Comparing the evidential strength for psychotropic drugs: a Bayesian meta-analysis

Abstract Approval and prescription of psychotropic drugs should be informed by the strength of evidence for efficacy. Using a Bayesian framework, we examined (1) whether psychotropic drugs are supported by substantial evidence (at the time of approval by the Food and Drug Administration), and (2) whether there are systematic differences across drug groups. Data from short-term, placebo-controlled phase II/III clinical trials for 15 antipsychotics, 16 antidepressants for depression, nine antidepressants for anxiety, and 20 drugs for attention deficit hyperactivity disorder (ADHD) were extracted from FDA reviews. Bayesian model-averaged meta-analysis was performed and strength of evidence was quantified (i.e. BFBMA). Strength of evidence and trialling varied between drugs. Median evidential strength was extreme for ADHD medication (BFBMA = 1820.4), moderate for antipsychotics (BFBMA = 365.4), and considerably lower and more frequently classified as weak or moderate for antidepressants for depression (BFBMA = 94.2) and anxiety (BFBMA = 49.8). Varying median effect sizes (ESschizophrenia = 0.45, ESdepression = 0.30, ESanxiety = 0.37, ESADHD = 0.72), sample sizes (Nschizophrenia = 324, Ndepression = 218, Nanxiety = 254, NADHD = 189.5), and numbers of trials (kschizophrenia = 3, kdepression = 5.5, kanxiety = 3, kADHD = 2) might account for differences. Although most drugs were supported by strong evidence at the time of approval, some only had moderate or ambiguous evidence. These results show the need for more systematic quantification and classification of statistical evidence for psychotropic drugs. Evidential strength should be communicated transparently and clearly towards clinical decision makers.

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Comparing the Evidential Strength for Psychotropic Drugs: A Bayesian Meta-Analysis

10.1101/2021.03.04.21252887 ◽

2021 ◽

Author(s):

Merle-Marie Pittelkow ◽

Ymkje Anna de Vries ◽

Rei Monden ◽

Jojanneke A. Bastiaansen ◽

Don van Ravenzwaaij

Keyword(s):

Psychotropic Drugs ◽

Bayes Factor ◽

Meta Analysis ◽

Drug Approval ◽

Clinical Decision ◽

Marketing Approval ◽

Strength Of Evidence ◽

Fda Approval ◽

Formal Policy

AbstractObjectiveApproval and prescription of drugs should be informed by the strength of evidence for efficacy. While there is no formal policy towards different standards for drug approval, the typical strength of evidence might differ for different psychotropic drug groups. Using a Bayesian framework, we examine (1) whether psychotropic drugs are supported by substantial evidence (at the time of Food and Drug Administration [FDA] approval), and (2) whether there are systematic differences across drug groups.MethodsData from short-term, placebo-controlled phase II/III clinical trials for 15 antipsychotics, 16 antidepressants for depression, nine antidepressants for anxiety, and 20 drugs for ADHD were extracted from FDA reviews evaluating efficacy prior to marketing approval. Bayesian model-averaged meta-analysis was performed and strength of evidence was quantified with the Bayes factor (BFBMA).ResultsWe observed substantial variation in strength of evidence and trialling between approved psychotropic drugs: Median evidential strength was extremely strong for ADHD medication (BFBMA = 1820.4), but considerably lower and more frequently classified as weak or moderate for antidepressants for both depression (BFBMA = 94.2) and anxiety (BFBMA = 49.8). Differences might be accounted for by varying median effect sizes (schizophrenia: ESBMA = 0.45, depression: ESBMA = 0.30, anxiety: ESBMA = 0.37, ADHD: ESBMA = 0.72), sample sizes (schizophrenia: N = 324, depression: N = 218, anxiety: N = 254, ADHD: N = 189.5), and numbers of trials (schizophrenia: Nr = 3, depression: Nr = 5.5, anxiety: Nr = 3, ADHD: Nr = 2).LimitationsThe analysis only included pre-marketing studies.ConclusionEvidential strength varied across drug groups: Although most psychotropic drugs were supported by strong evidence at the time of approval, some drugs only had moderate or even ambiguous evidence. These results show the need for more systematic quantification and classification of statistical evidence for psychotropic drugs, and for transparent and clear communication of evidential strength toward clinical decision makers.Registrationhttps://osf.io/5jn2d

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Effectiveness of COVID-19 Vaccines against Delta (B.1.617.2) Variant: A Systematic Review and Meta-Analysis of Clinical Studies

Vaccines ◽

10.3390/vaccines10010023 ◽

2021 ◽

Vol 10 (1) ◽

pp. 23

Author(s):

Ali Pormohammad ◽

Mohammad Zarei ◽

Saied Ghorbani ◽

Mehdi Mohammadi ◽

Saeideh Aghayari Sheikh Neshin ◽

...

