BACKGROUND: Social interaction and social communication are among the central areas of difficulty for autistic people. Music therapy uses music experiences and the relationships that develop through them to enable communication and expression, thus attempting to address some of the core problems of autistic people. Music therapy has been applied in autism since the early 1950s, but its availability to autistic individuals varies across countries and settings. The application of music therapy requires specialised academic and clinical training which enables therapists to tailor the intervention to the specific needs of the individual. The present version of this review on music therapy for autistic people is an update of the previous Cochrane review update published in 2014 (following the original Cochrane review published in 2006).
OBJECTIVES: To review the effects of music therapy, or music therapy added to standard care, for autistic people.
SEARCH METHODS: In August 2021, we searched CENTRAL, MEDLINE, Embase, eleven other databases and two trials registers. We also ran citation searches, checked reference lists, and contacted study authors to identify additional studies.
SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-randomised trials and controlled clinical trials comparing music therapy (or music therapy alongside standard care) to 'placebo' therapy, no treatment, or standard care for people with a diagnosis of autism spectrum disorder were considered for inclusion.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Four authors independently selected studies and extracted data from all included studies. We synthesised the results of included studies in meta-analyses. Four authors independently assessed risk of bias (RoB) of each included study using the original RoB tool as well as the certainty of evidence using GRADE. MAIN RESULTS: We included 16 new studies in this update which brought the total number of included studies to 26 (1165 participants). These studies examined the short- and medium-term effect of music therapy (intervention duration: three days to eight months) for autistic people in individual or group settings. More than half of the studies were conducted in North America or Asia. Twenty-one studies included children aged from two to 12 years. Five studies included children and adolescents, and/or young adults. Severity levels, language skills, and cognition were widely variable across studies. Measured immediately post-intervention, music therapy compared with 'placebo' therapy or standard care was more likely to positively effect global improvement (risk ratio (RR) 1.22, 95% confidence interval (CI) 1.06 to 1.40; 8 studies, 583 participants; moderate-certainty evidence; number needed to treat for an additional beneficial outcome (NNTB) = 11 for low-risk population, 95% CI 6 to 39; NNTB = 6 for high-risk population, 95% CI 3 to 21) and to slightly increase quality of life (SMD 0.28, 95% CI 0.06 to 0.49; 3 RCTs, 340 participants; moderate-certainty evidence, small to medium effect size). In addition, music therapy probably results in a large reduction in total autism symptom severity (SMD -0.83, 95% CI -1.41 to -0.24; 9 studies, 575 participants; moderate-certainty evidence). No clear evidence of a difference between music therapy and comparison groups at immediately post-intervention was found for social interaction (SMD 0.26, 95% CI -0.05 to 0.57, 12 studies, 603 participants; low-certainty evidence); non-verbal communication (SMD 0.26, 95% CI -0.03 to 0.55; 7 RCTs, 192 participants; low-certainty evidence); and verbal communication (SMD 0.30, 95% CI -0.18 to 0.78; 8 studies, 276 participants; very low-certainty evidence). Two studies investigated adverse events with one (36 participants) reporting no adverse events; the other study found no differences between music therapy and standard care immediately post-intervention (RR 1.52, 95% CI 0.39 to 5.94; 1 study, 290 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: The findings of this updated review provide evidence that music therapy is probably associated with an increased chance of global improvement for autistic people, likely helps them to improve total autism severity and quality of life, and probably does not increase adverse events immediately after the intervention. The certainty of the evidence was rated as 'moderate' for these four outcomes, meaning that we are moderately confident in the effect estimate. No clear evidence of a difference was found for social interaction, non-verbal communication, and verbal communication measured immediately post-intervention. For these outcomes, the certainty of the evidence was rated as 'low' or 'very low', meaning that the true effect may be substantially different from these results. Compared with earlier versions of this review, the new studies included in this update helped to increase the certainty and applicability of this review's findings through larger sample sizes, extended age groups, longer periods of intervention and inclusion of follow-up assessments, and by predominantly using validated scales measuring generalised behaviour (i.e. behaviour outside of the therapy context). This new evidence is important for autistic individuals and their families as well as for policymakers, service providers and clinicians, to help in decisions around the types and amount of intervention that should be provided and in the planning of resources. The applicability of the findings is still limited to the age groups included in the studies, and no direct conclusions can be drawn about music therapy in autistic individuals above the young adult age. More research using rigorous designs, relevant outcome measures, and longer-term follow-up periods is needed to corroborate these findings and to examine whether the effects of music therapy are enduring.
