J Autism Dev Disord (2012) 42:16711683 DOI 10.

1007/s10803-011-1409-4

ORIGINAL PAPER

Acupuncture for Children with Autism Spectrum Disorders: A Systematic Review of Randomized Clinical Trials
Myeong Soo Lee Tae-Young Choi Byung-Cheul Shin Edzard Ernst

Published online: 29 November 2011 Springer Science+Business Media, LLC 2011

Abstract This study aimed to assess the effectiveness of acupuncture as a treatment for autism spectrum disorders (ASD). We searched the literature using 15 databases. Eleven randomized clinical trials (RCTs) met our inclusion criteria. Most had signicant methodological weaknesses. The studies statistical and clinical heterogeneity prevented us from conducting a meta-analysis. Two RCTs found that acupuncture plus conventional language therapy was superior to sham acupuncture plus conventional therapy. Two other RCTs found that acupuncture produced significant effects compared with conventional language therapy or complex interventions. Three RCTs suggested that acupuncture plus conventional therapies had benecial effects compared with conventional therapy alone. Four more RCTs reported that subjects who received acupuncture experienced signicant effects compared with subjects who were waitlisted or received no treatment. The results of these studies provide mixed evidence of acupunctures effectiveness as a treatment for ASD symptoms.

Keywords Acupuncture Complementary medicine Autism spectrum disorders Effectiveness Systematic review

Introduction Autism spectrum disorders (ASD) are characterized by markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interests (American Psychiatric Association 2000). Commonly used therapies include a combination of specialized and supportive educational programming, communication training, psychosocial intervention, and behavioral and developmental interventions (Ospina et al. 2008; Parr 2010). A wide range of complementary and alternative medicine (CAM) treatments, such as biologically based therapies and mindbody interventions and manipulations, are also frequently recommended (Levy and Hyman 2008). Several surveys have reported that between 30 and 92% of patients have used CAMs and has shown that families often try a variety of these treatments simultaneously (Wong and Smith 2006; Wong 2009b; Zimmer et al. 2007). Acupuncture is one of the most popular forms of CAM in general. Acupuncture involves the insertion of needles into the skin and underlying tissues at particular sites, known as acupuncture points, for therapeutic or preventive purposes (Ernst 2006). The acupuncture points can also be stimulated with an acupuncture needle without any device (manual acupuncture or body acupuncture), electricity (electroacupuncture, EA), lasers (laser acupuncture), pressure (acupressure), heat (moxibustion) or ultrasound waves. There are several microacupuncture sites, which include the acupuncture points in the ear (auricular

Electronic supplementary material The online version of this article (doi:10.1007/s10803-011-1409-4) contains supplementary material, which is available to authorized users.
M. S. Lee (&) T.-Y. Choi Brain Disease Research Center, Korea Institute of Oriental Medicine, Daejeon 305-811, South Korea e-mail: drmslee@gmail.com B.-C. Shin School of Korean Medicine, Pusan National University, Yangsan 626-870, South Korea E. Ernst Complementary Medicine, Peninsula Medical School, University of Exeter, Exeter EX2 4SG, UK

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acupuncture), head (scalp acupuncture) and tongue (tongue acupuncture). Acupuncture is currently a widely used treatment for a variety of conditions, including pain and chemotherapy-related nausea and vomiting (Ernst 2006; Ernst et al. 2007). It is sometimes used to treat psychiatric conditions (Druss and Rosenheck 2000; Unutzer et al. 2000), and has been proposed to be effective for improving moods, such as anxiety and depression (Druss and Rosenheck 2000; Unutzer et al. 2000). However, the prevalence of acupuncture use to treat ASD varies from 1% (Hanson et al. 2007) to 43% (Wong 2009a), depending on the population. Considering the potential importance of and demand for acupuncture for ASD, a rigorous synthesis of high-quality evidence regarding its effectiveness would provide much-needed information for health care professionals, researchers and families. Currently, only one Cochrane systematic review protocol on this subject is available (Cheuk et al. 2011). The objective of this systematic review was to summarize and critically assess the evidence from randomized clinical trials (RCTs) supporting or refuting acupunctures effectiveness in treating ASD.