Keyword(s):

Meta Analysis ◽

Severe Infection ◽

Vaccination Rate ◽

Decision Makers ◽

Morbidity Rate ◽

Short Term ◽

Mortality And Morbidity ◽

Public Health Decision ◽

Health Decision

The high transmissibility, mortality, and morbidity rate of the SARS-CoV-2 Delta (B.1.617.2) variant have raised concerns regarding vaccine effectiveness (VE). To address this issue, all publications relevant to the effectiveness of vaccines against the Delta variant were searched in the Web of Science, Scopus, EMBASE, and Medline (via PubMed) databases up to 15 October 2021. A total of 15 studies (36 datasets) were included in the meta-analysis. After the first dose, the VE against the Delta variant for each vaccine was 0.567 (95% CI 0.520–0.613) for Pfizer-BioNTech, 0.72 (95% CI 0.589–0.822) for Moderna, 0.44 (95% CI 0.301–0.588) for AstraZeneca, and 0.138 (95% CI 0.076–0.237) for CoronaVac. Meta-analysis of 2,375,957 vaccinated cases showed that the Pfizer-BioNTech vaccine had the highest VE against the infection after the second dose, at 0.837 (95% CI 0.672–0.928), and third dose, at 0.972 (95% CI 0.96–0.978), as well as the highest VE for the prevention of severe infection or death, at 0.985 (95% CI 0.95–0.99), amongst all COVID-19 vaccines. The short-term effectiveness of vaccines, especially mRNA-based vaccines, for the prevention of the Delta variant infection, hospitalization, severe infection, and death is supported by this study. Limitations include a lack of long-term efficacy data, and under-reporting of COVID-19 infection cases in observational studies, which has the potential to falsely skew VE rates. Overall, this study supports the decisions by public health decision makers to promote the population vaccination rate to control the Delta variant infection and the emergence of further variants.

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Disentangling ADHD's Presentation-Related Decision-Making—A Meta-Analytic Approach on Predominant Presentations

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.519840 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marcel Schulze ◽

David Coghill ◽

Silke Lux ◽

Alexandra Philipsen

Keyword(s):

Decision Making ◽

Attention Deficit Hyperactivity Disorder ◽

Reinforcement Learning ◽

Risk Taking ◽

Attention Deficit ◽

Meta Analysis ◽

Analytic Approach ◽

Effect Sizes ◽

Hyperactivity Disorder ◽

The Relationship

Background: Deficient decision-making (DM) in attention deficit/hyperactivity disorder (ADHD) is marked by altered reward sensitivity, higher risk taking, and aberrant reinforcement learning. Previous meta-analysis aggregate findings for the ADHD combined presentation (ADHD-C) mostly, while the ADHD predominantly inattentive presentation (ADHD-I) and the predominantly hyperactive/impulsive presentation (ADHD-H) were not disentangled. The objectives of the current meta-analysis were to aggregate findings from DM for each presentation separately.Methods: A comprehensive literature search of the PubMed (Medline) and Web of Science Database took place using the keywords “ADHD,” “attention-deficit/hyperactivity disorder,” “decision-making,” “risk-taking,” “reinforcement learning,” and “risky.” Random-effects models based on correlational effect-sizes were conducted. Heterogeneity analysis and sensitivity/outlier analysis were performed, and publication biases were assessed with funnel-plots and the egger intercept.Results: Of 1,240 candidate articles, seven fulfilled criteria for analysis of ADHD-C (N = 193), seven for ADHD-I (N = 256), and eight for ADHD-H (N = 231). Moderate effect-size were found for ADHD-C (r = 0.34; p = 0.0001; 95% CI = [0.19, 0.49]). Small effect-sizes were found for ADHD-I (r = 0.09; p = 0.0001; 95% CI = [0.008, 0.25]) and for ADHD-H (r = 0.1; p = 0.0001; 95% CI = [−0.012, 0.32]). Heterogeneity was moderate for ADHD-H. Sensitivity analyses show robustness of the analysis, and no outliers were detected. No publication bias was evident.Conclusion: This is the first study that uses a meta-analytic approach to investigate the relationship between the different presentations of ADHD separately. These findings provide first evidence of lesser pronounced impairment in DM for ADHD-I and ADHD-I compared to ADHD-C. While the exact factors remain elusive, the current study can be considered as a starting point to reveal the relationship of ADHD presentations and DM more detailed.