BACKGROUND: It has been suggested that peptides from gluten and casein may have a role in the origins of autism and that the physiology and psychology of autism might be explained by excessive opioid activity linked to these peptides. Research has reported abnormal levels of peptides in the urine and cerebrospinal fluid of people with autism.
OBJECTIVES: To determine the efficacy of gluten and/or casein free diets as an intervention to improve behaviour, cognitive and social functioning in individuals with autism.
SEARCH METHODS: The following electronic databases were searched: CENTRAL(The Cochrane Library Issue 2, 2007), MEDLINE (1966 to April 2007), PsycINFO (1971 to April 2007), EMBASE (1974 to April 2007), CINAHL (1982 to April 2007), ERIC (1965 to 2007), LILACS (1982 to April 2007), and the National Research register 2007 (Issue1). Review bibliographies were also examined to identify potential trials.
SELECTION CRITERIA: All randomised controlled trials (RCT) involving programmes which eliminated gluten, casein or both gluten and casein from the diets of individuals diagnosed with an autistic spectrum disorder.
DATA COLLECTION AND ANALYSIS: Abstracts of studies identified in searches of electronic databases were assessed to determine inclusion by two independent authors The included trials did not share common outcome measures and therefore no meta-analysis was possible. Data are presented in narrative form.
MAIN RESULTS: Two small RCTs were identified (n = 35). No meta-analysis was possible. There were only three significant treatment effects in favour of the diet intervention: overall autistic traits, mean difference (MD) = -5.60 (95% CI -9.02 to -2.18), z = 3.21, p=0.001 (Knivsberg 2002) ; social isolation, MD = -3.20 (95% CI -5.20 to 1.20), z = 3.14, p = 0.002) and overall ability to communicate and interact, MD = 1.70 (95% CI 0.50 to 2.90), z = 2.77, p = 0.006) (Knivsberg 2003). In addition three outcomes showed no significant difference between the treatment and control group and we were unable to calculate mean differences for ten outcomes because the data were skewed. No outcomes were reported for disbenefits including harms.
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 randomised controlled trials are needed.
BACKGROUND: The rising prevalence of autism spectrum disorders (ASD) increases the need for evidence-based behavioral treatments to lessen the impact of symptoms on children's functioning. At present, there are no curative or psychopharmacological therapies to effectively treat all symptoms of the disorders. Early intensive behavioral intervention (EIBI) is a treatment based on the principles of applied behavior analysis. Delivered for multiple years at an intensity of 20 to 40 hours per week, it is one of the more well-established treatments for ASD. This is an update of a Cochrane review last published in 2012.
OBJECTIVES: To systematically review the evidence for the effectiveness of EIBI in increasing functional behaviors and skills, decreasing autism severity, and improving intelligence and communication skills for young children with ASD.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, 12 additional electronic databases and two trials registers in August 2017. We also checked references and contacted study authors to identify additional studies.
SELECTION CRITERIA: Randomized control trials (RCTs), quasi-RCTs, and controlled clinical trials (CCTs) in which EIBI was compared to a no-treatment or treatment-as-usual control condition. Participants must have been less than six years of age at treatment onset and assigned to their study condition prior to commencing treatment.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.We synthesized the results of the five studies using a random-effects model of meta-analysis, with a mean difference (MD) effect size for outcomes assessed on identical scales, and a standardized mean difference (SMD) effect size (Hedges' g) with small sample correction for outcomes measured on different scales. We rated the quality of the evidence using the GRADE approach.