Study Selection Types of Studies All prospective RCTs and quasi-RCTs were included in this systematic review. Trials in which acupuncture was part of a complex intervention were excluded. We excluded case studies, case series, qualitative studies and uncontrolled trials. Trials in which one type of acupuncture was compared with another type and studies that failed to provide detailed results were also excluded. No language restrictions were imposed. Dissertations and abstracts were included. Types of Participants Patients of both sexes and any age with autism spectrum disorders (i.e., autistic disorder or pervasive developmental disorder) diagnosed by standard criteria (i.e., the Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] or International Classication of Diseases, Tenth Revision [ICD-10] criteria) were included. We also included diagnoses made with assessment tools, including the Autism Behavioral Checklist, Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Scale (ADOS), Childhood Autism Rating Scale (CARS), Chinese Classication of Mental Disorder-3 (CCMD-3), and other validated tools. Types of Intervention Studies investigating any type of needle acupuncture, with or without electrical stimulation, for autistic patients were included. We also included studies that examined the use of auricular acupuncture, scalp acupuncture and tongue acupuncture for autistic patients. Types of Controls We included controls of no treatment, sham acupuncture (penetrating on a nonacupuncture point, shallow penetrating acupuncture on acupuncture points or non-penetrating acupuncture on an acupuncture point or a non-acupuncture point) and relevant standard therapies for ASD, including language therapy and rehabilitation therapies. Types of Outcome Measures The main outcomes were any scales that measured behavioral observations, response rates and standardized assessments of autistic behaviors.

Methods Data Sources The following electronic databases were searched from their inception date until June 2011: Medline, AMED, CINAHL, EMBASE, PsycInfo, Health Technology Assessments, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Psychology and Behavioral Sciences Collection, six Korean medical databases (Korean Studies Information, DBPIA, Korea Institute of Science and Technology Information, the Research Information Service System, KoreaMed, and the National Digital Library), and Chinese academic journals (via CNKI). The search phrase used was (acupuncture OR auricular acupuncture OR electroacupuncture OR scalp acupuncture) AND (autistic OR autism OR Aspergers Syndrome OR pervasive developmental disorder). We also hand searched our departmental les and relevant journals (Focus on Alternative and Complementary rmedizin und Therapies and Forschende Komplementa Klassische Naturheilkunde [Research in Complementary and Classical Natural Medicine] up to November 2010). The references for all located articles were searched manually for additional relevant articles.

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Data Extraction, Quality, and Validity Assessment All articles were read by two independent reviewers, who extracted data from the articles according to predened criteria (Table 1). The risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions assessment tool for risk of bias (Higgins et al. 2011). The following characteristics were assessed: (1) methods of randomization; (2) allocation concealment; (3) blinding; (4) incomplete outcome measures; and (5) selective outcome reporting. Our review used L, U, and H as judgment codes. L (low) indicated a low risk of bias; U (unclear) indicated that the risk of bias was uncertain; and H (high) indicated a high risk of bias (Higgins et al. 2011). Given the impossibility of blinding therapists to the use of acupuncture, we assessed patient and assessor blinding separately. For Chinese literature, two independent reviewers extracted and analyzed the data. Disagreements were resolved by discussion between the two reviewers. The quality of the acupuncture was assessed by two reviewers (BCS, TYC) as described previously by answering the question How would you treat the patients included in the study? with one of ve possible responses(exactly or almost exactly the same way; similarly; differently; completely differently; or could not assess due to insufcient information about the acupuncture or the patient). The degree of condence that acupuncture was applied appropriately was assessed using a 100-mm visual analog scale (with 0% = complete absence of evidence that the acupuncture was appropriate and 100% = total certainty that the acupuncture was appropriate). Discrepancies were resolved through discussions between the two reviewers.

Results Study Description The searches identied 69 potentially relevant articles, of which 11 met our inclusion criteria (Fig. 1). The key data are summarized in Table 1 (Allam et al. 2008; Chan et al. 2009; Liu and Yuan 2007; Wang et al. 2006; Wong 2008; Wong and Chen 2010; Wong and Sun 2002, 2007, 2010; Yan et al. 2007; Yuan et al. 2007). Ten of the included RCTs originated from China (Chan et al. 2009; Liu and Yuan 2007; Wang et al. 2006; Wong 2008; Wong and Chen 2010; Wong and Sun 2002, 2007, 2010; Yan et al. 2007; Yuan et al. 2007), and one originated from Egypt (Allam et al. 2008). Five of 11 included studies done by one same research group (Wong 2008; Wong and Chen 2010; Wong and Sun 2002, 2007, 2010). Manual acupuncture was used in four trials (Chan et al. 2009;

