OCD from the Brazilian Research Consortium of Obsessive-Compulsive Spectrum Disorders (C-TOC). Clinical characteristics in adult OCD patients with and without comorbid ADHD were compared using Fisher's exact test, t-tests or Mann-Whitney tests. Bivariate analyses were followed by logistic regression analysis to identify clinical characteristics independently associated with ADHD comorbidity. RESULTS: The lifetime prevalence of ADHD in adult OCD patients was 13.7%. The current results indicate that OCD + ADHD patients were more severe, had an earlier onset of the obsessive-compulsive symptoms, a higher history of rheumatic fever, with higher frequencies of sensory phenomena and comorbidity with Tourette syndrome. They also had an increased risk for academic impairment and suicide attempts. CONCLUSION: Adult OCD patients with ADHD present some specific clinical features and may represent a special subgroup of adult OCD. Future studies should focus on the development of interventions more tailored to the phenotype of this subgroup of patients.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/psicologia , Sucesso Acadêmico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Comorbidade , Correlação de Dados , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Tentativa de Suicídio/estatística & dados numéricos , Síndrome de Tourette/epidemiologia , Adulto Jovem
12.
CNS Drugs ; 33(5): 417-430, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30977108

RESUMO

Novel pharmacological treatments are needed for Tourette syndrome. Our goal was to examine the current evidence base and biological rationale for the use of cannabis-derived medications or medications that act on the cannabinoid system in Tourette syndrome. We conducted a comprehensive literature search of PubMed for randomized controlled trials or clinical trials of cannabis-derived medications in Tourette syndrome. Data regarding the population, intervention, safety profile, and outcomes for each trial were extracted and reported and the evidence supporting use of individual cannabis-derived medications was critiqued. There is a strong biological rationale regarding how cannabis-derived medications could affect tic severity. Anecdotal case reports and series have noted that many patients report that their tics improve after using cannabis. However, only two small randomized, placebo-controlled trials of Δ9-tetrahydrocannabinol have been published; these suggested possible benefits of cannabis-derived agents for the treatment of tics. Trials examining other agents active on the cannabinoid system for tic disorders are currently ongoing. Cannabinoid-based treatments are a promising avenue of new research for medications that may help the Tourette syndrome population. However, given the limited research available, the overall efficacy and safety of cannabinoid-based treatments is largely unknown. Further trials are needed to examine dosing, active ingredients, and optimal mode of administration of cannabis-derived compounds, assuming initial trials suggest efficacy. Clinical use for refractory patients should at the very least be restricted to adult populations, given the uncertain efficacy and risk of developmental adverse effects that cannabinoids may have in children. Even in adult populations, cannabis-derived medications are associated with significant issues such as the effects they have on driving safety and the fact that they cause positive urine drug screens that can affect employment.

13.
Front Psychiatry ; 10: 150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30967801

RESUMO

Illness anxiety disorder (IAD, formerly hypochondriasis) is characterized by preoccupation with fear of serious illness despite medical reassurance. IAD is common, debilitating, challenging to treat, and results in high healthcare utilization. Outpatient management of IAD is challenging because patients can compulsively seek reassurance from numerous providers, which interferes with learning more productive coping skills. We present the case of a woman with severe IAD who presented to the emergency room with increasing frequency over several months, despite regular outpatient medical visits and escalating psychiatric care. We made the unusual decision to hospitalize her for IAD for 1 month, in the absence of typical hospitalization criteria. This hospitalization allowed us to consolidate all medical and psychiatric care into a single provider team and train all staff and family to communicate with her in a consistent manner. We successfully treated her by integrating a general cognitive-behavioral therapy (CBT) protocol into medical care and decision-making. In response to her numerous health concerns, we minimized medical work-up, reassurance, and reactive medication changes, and instead used the concerns as opportunities to reinforce the psychotherapy. This approach allowed us to simplify her medication regimen and manage her co-morbid hypertension and vitamin deficiencies. Though inpatient hospitalization is likely infeasible in most cases of IAD, outpatient providers may create similar treatment plans based on the example of our case report, without needing highly specialized expertise. Such a plan would require a straightforward understanding of IAD psychology, which we review here, combined with readily accessible tools including a universal CBT protocol, online CBT courses, and clinical symptom scales. We discuss our approach for responding to health concerns, maintaining therapeutic alliance, integrating CBT principles into patient interactions, and managing medications. Since patients with IAD share health concerns with all providers, staff, and family, we also include our own IAD communication guide, appropriate for a general audience, that demonstrates how to respond in these conversations.

