Ifigeneia Mavranezouli

Psychological and pharmacological interventions for social anxiety disorder in adults: a systematic review and network meta-analysis

Summary Background Social anxiety disorder—a chronic and naturally unremitting disease that causes substantial impairment—can be treated with pharmacological, psychological, and self-help interventions. We aimed to compare these interventions and to identify which are most effective for the acute treatment of social anxiety disorder in adults. Methods We did a systematic review and network meta-analysis of interventions for adults with social anxiety disorder, identified from published and unpublished sources between 1988 and Sept 13, 2013. We analysed interventions by class and individually. Outcomes were validated measures of social anxiety, reported as standardised mean differences (SMDs) compared with a waitlist reference. This study is registered with PROSPERO, number CRD42012003146. Findings We included 101 trials (13 164 participants) of 41 interventions or control conditions (17 classes) in the analyses. Classes of pharmacological interventions that had greater effects on outcomes compared with waitlist were monoamine oxidase inhibitors (SMD −1·01, 95% credible interval [CrI] −1·56 to −0·45), benzodiazepines (−0·96, −1·56 to −0·36), selective serotonin-reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors (SSRIs and SNRIs; −0·91, −1·23 to −0·60), and anticonvulsants (−0·81, −1·36 to −0·28). Compared with waitlist, efficacious classes of psychological interventions were individual cognitive–behavioural therapy (CBT; SMD −1·19, 95% CrI −1·56 to −0·81), group CBT (−0·92, −1·33 to −0·51), exposure and social skills (−0·86, −1·42 to −0·29), self-help with support (−0·86, −1·36 to −0·36), self-help without support (−0·75, −1·25 to −0·26), and psychodynamic psychotherapy (−0·62, −0·93 to −0·31). Individual CBT compared with psychological placebo (SMD −0·56, 95% CrI −1·00 to −0·11), and SSRIs and SNRIs compared with pill placebo (−0·44, −0·67 to −0·22) were the only classes of interventions that had greater effects on outcomes than appropriate placebo. Individual CBT also had a greater effect than psychodynamic psychotherapy (SMD −0·56, 95% CrI −1·03 to −0·11) and interpersonal psychotherapy, mindfulness, and supportive therapy (−0·82, −1·41 to −0·24). Interpretation Individual CBT (which other studies have shown to have a lower risk of side-effects than pharmacotherapy) is associated with large effect sizes. Thus, it should be regarded as the best intervention for the initial treatment of social anxiety disorder. For individuals who decline psychological intervention, SSRIs show the most consistent evidence of benefit. Funding National Institute for Health and Care Excellence.

Network Meta-Analysis with Competing Risk Outcomes

BACKGROUND Cost-effectiveness analysis often requires information on the effectiveness of interventions on multiple outcomes, and commonly these take the form of competing risks. Nevertheless, methods for synthesis of randomized controlled trials with competing risk outcomes are limited. OBJECTIVE The aim of this study was to develop and illustrate flexible evidence synthesis methods for trials reporting competing risk results, which allow for studies with different follow-up times, and that take account of the statistical dependencies between outcomes, regardless of the number of outcomes and treatments. METHODS We propose a competing risk meta-analysis based on hazards, rather than probabilities, estimated in a Bayesian Markov chain Monte Carlo (MCMC) framework using WinBUGS software. Our approach builds on existing work on mixed treatment comparison (network) meta-analysis, which can be applied to any number of treatments, and any number of competing outcomes, and to data sets with varying follow-up times. We show how a fixed effect model can be estimated, and two random treatment effect models with alternative structures for between-trial variation. We suggest methods for choosing between these alternative models. RESULTS We illustrate the methods by applying them to a data set involving 17 trials comparing nine antipsychotic treatments for schizophrenia including placebo, on three competing outcomes: relapse, discontinuation because of intolerable side effects, and discontinuation for other reasons. CONCLUSIONS Bayesian MCMC provides a flexible framework for synthesis of competing risk outcomes with multiple treatments, particularly suitable for embedding within probabilistic cost-effectiveness analysis.

