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Evidence-Based Mental Health current issue



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Is placebo response in antidepressant trials rising or not? A reanalysis of datasets to conclude this long-lasting controversy

2018-01-23T07:30:28-08:00

It had long been believed that placebo response rates in antidepressant trials have been increasing and that they were responsible for rising numbers of so-called failed antidepressant trials. Two recent systematic reviews examined this issue and reached completely opposite findings. Furukawa and colleagues in a paper published in 2016 found that the placebo response rates are stable since 1991 and the apparent increase up to 2000 was confounded by changes in trial design features. By contrast, Khan and colleagues more recently concluded that placebo response rates had grown steadily in the past 30 years. The two reviews differed in the datasets they used, definitions of placebo response and statistical analyses. In this perspective article, we examined if such differences were responsible for the two reviews’ contrasting conclusions. Our reanalyses confirmed our previous results. We found that in any dataset and for any placebo response definition, there was no increase in placebo response over the years when the analysis was adjusted for the confounders related to study design features or when it was limited to studies published after 1990s. We conclude that placebo response in antidepressant trials has remained stable for the past 25 years, during which time the large majority of the studies have come to share similar design features.




Multiple indicators of ill health are evident in people with psychosis

2018-01-23T07:30:28-08:00

Commentary on: Stubbs B, Koyanagi A, Veronese N, et al. Physical multimorbidity and psychosis: comprehensive cross sectional analysis including 242,952 people across 48 low- and middle-income countries. BMC Med 2016 Nov 22;14:189.

What is already known on this topic?

There is a very strong association between mental and physical illness that challenges the typical focus of healthcare systems on either mental or physical disorders.1 The relationship between psychosis and physical illness, including multiple physical illnesses (multimorbidity), is of considerable interest because people with psychosis have a greatly reduced life expectancy2 and in high-income countries most of those excess early deaths are due to natural causes. The most common of these causes may be inter-related and may therefore form a distinctive pattern of ‘multimorbidity’ associated with psychosis.3 Unravelling that pattern by age and gender, and by exposure to salient risk factors, may provide...




NMDA receptor antibodies are found in a small subgroup of patients with first-episode psychosis, but their clinical relevance is unknown

2018-01-23T07:30:28-08:00

Commentary on: Lennox B, Palmer-Cooper E, Pollak T, et al. Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case–control study. Lancet Psychiatry 2017;4:42–8.

What is already known on this topic?

Antineuronal antibody-mediated encephalitis frequently presents with prominent psychiatric features. It has been hypothesised that antineuronal antibodies may play a pathophysiological role in subgroups of patients with psychotic disorders. Whereas a few large studies find a similar prevalence of antineuronal antibodies in patients with psychotic disorders, other psychiatric disorders and healthy controls,1 2 there is some evidence of an increased prevalence of N-methyl-D-aspartate receptor (NMDAR) antibodies in patients with first-episode psychosis.3 4 In their present study, the authors aimed to (1) investigate the prevalence of neuronal cell surface antibodies in patients with first-episode psychosis and healthy controls and (2) compare the clinical and cognitive profile of patient’s with and without...




Children with mental health disorders have lower symptoms of depression 3 years after contact with mental health services

2018-01-23T07:30:28-08:00

Commentary on: Neufeld SA, Dunn VJ, Jones PB, et al. Reduction in adolescent depression after contact with mental health services: a longitudinal cohort study in the UK. Lancet Psychiatry 2017;4:120–127.

What is already known about this topic

Adolescence is a critical period for the development of depression with prevalence rates rising sharply from childhood to early adulthood.1 Many adult depressive disorders have their first onset in adolescence2 with longer episode duration being the strongest predictor of future problems.3 In addition to increasing the risk of later mental health problems, adolescent depression is associated with significant educational and social impairment and is a major risk factor for suicide.1 Providing effective early interventions to shorten the duration of episodes and potentially reduce the impact on later life is therefore important.3 This study explores this question and compares the effects of...




Web-based cognitive behaviour therapy for insomnia shows long-term efficacy in improving chronic insomnia

2018-01-23T07:30:28-08:00

Commentary on: Ritterband LM, Thorndike FP, Ingersoll KS, et al. Effect of a web-based cognitive behavior therapy for insomnia intervention with 1-year follow-up: a randomized clinical trial. JAMA Psychiatry 2017;74:68–75.

What is already known on this topic?