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Harms of Antipsychotics in Children and Young Adults: A Systematic Review Update

The Canadian Journal of Psychiatry ◽

10.1177/0706743718779950 ◽

2018 ◽

Vol 63 (10) ◽

pp. 661-678 ◽

Cited By ~ 6

Author(s):

Jennifer Pillay ◽

Khrista Boylan ◽

Amanda Newton ◽

Lisa Hartling ◽

Ben Vandermeer ◽

...

Keyword(s):

Systematic Review ◽

Young Adults ◽

Weight Gain ◽

Meta Analysis ◽

Extrapyramidal Symptoms ◽

Short Term ◽

Strength Of Evidence ◽

Cholesterol Levels ◽

Children And Young Adults ◽

Meta Analyses

Objective: To update and extend our previous systematic review on first- (FGAs) and second-generation antipsychotics (SGAs) for treatment of psychiatric and behavioral conditions in children, adolescents, and young adults (aged ≤24 years). This article focuses on the evidence for harms. Method: We searched (to April 2016) 8 databases, gray literature, trial registries, Food and Drug Administration reports, and reference lists. Two reviewers conducted study screening and selection independently, with consensus for selection. One reviewer extracted and another verified all data; 2 reviewers independently assessed risk of bias. We conducted meta-analyses when appropriate and network meta-analysis across conditions for changes in body composition. Two reviewers reached consensus for ratings on the strength of evidence for prespecified outcomes. Results: A total of 135 studies (95 trials and 40 observational) were included, and 126 reported on harms. FGAs caused slightly less weight gain and more extrapyramidal symptoms than SGAs. SGAs as a class caused adverse effects, including weight gain, high triglyceride levels, extrapyramidal symptoms, sedation, and somnolence. They appeared to increase the risk for high cholesterol levels and type 2 diabetes. Many outcomes for individual drug comparisons were of low or insufficient strength of evidence. Olanzapine caused more short-term gains in weight and body mass index than several other SGAs. The dose of SGAs may not make a difference over the short term for some outcomes. Conclusions: Clinicians need to weigh carefully the benefit-to-harm ratio when using antipsychotics, especially when treatment alternatives exist. More evidence is needed on the comparative harms between antipsychotics over the longer term.

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The Effects of Corpus Use on Second Language Vocabulary Learning: A Multilevel Meta-analysis

Applied Linguistics ◽

10.1093/applin/amy012 ◽

2018 ◽

Vol 40 (5) ◽

pp. 721-753 ◽

Cited By ~ 26

Author(s):

Hansol Lee ◽

Mark Warschauer ◽

Jang Ho Lee

Keyword(s):

Second Language ◽

Vocabulary Learning ◽

Meta Analysis ◽

Vocabulary Knowledge ◽

Effect Sizes ◽

Short Term ◽

Different Dimensions ◽

L2 Vocabulary

Abstract This study investigates the effects of corpus use on second language (L2) vocabulary learning as well as the influence of moderators on effectiveness. Based on 29 studies representing 38 unique samples, all of which met several criteria for inclusion (e.g. with control groups), we found an overall positive medium-sized effect of corpus use on L2 vocabulary learning for both short-term (77 posttest effect sizes; Hedges’ g = 0.74, SE = 0.09, p < .001) and long-term periods (34 follow-up effect sizes; Hedges’ g = 0.64, SE = 0.17, p < .001). Furthermore, large variation in adjusted mean effect sizes across moderators was revealed. Above all, for the different dimensions of L2 vocabulary knowledge, in-depth knowledge (i.e. referential meanings as well as syntactic features of vocabulary) was associated with a large effect size. Moreover, the results revealed that learners’ L2 proficiency and several features of corpus use (i.e. interaction types, corpus types, training, and duration) influence the magnitude of the effectiveness of corpus use in improving L2 vocabulary learning.