Using Rasch analysis to form plausible health states amenable to valuation: the development of CORE-6D from a measure of common mental health problems (CORE-OM)

PurposeTo describe a new approach for deriving a preference-based index from a condition specific measure that uses Rasch analysis to develop health states.MethodsThe CORE-OM is a 34-item instrument monitoring clinical outcomes of people with common mental health problems. The CORE-OM is characterised by high correlation across its domains. Rasch analysis was used to reduce the number of items and response levels in order to produce a unidimensional measure and to generate a credible set of health states corresponding to different levels of symptom severity using the Rasch item threshold map.ResultsThe proposed methodology resulted in the development of CORE-6D, a 2-dimensional health state descriptive system consisting of a unidimensional 5-item emotional component (derived from Rasch analysis) and a physical symptom item. Inspection of the Rasch item threshold map of the emotional component helped identify a set of 11 plausible health states, which, combined with 3 physical symptom item levels, form 33 plausible health states that can be used for the valuation of the instrument, resulting in the development of a preference-based index.ConclusionsThis is a useful new approach to develop preference-based measures from existing instruments with high correlations across domains. The CORE-6D preference-based index will enable calculation of Quality-Adjusted Life Years in people with common mental health problems.

Recognition, assessment and treatment of social anxiety disorder: summary of NICE guidance

Social anxiety disorder is one of the most persistent and common of the anxiety disorders, with lifetime prevalence rates in Europe of 6.7% (range 3.9-13.7%).1 It often coexists with depression, substance use disorder, generalised anxiety disorder, panic disorder, and post-traumatic stress disorder.2 It can severely impair a person’s daily functioning by impeding the formation of relationships, reducing quality of life, and negatively affecting performance at work or school. Despite this, and the fact that effective treatments exist, only about half of people with this condition seek treatment, many after waiting 10-15 years.3 Although about 40% of those who develop the condition in childhood or adolescence recover before adulthood,4 for many the disorder persists into adulthood, with the chance of spontaneous recovery then limited compared with other mental health problems. This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on recognising, assessing, and treating social anxiety disorder in children, young people, and adults.5 NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Principles for working with all people with social anxiety disorder When the person arrives for the appointment, offer to meet them or alert them …

The cost-effectiveness of supported employment for adults with autism in the United Kingdom

Adults with autism face high rates of unemployment. Supported employment enables individuals with autism to secure and maintain a paid job in a regular work environment. The objective of this study was to assess the cost-effectiveness of supported employment compared with standard care (day services) for adults with autism in the United Kingdom. Thus, a decision-analytic economic model was developed, which used outcome data from the only trial that has evaluated supported employment for adults with autism in the United Kingdom. The main analysis considered intervention costs, while cost-savings associated with changes in accommodation status and National Health Service and personal social service resource use were examined in secondary analyses. Two outcome measures were used: the number of weeks in employment and the quality-adjusted life year. Supported employment resulted in better outcomes compared with standard care, at an extra cost of £18 per additional week in employment or £5600 per quality-adjusted life year. In secondary analyses that incorporated potential cost-savings, supported employment dominated standard care (i.e. it produced better outcomes at a lower total cost). The analysis suggests that supported employment schemes for adults with autism in the United Kingdom are cost-effective compared with standard care. Further research needs to confirm these findings.

A Review and Critique of Studies Reporting Utility Values for Schizophrenia-Related Health States

Economic evaluation of health technologies in the form of cost-utility analysis is increasingly advocated. The most common outcome measure in this type of analysis is the QALY. In order to estimate QALYs, appropriate utility values are required.The objective of this review was to identify and critique utility values for schizophrenia-related health states. A critical appraisal was performed on utility values for schizophrenia identified in the systematic literature review that informed the economic analysis of the updated edition of the National Institute for Health and Clinical Excellence (NICE) clinical guideline on schizophrenia for England and Wales.Seven studies reporting utility values for schizophrenia were identified. The studies employed a variety of methods for generating utility values. None of the reported sets of utility values for schizophrenia were generated using the EQ-5D, which is a measure widely used in cost-utility analysis and preferred by NICE. Nevertheless, the EQ-5D may be less sensitive in capturing aspects of health-related quality of life in patients with schizophrenia.A condition-specific preference-based instrument may be more appropriate than a generic measure to inform cost-utility analyses of interventions for schizophrenia.

Long-acting reversible contraceptives: not only effective, but also a cost-effective option for the National Health Service

The National Institute for Health and Clinical Excellence (NICE) clinical guideline on long-acting reversible contraception was published recently. The key themes of the guideline are: choice through better access and information; safety through clinical guidance and training for health care professionals; and cost effectiveness. It is this last aspect that we address in this commentary. While NICE guidance is applicable to England and Wales some aspects of it may be relevant to the provision of care and practice in Scotland and Northern Ireland. Long-acting reversible contraceptives (LARC) are among the most effective contraceptive methods. Unlike widely used methods such as the combined oral contraceptive pill (COC) and barrier methods the effectiveness of LARC is less dependent on users compliance/correct use of a method. This property makes LARC suitable in terms of contraceptive protection for certain subgroups of the population such as adolescents or women with no established regular routine who have been shown to comply poorly with commonly used contraceptive methods. (excerpt)

The Cost Effectiveness of Psychological and Pharmacological Interventions for Social Anxiety Disorder: A Model-Based Economic Analysis.