Liu and Yuan 2007; Yan et al. 2007; Yuan et al. 2007); EA was employed in three trials (Wang et al. 2006; Wong 2008; Wong and Chen 2010); scalp acupuncture was used in one trial (Allam et al. 2008); and tongue acupuncture was used in three trials (Wong and Sun 2002, 2007, 2010). A placebo procedure was employed in two trials (Wong and Chen 2010; Wong and Sun 2010); conventional intervention controls for autism were used in ve trials (Allam et al. 2008; Liu and Yuan 2007; Wang et al. 2006; Yan et al. 2007; Yuan et al. 2007); and waitlist or no treatment was employed in four trials (Chan et al. 2009; Wong 2008; Wong and Sun 2002, 2007). Ten of the included trials adopted a two-arm parallel group design (Allam et al. 2008; Chan et al. 2009; Liu and Yuan 2007; Wang et al. 2006; Wong 2008; Wong and Chen 2010; Wong and Sun 2002, 2007, 2010; Yan et al. 2007; Yuan et al. 2007), while one RCT used a crossover design (Wong 2008). Acupuncture point selection was based on traditional Chinese medicine (TCM) theory in eight RCTs (Chan et al. 2009; Wang et al. 2006; Wong 2008; Wong and Chen 2010; Wong and Sun 2002, 2007, 2010; Yan et al. 2007), TCM theory and clinical experience in two RCTs (Liu and Yuan 2007; Yuan et al. 2007), and clinical experience in one RCT (Allam et al. 2008). The details of the treatment regimens are summarized in Table 2. Three trials used the DSM-IV only (Allam et al. 2008; Liu and Yuan 2007; Yuan et al. 2007) for diagnosis, and the other three used the DSM-IV along with other diagnostic tools, including the ADI-S and ADOS (Wong 2008; Wong and Chen 2010; Wong and Sun 2010) (Supplment 2). Two RCTs accepted diagnoses based on the ABC, CARS and PPVT together (Yan et al. 2007) or the ICD-10 and CCMD-3 (Wang et al. 2006). The other RCTs did not mention the diagnostic methods employed (Chan et al. 2009; Wong and Sun 2002, 2007) because two RCTs were published as abstracts (Wong and Sun 2002, 2007). Fifteen validated scales were used in the included trials, and author-constructed structural scales were used in three trials (with no testing for validity and reliability). Seven RCTs employed parents or trained assistants as assessors (Chan et al. 2009; Liu and Yuan 2007; Wang et al. 2006; Wong 2008; Wong and Chen 2010; Wong and Sun 2010; Yuan et al. 2007), and the other four did not report assessor details (Allam et al. 2008; Wong and Sun 2002, 2007; Yan et al. 2007). Assessment of the Risk of Bias The risk of bias was low in two RCTs (Wong and Chen 2010; Wong and Sun 2010), whereas the other studies had a high risk of bias in most categories (Table 3). Four RCTs employed adequate sequence generation methods (Allam et al. 2008; Wong 2008; Wong and Chen 2010; Wong and Sun 2010), whereas the other RCTs failed

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Table 1 Summary of randomized clinical studies of the use of acupuncture to treat autism spectrum disorders Intervention group (regimen) (1) WeeFIM (2) PEDI (3) Leiter-R (4) CGI-I (5) Aberrant behavior checklist (3) NS (4) p = 0.003 (5)(7) NS (8) Social initiation (p = 0.01), receptive language (p = 0.006), motor skills (p = 0.034), attention span (p = 0.003) (1)(4) NS (6) RERLS (7) RDLS (8) Parental report (2) NS except self-care caregiver assistant Control group (regimen) Main outcomes Intergroup differences Comments Assessor

