Search

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies ( n = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13-83.76) when compared to placebo groups (71.21%, 67.00-75.09). Nausea was the most common adverse event (25.71%, CI 23.96-27.54), while weight change was the least common (3.56%, 1.68-7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance.

Question: Randomised controlled trials assessing treatments for anxiety, obsessive-compulsive and stress-related disorders often present high placebo response rates in placebo groups. Understanding the placebo response is essential in accurately estimating the benefits of pharmacological agents; nevertheless, no studies have evaluated the placebo response across these disorders using a lifespan approach., Study Selection and Analysis: We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies and international registers from inception to 9 September 2022. The primary outcome was the aggregate measure of internalising symptoms of participants in the placebo arms of randomised controlled trials designed to assess the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) in individuals diagnosed with anxiety, obsessive-compulsive or stress-related disorders. The secondary outcomes were placebo response and remission rates. Data were analysed through a three-level meta-analysis., Findings: We analysed 366 outcome measures from 135 studies (n=12 583). We found a large overall placebo response (standardised mean difference (SMD)=-1.11, 95% CI -1.22 to -1.00). The average response and remission rates in placebo groups were 37% and 24%, respectively. Larger placebo response was associated with a diagnosis of generalised anxiety disorder and post-traumatic stress disorder, when compared with panic, social anxiety and obsessive-compulsive disorder (SMD range, 0.40-0.49), and with absence of a placebo lead-in period (SMD=0.44, 95% CI 0.10 to 0.78). No significant differences were found in placebo response across age groups. We found substantial heterogeneity and moderate risk of bias., Conclusions: Placebo response is substantial in SSRI and SNRI trials for anxiety, obsessive-compulsive and stress-related disorders. Clinicians and researchers should accurately interpret the benefits of pharmacological agents in contrast to placebo response., Prospero Registration Number: CRD42017069090., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. Published by BMJ.)

Background: Anxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis., Methods and Findings: We searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies' databases. No restriction was made regarding comorbidities with any other mental disorder, participants' age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration's risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). All medications were more effective than placebo for the aggregate measure of internalizing symptoms (SMD -0.56, 95% CI -0.62 to -0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials., Conclusions: In this study, we observed that all SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This three-level network meta-analysis contributes to an ongoing discussion about the true benefit of antidepressants with robust evidence, considering the significantly larger quantity of data and higher statistical power when compared to previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aims of this study were (1) to assess obsessive-compulsive symptoms (OCS) dimensionally in a school-aged community sample and to correlate them with clinical and demographical variables; (2) to determine a subgroup with significant OCS ("at-risk for OCD") using the Child Behavior Checklist (CBCL-OCS) and (3) to compare it with the rest of the sample; (4) To review the CBCL-OCS subscale properties as a screening tool for pediatric OCD., Methods: Data from the Brazilian High Risk Cohort were analyzed. The presence and severity of OCS were assessed through the CBCL-OCS subscale. DSM-IV psychiatric diagnoses were obtained by the Developmental and Well-Being Assessment. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire, the Youth Strengths Inventory, and the CBCL internalizing and externalizing behavior subscales., Results: A total of 2512 (mean age: 8.86 ± 1.84 years; 55.0% male) children were included. Moderate correlations were found between OCS severity and functional impairment (r = 0.36, p < 0.001). Children with higher levels of OCS had higher rates of psychiatric comorbidity and behavioral problems (p < 0.001). A score of 5 or higher in the CBCL-OCS scale determined an "at-risk for OCD" subgroup, comprising 9.7% of the sample (n = 244), with behavioral patterns and psychiatric comorbidities (e.g., tics [odds ratios, OR = 6.41, p < 0.001]), anxiety disorders grouped [OR = 3.68, p < 0.001] and depressive disorders [OR = 3.0, p < 0.001] very similar to those described in OCD. Sensitivity, specificity, positive predictive value, and negative predictive value of the CBCL-OCS for OCD diagnosis were, respectively, 48%, 91.5%; 15.1%, and 98.2%., Conclusions: The dimensional approach suggests that the presence of OCS in children is associated with higher rates of comorbidity, behavioral problems, and impairment. The "at-risk for OCD" group defined by the CBCL revealed a group of patients phenotypically similar to full blown OCD.

Pediatric-onset obsessive-compulsive disorder (OCD) is underdiagnosed, and many affected children are untreated. The present study seeks to evaluate the presence and the clinical impact of OCD and obsessive-compulsive symptoms (OCS) in a large sample of school-age children. In Phase I, we performed an initial screening using the Family History Screen (FHS). In Phase II, we identified an "at-risk" sample, as well as a randomly selected group of children. A total of 2,512 children (6-12 years old) were assessed using the FHS, the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), and the Child Behavior Checklist (CBCL). Data analyses included descriptive and multivariate analytical techniques. 2,512 children (mean age: 8.86 ± 1.84 years; 55.0% male) were categorized into one of the three diagnostic groups: OCD (n = 77), OCS (n = 488), and unaffected controls (n = 1,947). There were no significant socio-demographic differences (age, gender, socioeconomic status) across groups. The OCS group resembled the OCD on overall impairment, including school problems and delinquent behaviors. However, the OCD group did have significantly higher rates of several comorbid psychiatric disorders, including separation anxiety, generalized anxiety, and major depressive disorder, than OCS or unaffected controls. Moreover, the OCD group also scored higher than the SDQ, as well as on each of CBCL items rated by the parent. Our findings suggest that there is a psychopathological continuum between OCS and OCD in school-aged children. The presence of OCS is associated with functional impairment, which needs further investigation in longitudinal studies.

