Current scientific evidence shows efficacy in ASD

Aripiprazole for autism spectrum disorders (ASD) Cochrane Review *Warning: Notable Side Effects

Authors’ conclusions

Evidence from two RCTs suggests that aripiprazole can be effective as a short-term medication intervention for some behavioural aspects of ASD in children/adolescents. After a short-term medication intervention with aripiprazole, children/adolescents showed less irritability and hyperactivity and fewer stereotypies (repetitive, purposeless actions). However, notable side effects, such as weight gain, sedation, drooling and tremor, must be considered. One long-term, placebo discontinuation study found that relapse rates did not differ between children/adolescents randomised to continue aripiprazole versus children/adolescents randomised to receive placebo, suggesting that re-evaluation of aripiprazole use after a period of stabilisation in irritability symptoms is warranted. Studies included in this review used criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (APA 2000) for ASD diagnosis; however, the diagnostic criteria for ASD changed significantly with release of the fifth edition of the DSM (DSM-5) in 2013 (APA 2013).

Early intensive behavioral intervention (EIBI) for increasing functional behaviors and skills in young children with autism spectrum disorders (ASD) Cochrane Review

Authors’ conclusions

There is some evidence that EIBI is an effective behavioral treatment for some children with ASD. However, the current state of the evidence is limited because of the reliance on data from non-randomized studies (CCTs) due to the lack of RCTs. Additional studies using RCT research designs are needed to make stronger conclusions about the effects of EIBI for children with ASD.

Early intervention delivered by parents for young children with autism spectrum disorders Cochrane Review

Authors’ conclusions

The review finds some evidence for the effectiveness of parent-mediated interventions, most particularly in proximal indicators within parent-child interaction, but also in more distal indicators of child language comprehension and reduction in autism severity. Evidence of whether such interventions may reduce parent stress is inconclusive. The review reinforces the need for attention to be given to early intervention service models that enable parents to contribute skilfully to the treatment of their child with autism. However, practitioners supporting parent-mediated intervention require to monitor levels of parent stress. The ability to draw conclusions from studies would be improved by researchers adopting a common set of outcome measures as the quality of the current evidence is low.

Music therapy for people with autism spectrum disorder Cochran Review

Authors’ conclusions

The findings of this updated review provide evidence that music therapy may help children with ASD to improve their skills in primary outcome areas that constitute the core of the condition including social interaction, verbal communication, initiating behaviour, and social-emotional reciprocity. Music therapy may also help to enhance non-verbal communication skills within the therapy context. Furthermore, in secondary outcome areas, music therapy may contribute to increasing social adaptation skills in children with ASD and to promoting the quality of parent-child relationships. In contrast to the studies included in an earlier version of this review published in 2006, the new studies included in this update enhanced the applicability of findings to clinical practice. More research using larger samples and generalised outcome measures is needed to corroborate these findings and to examine whether the effects of music therapy are enduring. When applying the results of this review to practice, it is important to note that the application of music therapy requires specialised academic and clinical training.

Social skills groups for people aged 6 to 21 years with autism spectrum disorders (ASD) Cochrane Review

Authors’ conclusions

There is some evidence that social skills groups can improve social competence for some children and adolescents with ASD. More research is needed to draw more robust conclusions, especially with respect to improvements in quality of life.

Oxytocin and autism: a systematic review of randomized controlled trials.



Little is known about the effectiveness of pharmacological interventions on autism spectrum disorder (ASD). This is a systematic review of the randomized controlled trials (RCTs) of oxytocin interventions in autism, made from January 1990 to September 2013.


A search of computerized databases was supplemented by manual search in the bibliographies of key publications. The methodological quality of the studies included in the review was evaluated independently by two researchers, according to a set of formal criteria. Discrepancies in scoring were resolved through discussion.


The review yielded seven RCTs, including 101 subjects with ASD (males=95) and 8 males with Fragile X syndrome. The main categories of target symptoms tested in the studies were repetitive behaviors, eye gaze, and emotion recognition. The studies had a medium to high risk of bias. Most studies had small samples (median=15). All the studies but one reported statistically significant between-group differences on at least one outcome variable. Most findings were characterized by medium effect size. Only one study had evidence that the improvement in emotion recognition was maintained after 6 weeks of treatment with intranasal oxytocin. Overall, oxytocin was well tolerated and side effects, when present, were generally rated as mild; however, restlessness, increased irritability, and increased energy occurred more often under oxytocin.