14.
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
15.
Artigo em Inglês | MEDLINE | ID: mdl-30336171

RESUMO

BACKGROUND: Symptom severity in trichotillomania clinical trials is typically rated using the Massachusetts General Hospital Hair Pulling Scale (MGH-HPS) and the National Institute of Mental Health Trichotillomania Severity Scale (NIMH-TSS). There are no universal definitions of treatment response on these scales. The absence of empirically supported definitions of treatment response hampers advances in trichotillomania treatment. METHODS: PubMed and CENTRAL databases were searched for trichotillomania clinical trials. A total of 14 studies were identified and 7 provided adequate data to be included in the meta-analysis (n = 270). Meta-DiSc software was employed. The Youden index and distance to corner were used to determine the optimal cut-point. Response was defined by the Clinical Global Impressions Improvement scale score ≤ 2. RESULTS: The optimal cut-points for identifying response on the MGH-HPS was a 35% percent reduction [Youden Index 0.48; distance to corner 0.37] or a seven-point reduction [Youden Index 0.43; distance to corner 0.40]. The optimal cut-points for the NIMH-TSS was a 50% reduction [Youden Index 0.57; distance to corner 0.34] or a six-point reduction [Youden Index 0.53; distance to corner 0.36]. The optimal cut-points were similar when the analysis was confined to only trichotillomania trials involving adult subjects, but the scales appeared to have improved ability to define treatment response when pediatric subjects were excluded. CONCLUSION: This study provides empirically determined cut-points of treatment response on the MGH-HPS and NIMH-TSS. These data-driven cut-points will benefit future research in trichotillomania by providing definitions of treatment response that can be defined a priori in clinical trials.


Assuntos
Tricotilomania/diagnóstico , Tricotilomania/terapia , Humanos , Resultado do Tratamento
16.
Depress Anxiety ; 36(3): 198-212, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30479005

RESUMO

BACKGROUND: We aimed to examine the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) for anxiety disorders examining overall symptom improvement, likelihood of treatment response, time course of treatment response, individual pharmacological agent, diagnostic indication dose, and tolerability. METHODS: We searched PubMed and Cochrane Central Register of Controlled Trials. We included randomized placebo-controlled clinical trials of SSRIs/SNRIs in adult patients with anxiety disorders that provided data at three or more time points. Extracted data included trial duration, weekly/biweekly anxiety scores for 12 weeks. RESULTS: Meta-analysis included 57 trials (N = 16,056). A linear mixed model analysis based on weekly outcome data suggested that for SNRI a logarithmic model offered the best fit compared to placebo (indicating the greatest incremental improvement from baseline occurred early in treatment); whereas for SSRI a linear model provided the best fit (indicating a similar improvement over the duration of the acute treatment phase). There were no significant differences in efficacy between pharmacological agents within each class or when comparing SSRIs to SNRIs. The greatest treatment benefits were observed for social anxiety disorder for both medication classes. Higher doses of SSRIs, but not SNRIs, were associated with significantly greater symptom improvement and likelihood of treatment response. For both medical classes, higher doses were associated with an increased likelihood of dropout due to side effects. CONCLUSIONS: SSRIs and SNRIs are effective in treating anxiety disorders. Higher doses of SSRIs within the therapeutic range are associated with greater treatment benefit, whereas higher doses of SNRIs are not.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Transtornos de Ansiedade/metabolismo , Humanos , Norepinefrina/metabolismo , Fobia Social/tratamento farmacológico , Fobia Social/metabolismo , Serotonina/metabolismo , Inibidores de Captação de Serotonina/farmacologia , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacologia
17.
Nutr Health ; : 260106018772170, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29921155