Background: Obsessive-compulsive disorder can be expressed as four potentially overlapping obsessive-compulsive symptom (OCS) dimensions (OCSD) ("symmetry/ordering", "contamination/cleaning", "aggressive/sexual/religious" and "collecting/hoarding"). In clinical samples, some dimensions are more familial and associated with increased psychiatric comorbidity and malfunctioning. However, data concerning OCS and OCSD are scarce in non-clinical samples, particularly among children. The present study aims to estimate: (1) the prevalence and sex/age distribution of OCS/OCSD in a community-based sample of schoolchildren; (2) the association between OCS and additional clinical factors; and (3) the degree of familial aggregation of OCS/OCSD., Methods: OCS and OCSD were evaluated in 9937 Brazilian school-children (6-12 years-old) and their biological relatives using the Family History Screen. Data analyses included gradient estimated equations and post-hoc tests., Results: We included data on 9937 index-children, 3305 siblings (13-18 years-old), and 16,218 parents. Biological mothers were the informants in 87.6% of the interviews. OCS were present in 14.7% of the index-children; 15.6% of their siblings; 34.6% of their mothers and 12.1% of their fathers. The prevalence of OCS and each of the OCSD gradually increased from ages 6 to 12 years. Overall, OCS in children were associated with the presence of other psychiatric symptoms, as well as behavioral/school impairment. OCS and each of the four OCSD aggregated significantly within families., Conclusions: OCS are prevalent and associated with psychiatric symptoms and clinical impairment among school-aged children. OCSD aggregate within families in a dimension-specific fashion. These findings suggest a natural continuum between OCS and OCD with regard to their dimensional character., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to assess whether the results obtained with 12 sessions of cognitive-behavioral group therapy with obsessive-compulsive patients were maintained after two years, and whether the degree of symptom remission was associated with relapse., Method: Forty-two patients were followed. The severity of symptoms was measured at the end of cognitive-behavioral group therapy and at 18 and 24 months of follow-up. The assessment scales used were the Yale-Brown Obsessive-Compulsive Scale, Clinical Global Impression, Beck Depression Inventory, and Beck Anxiety Inventory., Results: The reduction in symptom severity observed at the end of treatment was maintained during the two-year follow-up period (F = 57.881; p < 0.001). At the end of the treatment, 9 (21.4%) patients presented full remission, 22 (52.4%) presented partial remission, and 11 (26.2%) had unchanged scores in the Yale-Brown Obsessive-Compulsive Scale. After two years, 13 patients (31.0%) presented full remission, 20 (47.6%) had partial remission, and 9 (21.4%) had unchanged Yale-Brown Obsessive-Compulsive Scale scores. The full remission of symptoms at the end of the treatment was a protective factor against relapse (chi2 = 4,962; df = 1; p = 0.026)., Conclusion: Our findings underscore the importance of attaining full remission of obsessive-compulsive symptoms during treatment and the need for new therapeutic strategies to achieve this.

Background: Cognitive-behavioral group therapy (CBGT) and serotonin reuptake inhibitors have proven efficacy in reducing symptoms of obsessive-compulsive disorder (OCD). There is no consensus about which of these forms of treatment is more effective. This study was conducted to evaluate the efficacy of CBGT as compared to that of sertraline in reducing OCD symptoms., Method: Fifty-six outpatients with an OCD diagnosis, according to DSM-IV criteria, participated in the randomized clinical trial: 28 took 100 mg/day of sertraline and 28 underwent CBGT for 12 weeks. Efficacy of treatments was rated according to the reduction in scores on the Yale-Brown Obsessive Compulsive Scale (YBOCS) and the Clinical Global Impressions-Severity of Illness scale. The trial was performed in 4 successive periods from March 2002 to December 2003., Results: Both treatments were effective, although patients treated with CBGT obtained a mean YBOCS reduction of symptoms of 44%, while those treated with sertraline obtained only a 28% reduction (p = .033). Cognitive-behavioral group therapy was also significantly more effective in reducing the intensity of compulsions (p = .030). Further, 8 patients (32%) treated with CBGT presented a complete remission of OCD symptoms (YBOCS score < or = 8) as compared to only 1 patient (4%) among those who received sertraline (p = .023)., Conclusion: Cognitive-behavioral group therapy and sertraline have shown to be effective in reducing OCD symptoms. Nevertheless, the rate of symptom reduction, intensity reduction of compulsions, and percentage of patients who obtained full remission were significantly higher in patients treated with CBGT.

Objective: The aim of this study was to evaluate the results of cognitive-behavioral group therapy (CBGT) for obsessive-compulsive disorder (OCD) over a 1-year follow-up period., Method: Forty-two OCD patients, who completed 12 sessions of CBGT, were followed for 1 year. Measures of the severity of symptoms were obtained at the end of the acute treatment and at 3, 6, and 12 months post-treatment using the Yale-Brown obsessive-compulsive scale (Y-BOCS) and the clinical global impression (CGI)., Results: The reduction in the severity of symptoms observed at the end of the treatment was maintained during 1 year (F2,41=1.1; P=0.342). Eleven patients (35.5%) relapsed in the follow-up period. The intensity of improvement (log rank=12.97, GL=1, P=0.0003) and full remission (log rank=6.17; GL=1; P=0.001) were strong predictors for non-relapsing., Conclusion: The CBGT is an effective treatment for OCD and its results are maintained for 1 year. However, further long-term randomized controlled trials are needed in order to confirm this finding., (Copyright (c) 2005 Blackwell Munksgaard)