RCTs of oxytocin interventions in autism yielded potentially promising findings in measures of emotion recognition and eye gaze, which are impaired early in the course of the ASD condition and might disrupt social skills learning in developing children. There is a need for larger, more methodologically rigorous RCTs in this area. Future studies should be better powered to estimate outcomes with medium to low effect size, and should try to enroll female participants, who were rarely considered in previous studies. Risk of bias should be minimized. Human long-term administration studies are necessary before clinical recommendations can be made.

Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy.


The popularity of oxytocin (OT) has grown exponentially during the past decade, and so has the number of OT trials in healthy and clinical groups. We take stock of the evidence from these studies to explore potentials and limitations of pharmacotherapeutic applications. In healthy participants, intranasally administered OT leads to better emotion recognition and more trust in conspecifics, but the effects appear to be moderated by context (perceived threat of the ‘out-group’), personality and childhood experiences. In individuals with untoward childhood experiences, positive behavioral or neurobiological effects seem lowered or absent. In 19 clinical trials, covering autism, social anxiety, postnatal depression, obsessive-compulsive problems, schizophrenia, borderline personality disorder and post-traumatic stress, the effects of OT administration were tested, with doses ranging from 15 IU to more than 7000 IU. The combined effect size was d=0.32 (N=304; 95% confidence interval (CI): 0.18-0.47; P<0.01). However, of all disorders, only studies on autism spectrum disorder showed a significant combined effect size (d=0.57; N=68; 95% CI: 0.15-0.99; P<0.01). We hypothesize that for some of the other disorders, etiological factors rooted in negative childhood experiences may also have a role in the diminished effectiveness of treatment with OT.

Promising evidence and remaining issues regarding the clinical application of oxytocin in autism spectrum disorders.


Oxytocin is a potential therapeutic for the core symptoms of autism spectrum disorder (ASD), which is currently untreatable with pharmacotherapy. Previous clinical trials of a single dose of oxytocin have consistently reported significantly positive effects on various experimental measures associated with the core symptoms of ASD. These studies used various experimental measures as surrogate endpoints of the trials. However, to date, randomized clinical trials of continual administration of oxytocin have failed to reveal significant positive effects on clinically meaningful endpoints, such as how those with ASD interact during interpersonal interactions. This article reviews both the negative and positive effects of oxytocin on the core symptoms of ASD and their surrogate markers. Some unresolved and critical issues on the development of oxytocin as a new therapeutic have been extracted: optimization of dose, duration of oxytocin treatment, and the development of objective and reliable measurements of clinically meaningful endpoints for the core symptoms of ASD. Furthermore, optimization to the intranasal delivery system and careful consideration of how individuals respond differently to treatments should be addressed in future studies.

Beyond the hype and hope: Critical considerations for intranasal oxytocin research in autism spectrum disorder.


Extensive research efforts in the last decade have been expended into understanding whether intranasal oxytocin may be an effective therapeutic in treating social communication impairments in individuals with autism spectrum disorder (ASD). After much hyped early findings, subsequent clinical trials of longer-term administration have yielded more conservative and mixed evidence. However, it is still unclear at this stage whether these more disappointing findings reflect a true null effect or are mitigated by methodological differences masking true effects. In this review, we comprehensively evaluate the rationale for oxytocin as a therapeutic, evaluating evidence from randomized controlled trials, case reports, and open-label studies of oxytocin administration in individuals with ASD. The evidence to date, including reviews of preregistered trials, suggests a number of critical considerations for the design and interpretation of research in this area. These include considering the choice of ASD outcome measures, dosing and nasal spray device issues, and participant selection. Despite these limitations in the field to date, there remains significant potential for oxytocin to ameliorate aspects of the persistent and debilitating social impairments in individuals with ASD. Given the considerable media hype around new treatments for ASD, as well as the needs of eager families, there is an urgent need for researchers to prioritise considering such factors when conducting well-designed and controlled studies to further advance this field.



Current scientific evidence is limited or lackingĀ 

Acupuncture for people with autism spectrum disorders (ASD) Cochrane Review

Authors’ conclusions

Current evidence does not support the use of acupuncture for treatment of ASD. There is no conclusive evidence that acupuncture is effective for treatment of ASD in children and no RCTs have been carried out with adults. Further high quality trials of larger size and longer follow-up are needed.