Background Social anxiety disorder is one of the most persistent and common anxiety disorders. Individually delivered psychological therapies are the most effective treatment options for adults with social anxiety disorder, but they are associated with high intervention costs. Therefore, the objective of this study was to assess the relative cost effectiveness of a variety of psychological and pharmacological interventions for adults with social anxiety disorder. Methods A decision-analytic model was constructed to compare costs and quality adjusted life years (QALYs) of 28 interventions for social anxiety disorder from the perspective of the British National Health Service and personal social services. Efficacy data were derived from a systematic review and network meta-analysis. Other model input parameters were based on published literature and national sources, supplemented by expert opinion. Results Individual cognitive therapy was the most cost-effective intervention for adults with social anxiety disorder, followed by generic individual cognitive behavioural therapy (CBT), phenelzine and book-based self-help without support. Other drugs, group-based psychological interventions and other individually delivered psychological interventions were less cost-effective. Results were influenced by limited evidence suggesting superiority of psychological interventions over drugs in retaining long-term effects. The analysis did not take into account side effects of drugs. Conclusion Various forms of individually delivered CBT appear to be the most cost-effective options for the treatment of adults with social anxiety disorder. Consideration of side effects of drugs would only strengthen this conclusion, as it would improve even further the cost effectiveness of individually delivered CBT relative to phenelzine, which was the next most cost-effective option, due to the serious side effects associated with phenelzine. Further research needs to determine more accurately the long-term comparative benefits and harms of psychological and pharmacological interventions for social anxiety disorder and establish their relative cost effectiveness with greater certainty.

Heightened risk of false positives in a network meta-analysis of social anxiety-Author's reply

www.thelancet.com/psychiatry Vol 2 April 2015 293 positives. The present network metaanalysis does not adequately address these methodological hazards, impairing its ability to detect only true treatment diff erences. In the context of network metaanalysis, transitivity is the crucial assumption that studies share similar clinical and design characteristics relevant to estimating an eff ect size. Transitivity permits the use of indirect evidence—that is, it permits the comparison of treatments that have never been directly contrasted. Without transitivity, any indirect evidence might be misestimated, since diff erent treatments might have been tested in diff erent contexts, such as varying degrees of disease severity. Cipriani and colleagues provide an example of violation of transitivity with the treatments A, B, and C: “Suppose that all AC studies include patients with severe illness and all BC studies include patients with moderate illness. Each study set is similar within itself... but the two sets deal with clinically different populations of patients. So, if severity is an effect modifi er, the transitivity assumption would not hold, and synthesis of these two meta-analyses would not give a valid AB estimate.” To summarise, indirect AB comparisons will be inaccurate because treatment A tends to be tested among more intractable patients than does B. In this network meta-analysis, transitivity per se is left unmentioned, and no moderator analyses were done. As study-characteristic heterogeneity is the norm in psychiatric trials, transitivity cannot be assumed. These omissions are therefore problematic. Moreover, some treatments contributed few studies. Treatments contributing fewer studies might not portray a representative range of treatment contexts, biasing an eff ect estimate compared with those with more studies. Unsurprisingly, the authors detect significant effect heterogeneity. Furthermore, at least nine of 44 comparisons with both direct and indirect evidence were potentially inconsistent, meaning that direct evidence was in signifi cant disagreement with indirect evidence. In such a case, treatment A could be equivalent in direct comparison with treatment B, while indirect evidence about treatment B used in other trials estimates that treatment B is better than treatment A. It would have been judicious to highlight the disputed comparisons indicated by inconsistency. Importantly, both inconsistency and heterogeneity can imply violation of transitivity. Simulations suggest that the risk of false positives is high in network metaanalysis because of the sheer number of comparisons made. In a simulation comparing only 12 antidepressants, an average of 2·7 false positives were recorded. That 38 active treatments and three controls were compared in this network meta-analysis is concerning. Type-I error correction (eg, Bonferroni) would have been appropriate to use. It is unfortunate that these signifi cant limitations are largely unaddressed, since they set the stage for the detection of false superiorities between treatments. Until these concerns are resolved, it is inappropriate to make stark treatment recommendations based on indirect evidence provided by this network meta-analysis.