Meta-analysis: Pharmacologic Treatment of Restricted and Repetitive Behaviors in Autism Spectrum Disorders

Zhou, Melissa; Nasir, Madeeha; Farhat, Luis C.; Kook, Minjee; Artukoğlu, Bekir B.; Bloch, Michael H.

doi:10.1016/j.jaac.2020.03.007

Cited by 76 publications

(53 citation statements)

References 92 publications

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“…We ultimately included 14 NMAs and 90 MAs, reporting on 15 disorders or groups of disorders. For ADHD, we included three NMAs 5,20,21 and 21 MAs 22‐42 ; for autism, one NMA 43 and 21 MAs 12,44‐63 (including one focusing on comorbid anxiety disorders and autism) 12 ; for depressive disorders, two NMA 7,10 and seven MAs 64‐70 ; for obsessive‐compulsive disorder, one NMA 71 and six MAs 72‐77 ; for anxiety disorders, two NMAs 11,78 and five MAs 12,79‐82 (plus two MAs specific on social anxiety disorder 83,84 ); for enuresis, one NMA 85 and six MAs 86‐91 , for disruptive behavior/dissocial/conduct disorders, five MAs 92‐96 (plus one focusing on youth with comorbid ADHD) 25 ; for eating disorders, one NMA 97 and four MAs 98‐101 ; for schizophrenia spectrum disorders, three NMAs 8,102,103 and two MAs 104,105 ; for bipolar disorder, four MAs 106‐109 ; for tic disorder, two MAs 110,111 ; for Tourette's disorder, two MAs 112,113 ; for encopresis, two MAs 114,115 ; for developmental coordination disorder, one MA 116 ; and for PTSD, one MA 117 .…”

Section: Resultsmentioning

confidence: 99%

Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review

et al. 2021

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Top‐tier evidence on the safety/tolerability of 80 medications in children/adolescents with mental disorders has recently been reviewed in this journal. To guide clinical practice, such data must be combined with evidence on efficacy and acceptability. Besides medications, psychosocial interventions and brain stimulation techniques are treatment options for children/adolescents with mental disorders. For this umbrella review, we systematically searched network meta‐analyses (NMAs) and meta‐analyses (MAs) of randomized controlled trials (RCTs) evaluating 48 medications, 20 psychosocial interventions, and four brain stimulation techniques in children/adolescents with 52 different mental disorders or groups of mental disorders, reporting on 20 different efficacy/acceptability outcomes. Co‐primary outcomes were disease‐specific symptom reduction and all‐cause discontinuation (“acceptability”). We included 14 NMAs and 90 MAs, reporting on 15 mental disorders or groups of mental disorders. Overall, 21 medications outperformed placebo regarding the co‐primary outcomes, and three psychosocial interventions did so (while seven outperformed waiting list/no treatment). Based on the meta‐analytic evidence, the most convincing efficacy profile emerged for amphetamines, methylphenidate and, to a smaller extent, behavioral therapy in attention‐deficit/hyperactivity disorder; aripiprazole, risperidone and several psychosocial interventions in autism; risperidone and behavioral interventions in disruptive behavior disorders; several antipsychotics in schizophrenia spectrum disorders; fluoxetine, the combination of fluoxetine and cognitive behavioral therapy (CBT), and interpersonal therapy in depression; aripiprazole in mania; fluoxetine and group CBT in anxiety disorders; fluoxetine/selective serotonin reuptake inhibitors, CBT, and behavioral therapy with exposure and response prevention in obsessive‐compulsive disorder; CBT in post‐traumatic stress disorder; imipramine and alarm behavioral intervention in enuresis; behavioral therapy in encopresis; and family therapy in anorexia nervosa. Results from this umbrella review of interventions for mental disorders in children/adolescents provide evidence‐based information for clinical decision making.