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(1) NS except comprehension in cognition, p = 0.02 NS in acupuncture compliance in both groups Parents and blinded assessor (A) EA (30 min, 3 times weekly for 4 weeks, n = 30) plus conventional intervention or educational programs for ASD (B) Sham EA (30 min, supercial, nonacupuncture points, electric stimulation, n = 25), plus conventional intervention or educational programs for ASD (1) GMDS (2) RFRLS (3) RDLS (4) SPT (5) WeeFIM (B) Sham TAC (rough needle, nonacupuncture points, n = 25), plus conventional educational and behavior models for autistic children AT was effective in improving various developmental and behavioral aspects of the childrens autism. (5) Total, p \ 0.0005; selfcare, p \ 0.005; cognition, p = 0.006; WeeFIM Quotient: total, p \ 0.005; self-care, p = 0.007; cognition, p \ 0.0005 (1) p \ 0.05, in favor of AT (1) CARS (2) ABC (2) p \ 0.05, in favor of AT Trained research assistants (A) TAC (\15 s, 5 sessions weekly for 8 weeks, total of 40 sessions, n = 25) plus a conventional educational and behavioral model for autistic children (A) AT (1 session = once a day, 30 min once every 30 min, 6 times per week for 12 weeks, n = 33) (B) Sensory integration training (4 * 6 h/day, 6 times per week for 12 weeks, n = 34) AT can improve the ability of social communication; sport; felling; language and self-care. It is an effect treatment for autism. Parents, with instruction from a specialist C-PEP (A) AT (1 session = once a day, 45 min, 6 times per week, total of 120 times, n = 40) p \ 0.05, in favor of AT (in sensation and perception, ne motor, gross motor, and speech) (B) Complex therapies (physical therapy, cognitive training, behavior analysis and correction, linguistic training, 1 session = once a day, 4 h each time, 6 times per week, total 120 times, n = 40) AT exerts a certain therapeutic effect for autistic children. Specialist (no details were reported)

First author (year)

Sample size (male/female) Mean age (range)

Wong and Chen (2010)

55 (47/8)

(A) 9.2/(B) 9.6

Wong and Sun (2010)

50 (44/6)

n.r. (311)

Liu and Yuan (2007)

67 (60/7)

5.4 (39)

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Yuan et al. (2007)

80 (51/29)

n.r. (2.1-14)

Table 1 continued Intervention group (regimen) (1) Curative effect rate by C-PEP (2) C-PEP (2) p \ 0.01, in favor of A (1) A (55.0%) vs. B (15.0%); p \ 0.01 Control group (regimen) Main outcomes Intergroup differences Comments Assessor

First author (year)

Sample size (male/female) Mean age (range)

Yan et al. (2007) (B) Rehabilitation training (ABA training conductive education approach ? sensory integration training; 1 session = once a day, 45 min, total of 90 times, n = 20) (B) Language therapy (twice weekly, n = 10) (1) Attention (2) Receptive semantics (3) Expressive semantics (4) Receptive syntax (5) Expressive syntax (6) Phonology (7) Pragmatics (B) Behavior therapy (n.r., n = 30) (1) ADQ (2) Curative effect rate (1) p \ 0.05, in favor of A (2) A(33.3%) versus B (10%): p \ 0.05, in favor of A (37) NS. Arabic Language Test (1) p = 0.008, in favor of A (2) p = 0.034, in favor of A

40 (38/2)

(A) 5.5/(B) 4.6 (2.58)

(A) AT (1 session = once a day, 25 min, 5 times per week for 30 times, total of 23 sessions, n = 20) plus (B)

AT combined with scientic and effective rehabilitation training has a better therapeutic effect than simple rehabilitation training for autism in children. Assessor details were not reported. Scalp AT is a safe complementary modality when combined with language therapy and has a signicantly positive effect on language development in children with autism. Assessor details were not reported.

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Allam et al. (2008)

20 (12/8)

5.5 (47)

(A) Scalp-AT (once daily for 20 min, twice weekly for 2 months, followed by a period of 2 weeks rest, total of 9 months, n = 10) plus (B)

Wang et al. (2006)

60 (47/13)

n.r. (n.r.-12)

EA plus behavioral therapy can improve social adaptive behavior abilities in autistic children. Special person (no details were reported).

