Antipsychotics and Autism Ranking:

Current Research

Current Research Studies

We carried out a systematic search for research reviews, and clinical guidance, on the topic of antipsychotics as a treatment for autistic people in 2014.  We identified more than 60 scientific reviews on the topic of medications for autism, seven of which looked specifically at antipsychotics. We also examined the clinical guidance published by NICE. 

NICE (2012) reported

“The majority of the evidence on the use of antipsychotics for behaviour management in adults with autism compared risperidone with placebo, and there is limited evidence for a modest treatment effect of risperidone on irritability and aggression. In addition, there is some evidence that autistic behaviours, the core autistic symptom of repetitive behaviour, and global symptom severity may respond favourably to treatment with risperidone. However, the data from placebo-controlled and observational studies of risperidone in adults with a learning disability is inconsistent. In addition, most of the studies in autism and learning disabilities populations report data suggestive of adverse events associated with risperidone, in particular, sedation and weight gain. (Note, this is consistent with the evidence of adverse effects associated with the use of these drugs for schizophrenia.) It is also important to note that these trials were run over short time periods and very little is known about the long-term effects of antipsychotics in adults with autism. The evidence for haloperidol was very limited and inconsistent, with no evidence for significant treatment effects in adults with autism. The results for clopenthixol provided limited evidence ...   for a beneficial effect on the management of challenging behaviour in adults with a learning disability. The evidence for olanzapine for behaviour management is extremely limited ... with just one open-label study.”

NICE (2013) reported

“There is evidence for positive treatment effects of antipsychotic drugs on behaviour that challenges. The majority of the evidence on the use of antipsychotics for behaviour that challenges in children and young people with autism compared risperidone or aripiprazole with placebo, and there is moderate to low quality evidence for treatment effects on irritability, lethargy, stereotypic behaviour, hyperactivity, inappropriate speech and parent-defined target behaviours that challenge. However, there are also robust data suggestive of adverse events associated with risperidone or aripiprazole, in particular, weight gain, prolactin concentration and tachycardia. It is also important to note that these trials were run over short time periods and very little is known about the long-term effects of antipsychotic drugs in children and young people with autism.”

Barnard et al (2002) reported

“Conventional antipsychotic medication is commonly prescribed to patients with autistic spectrum disorder. However, a high incidence of severe adverse reactions highlights the need to find more favourable treatments. Atypical antipsychotics may combine efficacy in ameliorating some autistic symptoms with a lower incidence of some adverse reactions. This article reviews the use of atypical antipsychotics in autistic disorder, with particular focus on behaviour, cognition and physical well-being. Thirteen studies using risperidone, three using olanzapine, one using clozapine, one using amisulpride and one using quetiapine were identified. Few firm conclusions can be drawn due to the limitations of the studies; however, there is an indication that risperidone may be effective in reducing hyperactivity, aggression and repetitive behaviours, often without inducing severe adverse reactions. Olanzapine and clozapine may also be effective; however, there is little evidence for using amisulpride or quetiapine in this population. Randomized trials are required to clarify the effectiveness of these agents.”

Chavez et al (2007) reported

“Of the AAs [atypical antipsychotics], risperidone has the largest amount of evidence with five published double-blinded, placebo-controlled trials and nine open-label trials. These risperidone trials have consistently shown improvements in aggression, irritability, self-injurious behavior, temper tantrums, and quickly changing moods associated with autistic disorder and other PDDs. Data for the other AAs are limited, but ziprasidone and aripiprazole appear to be promising treatment options. Based on clinical trials, olanzapine and quetiapine have shown minimal clinical benefit and a high incidence of weight gain and sedation. It should be noted that all AAs do have a risk of metabolic syndrome, and patients should be monitored appropriately while receiving these medications. Overall, AAs can be beneficial in alleviating behavioral symptoms, and should be considered an appropriate therapeutic option, as part of a comprehensive treatment strategy, for children with PDD.”

Malone et al (2009) reported

“Antipsychotics are beneficial for reducing problematic behaviours and improving overall functioning in patients with autism. These drugs should always be used as an adjunctive treatment to other interventions such as psychosocial and educational programmes. Among antipsychotics, the second-generation agents appear promising, especially risperidone, which has recently gained FDA approval for treatment in youths with autistic disorder. Most second generation agents have the potential to cause weight gain and associated metabolic syndrome. Therefore, regular monitoring of weight, blood pressure, glucose and lipids is required. Among the second-generation agents, ziprasidone and aripiprazole appear to have a lesser risk of metabolic adverse effects. More controlled studies are needed to assess efficacy and safety of these agents on a short- and long-term basis. Also needed are head-to-head studies of antipsychotics to address differences.”

Politte and McDougle (2014) reported

“The efficacy and tolerability of risperidone and aripiprazole for the treatment of irritability in autism have been established with multi-site, randomized, controlled trials. Studies supporting the use of other atypical antipsychotics are either limited in scope or less robust in their findings, though newer agents such as ziprasidone and paliperidone show promise. Atypical antipsychotics are currently first-line pharmacological agents for the treatment of irritability and associated behaviors in children with PDD. Further placebo controlled studies are warranted to characterize the efficacy and tolerability of the majority of these medications. There is also a need for the development of novel, targeted drugs with more favorable long-term side effect profiles.”

Posey et al (2008) reported

“Both haloperidol and risperidone have been shown to be efficacious for treating several of the behavioral symptoms associated with autism. The current role of haloperidol is limited due to the risk of EPS, especially TD. Because of this, atypical antipsychotics are more commonly used today in treating persons with autism. Despite the efficacy of risperidone, the decision to prescribe this drug needs to include consideration of the potential side effects, especially those of weight gain, hyperprolactinemia, and TD... Despite its efficacy for reducing behavioral symptoms, it is unclear whether risperidone improves the core social and communication impairment of autism. Indeed, a study that included less irritable children found a lower rate or magnitude of response. Additional studies of risperidone and other atypical antipsychotics in nonirritable children with autism or studies using other measures of social impairment might be informative. It also remains to be determined whether atypical antipsychotics other than risperidone are effective in the treatment of disruptive science in medicine behavior in autism. Large placebo-controlled studies of olanzapine and aripiprazole are underway. The long-term significance of hyperprolactinemia, as well as the long-term risk of TD, needs to be determined in either prospectively defined cohorts or via larger controlled studies of longer duration. Finally, further research that informs the clinical management of weight gain occurring with these drugs when used in autism is needed. This might include identifying patients who are genetically more susceptible to this side effect as well as determining the best approach to management (e.g., diet and/or exercise, switching drugs, or pharmacologic treatments).”

Sochocky and Milin (2013) reported

“There is a lack of robustly conducted trials on the use of SGAs in the management of AD and HFA. More research in pharmacological and psychosocial treatments is warranted. Clinicians are cautioned to approach pharmacological treatment prudently balancing benefit with potential cardiometabolic risk.”

Stachnik and Nunn-Thompson (2007) (reported)

“Based on available information, atypical antipsychotics may improve behavior in individuals with AD, but do not affect the core symptoms of the disorder. However, given that AD requires life-long treatment and that data are limited on the safety of these agents in children, vigilance is especially necessary when prescribing any of the atypical antipsychotics. Long-term clinical trials that incorporate realistic inclusion criteria and uniform outcome and safety assessment tools are critical before these drugs can be broadly recommended for chronic administration to children with AD.”

Updated

17 Jun 2022

Last Review

01 Nov 2016

Next Review

01 Mar 2023