Insomnia is a widespread health problem, with cognitive behavioural therapy for insomnia (CBT-I) considered as first-line treatment.1 Unfortunately, access to CBT-I treatment is limited due to limited numbers of trained therapists and cost. Randomised controlled trials (RCTs) have provided strong evidence for web-based CBT-I as an effective treatment for insomnia.2 However, these studies have been of short duration and excluded people with comorbidities.3–5

Methods of the study

One thousand two hundred and twelve US-based participants were screened after indicating interest in the trial. The final study comprised 303 adults, aged 21–65 years (mean age: 43.28 years); 72% were female; 84% were white; and...




The limitations of using randomised controlled trials as a basis for developing treatment guidelines

2018-01-23T07:30:28-08:00

Randomised controlled trials (RCTs) are considered the ‘gold standard’ by which novel psychotropic medications and psychological interventions are evaluated and consequently adopted into widespread clinical practice. However, there are some limitations to using RCTs as the basis for developing treatment guidelines. While RCTs allow researchers to determine whether a given medication or intervention is effective in a specific patient sample, for practicing clinicians it is more important to know whether it will work for their particular patient in their particular setting. This information cannot be garnered from an RCT. These inherent limitations are exacerbated by biases in design, recruitment, sample populations and data analysis that are inevitable in real-world studies. While trial registration and CONSORT have been implemented to correct and improve these issues, it is worrying that many trials fail to achieve such standards and yet their findings are used to inform clinical decision making. This perspective piece questions the assumptions of RCTs and highlights the widespread distortion of findings that currently undermine the credibility of this powerful design. It is recommended that the clinical guidelines include advice as to what should be considered good and relevant evidence and that external bodies continue to monitor RCTs to ensure that the outcomes published indeed reflect reality.




Multifamily therapy may add to the effectiveness of single-family therapy for adolescents with anorexia nervosa

2018-01-23T07:30:28-08:00

Commentary on: Eisler I, Simic M, Hodsoll JA, et al. Pragmatic randomised multicentre trial of multifamily and single-family therapy for adolescent anorexia nervosa. BMC Psychiatry 2016;16:422.

What is already known on this topic

Family therapy for anorexia nervosa (FT-AN) currently has the strongest evidence base for the treatment of medically stable adolescents; however, many adolescents treated with FT-AN do not respond.1 Efforts are therefore being directed at improving FT-AN through adjuncts and adaptations. Multifamily therapy for AN (MFT-AN) is a FT-AN informed treatment in which 5-7 families attend day treatment together. MFT has shown promise in open trials,2 3 but until now no randomised trial has been conducted.

Methods of the study

The study was a two-arm randomised trial conducted across six specialist eating disorder services in and around London, UK. The sample was drawn from consecutive referrals of adolescents...




Establishing benefit of emotion-focused, carer-based interventions for adolescents with anorexia nervosa

2018-01-23T07:30:28-08:00

Commentary on: Salerno L, Rhind C, Hibbs R et al. A longitudinal examination of dyadic distress patterns following a skills intervention for carers of adolescents with anorexia nervosa. Eur Child Adolesc Psychiatry 2016;25:1337–47.

What is already known on this topic

Family-based interventions are considered a mainstay of treatment for adolescents with AN. Although family-based therapy has provided the greatest evidence base, clinicians employ a variety of treatment methods for AN, and fidelity to the first-line approach varies considerably.1 Primary outcomes of studies of adolescent AN are typically limited to patients; little research exists on how carers influence outcomes, and how family dynamics interact with and, in complex cases, potentially maintain the illness.

Methods of the study

The present study reports outcomes from a longitudinal UK 38-site randomised controlled trial that examined the effects of a carer intervention on individuals aged 12–21 years referred for outpatient treatment of...




L-methylfolate cannot yet be recommended as an add-on treatment in schizophrenia

2018-01-23T07:30:28-08:00

Commentary on: Roffman JL, Petruzzi LJ, Tanner AS, et al. Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial. Mol Psychiatry 2017 (Epub ahead of print: 14 Mar 2017).