Chan et al. (2009)

32 (26/6)

6.9/6.9

(B) Waitlist (6 weeks) (n = 16)

Parent rating scale

Used an unvalidated questionnaire Parents

(A) EA (1 session = dilatational wave, 1.25 Hz, once a day, 50 min, 5 times per week for 2 months, total of 2 sessions, n = 30), plus (B) (A) AT (Seven-star needle, 1 session = 510 min, 6 weeks, total of 30 sessions, n = 16)

Total, p \ 0.05; language, p \ 0.01; social interaction, p \ 0.01; stereotyped behavior, NS; motor function, NS

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Table 1 continued Intervention group (regimen) (B) No treatment (n = 18) (2) ABC (3) ATEC (4) RERLS (5) WeeFIM (3) NS (4) Language subscale, p = 0.05 (5) NS (6) p = 0.012 (7) NS (B) No treatment (n = n.r.) (2) RFRLS (1) WeeFIM Abstract (A) TAC (n.r., 5 sessions weekly for 8 weeks, total of 40 sessions, n = n.r.) (B) No treatment (n = n.r.) (2) GMDS (3) CGIS (4) RFRLS (1) WeeFIM (1) Mobility, p = 0.0002; self-care, p = 0.0071; cognitive, p = 0.0004 (2) p = 0.004 Abstract (A) TAC (n.r,, once a day for 40 sessions over 8 weeks, n = n.r.) (1) Self-care, p = 0.0143; cognition, p = 0.0075; total score: p = 0.0043 (2) Hearing and speech, p = 0.009 (3) p \ 0.001 (4) NS (6) CGI (7) SPT Parents (2) Irritability (p = 0.049) and stereotypy (p = 0.019); subscales of ABC Dissertation (1) ADOS (1) NS Crossover study Control group (regimen) Main outcomes Intergroup differences Comments Assessor

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(A) EA (30 min a day, 25 Hz or 50 Hz or 75 Hz electrical stimulation, 3 sessions per week, over 8 weeks, total 24 sessions, n = 18)

First author (year)

Sample size (male/female) Mean age (range)

Wong (2008)

36 (34/2)

7.4/7.6

Wong and Sun (2007)

30 (n.r.)

n.r.

Wong and Sun (2002)

28 (n.r.)

n.r.

ABA Applied behaviour analysis, ABC Autism behavior checklist, ADOS autism diagnostic observation schedule, ADQ social adaptive quotient, ATEC autism treatment evaluation checklist; CARS childhood autism rating scale, CGIS clinical global impression scale, C-PEP revised Chinese version of the psycho-educational prole, GMDS Grifths mental developmental scale, Leiter-R Leiter international performance scale, n.r. not reported, NS not signicant, PEDI pediatric evaluation of disability inventory, RDLS Reynell developmental language scale, RFRLS Ritvo-Freeman real life scale, SPT symbolic play test, TAC Tongue acupuncture, WeeFIM the functional independence measure for children, TAC Tongue acupuncture, ABA ???

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symptoms (Wong and Chen 2010; Wong and Sun 2010). The results showed statistically signicant improvements in comprehension, cognition and parental reports regarding social initiation, receptive language, motor skills and attention span in those who received EA compared with sham EA (Wong and Chen 2010). The other RCT reported that TAC had signicant effects on functional independence compared with sham TAC (Wong and Sun 2010). Acupuncture Versus Conventional Treatment Two RCTs compared the effects of manual acupuncture with conventional treatments, such as sensory integration training or complex therapies (Liu and Yuan 2007; Yuan et al. 2007). One RCT showed that acupuncture had statistically signicant effects on the Autism Behavior Checklist and the Childhood Autism Rating Scale (Liu and Yuan 2007). The other RCT also showed that acupuncture had signicant effects on the psycho-educational proles of autistic and developmentally disabled children (Yuan et al. 2007).
Fig. 1 Flowchart of trial selection process

to report their methods (Chan et al. 2009; Liu and Yuan 2007; Wang et al. 2006; Wong and Sun 2002, 2007; Yuan et al. 2007) or used inadequate sequence generation (Yan et al. 2007). Only three RCTs used allocation concealment (Allam et al. 2008; Wong and Chen 2010; Wong and Sun 2010). Two RCTs blinded both the patients and the assessor (Wong and Chen 2010; Wong and Sun 2010), and one RCT blinded the assessor only (Wong 2008). All but four RCTs (Chan et al. 2009; Wong 2008; Wong and Chen 2010; Wong and Sun 2010) had a high risk of bias for incomplete outcome measures. One RCT reported the use of doubleblinding, but provided no details (Yuan et al. 2007). Validity of Acupuncture Regarding our assessment of the quality of the acupuncture treatments, the authors would have treated the patients completely differently in four trials, differently in one trial, similarly in two trials, and exactly or almost exactly the same way in three trials. The degree of condence that acupuncture was applied appropriately ranged from 30 to 85%. Outcomes Acupuncture Plus Conventional Treatments Versus Sham Acupuncture Plus Conventional Treatments Two RCTs tested the effectiveness of EA or tongue acupuncture plus conventional treatments (TAC) on ASD

