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

Limbu, Bharati; Roy, Meera; Lee, Rachel; Roy, Ashok; Taiwo, O.

doi:10.1192/bjo.2022.18

Cited by 12 publications

(4 citation statements)

References 44 publications

(161 reference statements)

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“…We also hand-searched four relevant journals in the field of ASD (Autism, Journal of Autism and Developmental Disorders, Autism Research, Journal of Autism Spectrum Disorder) and six in psychopharmacology (Psychopharmacology, Neuropsychopharmacology, International Journal of Neuropsychopharmacology, Journal of Clinical Psychopharmacology, Human Psychopharmacology, Journal of Child and Adolescent Psychopharmacology) for relevant articles between 2000 and 30th May 2022. Search terms using descriptors for ASD, antipsychotics, outcomes (ASD core symptoms, associated symptoms such as challenging behaviour and psychiatric disorders such as psychoses, schizophrenia and mania) and RCTs (online Supplementary Appendix 2) were developed after a scoping search and based on our previous systematic reviews on psychotropic medications in ASD (Deb et al, 2021; Limbu et al, 2022). Two authors (MR and JS) independently screened titles, abstracts and full papers using the eligibility criteria (online Supplementary Appendix 2).…”

Section: Methodsmentioning

confidence: 99%

“…Recent meta-analyses showed no definitive evidence of antidepressants, anti-anxiety medication (Deb et al, 2021), and mood stabiliser medications’ efficacy (Limbu et al, 2022) on the core (such as restrictive and repetitive behaviour, RRB and impaired communication skills) or associated symptoms (such as aggression, irritability and agitation) of ASD. The evidence for the efficacy of antipsychotic medications for people with ASD without a psychiatric diagnosis is unclear (Deb et al, 2022; Unwin & Deb, 2011).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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“…A recent systematic review and meta-analysis (Limbu 2022) found eight RCTs (four on valproate, two on levetiracetam and one each on lamotrigine and topiramate) involving 310 people with ASD, primarily children, that assessed the efficacy of mood stabilisers on core ASD symptoms and associated behaviours, including irritability and aggression but not bipolar disorder. Only two small studies (25%) from the same research group (Hollander 2006(Hollander , 2010 showed superiority of divalproex sodium over placebo.…”

Section: Children With Asdmentioning

confidence: 99%

Pharmacological management of psychopathology in people with intellectual disabilities and/or autism spectrum disorder

Roy

Limbu

2022

BJPsych advances

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SUMMARY On average, 49–63% of people with intellectual disabilities and/or autism spectrum disorder (ASD) are prescribed psychotropic medications to treat psychopathology, including psychiatric illness, behaviours that challenge and the core symptoms and associated behaviours of these developmental disorders. In many cases, psychotropics, particularly antipsychotics, are used off-label without a proper indication, particularly to manage behaviours that challenge. The RCTs show moderate evidence supporting the efficacy of low-dose risperidone and some preliminary evidence for aripiprazole in treating behaviours that challenge among children with ASD and/or intellectual disabilities. The RCT-based evidence for the other psychotropics is equivocal, so no definitive conclusions can be made on their efficacy. Polypharmacy and the use of high doses of antipsychotics are prevalent in this population, leading to the risk of adverse events and drug–drug interactions. Despite various national and international guidelines, and government initiatives encouraging reduced psychotropic use, there is little evidence of this happening; on the contrary, the use of antidepressants, mood stabilisers and benzodiazepines may be increasing. A concerted multi-agency effort is urgently needed to address this significant public health concern of the overmedication of people with intellectual disabilities and/or ASD.

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“…Autism spectrum disorder (ASD) defines a group of heterogenous neurodevelopmental conditions characterized by persistent deficits in social communication and interaction, repetitive and restricted behaviors, and sensory anomalies [1] In the last few decades, numerous pharmacological treatments for these core symptoms of ASD have been investigated, with the majority failing to demonstrate higher efficacy when compared to placebo, in part due to a relatively high placebo response [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Mediators of Placebo Response to Cannabinoid Treatment in Children with Autism Spectrum Disorder

Aran

Harel

Ovadia

et al. 2023

JCM

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The placebo response has a substantial impact on treatment outcome. However, data regarding mediators of the placebo response in children with autism spectrum disorder (ASD) are sparse. This retrospective study investigated possible mediators of the placebo response among participants of a placebo-controlled trial of cannabinoid treatment for behavioral problems in children with ASD (CBA trial, age 5–21 years). We used a specifically designed questionnaire to explore possible mediators of the placebo response in 88 participants of the CBA trial who received a placebo and had valid outcome scores. The parents of 67 participants completed the questionnaire. The placebo response was positively associated with the child’s comprehension of the treatment purpose (p = 0.037). There was also a trend for participants who had a relative aggravation of symptoms before treatment onset to improve following placebo treatment (p = 0.053). No other domains, including parental expectations, previous positive experience with similar treatments (behavioral conditioning), parental locus of control, quality of the patient–physician relationships, and adherence to study medications were associated with placebo-response. This finding suggests that efforts to explain the treatment purpose to children with disabilities may enhance treatment efficacy in clinical practice and decrease differences in the placebo response between study arms. Contrary to our hypothesis, parental expectations regarding cannabinoid treatment were not associated with the placebo response.

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

Cited by 12 publications

References 44 publications

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

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

Pharmacological management of psychopathology in people with intellectual disabilities and/or autism spectrum disorder

Mediators of Placebo Response to Cannabinoid Treatment in Children with Autism Spectrum Disorder

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