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Section: Resultsmentioning

confidence: 99%

Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review

et al. 2021

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“…RRBs in autism spectrum disorder (ASD) refer to stereotyped motor actions, for example, hand flapping and sensory manipulation of objects, as well as insistence of sameness features that include circumscribed interests, rituals, and compulsions ( Szatmari et al, 2006 ; Lam et al, 2008 ). A recent meta-analysis revealed that pharmacological treatments have limited effects in reducing RRBs, with anti-psychotics showing modest effects ( Zhou et al, 2020 ), although these treatments also have negative side effects ( Hesapcioglu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of the Partial M1 Muscarinic Cholinergic Receptor Agonist CDD-0102A on Stereotyped Motor Behaviors and Reversal Learning in the BTBR Mouse Model of Autism

Athnaiel

Job

Ocampo

et al. 2021

International Journal of Neuropsychopharmacology

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Background Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders marked by a lack of social interaction, restrictive interests and repetitive behaviors. There is a paucity of pharmacological treatments to reduce core ASD symptoms. Various lines of evidence indicate that reduced brain muscarinic cholinergic receptor activity may contribute to an ASD phenotype. Methods The present experiments examined whether the partial M1 muscarinic receptor agonist, CDD-0102A, alleviates behavioral flexibility deficits and/or stereotyped motor behaviors in the BTBR mouse model of autism. Behavioral flexibility was tested using a reversal learning test. Stereotyped motor behaviors were measured by eliciting digging behavior after removal of nesting material in a home cage and by measuring repetitive grooming. Results CDD-0102A (0.2 and 0.6 mg/kg but not 1.2 mg/kg) injected prior to reversal learning attenuated a deficit in BTBR mice, but did not affect performance in B6 mice. Acute CDD-0102A treatment (1.2 and 3 mg/kg) reduced self-grooming in BTBR mice and reduced digging behavior in B6 and BTBR mice. The M1 muscarinic receptor antagonist, VU0255035 (3 mg/kg) blocked the effect of CDD-0102A on grooming behavior. Chronic treatment with CDD-0102A (1.2 mg/kg) attenuated self-grooming and digging behavior in BTBR mice. Direct CDD-0102A infusions (1 µg) into the dorsal striatum reduced elevated digging behavior in BTBR mice. In contrast, CDD-0102A injections in the frontal cortex were not effective. Conclusions The results suggest that treatment with a partial M1 muscarinic receptor agonist may reduce repetitive behaviors and restricted interests in autism in part by stimulating striatal M1 muscarinic receptors.

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“…There was one previous meta-analysis examining the efficacy of pharmacological treatments for RRBs in ASD. Bumetanide was one of the included pharmacological options in their study and was significantly associated with the improvement of RRB outcomes compared with placebo ( 27 ). Our results are congruent with this study.…”

Section: Discussionmentioning

confidence: 99%

Treatment Effect of Bumetanide in Children With Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

et al. 2021

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Background: The therapeutic effect of bumetanide on autism spectrum disorder (ASD) seems to be controversial. To obtain better evidence on the efficacy of bumetanide, a systematic review and meta-analysis were performed.Methods: Randomized, placebo-controlled trials (RCTs) of bumetanide treatment in children with ASD were identified through systematic review from database inception to January 17, 2021. Subsequently, a meta-analysis was carried out to examine the effect of bumetanide on the severity of symptoms of ASD as assessed by the Childhood Autism Rating Scale (CARS) and Social Responsive Scale (SRS); core symptoms according to criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 of the American Psychiatric Association [social affect (SA), restricted, repetitive patterns of behavior, interests, or activities (RRB) and sensory symptoms]; and the therapeutic effect as assessed by Clinical Global Impressions-Efficacy (CGI-E).Results: In total, six RCTs involving 496 participants with ASD were identified in our study. The results showed that bumetanide could significantly improve the severity of the ASD symptoms measured by CARS and SRS. There was also evidence that bumetanide had positive effect on the core symptoms of ASD such as the SA and RRB, but there was no statistically significant effect on sensory symptoms. A significant positive effect on CGI-E scores in ASD patients was also observed.Conclusion: Our meta-analysis provided some support that bumetanide could improve the symptoms of children with ASD. However, additional large-scale longitudinal studies that provide clearer information and better control for confounding factors are needed to confirm our findings.

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Meta-analysis: Pharmacologic Treatment of Restricted and Repetitive Behaviors in Autism Spectrum Disorders

Cited by 76 publications

References 92 publications

Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review

Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review

Effects of the Partial M1 Muscarinic Cholinergic Receptor Agonist CDD-0102A on Stereotyped Motor Behaviors and Reversal Learning in the BTBR Mouse Model of Autism

Treatment Effect of Bumetanide in Children With Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

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