Auditory integration therapy for autism spectrum disorders Cochrane Review

Authors’ conclusions

There is no evidence that auditory integration therapy or other sound therapies are effective as treatments for autism spectrum disorders. As synthesis of existing data has been limited by the disparate outcome measures used between studies, there is not sufficient evidence to prove that this treatment is not effective. However, of the seven studies including 182 participants that have been reported to date, only two (with an author in common), involving a total of 35 participants, report statistically significant improvements in the auditory intergration therapy group and for only two outcome measures (Aberrant Behaviour Checklist and Fisher’s Auditory Problems Checklist). As such, there is no evidence to support the use of auditory integration therapy at this time.

Chelation for autism spectrum disorder (ASD) Cochrane Review

Authors’ conclusions

This review included data from only one study, which had methodological limitations. As such, no clinical trial evidence was found to suggest that pharmaceutical chelation is an effective intervention for ASD. Given prior reports of serious adverse events, such as hypocalcaemia, renal impairment and reported death, the risks of using chelation for ASD currently outweigh proven benefits. Before further trials are conducted, evidence that supports a causal link between heavy metals and autism and methods that ensure the safety of participants are needed.

Gluten and casein-free diets for autism spectrum disorder Cochrane Review

Authors’ conclusions

Research has shown of high rates of use of complementary and alternative therapies (CAM) for children with autism including gluten and/or casein exclusion diets. Current evidence for efficacy of these diets is poor. Large scale, good quality randomized controlled trials are needed.

High-pressure oxygen therapy for children and adults with autism spectrum disorder (ASD)

Authors’ conclusions

To date, there is no evidence that hyperbaric oxygen therapy improves core symptoms and associated symptoms of ASD. It is important to note that adverse effects (minor-grade ear barotrauma events) can occur. Given the absence of evidence of effectiveness and the limited biological plausibility and possible adverse effects, the need for future RCTs of hyperbaric oxygen therapy must be carefully considered.

Intravenous secretin for autism spectrum disorders (ASD) Cochrane Review

Authors’ conclusions

There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin’s effectiveness for ASD can only be justified if there is new high-quality and replicated scientific evidence that either finds that secretin has a role in neurotransmission in a way that could benefit all children with ASD or identifies important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing.

Omega-3 fatty acids for autism spectrum disorders (ASD)Cochrane Review

Authors’ conclusions

To date there is no high quality evidence that omega-3 fatty acids supplementation is effective for improving core and associated symptoms of ASD. Given the paucity of rigorous studies in this area, there is a need for large well-conducted randomised controlled trials that examine both high and low functioning individuals with ASD, and that have longer follow-up periods.

Risperidone for autism spectrum disorder Cochrane Review

Authors’ conclusions

Risperidone can be beneficial in some features of autism. However there are limited data available from studies with small sample sizes. In addition, there lacks a single standardised outcome measure allowing adequate comparison of studies, and long-term followup is also lacking. Further research is necessary to determine the efficacy pf risperidone in clinical practice.

Selective serotonin reuptake inhibitors for treating people with autism spectrum disorders Cochrane Review

Authors’ conclusions

There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.

A review of evidence on the use of interventions for people with autism spectrum disorder, based on the psychological model 'Theory of Mind' Cochrane Review

Authors’ conclusions

While there is some evidence that ToM, or a precursor skill, can be taught to people with ASD, there is little evidence of maintenance of that skill, generalisation to other settings, or developmental effects on related skills. Furthermore, inconsistency in findings and measurement means that evidence has been graded of ‘very low’ or ‘low’ quality and we cannot be confident that suggestions of positive effects will be sustained as high-quality evidence accumulates. Further longitudinal designs and larger samples are needed to help elucidate both the efficacy of ToM-linked interventions and the explanatory value of the ToM model itself. It is possible that the continuing refinement of the ToM model will lead to better interventions which have a greater impact on development than those investigated to date.

Tricyclic antidepressant medication for treating children and adolescents with an autism spectrum disorder Cochrane Review

Authors’ conclusions

Clinicians considering the use of TCAs need to be aware of the limited and conflicting evidence of effect and the side effect profile when discussing this treatment option with people who have ASD and their carers. Further research is required before TCAs can be recommended for treatment of individuals with ASD.

Vitamin B6 and magnesium in combination for children with autism spectrum disorder Cochrane Review

Authors’ conclusions

Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism.