Randomised controlled trials of antipsychotics for people with autism spectrum disorder: a systematic review and a meta-analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Randomised controlled trials of mood stabilisers for people with autism spectrum disorder: systematic review and meta-analysis.

BACKGROUND: 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. AIMS: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Randomised controlled trials of antidepressant and anti-anxiety medications for people with autism spectrum disorder: systematic review and meta-analysis.

BACKGROUND: Although widely used, the current evidence for the efficacy of antidepressant and anti-anxiety medications for people with autism spectrum disorder (ASD) is limited and conflicting. AIMS: We carried out a systematic review and meta-analysis of randomised controlled trials that assessed the effectiveness of these medications in people with ASD. METHOD: We searched the following databases: Cochrane Library, Medline, EMBASE, CINAHL, PsycINFO, ERIC, DARE and ClinicalTrials.gov. Additionally, we hand-searched 11 relevant journals. We used the Cochrane risk-of-bias tool and Jadad score to assess the quality of each included study. We carried out a meta-analysis using a random effects model. RESULTS: We included 15 randomised controlled trials (13 on antidepressants and two on anti-anxiety medications) for a total of 958 people with ASD. Data showed contradictory findings among the studies, with larger studies mostly showing a non-significant difference in outcomes between the treatment and the placebo groups. Meta-analysis of pooled Yale-Brown Obsessive Compulsive Scale and Clinical Global Impression Scale data from nine studies (60%) did not show any statistically significant inter-group difference on either of the outcome measures. The adverse effects reported were mild and, in most studies, their rates did not show any significant inter-group difference. CONCLUSIONS: Given the methodological flaws in the most included studies and contradictory findings, it is difficult to draw any definitive conclusion about the effectiveness of either antidepressant or anti-anxiety medications to treat either ASD core symptoms or associated behaviours. Robust, large-scale, randomised controlled trials are needed to address this issue.

The effectiveness of parent training for children with autism spectrum disorder: a systematic review and meta-analyses.

BACKGROUND: Various parent training interventions have been shown to have some effect on the symptoms of children with autism. We carried out a systematic review and meta-analyses to assess effectiveness of parental training for children with autism on their symptoms and parental stress. METHODS: Four electronic databases, CINAHL, EMBASE, MEDLINE and PsycINFO were searched until March 2020 for relevant literature. Two reviewers independently screened bibliographies using an eligibility checklist and extracted data using a structured proforma. We have also carried out meta-analyses when data were available for pooling. RESULTS: Seventeen papers from 15 studies were included for data analysis. Fifteen papers showed a positive treatment effect when compared with the control group, although not always significant. Meta-analysis based on pooled data from only two studies in each respective intervention, showed small to moderate treatment effects for three interventions, DIR/Floortime, Pivotal Response and Parent focused training respectively. CONCLUSIONS: As in previous systematic reviews there was a mild to moderate treatment effects of three specific types of interventions respectively. However, it was difficult to draw any definitive conclusion about the effectiveness and generalisability of any intervention because of the wide variation in the interventions, control groups, outcome measures, small sample size, small number of studies in meta-analysis, overlap between the intervention and control procedures used in the included studies. There is an urgent need for experts in various international centres to jointly standardise a parent training intervention for children with autism and carry out a large scale RCT to assess its clinical and economic effectiveness. Research Registry Unique Identifying Number: reviewregistry915.

The effectiveness of methylphenidate in the management of Attention Deficit Hyperactivity Disorder (ADHD) in people with intellectual disabilities: A systematic review.

BACKGROUND: The effectiveness of psychostimulants, primarily methylphenidate (MPH), in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in the general population of typically growing children and adolescents is well established through many Randomised Controlled Trials (RCTs). AIMS AND METHODS: We carried out a systematic review of all the RCTs in people with intellectual disabilities (ID) that assessed effectiveness of MPH on the core ADHD symptoms. OUTCOMES AND RESULTS: We included 15 papers from 13 studies that were all on children and adolescents with ID (315 participants were on MPH and placebo respectively), 12 of which used a cross over design, and one used a parallel design. On average around 40-50% responded to MPH in the ID group whereas around 70-80% response rate is reported among the non-ID children. Because of the heterogeneity of the outcome data it was not possible to carry out a meta-analysis. Significant adverse events included sleep difficulties and poor appetite along with weight loss and also irritability, social withdrawal and increased motor activities including tic. CONCLUSIONS AND IMPLEMENTATION: On the basis of the poor quality evidence that is available, it seems that MPH may be effective in some but not all children and adolescents with ID and ADHD.

Intellectual disability in Indigenous Australians: issues and challenges.

OBJECTIVES: Literature on Indigenous Australians (Aboriginal and Torres Strait Islander people) and intellectual disability (ID) is summarized in order to identify current state of knowledge, gaps, and areas for further research. METHODS: A selective review of psychiatric literature using relevant medical databases was undertaken. Key articles were identified and their findings described. RESULTS: ID is reported to be more prevalent in Indigenous Australians. Sociocultural constructs and a lack of validated psychometric measures affect what is considered to be ID in Indigenous communities. Prenatal, perinatal, and postnatal factors impair brain development and contribute to ID in Indigenous communities. Comorbid physical and psychiatric disorders need to be assessed and managed. CONCLUSIONS: ID is an emerging area of health concern for general and mental health professionals working with Indigenous Australians. This important area requires further research, appropriate training, and resourcing.

Personality development and intellectual disability.

PURPOSE OF REVIEW: This review examines the factors that shape personality and how they can inform on the behaviour of people with intellectual disability both to help them function at least at their cognitive level and add a developmental dimension to treatment plans. RECENT FINDINGS: People with intellectual disability experience more failure, rejection and social deprivation leading to personality traits that may impede their ability to learn and predispose them to depression. Brain changes due to genetic conditions may be responsible for the behavioural phenotypes, although the autism phenotype is associated with different causes. Schizophrenia has a strong neurodevelopmental component and it could be on a gradient of decreasing neurodevelopmental impairment between intellectual disability and autism on one hand and bipolar disorder on the other. SUMMARY: Understanding how early-life experience and current-life situations give rise to personality traits and taking a developmental perspective, for example, mental age, could clarify the clinical presentation. Developments in molecular genetics and brain imaging may clarify how brain changes lead to personality features. Finally, it may be time to address whether it is still helpful to have categorical diagnoses when there is increasing evidence from genetic studies supporting a continuum of neurodevelopmental disorders.

Intellectual disability and indigenous Australians: an overview.

The review summarizes important literature in the emerging field of intellectual disability (ID) in indigenous Australians. Search of various electronic databases revealed 19 papers that provide information regarding prevalence, sociodemographic factors, and issues in assessment and management. Overall, there is limited information regarding ID in indigenous Australians, which is reported to be more prevalent compared with nonindigenous Australians. Sociocultural constructs affect what is considered to be ID in indigenous communities and this may be at odds with western notions. Other difficulties include lack of validated psychometric instruments to effectively measure cognitive functioning in indigenous Australians. Prenatal, perinatal, and postnatal factors are significant factors that impair brain development and contribute to ID in indigenous communities. Comorbid physical and psychiatric disorders need to be assessed and managed. This paper provides an overview of current knowledge regarding this important area that requires further research, appropriate training, and resourcing.

The effectiveness of aripiprazole in the management of problem behaviour in people with intellectual disabilities, developmental disabilities and/or autistic spectrum disorder--a systematic review.

The management of problem behaviours (PB) in individuals with intellectual disabilities (ID), developmental disabilities (DD) and/or autistic spectrum disorders (ASD) can be challenging. Antipsychotic medications are commonly prescribed where other strategies have failed. A systematic review (SR) was conducted to establish the research evidence for the efficacy of aripiprazole in the management of PB in adults and children with ID, DD and/or ASD. Although included studies supported the efficacy of aripiprazole for this indication, the overall quality of studies was poor. Of the 20 studies included in this systematic review there were only two randomised controlled trials (RCTs) on children with ASD and/or ID/DD, both of which were conducted by the pharmaceutical company that manufactures aripiprazole, and it is not clear whether a number of same participants were included in both RCTs. One of the RCTs was extended into an open label long term follow up, which showed that aripiprazole's efficacy lasted over 52 weeks and the adverse effects were tolerable. Four studies were open label prospective studies, 11 were retrospective case reports which included four single case reports, and two were prospective case series. Most studies reported adverse effects from aripiprazole in the form of weight gain, increased appetite, sedation, tiredness, drooling and tremor. However, aripiprazole improved serum prolactin level in some participants and overall did not show any adverse effect on QTc interval. There is a need for more carefully designed RCTs into the use of aripiprazole in the management of PB in people with ID/DD and/or ASD, which should be carried out independent of pharmaceutical companies.

Efficacy of beta blockers in the management of problem behaviours in people with intellectual disabilities: a systematic review.

Both medication and non-medication based strategies are used in the management of problem behaviours in individuals with intellectual disabilities. Beta-adrenoceptor blocking medications are one group of drugs used for this purpose. However, despite its regular use, the evidence for the efficacy of these drugs for in this context is lacking. A systematic review was conducted to establish the research evidence for the efficacy of beta blockers in problem behaviours in adults and children with intellectual disabilities. Although the research identified supported the efficacy of beta blockers for this indication the overall quality of studies identified was poor and no randomised controlled trials were identified. There is a need for more robust research into the use of beta blockers for people with intellectual disabilities who show problem behaviours.

Monitoring metabolic side effects of atypical antipsychotics in people with an intellectual disability.

This audit was undertaken prospectively to examine the compliance of a group of psychiatrists against guidelines they developed for monitoring the onset of metabolic syndrome, a potential side effect of antipsychotic medication, especially second generation or atypical ones. Phase 1 of the audit was to set standards by a questionnaire survey of participating psychiatrists against Consensus Guidelines on monitoring (American Diabetic Association, 2004), which they favoured. The results led to modifying these guidelines to develop minimum acceptable standards against which their practice was audited in Phase 2. Although in Phase 1, 77% of the psychiatrists felt that they did some baseline recording, Phase 2 finding did not corroborate this--only 53.8% of the notes recorded the assessment of risk factors in personal history; 37.5% risk factors in family history; 31.7% baseline weight and 26.4% baseline blood sugar/lipid levels. In Phase 1, 85% of the psychiatrists thought that they carried out some of the recommended monitoring; our audit found the records of weight monitoring in 69.7% of the notes and blood sugar and lipids monitoring in 44.2%. People with intellectual disability have a shorter life expectancy and increased risk of early death when compared with the general population. Obesity is already a health issue for people with intellectual disability. We discuss the challenges faced by psychiatrists in implementing their own minimum acceptable standards and suggest measures to reduce the metabolic risk associated with antipsychotic medication through increasing awareness--use of information leaflets in accessible format, health promotion and use of side effect checklists and improving access--by working collaboratively with general practitioners utilising the forum of annual health checks.

Improving recording of capacity to consent and explanation of medication side effects in a psychiatric service for people with learning disability: audit findings.

This study aimed to examine the practice of psychiatrists in a large learning disability service in recording capacity to consent to treatment and side effect discussion, and the impact of measures aimed at improving this. Three audit cycles were completed between 2007 and 2009, each examining 26 case notes selected at random. Information was gathered on recording of capacity and documentation of explanation of potential side effects. Changes in practice following the introduction of a rubber stamp in 2008, as a visual prompt for clinicians, were examined. Rates of recording of capacity rose from 30% in 2007 to 51% in 2009 (P = 0.000006). Capacity was more likely to have been recorded if the stamp was present (odds ratio 13.5, p < 0.0001). Recording of side effect discussion was consistently higher than that of capacity and showed little change between cycles. We conclude that the use of a rubber stamp in case notes was associated with improvements in the recording of capacity assessments.

Intellectual disability and Aboriginal Australians - training needs for psychiatrists.

Aboriginal Australians have relatively high rates of intellectual disability, a situation that is probably due mainly to poor health and social disadvantage. Populations with high rates of intellectual disability are more at risk of developmental disorders and mental ill health. We explore the training needs for psychiatrists working with indigenous people and how they can be met.

Missed diagnosis of autism in an Australian indigenous psychiatric population.

OBJECTIVE: The aim of this paper is to review the diagnosis among adult Indigenous patients from the Kimberley region of Western Australia who had an existing diagnosis of schizophrenia. A visit from a psychiatrist specializing in intellectual disability provided the opportunity for conducting psychiatric assessments from a developmental perspective. METHOD: Selected patients with schizophrenia were assessed from an intellectual disability perspective from an active case load of 215 patients. RESULT: Thirteen out of 14 selected patients were considered to have a diagnosis of autism when a developmental history was undertaken. Case studies are presented to illustrate the overlap in symptoms and potential for the diagnosis of autism to be missed. CONCLUSIONS: Autism spectrum disorders may be missed in Indigenous population groups. This has implications for treatment and service provision. Clinicians need to be mindful of the diagnostic possibility that an autism spectrum disorder might be masquerading as schizophrenia in the context of intellectual disability and atypical presentation.

A case note follow-up of women with intellectual disability referred for sterilization.

A case note audit was carried out to follow up women with intellectual disabilities referred for contraceptive sterilization 20 years ago. None of the women had been sexually active or become pregnant. Two had hysterectomies for medical indications at a younger age. Women with intellectual disability may use reversible and less invasive methods of contraception before considering contraceptive sterilization. Although the assessments predated the Mental Capacity Act 2005, they were largely compliant with it.

Elimination of high-risk human papillomavirus type HPV16 infection by 'Praneem' polyherbal tablet in women with early cervical intraepithelial lesions.

PURPOSE: 'Praneem', a polyherbal formulation developed by us, has successfully completed Phase II efficacy study for treatment of abnormal vaginal discharge due to reproductive tract infections that act as co-factors for HPV persistence. In the present study we evaluated potential anti-HPV activity of Praneem in women infected with high risk HPV type 16. METHODS: Twenty women molecularly diagnosed positive for HPV16 infection without or with low grade squamous intraepithelial lesion (LSIL) or inflammation were assigned to receive intra-vaginal, topical application of either Praneem tablet or placebo for 30 days excluding the days of menstrual period and were evaluated for persistence of HPV infection using HPV L1 consensus and HPV type 16-specific PCR as primary outcome. RESULTS: One course of Praneem treatment resulted in elimination of HPV in 6 out of 10 (60%) cases. A repeat treatment of four patients with persisting HPV infection resulted in clearance of HPV in two additional cases resulting in an overall 80% clearance of HPV 16 as against a spontaneous clearance of 10% (1/10) seen in the placebo arm. The elimination of HPV DNA was found to be accompanied by marked improvement in clinical symptoms and cytological abnormalities of Praneem-treated patients. CONCLUSION: Our results showed for the first time that a 30-day intra-vaginal application of the Praneem can result in elimination of HPV infection from the uterine cervix.