Acupuncture Plus Conventional Treatment Versus Conventional Treatment Three RCTs tested manual acupuncture or scalp acupuncture with conventional interventions, such as rehabilitation training (Yan et al. 2007), language therapy (Allam et al. 2008) or behavioral therapy (Wang et al. 2006). All of the RCTs showed that acupuncture had favorable effects on ADS symptoms compared with conventional treatments. One RCT reported that acupuncture signicantly improved C-PEP scores when compared with rehabilitation training (Yan et al. 2007). The second RCT showed that acupuncture had signicant effects on the social adaptive quotient and response rate compared with behavioral therapy (Allam et al. 2008). The third RCT found that scalp acupuncture was associated with signicant differences in attention and receptive semantics compared with language therapy (Wang et al. 2006). Acupuncture Versus Waitlist or No Treatment Four RCTs tested manual acupuncture, EA or TAC compared with waitlist or no treatment (Chan et al. 2009; Wong 2008; Wong and Sun 2002, 2007). One RCT found that acupuncture had benecial effects on the parent rating scale (Chan et al. 2009), whereas the other two RCTs showed that TAC had statistically signicant effects on functional independence and receptive and expressive language ability (Wong and Sun 2002, 2007).

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Table 2 Summary of included studies acupuncture treatment points and other acupuncture-related information Total treatment (times) Acupuncture points De-qi Rationales for acupuncture point selection TCM theory 4/85 Minor supercial bleeding or crying and irritability during treatment None n.r. Acupuncture validity (a/b) Adverse events 12 EX-HN1, EX-NH3, PC6, HT7, LR3, AT3, TF4, SP6 Tongue acupoints, Ren Ze, Guan Zhu, Tian Men, Di You Sishenzhen, Niesanzhen, Naosanzhen,Touzhizen, Shesanzhen, Shousanzhen, Shouzhizhen, Zusanzhen, Siguanxue n.r. TCM theory and Dr. Jins clinical experience 2/70 Heat in the heart and liver: HT8, LR2; phlegm confuses the mind: ST40, PC7; deciency of the kidney essence: KI3 120 n.r. TCM theory and Dr. Jins clinical experience Sishenzhen, Niesanzhen, Naosanzhen, Touzhizhen, Shesanzhen, Shousanzhen, Shouzhizhen, Zusanzhen Siguanxue Stagnation of liver qi: LI4, LR3; heat in the heart and liver: HT8, LR2; phlegm confuses the mind: ST40, PC7; deciency of the kidney essence: KI3 6090 (23 sessions) GV24, GV20, EX-HN1, GV17, GV18, PC6, HT7, PC8, ST36, KI7, KI3, scalp AT at speech areas 2, 3, mental area, visual area, vertigoauditorial area, forehead 5 needles Hyperactivity: SI3, TE6, LU7, LR3; static: ST40, LR3; insomnia: KI5, BL62 60 Du20, Du26, GV17, 3 temple needles, Yamamoto YNSA 2 points; cerebrum and aphasia points n.r. Yamamotos clinical experience 3/80 n.r. Egypt n.r. TCM theory 4/85 n.r. China 2/75 n.r. China n.r. TCM theory 1/45 n.r. Country

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China 40 72 China China

Author (year)

Acupuncture method

Wong and Chen (2010)

Fixed acupuncture points

Wong and Sun (2010)

Fixed acupuncture points

Liu and Yuan (2007)

Fixed ? individualized by pattern classication

Yuan et al. (2007)

Fixed ? individualized by pattern classication

Yan et al. (2007)

Fixed ? individualized by symptoms

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Allam et al. (2008)