RESUMO

While pharmacotherapy and psychosocial interventions are recommended as the primary frontline treatment for attention deficit hyperactivity disorder (ADHD), alternative approaches to managing ADHD are becoming increasingly popular among patients and their families. Supplementation with polyunsaturated fatty acids (PUFAs) is an example of this. PUFA supplementation is not recommended by guidelines for managing ADHD; however, patients may still decide to use it. To provide direction to healthcare professionals (HCPs) managing ADHD, eight international experts in the field of adult and child ADHD came together for the Continuum Education Board: Omega Supplements in ADHD meeting. This commentary summarises the panel's consensus that current evidence suggests PUFA supplementation has a small beneficial effect on behaviour in children with ADHD, and that further high-quality research is needed to clearly evaluate and define its role in the management of ADHD of children, adolescents and adults. The panel concluded that in cases where patients use PUFA supplementation, HCPs should be comfortable explaining the potential gains that they may have and their possible side effects. The panel also concluded HCPs should not reinforce the idea that PUFA supplementation should replace treatment approaches with a more robust evidence base for managing ADHD.

18.
J Child Adolesc Psychopharmacol ; 28(7): 474-484, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29920116

RESUMO

BACKGROUND: Antipsychotic-related weight gain is a common clinically relevant side effect when treating psychotic disorders in pediatric populations, yet few predictors and no moderators of antipsychotic-related weight gain are known. METHODS: The Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) study randomized 119 youths (age 8-19 years) with schizophrenia or schizoaffective disorder to 8 weeks of antipsychotic treatment with molindone, risperidone, or olanzapine and assessed treatment response and side effects. In this secondary analysis, we used multivariable linear regression and receiver operating characteristic analysis to investigate predictors and moderators of weight change and percent weight change from baseline to week 8. RESULTS: Treatment assignment was the most discriminant predictor of weight change [F(2, 66) = 17.00, p < 0.001] and percent weight change [F(2, 66) = 16.85, p < 0.001]. Mean weight gain was 0.74 (standard deviation ±3.51) kg for molindone, 4.13 ± 3.79 kg for risperidone, and 7.29 ± 3.44 kg for olanzapine. After adjusting for treatment assignment, lower pretreatment hemoglobin A1C (HgbA1C) predicted more weight gain [F(1, 55) = 4.71, p = 0.03]. Diagnosis (schizoaffective vs. schizophrenia) moderated weight change [F(2, 63) = 6.02, p = 0.004] and percent weight change [F(2, 63) = 5.26, p = 0.008] such that schizoaffective diagnosis predicted larger weight gain for youths in the risperidone treatment arm. Age, sex, family income, baseline weight, and symptoms neither predicted nor moderated weight change or percent weight change. CONCLUSION: We identified prognostic subgroups and novel risk factors for antipsychotic-related weight gain. We confirmed that antipsychotic choice is extremely important for predicting future weight gain. We also found that younger age did not predict greater weight gain, in contrast to prior studies. Our findings require replication in an independent sample because we did not adjust for multiple comparisons to minimize false negatives. ClinicalTrials.gov Identifier: NCT00053703.


