Despite unclear evidence to support the long-term use of antipsychotics to treat challenging (problem) behaviours in people with autism in the absence of a psychiatric disorder, this practice is common.

We conducted a systematic review and meta-analysis of all randomised controlled trials (RCTs) involving antipsychotics for people with autism of all ages, irrespective of the outcomes assessed. We searched seven databases and hand-searched ten relevant journals. Two authors independently screened titles, abstracts and full papers and extracted data using the Cochrane Handbook template. We conducted meta-analyses of outcomes and the rate of adverse events.

We included 39 papers based on 21 primary RCTs that recruited 1482 people with autism. No RCT assessed any psychiatric disorder outcome, such as psychoses or bipolar disorder. A meta-analysis of ten placebo-controlled RCTs showed a significantly improved Aberrant Behaviour Checklist-Irritability score in the antipsychotic group with an effect size of −6.45 [95% confidence interval (CI) −8.13 to −4.77] (low certainty). Pooled Clinical Global Impression data on 11 placebo-controlled RCTs showed an overall effect size of 0.84 (95% CI 0.48 to 1.21) (moderate certainty). There was a significantly higher risk of overall adverse effects (p = 0.003) and also weight gain (p < 0.00001), sedation (p < 0.00001) and increased appetite (p = 0.001) in the antipsychotic group.

There is some evidence for risperidone and preliminary evidence for aripiprazole to significantly improve scores on some outcome measures among children with autism but not adults or for any other antipsychotics. There is a definite increased risk of antipsychotic-related different adverse effects.

Despite the widespread use of psychotropic medications in people with autism spectrum disorder (ASD), there is limited evidence to suggest that psychotropic medications including mood stabilisers are effective in individuals with ASD.

To carry out a systematic review and meta-analysis of randomised controlled trials (RCTs) that assessed the effectiveness of mood stabilisers in people with ASD.

We searched the following databases: Cochrane Library, MEDLINE, Embase, CINAHL, PsycINFO, ERIC, DARE, and ClinicalTrials.gov. In addition, we hand-searched 12 relevant journals. We used the Cochrane Risk of Bias and Jadad scores to assess the quality of included RCTs. We carried out a meta-analysis using a random-effects model.

We included eight RCTs (four on valproate, two on levetiracetam, and one each on lamotrigine and topiramate) that included a total of 310 people with ASD, primarily children. Outcomes were based on core and associated ASD symptoms including irritability and aggression but not bipolar disorder. Only two small studies (25%) from the same group showed definite superiority over placebo and one over psychoeducation alone. Meta-analysis of pooled data on the Aberrant Behaviour Checklist-irritability, Clinical Global Impression Scale-improvement, and Overt Aggression Scale (OAS)/OAS-modified did not show any significant inter-group difference. The rates of adverse effects did not show any significant inter-group difference.

Given the methodological flaws in the included studies and the contradictory findings, it is difficult to draw any definitive conclusion about the effectiveness of mood stabilisers to treat either ASD core symptoms or associated behaviours. Robust large-scale RCTs are needed in the future to address this issue.

PROSPERO registration: CRD42021255467 on 18 May 2021.

Over the past 15 years, there has been substantial growth in web-based psychological interventions. We summarize evidence regarding the efficacy of web-based self-directed psychological interventions on depressive, anxiety and distress symptoms in people living with a chronic health condition.

We searched Medline, PsycINFO, CINAHL, EMBASE databases and Cochrane Database from 1990 to 1 May 2019. English language papers of randomized controlled trials (usual care or waitlist control) of web-based psychological interventions with a primary or secondary aim to reduce anxiety, depression or distress in adults with a chronic health condition were eligible. Results were assessed using narrative synthases and random-effects meta-analyses.

In total 70 eligible studies across 17 health conditions [most commonly: cancer (k = 20), chronic pain (k = 9), arthritis (k = 6) and multiple sclerosis (k = 5), diabetes (k = 4), fibromyalgia (k = 4)] were identified. Interventions were based on CBT principles in 46 (66%) studies and 42 (60%) included a facilitator. When combining all chronic health conditions, web-based interventions were more efficacious than control conditions in reducing symptoms of depression g = 0.30 (95% CI 0.22–0.39), anxiety g = 0.19 (95% CI 0.12–0.27), and distress g = 0.36 (95% CI 0.23–0.49).

Evidence regarding effectiveness for specific chronic health conditions was inconsistent. While self-guided online psychological interventions may help to reduce symptoms of anxiety, depression and distress in people with chronic health conditions in general, it is unclear if these interventions are effective for specific health conditions. More high-quality evidence is needed before definite conclusions can be made.

To investigate the reasons behind difficulties in recruiting patients to randomized controlled trials (RCTs) in psychiatry and to examine a database of RCTs for differences between studies in mental health and other specialities.

A discussion of recent changes in research governance in the UK and Europe followed by an examination of the database of all trials supported by the Health Technology Assessment programme of the National Institute of Health Research in the UK between 1993 and 2007 to determine if three different measures, (i) time between grant approval and study start date, (ii) percentage of additional time given to extend recruitment and (iii) percentage of planned recruitment achieved, changed over the time period studied and differed between mental health, cancer and other medical disciplines.

Despite attempts in the UK to accelerate the process of clinical trials in recent years, there was a significant increase in the extension time for trials to be completed (p = 0.038) and the percentage of planned recruitment to mental health studies (71%) was significantly less than for cancer (90.3%) and other studies (86.1%) (p = 0.032).

These results suggest that, despite the priority afforded to the advancement of RCTs in healthcare, such studies are encountering increasing difficulty in recruiting to time and target. We suggest that this difficulty can be attributed, at least in part, to the excessively byzantine regulation and governance processes for health research in the UK, and unnecessary bureaucracy in the current National Health Service system. Mental health studies appear particularly vulnerable to delay and better systems to facilitate recruitment are required urgently for the evidence base to be improved and facilitate new cost-effective interventions.

One aim of personalized medicine is to determine which treatment is to be preferred for an individual patient, given all patient information available. Particularly in mental health, however, there is a lack of a single objective, reliable measure of outcome that is sensitive to crucial individual differences among patients.

We examined the feasibility of quantifying the total clinical value provided by a treatment (measured by both harms and benefits) in a single metric. An expert panel was asked to compare 100 pairs of patients, one from each treatment group, who had participated in a randomized clinical trial (RCT) involving interpersonal psychotherapy (IPT) and escitalopram, selecting the patient with the preferred outcome considering both benefits and harms.

From these results, an integrated preference score (IPS) was derived, such that the differences between any two patients' IPSs would predict the clinicians' preferences. This IPS was then computed for all patients in the RCT. A second set of 100 pairs was rated by the panel. Their preferences were highly correlated with the IPS differences (r=0.84). Finally, the IPS was used as the outcome measure comparing IPT and escitalopram. The 95% confidence interval (CI) for the effect size comparing treatments indicated clinical equivalence of the treatments.

A metric that combines benefits and harms of treatments could increase the value of RCTs by making clearer which treatments are preferable and, ultimately, for whom. Such methods result in more precise estimation of effect sizes, without increasing the required sample size.