MAIN RESULTS: We included five studies (one RCT and four CCTs) with a total of 219 children: 116 children in the EIBI groups and 103 children in the generic, special education services groups. The age of the children ranged between 30.2 months and 42.5 months. Three of the five studies were conducted in the USA and two in the UK, with a treatment duration of 24 months to 36 months. All studies used a treatment-as-usual comparison group.Primary outcomesThere is low quality-evidence at post-treatment that EIBI improves adaptive behaviour (MD 9.58 (assessed using Vineland Adaptive Behavior Scale (VABS) Composite; normative mean = 100, normative SD = 15), 95% confidence interval (CI) 5.57 to 13.60, P < 0.0001; 5 studies, 202 participants), and reduces autism symptom severity (SMD −0.34, 95% CI −0.79 to 0.11, P = 0.14; 2 studies, 81 participants; lower values indicate positive effects) compared to treatment as usual.No adverse effects were reported across studies.Secondary outcomesThere is low-quality evidence at post-treatment that EIBI improves IQ (MD 15.44 (assessed using standardized IQ tests; scale 0 to 100, normative SD = 15), 95% CI 9.29 to 21.59, P < 0.001; 5 studies, 202 participants); expressive (SMD 0.51, 95% CI 0.12 to 0.90, P = 0.01; 4 studies, 165 participants) and receptive (SMD 0.55, 95% CI 0.23 to 0.87, P = 0.001; 4 studies, 164 participants) language skills; and problem behaviour (SMD -0.58, 95% CI -1.24 to 0.07, P = 0.08; 2 studies, 67 participants) compared to treatment as usual.
AUTHORS' CONCLUSIONS: There is weak evidence that EIBI may be an effective behavioral treatment for some children with ASD; the strength of the evidence in this review is limited because it mostly comes from small studies that are not of the optimum design. Due to the inclusion of non-randomized studies, there is a high risk of bias and we rated the overall quality of evidence as 'low' or 'very low' using the GRADE system, meaning further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.It is important that providers of EIBI are aware of the current evidence and use clinical decision-making guidelines, such as seeking the family’s input and drawing upon prior clinical experience, when making recommendations to clients on the use EIBI. Additional studies using rigorous research designs are needed to make stronger conclusions about the effects of EIBI for children with ASD.
BACKGROUND: Autism spectrum disorders (ASD) include autistic disorder, Asperger's disorder and pervasive developmental disorder - not otherwise specified (PDD-NOS). Antipsychotics have been used as a medication intervention for irritability related to ASD. Aripiprazole, a third-generation, atypical antipsychotic, is a relatively new drug that has a unique mechanism of action different from that of other antipsychotics. This review updates a previous Cochrane review on the safety and efficacy of aripiprazole for individuals with ASD, published in 2011 (Ching 2011).
OBJECTIVES: To assess the safety and efficacy of aripiprazole as medication treatment for individuals with ASD.
SEARCH METHODS: In October 2015, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and seven other databases as well as two trial registers. We searched for records published in 1990 or later, as this was the year aripiprazole became available.
SELECTION CRITERIA: Randomised controlled trials (RCTs) of aripiprazole (administered orally and at any dosage) versus placebo for treatment of individuals with a diagnosis of ASD.
DATA COLLECTION AND ANALYSIS: Two review authors independently collected, evaluated and analysed data. We performed meta-analysis for primary and secondary outcomes, when possible. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach to rate the overall quality of the evidence.
MAIN RESULTS: We included three trials in this review. Two were included in the previous published review, and the results of one, placebo-controlled discontinuation study were added to this review. Although we searched for studies across age groups, we found only studies conducted in children and youth. Included trials had low risk of bias across most domains. High risk of bias was seen in only one trial with incomplete outcome data. We judged the overall quality of the evidence for most outcomes to be moderate.Two RCTs with similar methods evaluated use of aripiprazole for a duration of eight weeks in 316 children/adolescents with ASD. Meta-analysis of study results revealed a mean improvement of -6.17 points on the Aberrant Behavior Checklist (ABC) - Irritability subscale (95% confidence intervals (CIs) -9.07 to -3.26, two studies, 308 children/adolescents, moderate-quality evidence), -7.93 points on the ABC - Hyperactivity subscale (95% CI -10.98 to -4.88, two studies, 308 children/adolescents, moderate-quality evidence) and -2.66 points on the ABC - Stereotypy subscale (95% CI -3.55 to -1.77, two studies, 308 children/adolescents, moderate-quality evidence) in children/adolescents taking aripiprazole relative to children/adolescents taking placebo. In terms of side effects, children/adolescents taking aripiprazole had a greater increase in weight, with a mean increase of 1.13 kg relative to placebo (95% CI 0.71 to 1.54, two studies, 308 children/adolescents, moderate-quality evidence), and had a higher risk ratio (RR) for sedation (RR 4.28, 95% CI 1.58 to 11.60, two studies, 313 children/adolescents, moderate-quality evidence) and tremor (RR 10.26, 95% CI 1.37 to 76.63, two studies, 313 children/adolescents, moderate-quality evidence). A randomised, placebo-controlled discontinuation study found that 35% of children/adolescents randomised to continue intervention with aripiprazole relapsed with respect to their symptoms of irritability, compared with 52% of children/adolescents randomised to placebo, for a hazard ratio of 0.57 (95% CI 0.28 to 1.12, 85 children/adolescents, low-quality evidence).All three included trials were supported by Bristol-Myers Squibb (Princeton, NJ) and Otsuka Pharmaceutical Company, Ltd. (Tokyo, Japan), with editorial support provided by Ogilvy Healthworld Medical Education and Bristol-Myers Squibb.