What is already known on this topic

Accumulating evidence indicates that one-carbon metabolism dysregulation, manifesting in low folate levels and elevated homocysteine levels, frequently occurs in patients with schizophrenia.1 Additionally, it has been found that these metabolic alterations are associated with a higher severity of negative symptoms.2 Previous studies investigating the efficacy of supplementation strategies have found small but significant improvement of negative symptoms that might be influenced by folate-related gene polymorphisms.3–5

Methods of the study

This was a 12-week, single-site, randomised, double-blind, placebo-controlled and parallel-group trial. The study was followed by an open-label 12-week extension that was designed to assess safety outcomes. Out...




A systematic review of network meta-analyses for pharmacological treatment of common mental disorders

2018-01-23T07:30:28-08:00

Question

Network meta-analyses (NMAs) of treatment efficacy across different pharmacological treatments help inform clinical decision-making, but their methodological quality may vary a lot depending also on the quality of the included primary studies. We therefore conducted a systematic review of NMAs of pharmacological treatment for common mental disorders in order to assess the methodological quality of these NMAs, and to relate study characteristics to the rankings of efficacy and tolerability.

Study selection and analysis

We searched three databases for NMAs of pharmacological treatment used in major depression, generalised anxiety disorder (GAD), social anxiety disorder (SAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD) and specific phobia.

Studies were appraised using the International Society for Pharmacoeconomics and Outcomes Research checklist of good research practices for indirect-treatment-comparison and network-meta-analysis studies.

Findings

Twenty NMAs were eligible for inclusion. The number of randomised controlled trials per NMA ranged from 11 to 234, and included between 801 to more than 26 000 participants. Overall, antidepressants were found to be efficacious and tolerable agents for several disorders based on rankings (45%) or statistical significance (55%). The majority of NMAs in this review adhered to guidelines by including a network diagram (70%), assessing consistency (75%), making use of a random effects model (75%), providing information on the model used to fit the data (75%) and adjusting for covariates (75%).

Conclusions

The 20 NMAs of depression and anxiety disorders, PTSD and/or OCD included in this review demonstrate some methodological strengths in comparison with the larger body of published NMAs for medical disorders, support current treatment guidelines and help inform clinical decision-making.




Effects of drinking on late-life brain and cognition

2018-01-23T07:30:28-08:00

Alcohol consumption is common in Western countries and has been increasing in older adults. Latest figures from Great Britain suggest 75% of those over 65 years drink, an increase from 71% 10 years ago. Chronic heavy intake is a well-established cause of brain atrophy and dementia, with a recent long-term prospective study from the USA reporting a doubling of the odds of later severe memory impairment in those with a history of an alcohol use disorder. Drinking of moderate amounts has been reported to be protective for brain health in a number of epidemiological studies, including some claims of possibly reducing dementia risk. Rigorous recent research has questioned this belief, with new evidence of harmful associations in moderate drinkers compared with abstainers. This has raised suspicion that reported protective effects of moderate drinking were due to confounding by socioeconomic class and intelligence. Clinicians should look out for cognitive impairment in heavy drinkers, considering that abstinence may induce a degree of clinical improvement. Discussions with patients regarding moderate drinking should be informed by recent research. Health benefits of moderate drinking at least for cognitive function are questionable, and if they exist are probably limited to one unit of alcohol daily with respect to other body systems.




Engaging families in the management of adolescent self-harm

2018-01-23T07:30:28-08:00

Adolescent self-harm is an emerging public health challenge. It is associated with later psychiatric and substance use disorders, unemployment and suicide. Family interventions have been effective in a range of adolescent mental health problems and for that reason were reviewed for their effectiveness in the management of adolescent self-harm. The search identified 10 randomised and 2 non-randomised controlled trial conducted in the high-income countries. For the most part the evidence is of low quality. The interventions were classified as brief single session, intermediate-level and intensive family interventions depending on the intensity and duration of treatment. Brief interventions did not reduce adolescent self-harm. Intermediate interventions such as the Resourceful Adolescent Parent Programme, Safe Alternatives for Teens and Youth Programme and attachment-based family treatment were effective in reducing suicidal behaviour (effect size 0.72), suicide attempts (P=0.01) and suicidal ideations (effect size 0.95), respectively in the short-term with an absence of long-term follow-up data. Intensive adolescent interventions such as dialectical behaviour therapy and mentalisation-based therapy reduced suicidal ideation (effect size 0.89) and self-harm (56% vs 83%, P=0.01), respectively. The persistence of effects beyond the intervention end point is not known in many interventions. Early involvement of the family, an evaluation of the risks at the end of an acute crisis episode and a stepped-care model taking into account level of suicide risk and resources available to an adolescent and her/his family are likely to promote better outcomes in adolescents who self-harm.




