BackgroundAttention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents.Methods and findingsWe performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants and their combination showed the best profile of acceptability. Stimulants and non-stimulants seemed well tolerated. Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and clonidine seemed significantly more efficacious than placebo. Methylphenidate and amphetamine seemed more efficacious than atomoxetine and guanfacine. Methylphenidate and clonidine seemed better accepted than placebo and atomoxetine. Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed. There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine. Overall findings were limited by the clinical and methodological heterogeneity, small sample sizes of trials, short-term follow-up, and the absence of high-quality evidence; consequently, results should be interpreted with caution.ConclusionsClinical differences may exist between the ph...

BackgroundAttention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of children and adolescents, with a significant impact on health services and the community in terms of economic and social burdens. The objective of this systematic review will be to evaluate the comparative efficacy and safety of pharmacological and non-pharmacological treatments in children and adolescents with ADHD.MethodsSearches involving PubMed/MEDLINE and the Cochrane Database of Systematic Reviews will be used to identify related systematic reviews and relevant randomized trials. Search results will be supplemented by reports from the regulatory and health technology agencies, clinical trials registers and by data requested from trialists and/or pharmaceutical companies. We will consider studies evaluating pharmacological interventions (e.g. stimulants, non-stimulants, antidepressants), psychological interventions (e.g. behavioural interventions, cognitive training and neurofeedback) and complementary and alternative medicine interventions (e.g. dietary interventions, supplement with fatty acids, vitamins, minerals, aminoacids, herbal treatment, homeopathy, and mind-body interventions including massage, chiropractic, acupuncture, yoga, meditation, Tai chi). Eligible control conditions will be placebo, waitlist, no treatment and usual care. Randomized controlled trials of a minimum of 3 weeks duration will be included. The primary outcomes of interest will be the proportion of patients who responded to treatment and who dropped out of the allocated treatment, respectively. Secondary outcomes will include treatment discontinuation due to adverse events, as well as the occurrences of serious adverse events and specific adverse events (decreased weight, anorexia, insomnia and sleep disturbances, anxiety, syncope and cardiovascular events). Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles in duplicate. Data will be abstracted and risk of bias will be appraised by two team members independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects pairwise meta-analyses and Bayesian network meta-analyses will be conducted where appropriate.DiscussionThis systematic review and network meta-analysis will compare the efficacy and safety of treatments used for ADHD in children and adolescents. The findings will assist patients, clinicians and healthcare providers to make evidence-based decisions regarding treatment selection.Systematic review registrationPROSPERO CRD42014015008.

Objective: To determine whether testosterone levels differ in male suicide attempters versus healthy controls and to explore the associations between testosterone levels and time of blood collection, and between testosterone levels and characteristics of suicide attempts. Method: A sample of 112 male suicide attempters was studied. Thirty-seven male blood donors were recruited as controls. Results: The mean testosterone levels were 5.1 ± 2.9 ng/ml in male attempters and 4.6 ± 1.6 ng/ml in controls. Group differences in testosterone levels were not significant when we studied the interaction with time of extraction (F = 0.37; d.f. = 2; p = 0.70) or when matched by age and time of extraction (t = –0.74; d.f. = 26; p = 0.47). When partial correlations were performed correcting for the effect of time of extraction, significant partial correlations were found in testosterone levels with history of aggressive behavior and lethality of the attempt. Conclusions: When circadian variation and age were considered, we found no support for the putative role of testosterone as a biological marker of suicidal behavior. Further research should consider: (1) testosterone and neurosteroids; (2) serial determinations with a minimal time gap between the attempt and the blood extraction; (3) controls within the same time periods, and (4) other variables that may affect testosterone levels, such as body mass index, physical activity and sleep disturbances.

Background Autism spectrum disorder (ASD) is a complex developmental disorder characterised by impaired social interaction and communication, and restrictive and repetitive behaviour. Previous systematic reviews have traditionally assessed the prevalence of ASD on global or regional context, with very few meta-analyses at the country level. The objective of this study will be to systematically evaluate published and unpublished observational studies that present prevalence and comorbidity of ASD among children, adolescent and adult population in Spain. Methods/design We designed and registered a study protocol for a systematic review and meta-analysis of descriptive epidemiology data. Observational studies (cohort, cross-sectional) reporting the prevalence of ASD and conducted in a wide range of people (e.g. general population, outpatient and/or school settings) will be included. The primary outcome will be the prevalence of ASD. Secondary outcomes will be the prevalence of any physical or mental comorbidity in association with ASD. No limitations will be imposed on publication status, study conduct period, and language of dissemination. Comprehensive literature searches will be conducted in seven electronic databases (from January 1980 onwards), including PubMed/MEDLINE, EMBASE, Scopus, Web of Science, PsycINFO, IME—Spanish Medical Index and IBECS—Spanish Bibliographic Index of Health Sciences. Grey literature will be identified through searching dissertation databases, Google Scholar and conference abstracts. Two team members will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct random effects meta-analysis of observational data. Prevalence estimates will be stratified according to gender, age and geographical location. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g. methodological quality, sample size, diagnostic criteria). Discussion This systematic review and meta-analysis of observational data will identify, evaluate and integrate the epidemiological knowledge underlying the prevalence of ASD in Spain. The results of this study will be of interest to multiple audiences including patients, their families, caregivers, healthcare professional, scientists and policy makers. Results will be published in a peer-reviewed journal. Implications for future epidemiological research will be discussed. Systematic review registration PROSPERO CRD42018090372 Electronic supplementary material The online version of this article (10.1186/s13643-019-1061-1) contains supplementary material, which is available to authorized users.