Assuntos
Antipsicóticos/uso terapêutico , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adolescente , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Fatores de Risco , Ganho de Peso
19.
J Affect Disord ; 236: 60-68, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29715610

RESUMO

BACKGROUND: To assess the risk of headache associated with commonly prescribed antidepressant medications and to examine the impact of medication class, pharmacodynamics and dosage on risk of headache. METHODS: We searched PubMed to identify all randomized, double-blind, placebo-controlled trials examining the efficacy of second generation antidepressant medications in the treatment of adults with depression, anxiety or obsessive-compulsive disorders. We used a fixed-effect meta-analysis to examine the pooled risk ratio of headache reported as a side-effect in adults treated with second generation antidepressants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of medication type, class, dosage, indication, and receptor affinity profile on the measured risk of headache. RESULTS: SSRIs were associated with a significantly increased risk of headache (RR = 1.06, 95%CI = 1.00-1.13, z = 2.0, p = 0.045) when compared to placebo. There was no significant difference (test for subgroup differences χ2 = 2.2, df = 1, p = 0.14) in the risk of headache between SSRIs and SNRIs (RR = 0.97, 95%CI = 0.88-1.06, p = 0.63). There was no significant difference in the relative risk of headache with second generation antidepressants based on diagnostic indication, pharmacological properties and dosage of medications. The only antidepressants that were found to be significantly associated with increased risk of headache compared to placebo were bupropion (RR = 1.22, 95%CI = 1.06-1.41, z = 2.73, p = 0.006) and escitalopram (RR = 1.18, 95%CI = 1.01-1.37, z = 2.11, p = 0.04). LIMITATIONS: The small number of studies that examined side effects within fixed-dose trials may have limited the power to examine the association between medication dosing and risk of headache. Additionally, reporting bias could potentially occur non-randomly across agents and therefore effect meta-analysis results. CONCLUSIONS: Headaches reported after the initiation of second generation antidepressant medications are more likely to be coincidental than a treatment-emergent side effect of these medications.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Cefaleia/induzido quimicamente , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Adulto , Bupropiona/efeitos adversos , Citalopram/efeitos adversos , Método Duplo-Cego , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos
20.
J Child Adolesc Psychopharmacol ; 28(6): 368-378, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29741917

RESUMO

OBJECTIVE: School refusal is an important pediatric problem with significant negative short- and long-term outcomes. Specific psychosocial treatments appear effective in reducing school refusal, but many children do not respond to these treatments. Although systematic reviews have examined the efficacy of psychological interventions for school refusal, no systematic reviews on pharmacological interventions exist. METHODS: We conducted a comprehensive literature search of MEDLINE, PsycINFO, Scopus, and Embase for randomized controlled trials (RCTs) or quasi-experimental pharmacologic trials in children and adolescents with school refusal reported in English or Spanish until July 1, 2017. Two authors screened study titles and abstracts for eligibility. Data regarding the population, intervention, comparison, and outcomes for each trial were extracted and reported. Effect sizes for school attendance are presented. RESULTS: The search identified 6 articles, including 7 trials (6 RCTs and 1 open label) and 306 youths. Pharmacologic treatments investigated for school refusal included antidepressants (imipramine, clomipramine, and fluoxetine) and benzodiazepines (alprazolam). All pharmacotherapies studied had pretreatment to posttreatment improvements on school refusal, depression, and anxiety symptoms. However, included trials were severely underpowered and did not demonstrate significant improvement compared to placebo. CONCLUSIONS: Data regarding pharmacological treatments for school refusal are sparse. Most trials in this area were conducted before development of newer antidepressants, were underpowered, and have significant methodological limitations that are characteristic of the time in which they were conducted. This systematic review highlights the need for more trials with newer pharmacologic agents, larger sample sizes, and improved systematic assessments of school refusal and comorbidities. School refusal represents an important functional outcome for many children, especially those with anxiety and depression. Future pharmacologic studies of anxiety and depression in children may benefit from incorporating specific school refusal measures as secondary outcomes.


Assuntos
Antidepressivos/uso terapêutico , Benzodiazepinas/uso terapêutico , Recusa de Participação/psicologia , Instituições Acadêmicas , Estudantes/psicologia , Adolescente , Comportamento do Adolescente/psicologia , Ansiedade/tratamento farmacológico , Criança , Comportamento Infantil/psicologia , Depressão/tratamento farmacológico , Humanos
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