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Sensory Recruitment in Visual Short-Term Memory: A Systematic Review and Meta-Analysis of Sensory Visual Cortex Interference Using Transcranial Magnetic Stimulation

10.31222/osf.io/hxu84 ◽

2021 ◽

Author(s):

Phivos Phylactou ◽

Artemis Traikapi ◽

Marietta Papadatou-Pastou ◽

Nikos Konstantinou

Keyword(s):

Visual Cortex ◽

Visual Information ◽

Short Term Memory ◽

Meta Analysis ◽

Maintenance Phase ◽

Brain Network ◽

Effect Sizes ◽

Short Term ◽

Term Memory ◽

Meta Analyses

Visual short-term memory (VSTM) links perception with higher cognitive processes by maintaining visual information that is absent from the environment. Yet, it remains unclear if sensory visual cortex is a necessary component of the brain network that underlies short-term maintenance of visual information. Previous reviews remain inconclusive and open to interpretation. Here, we aimed to systematically identify and review studies that have investigated the role of the sensory visual cortex in VSTM using transcranial magnetic stimulation (TMS), a method that allows exploration of causal relationships, and to quantitatively explore the effect of TMS interference on the sensory visual cortex during VSTM using meta-analytic methodology. Thirteen studies were identified and qualitatively reviewed. Out of those, seven studies provided sufficient statistical data for meta-analysis and yielded a total of 30 effect sizes, which were included in the meta-analyses. Two meta-analyses were conducted, one regarding the encoding phase of VSTM (19 effect sizes), and one regarding the maintenance phase of VSTM (11 effect sizes). The results from the systematic review and the two meta-analyses indicate that the sensory visual cortex is likely involved in both the encoding and maintenance phase of VSTM. In some cases, evidence did not show significant effects of TMS, however, this is suggested to be due to low memory load or low perceptual task demands. Overall, these findings support the idea that sensory visual areas are part of the brain network responsible for successfully maintaining information in short-term memory when no physical stimulus is present in the environment.

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Invited Commentary: The Disillusionment of Developmental Origins of Health and Disease (DOHaD) Epidemiology

American Journal of Epidemiology ◽

10.1093/aje/kwz214 ◽

2019 ◽

Vol 189 (1) ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Stephen E Gilman ◽

Mady Hornig

Keyword(s):

Observational Studies ◽

Meta Analysis ◽

Autism Spectrum ◽

Developmental Origins ◽

Short Term ◽

Hyperactivity Disorder ◽

Health And Disease ◽

The Individual ◽

Meta Analyses

Abstract The developmental origins of health and disease (DOHaD) model promises a greater understanding of early development but has left unresolved the balance of risks and benefits to offspring of medication use during pregnancy. Masarwa et al. (Am J Epidemiol. 2018;187(8):1817–1827) conducted a meta-analysis of the association between in utero acetaminophen exposure and risks of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). A challenge of meta-analyzing results from observational studies is that summary measures of risk do not correspond to well-defined interventions when the individual studies adjusted for different covariate sets, which was the case here. This challenge limits the usefulness of observational meta-analyses for inferences about etiology and treatment planning. With that limitation understood, Masarwa et al. reported a 20%–30% higher risk of ADHD and ASD following prenatal acetaminophen exposure. Surprisingly, most of the original studies did not report diagnoses of ADHD or ASD. As a result, their summary estimates of risk are not informative about children’s likelihood of ADHD and ASD diagnoses. The long-term promise of DOHaD remains hopeful, but more effort is needed in the short-term to critically evaluate observational studies suggesting risks associated with medications used to treat conditions during pregnancy that might have adverse consequences for a developing fetus.