Heart rate variability in bipolar disorder and borderline personality disorder: a clinical review

2018-01-23T07:30:28-08:00

Heart rate variability (HRV) in psychiatric disorders has become an increasing area of interest in recent years following technological advances that enable non-invasive monitoring of autonomic nervous system regulation. However, the clinical interpretation of HRV features remain widely debated or unknown. Standardisation within studies of HRV in psychiatric disorders is poor, making it difficult to reproduce or build on previous work. Recently, a Guidelines for Reporting Articles on Psychiatry and Heart rate variability checklist has been proposed to address this issue. Here we assess studies of HRV in bipolar disorder and borderline personality disorder against this checklist and discuss the implication for ongoing research in this area.




WHO Mental Health Gap Action Programme (mhGAP) Intervention Guide: a systematic review of evidence from low and middle-income countries

2018-01-23T07:30:28-08:00

Question

Despite mental, neurological and substance use (MNS) disorders being highly prevalent, there is a worldwide gap between service need and provision. WHO launched its Mental Health Gap Action Programme (mhGAP) in 2008, and the Intervention Guide (mhGAP-IG) in 2010. mhGAP-IG provides evidence-based guidance and tools for assessment and integrated management of priority MNS disorders in low and middle-income countries (LMICs), using clinical decision-making protocols. It targets a non-specialised primary healthcare audience, but has also been used by ministries, non-governmental organisations and academics, for mental health service scale-up in 90 countries. This review aimed to identify evidence to date for mhGAP-IG implementation in LMICs.

Study selection and analysis

We searched MEDLINE, Embase, PsycINFO, Web of Knowledge/Web of Science, Scopus, CINAHL, LILACS, SciELO/Web of Science, Cochrane, Pubmed databases and Google Scholar for studies reporting evidence, experience or evaluation of mhGAP-IG in LMICs, in any language. Data were extracted from included papers, but heterogeneity prevented meta-analysis.

Findings

We conducted a systematic review of evidence to date, of mhGAP-IG implementation and evaluation in LMICs. Thirty-three included studies reported 15 training courses, 9 clinical implementations, 3 country contextualisations, 3 economic models, 2 uses as control interventions and 1 use to develop a rating scale. Our review identified the importance of detailed reports of contextual challenges in the field, alongside detailed protocols, qualitative studies and randomised controlled trials.

Conclusions

The mhGAP-IG literature is substantial, relative to other published evaluations of clinical practice guidelines: an important contribution to a neglected field.




Causal inference from experiment and observation

2018-01-23T07:30:28-08:00

Results from well-conducted randomised controlled studies should ideally inform on the comparative merits of treatment choices for a health condition. In the absence of this, one attempts to use evidence from the impact of treatment when administered according to decisions of the physicians and the patients (observational evidence). Naïve comparisons between treatment options using observational evidence will lead to biased results. Under certain conditions, however, it is possible to obtain valid estimates of the comparative merits of different treatments from observational data. Causal inference can be conceptualised as a framework aiming to provide valid information about causal effects of treatments using observational evidence. It can be viewed as a missing data problem in which each patient has two outcomes: the observed outcome under the treatment actually received and a counterfactual (unobserved) outcome had the patient received a different treatment. Methodological developments over the last decades clarified the appropriate conditions and methods to obtain valid comparisons. This article provides an introduction to some of these methods.




The role of rTMS for patients with severe PTSD and depression

2018-01-23T07:30:28-08:00

Clinical casePatient

A 27-year-old woman.

Present illness

A 27-year-old female patient with chronic post-traumatic stress disorder (PTSD) and recurrent major depressive sisorder (MDD) is referred for consultation regarding possible repetitive transcranial magnetic stimulation (rTMS) treatment for her medication-resistant depression. She has no other medical diagnoses and had no history of substance abuse.

Present status

At the time of initial consult, psychometrics indicated that both PTSD symptoms and MDD symptoms were severe. While the patient passively endorses suicidal thoughts, she denies active intent or plan to harm herself. She has taken medical leave of absence from her job in order to get treatment for her depression. To review how rTMS may affect their patient’s PTSD symptoms, the consulting team conducts a review of published literature.

Background

PTSD is a severe psychiatric illness characterised by four core symptom clusters: re-experiencing, avoidance, negative cognition and mood...