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).
BACKGROUND: The rising prevalence of autism spectrum disorder (ASD) has increased the need for evidence-based treatments to lessen the impact of symptoms. Presently, no therapies are available to effectively treat individuals with all of the symptoms of this disorder. It has been suggested that hyperbaric oxygen therapy may alleviate the biochemical dysfunction and clinical symptoms of ASD.
OBJECTIVES: To determine whether treatment with hyperbaric oxygen:1. improves core symptoms of ASD, including social communication problems and stereotypical and repetitive behaviors;2. improves noncore symptoms of ASD, such as challenging behaviors;3. improves comorbid states, such as depression and anxiety; and4. causes adverse effects.
SEARCH METHODS: On 10 December 2015, we searched CENTRAL, Ovid MEDLINE, Embase, and 15 other databases, four of which were Chinese language databases. We also searched multiple trial and research registers.
SELECTION CRITERIA: We selected randomized controlled trials (RCTs) and quasi-RCTs of any dose, duration, and frequency for hyperbaric oxygen therapy compared with no treatment or sham treatment for children and adults with ASD.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration, in that three review authors independently selected studies, assessed them for risk of bias, and extracted relevant data. We also assessed the quality of the evidence by using the GRADE approach.
MAIN RESULTS: We included one trial with a total of 60 children with a diagnosis of ASD who randomly received hyperbaric oxygen therapy or a sham treatment. Using GRADE criteria, we rated the quality of the evidence as low because of the small sample size and wide confidence intervals (CIs). Other problems included selection bias and short duration or follow-up.Overall, study authors reported no improvement in social interaction and communication, behavioral problems, communication and linguistic abilities, or cognitive function. With regard to the safety of hyperbaric oxygen therapy (adverse events), they reported minor-grade ear barotrauma events. Investigators found significant differences between groups in total number of side effect events (Peto odds ratio (OR) 3.87, 95% CI 1.53 to 9.82) and in the number of children who experienced side effects (Peto OR 4.40, 95% CI 1.33 to 14.48).
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.
BACKGROUND: It has been suggested that the severity of autism spectrum disorder (ASD) symptoms is positively correlated with the level of circulating or stored toxic metals, and that excretion of these heavy metals, brought about by the use of pharmaceutical chelating agents, results in improved symptoms.
OBJECTIVES: To assess the potential benefits and adverse effects of pharmaceutical chelating agents (referred to as chelation therapy throughout this review) for autism spectrum disorder (ASD) symptoms.
SEARCH METHODS: We searched the following databases on 6 November 2014: CENTRAL, Ovid MEDLINE, Ovid MEDLINE In-Process, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and 15 other databases, including three trials registers. In addition we checked references lists and contacted experts.
SELECTION CRITERIA: All randomised controlled trials of pharmaceutical chelating agents compared with placebo in individuals with ASD.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed them for risk of bias and extracted relevant data. We did not conduct a meta-analysis, as only one study was included.