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Long-term psychodynamic psychotherapy in complex mental disorders: update of a meta-analysis

The British Journal of Psychiatry ◽

10.1192/bjp.bp.110.082776 ◽

2011 ◽

Vol 199 (1) ◽

pp. 15-22 ◽

Cited By ~ 174

Author(s):

Falk Leichsenring ◽

Sven Rabung

Keyword(s):

Mental Disorders ◽

Psychodynamic Psychotherapy ◽

Meta Analysis ◽

Dose Effect ◽

Effect Sizes ◽

Inclusion Criteria ◽

Comparative Efficacy ◽

Short Term ◽

Prospective Design

BackgroundDose–effect relationship data suggest that short-term psychotherapy is insufficient for many patients with chronic distress or personality disorders (complex mental disorders).AimsTo examine the comparative efficacy of long-term psychodynamic psychotherapy (LTPP) in complex mental disorders.MethodWe conducted a meta-analysis of controlled trials of LTPP fulfilling the following inclusion criteria: therapy lasting for at least a year or 50 sessions; active comparison conditions; prospective design; reliable and valid outcome measures; treatments terminated. Ten studies with 971 patients were included.ResultsBetween-group effect sizes in favour of LTPP compared with less intensive (lower dose) forms of psychotherapy ranged between 0.44 and 0.68.ConclusionsResults suggest that LTPP is superior to less intensive forms of psychotherapy in complex mental disorders. Further research on long-term psychotherapy is needed, not only for psychodynamic psychotherapy, but also for other therapies.

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The efficacy of cognitive behavioral therapy for Chinese people: A meta-analysis

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867417741555 ◽

2017 ◽

Vol 52 (7) ◽

pp. 620-637 ◽

Cited By ~ 8

Author(s):

Ting Kin Ng ◽

Daniel Fu Keung Wong

Keyword(s):

Cognitive Behavioral Therapy ◽

Literature Search ◽

Primary Outcome ◽

Behavioral Therapy ◽

Meta Analysis ◽

Term Effect ◽

Cognitive Behavioral ◽

Effect Sizes ◽

Chinese People ◽

Short Term

Objective: Over the past decade, cognitive behavioral therapy has been applied to an increasingly wider range of disorders and problems in Chinese societies. However, no meta-analysis has been conducted to synthesize the studies on cognitive behavioral therapy for Chinese clients. The purpose of this meta-analytic study was to examine the overall efficacy of cognitive behavioral therapy for Chinese people. Method: A literature search was conducted using electronic databases, including Web of Science, PsycINFO and PubMed. Pooled mean effect sizes were calculated using the random-effects model. Results: The literature search identified 55 studies with 6763 Chinese participants. The overall short-term effect of cognitive behavioral therapy on the primary outcome was medium in size. Effect sizes were medium for anxiety, depression/well-being and caregiving stress and small for psychotic symptoms and addictive behaviors. The effects of cognitive behavioral therapy on process variables, dysfunctional thoughts and coping, were in the small range. The overall longer-term effect of cognitive behavioral therapy on the primary outcome was medium in size. Moderator analyses showed that the short-term effect was stronger for culturally adapted cognitive behavioral therapy than for unadapted cognitive behavioral therapy. Type of primary outcome, type of control group, recruitment method, study design, the format of delivery and region were found to moderate the efficacy of cognitive behavioral therapy. Conclusion: The findings of this study provide evidence for the overall efficacy of cognitive behavioral therapy for Chinese people and the benefit of cultural adaptation of cognitive behavioral therapy to Chinese culture.

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Cultural Sexism Moderates Efficacy of Psychotherapy: Results from a Spatial Meta-Analysis

10.31219/osf.io/n9x4u ◽

2021 ◽

Cited By ~ 1

Author(s):

Maggi Price ◽

Sarah McKetta ◽

John R. Weisz ◽

Jessie VanNess Ford ◽

Micah Lattanner ◽

...

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Meta Analysis ◽

State Level ◽

Effect Sizes ◽

Gender Attitudes ◽

Controlled Trials ◽

County Level ◽

Hyperactivity Disorder ◽

Randomized Controlled ◽

Youth Psychotherapy

We examined whether cultural sexism (county- and state-level gender attitudes) moderates the efficacy of psychotherapies by re-analyzing data from a previous meta-analysis of randomized controlled trials of youth psychotherapy for the most commonly targeted problems (depression, anxiety, conduct, attention-deficit hyperactivity disorder; 2,698 effect sizes (ESs);314 studies; N=19,739; ages 4-18). Higher cultural sexism was associated with lower ESs for studies with ³50% girls; this association became stronger as the proportion of girls in thesamples increased. Cultural sexism was unrelated to ESs for studies with >50% boys. An interaction between state- and county-level sexism revealed that psychotherapies were mostbeneficial when they were conducted in states and counties with the lowest cultural sexism. Thus, the context in which psychotherapies are delivered is associated with psychotherapy efficacy for girls.

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