Impact of antipsychotics in children and adolescents with autism spectrum disorder: a systematic review and meta-analysis

Abstract

Background The net health benefit of using antipsychotics in children and adolescents with ASD is unclear. This review was performed to provide the evidence necessary to inform the Italian national guidelines for the management of ASD. Methods We performed a systematic review of randomized controlled trials (RCTs) comparing antipsychotics versus placebo for the treatment of ASD in children and adolescents. For efficacy, acceptability and safety we considered outcomes evaluated by the guideline panel critical and important for decision-making. Continuous outcomes were analyzed by using standardized mean difference (SMD), and dichotomous outcomes by calculating the risk ratio (RR), with their 95% confidence interval (95% CI). Data were analyzed using a random effects model. We used the Cochrane tool to assess risk of bias of included studies. Certainty in the evidence of effects was assessed according to the GRADE approach. Results We included 21 RCTs with 1,309 participants, comparing antipsychotics to placebo. Antipsychotics were found effective on “restricted and repetitive interests and behaviors” (SMD − 0.21, 95% CI − 0.35 to − 0.07, moderate certainty), “hyperactivity, inattention, oppositional, disruptive behavior” (SMD − 0.67, 95% CI − 0.92 to − 0.42, moderate certainty), “social communication, social interaction” (SMD − 0.38, 95% CI − 0.59 to − 0.16, moderate certainty), “emotional dysregulation/irritability” (SMD − 0.71, 95% CI − 0.98 to − 0.43, low certainty), “global functioning, global improvement” (SMD − 0.64, 95% CI − 0.96 to − 0.33, low certainty), “obsessions, compulsions” (SMD − 0.30, 95% CI − 0.55 to − 0.06, moderate certainty). Antipsychotics were not effective on “self-harm” (SMD − 0.14, 95% CI − 0.58 to 0.30, very low certainty), “anxiety” (SMD − 0.38, 95% CI − 0.82 to 0.07, very low certainty). Antipsychotics were more acceptable in terms of dropout due to any cause (RR 0.61, 95% CI 0.48 to 0.78, moderate certainty), but were less safe in terms of patients experiencing adverse events (RR 1.19, 95% CI 1.07 to 1.32, moderate certainty), and serious adverse events (RR 1.07, 95% CI 0.48 to 2.43, low certainty). Conclusions Our systematic review and meta-analysis found antipsychotics for children and adolescents with ASD more efficacious than placebo in reducing stereotypies, hyperactivity, irritability and obsessions, compulsions, and in increasing social communication and global functioning. Antipsychotics were also found to be more acceptable, but less safe than placebo.

A Pediatric Patient With Autism Spectrum Disorder and Comorbid Compulsive Behaviors Treated With Robot-Assisted Relaxation: A Case Report

“…Pharmacological treatment options including antipsychotic agents and stimulant medications are often used to address the symptoms of ASD and co-occurring conditions [ 5 ] and are considered effective in alleviating stereotypies, irritability, and obsessions [ 6 ], yet a risk-benefit analysis of pharmacotherapy should be performed in each case [ 7 ]. On top of that, caregivers appear to have a hesitant attitude towards psychotropic medications [ 8 ].…”

Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer’s Disease

“…Recently, many correlated medicinal interventions against the common symptoms in both diseases have been adopted. For example, for aggressive and agitated ASD and AD patients, antipsychotics, including quetiapine and risperidone, have been found effective [ 22 , 23 , 24 ]. For depression and anxiety, SSRIs (selective serotonin reuptake inhibitors), such as venlafaxine and citalopram, have been recommended [ 24 , 25 , 26 ].…”

“…For example, for aggressive and agitated ASD and AD patients, antipsychotics, including quetiapine and risperidone, have been found effective [ 22 , 23 , 24 ]. For depression and anxiety, SSRIs (selective serotonin reuptake inhibitors), such as venlafaxine and citalopram, have been recommended [ 24 , 25 , 26 ]. Furthermore, to manage sleep problems and improve neuron health and physiology, melatonin has been found effective [ 27 , 28 ].…”

The Use of Psychotropic Medication in Iranian Children with Developmental Disabilities

“…There is limited evidence that medications influence the core symptoms of ASD, such as social interaction and communication, and the presence of restricted behaviors, interests, and activities [7]. Rather, the medications are aimed at addressing associated behavioral symptoms, such as irritability, tantrums, aggression, self-harm, hyperactivity, and impulsivity.…”

“…Rather, the medications are aimed at addressing associated behavioral symptoms, such as irritability, tantrums, aggression, self-harm, hyperactivity, and impulsivity. Recent reviews of well-conducted randomized control trials contrasting risperidone with placebos report improvements in irritability and tantrums with some reduction in aggressive episodes and self-injurious behaviors [7,8]. Likewise, methylphenidate (Ritalin) has been well studied with improvements noted in hyperactivity and impulsivity across multiple studies, but no benefits were found for other common ASD-related behaviors, including stereotypies, repetitive behaviors, and oppositional behaviors [8].…”