MAIN RESULTS: We excluded nine studies because they were non-randomised trials or were withdrawn before enrolment. We included one study, which was conducted in two phases. During the first phase of the study, 77 children with ASD were randomly assigned to receive seven days of glutathione lotion or placebo lotion, followed by three days of oral dimercaptosuccinic acid (DMSA). Forty-nine children who were found to be high excreters of heavy metals during phase one continued on to phase two to receive three days of oral DMSA or placebo followed by 11 days off, with the cycle repeated up to six times. The second phase thus assessed the effectiveness of multiple doses of oral DMSA compared with placebo in children who were high excreters of heavy metals and who received a three-day course of oral DMSA. Overall, no evidence suggests that multiple rounds of oral DMSA had an effect on ASD symptoms.
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.
BACKGROUND: The 'Theory of Mind' (ToM) model suggests that people with autism spectrum disorder (ASD) have a profound difficulty understanding the minds of other people - their emotions, feelings, beliefs, and thoughts. As an explanation for some of the characteristic social and communication behaviours of people with ASD, this model has had a significant influence on research and practice. It implies that successful interventions to teach ToM could, in turn, have far-reaching effects on behaviours and outcome.
OBJECTIVES: To review the efficacy of interventions based on the ToM model for individuals with ASD.
SEARCH METHODS: In August 2013 we searched CENTRAL, Ovid MEDLINE, Embase, CINAHL, PsycINFO, ERIC, Social Services Abstracts, AutismData, and two trials registers. We also searched the reference lists of relevant papers, contacted authors who work in this field, and handsearched a number of journals.
SELECTION CRITERIA: Review studies were selected on the basis that they reported on an applicable intervention (linked to ToM in one of four clearly-defined ways), presented new randomised controlled trial data, and participants had a confirmed diagnosis of an autism spectrum disorder. Studies were selected by two review authors independently and a third author arbitrated when necessary.
DATA COLLECTION AND ANALYSIS: Risk of bias was evaluated and data were extracted by two review authors independently; a third author arbitrated when necessary. Most studies were not eligible for meta-analysis, the principal reason being mis-matching methodologies and outcome measures. Three small meta-analyses were carried out.
MAIN RESULTS: Twenty-two randomised trials were included in the review (N = 695). Studies were highly variable in their country of origin, sample size, participant age, intervention delivery type, and outcome measures. Risk of bias was variable across categories. There were very few studies for which there was adequate blinding of participants and personnel, and some were also judged at high risk of bias in blinding of outcome assessors. There was also evidence of some bias in sequence generation and allocation concealment. Not all studies reported data that fell within the pre-defined primary outcome categories for the review, instead many studies reported measures which were intervention-specific (e.g. emotion recognition). The wide range of measures used within each outcome category and the mixed results from these measures introduced further complexity when interpreting results.
Studies were grouped into four main categories according to intervention target/primary outcome measure. These were: emotion recognition studies, joint attention and social communication studies, imitation studies, and studies teaching ToM itself. Within the first two of these categories, a sub-set of studies were deemed suitable for meta-analysis for a limited number of key outcomes.
There was very low quality evidence of a positive effect on measures of communication based on individual results from three studies. There was low quality evidence from 11 studies reporting mixed results of interventions on measures of social interaction, very low quality evidence from four studies reporting mixed results on measures of general communication, and very low quality evidence from four studies reporting mixed results on measures of ToM ability.
The meta-analysis results we were able to generate showed that interventions targeting emotion recognition across age groups and working with people within the average range of intellectual ability had a positive effect on the target skill, measured by a test using photographs of faces (mean increase of 0.75 points, 95% confidence interval (CI) 0.22 to 1.29 points, Z = 2.75, P < 0.006, four studies, N = 105). Therapist-led joint attention interventions can promote production of more joint attention behaviours within adult-child interaction (mean increase of 0.55 points, 95% CI 0.11 to 0.99 points, Z = 2.45, P value = 0.01, two studies, N = 88). Further analysis undermines this conclusion somewhat by demonstrating that there was no clear evidence that intervention can have an effect on joint attention initiations as measured using a standardised assessment tool (mean increase of 0.23 points, 95% CI -0.48 to 0.94 points, Z = 0.63, P value = 0.53, three studies, N = 92). No adverse effects were apparent.
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.
BACKGROUND: Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of conditions often comorbid with ASD such as depression, anxiety and obsessive-compulsive behaviours.
OBJECTIVES: To determine if treatment with an SSRI.:
1. improves the core features of autism (social interaction, communication and behavioural problems);
2. improves other non-core aspects of behaviour or function such as self-injurious behaviour;
3. improves the quality of life of adults or children and their carers;
4. has short- and long-term effects on outcome;
5. causes harm.
SEARCH METHODS: We searched the following databases up until March 2013: CENTRAL, Ovid MEDLINE, Embase, CINAHL, PsycINFO, ERIC and Sociological Abstracts. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). This was supplemented by searching reference lists and contacting known experts in the field.
SELECTION CRITERIA: Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in people with ASD.
DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, extracted data and appraised each study's risk of bias.
MAIN RESULTS: Nine RCTs with a total of 320 participants were included. Four SSRIs were evaluated: fluoxetine (three studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (two studies). Five studies included only children and four studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence quotient of participants. Eighteen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis, except for one outcome (proportion improvement). One large, high-quality study in children showed no evidence of positive effect of citalopram. Three small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression, and another in anxiety.
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.
Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders, ranging in severity and characterised by early onset of delay and deviance in the development of social interaction, and verbal and nonverbal communication. ASD is associated with restricted and/or stereotyped interests or behaviours. Tricyclic antidepressants (TCAs) block noradrenaline and serotonin reuptake, increasing the availability of these neurotransmitters in the central nervous system. Via their impact on serotonin, TCAs have been used in the treatment of autistic symptoms and comorbidities in individuals with ASD. To determine if treatment with tricyclic antidepressants:1) improves the core features of autism, including restricted social interaction, restricted communication, and stereotypical and repetitive behaviours; 2) improves non-core features such as challenging behaviours; 3) improves comorbid states, such as depression and anxiety; 4) causes adverse effects. We ran the latest searches for this review on 23 May 2011. We searched: Cochrane Central Register of Controlled Trials (CENTRAL), 2011 Issue 2, MEDLINE (1948 to May Week 2, 2011), EMBASE (1980 to 2011 Week 2), PsycINFO (1887 to current), CINAHL (1937 to current). We also searched Dissertation Abstracts International via Dissertation Express, and the metaRegister of Controlled Trials. Randomised controlled trials of any dose, duration and frequency of oral TCAs compared with placebo, in children and adolescents with a diagnosis of ASD, where at least one standardised outcome measure had been used. Two review authors independently selected and appraised the studies for inclusion and risk of bias. All data were continuous. Three studies met the inclusion criteria for this review. Two studies used clomipramine and one used tianeptine. All three trials were small, with between 12 and 32 participants. One of the clomipramine trials involved children and young adults, while the other two trials enrolled only children. Due to heterogeneity in study participant characteristics, the TCA medications investigated and the outcome measures used, we were not able to perform any meta-analysis.In only one of the three studies was there any indication that giving children tianeptine could be effective in the short term. In this study, parents and teachers reported that it reduced irritability, hyperactivity, inadequate eye contact and inappropriate speech, but clinician ratings found no significant impact on these symptoms. There were also significant adverse effects, including increased drowsiness and reduced activity levels in these individuals while being treated with tianeptine. The evidence of the impact of clomipramine in the two studies is contradictory. There was evidence of improvement in autistic symptoms, irritability and obsessive-compulsive disorder type symptoms, but conflicting evidence in relation to hyperactivity across the two studies, and no significant changes found with inappropriate speech. There were also adverse effects reported with the use of clomipramine. Although side effect ratings were not significantly different to placebo, there were significant dropout rates in the clomipramine arm of one study. 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.[CINAHL Note: The Cochrane Collaboration systematic reviews contain interactive software that allows various calculations in the MetaView.]
Social interaction and social communication are among the central areas of difficulty for autistic people. Music therapy uses music experiences and the relationships that develop through them to enable communication and expression, thus attempting to address some of the core problems of autistic people. Music therapy has been applied in autism since the early 1950s, but its availability to autistic individuals varies across countries and settings. The application of music therapy requires specialised academic and clinical training which enables therapists to tailor the intervention to the specific needs of the individual. The present version of this review on music therapy for autistic people is an update of the previous Cochrane review update published in 2014 (following the original Cochrane review published in 2006).
OBJECTIVES:
To review the effects of music therapy, or music therapy added to standard care, for autistic people.
SEARCH METHODS:
In August 2021, we searched CENTRAL, MEDLINE, Embase, eleven other databases and two trials registers. We also ran citation searches, checked reference lists, and contacted study authors to identify additional studies.
SELECTION CRITERIA:
All randomised controlled trials (RCTs), quasi-randomised trials and controlled clinical trials comparing music therapy (or music therapy alongside standard care) to 'placebo' therapy, no treatment, or standard care for people with a diagnosis of autism spectrum disorder were considered for inclusion.
DATA COLLECTION AND ANALYSIS:
We used standard Cochrane methodological procedures. Four authors independently selected studies and extracted data from all included studies. We synthesised the results of included studies in meta-analyses. Four authors independently assessed risk of bias (RoB) of each included study using the original RoB tool as well as the certainty of evidence using GRADE.
MAIN RESULTS:
We included 16 new studies in this update which brought the total number of included studies to 26 (1165 participants). These studies examined the short- and medium-term effect of music therapy (intervention duration: three days to eight months) for autistic people in individual or group settings. More than half of the studies were conducted in North America or Asia. Twenty-one studies included children aged from two to 12 years. Five studies included children and adolescents, and/or young adults. Severity levels, language skills, and cognition were widely variable across studies. Measured immediately post-intervention, music therapy compared with 'placebo' therapy or standard care was more likely to positively effect global improvement (risk ratio (RR) 1.22, 95% confidence interval (CI) 1.06 to 1.40; 8 studies, 583 participants; moderate-certainty evidence; number needed to treat for an additional beneficial outcome (NNTB) = 11 for low-risk population, 95% CI 6 to 39; NNTB = 6 for high-risk population, 95% CI 3 to 21) and to slightly increase quality of life (SMD 0.28, 95% CI 0.06 to 0.49; 3 RCTs, 340 participants; moderate-certainty evidence, small to medium effect size). In addition, music therapy probably results in a large reduction in total autism symptom severity (SMD -0.83, 95% CI -1.41 to -0.24; 9 studies, 575 participants; moderate-certainty evidence). No clear evidence of a difference between music therapy and comparison groups at immediately post-intervention was found for social interaction (SMD 0.26, 95% CI -0.05 to 0.57, 12 studies, 603 participants; low-certainty evidence); non-verbal communication (SMD 0.26, 95% CI -0.03 to 0.55; 7 RCTs, 192 participants; low-certainty evidence); and verbal communication (SMD 0.30, 95% CI -0.18 to 0.78; 8 studies, 276 participants; very low-certainty evidence). Two studies investigated adverse events with one (36 participants) reporting no adverse events; the other study found no differences between music therapy and standard care immediately post-intervention (RR 1.52, 95% CI 0.39 to 5.94; 1 study, 290 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS:
The findings of this updated review provide evidence that music therapy is probably associated with an increased chance of global improvement for autistic people, likely helps them to improve total autism severity and quality of life, and probably does not increase adverse events immediately after the intervention. The certainty of the evidence was rated as 'moderate' for these four outcomes, meaning that we are moderately confident in the effect estimate. No clear evidence of a difference was found for social interaction, non-verbal communication, and verbal communication measured immediately post-intervention. For these outcomes, the certainty of the evidence was rated as 'low' or 'very low', meaning that the true effect may be substantially different from these results. Compared with earlier versions of this review, the new studies included in this update helped to increase the certainty and applicability of this review's findings through larger sample sizes, extended age groups, longer periods of intervention and inclusion of follow-up assessments, and by predominantly using validated scales measuring generalised behaviour (i.e. behaviour outside of the therapy context). This new evidence is important for autistic individuals and their families as well as for policymakers, service providers and clinicians, to help in decisions around the types and amount of intervention that should be provided and in the planning of resources. The applicability of the findings is still limited to the age groups included in the studies, and no direct conclusions can be drawn about music therapy in autistic individuals above the young adult age. More research using rigorous designs, relevant outcome measures, and longer-term follow-up periods is needed to corroborate these findings and to examine whether the effects of music therapy are enduring.