Fixed

Table 2 continued Total treatment (times) 80 (2 sessions) GV20, EX-HN1, GV24, GB13, EX-HN3, GV17, GB19, PC6, scalp AT at speech areas 1, 2, 3 Seven-star needle stimulation; skin stimulation used to stimulate the internal organs GV20, EX-HN3, HT7, SP6, and the auricular brain point (bilateral) Tongue acupoints Tongue acupoints n.r. TCM theory 1/45 n.r. TCM theory 1/45 Yes TCM theory 4/85 n.r. TCM theory 1/30 n.r. Yes TCM theory 3/85 n.r. Acupuncture points De-qi Rationales for acupuncture point selection Acupuncture validity (a/b) Adverse events Country

Author (year)

Acupuncture method

Wang et al. (2006)

Fixed acupuncture points

China

Chan et al. (2009) 24

Fixed acupuncture points

30

China

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Wong (2008)

Fixed ? individualized by syndrome

Worsening sleep pattern (AT:1)

China

Wong and Sun (2007) 40

n.r.

40

Worsening hyperactivity and ritualistic behavior n.r. n.r.

China China

Wong and Sun (2002)

n.r.

AT acupuncture; n.r. not reported, YNSA Yamamotos New Scalp Acupuncture a Quality of acupuncture: 0, could not assess; 1, completely differently; 2, differently; 3, similarly; 4, exactly or almost exactly the same way

Degree of condence: condence that acupuncture was applied appropriately, measured on a 100-mm visual scale (0% = complete absence of evidence that the acupuncture was appropriate; 100% = total certainty that the acupuncture was appropriate

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1680 Table 3 Risk of bias of included randomized clinical trials Author (year) Wong and Chen (2010) Wong and Sun (2010) Liu and Yuan (2007) Yuan et al. (2007) Yan et al. (2007) Allam et al. (2008) Wang et al. (2006) Chan et al. (2009) Wong (2008) Wong and Sun (2007) Wong and Sun (2002) Random sequence generation L L U U H L U U L U U Allocation concealment L L U U U L U U U U U Patients blinding L L H H H H H H H H H Assessor blinding L L U U U U U U L U U

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Incomplete outcome measures L L U U U U U L L U U

Selective outcome reporting L L L L L L L L L U U

L: low risk of bias; H: high risk of bias; U: unclear

We had originally intended to submit these data to formal meta-analyses; however, the studies statistical and clinical heterogeneity prevented us from doing so. Adverse Events Adverse events were mentioned in three of the included studies (Wong 2008; Wong and Chen 2010; Wong and Sun 2010). One study reported no adverse events (Wong and Sun 2010), while two RCTs reported minor side effects (Wong 2008; Wong and Chen 2010). The other RCTs failed to report adverse events.

Discussion Few rigorous trials have tested acupunctures effects on ASD. Our systematic review provides mixed evidence of acupunctures effectiveness on functional independence compared with sham acupuncture. There also limited evidence to support the use of acupuncture as an adjunct to conventional therapies for ASD symptom treatment compared with conventional therapy alone. Other data suggest that EA or TAC plus conventional therapy offer statistically signicant effects compared with sham EA or TAC plus conventional therapy. However, the total number of RCTs included in the analysis was small, and their risk of bias quality was too high to draw rm conclusions about the effectiveness of this approach. Only two studies might offer reliable evidence about adaptive behaviour (Wong and Chen 2010; Wong and Sun 2010). Of these, the rst did not show changes on most standardized measures (including two adaptive behavior inventories), though parents did report gains in this domain (Wong and Chen 2010). Thus, this study contains mostly

null ndings, and the pattern of results raises the concern that parents were somehow unblinded. The second study (Wong and Sun 2010) did report consistent changes in adaptive behavior using one of the inventories that did not show change in the other study (WeeFIM) (Wong and Chen 2010), but null ndings on all other measures. Moreover, the two studies were completely different in their selection of acupuncture sites and devices. Of the eleven RCTs, only two blinded both patients and assessors (Wong and Chen 2010; Wong and Sun 2010); an additional study blinded the assessor (Wong 2008). Eight of the studies did not make any attempt to blind either subjects or assessors (Allam et al. 2008; Chan et al. 2009; Liu and Yuan 2007; Wang et al. 2006; Wong and Sun 2002, 2007; Yan et al. 2007; Yuan et al. 2007). Three RCTs reported treatment allocation concealment (Allam et al. 2008; Wong and Chen 2010; Wong and Sun 2010). Trials with inadequate blinding and inadequate allocation concealment are likely to show exaggerated treatment effects (Day and Altman 2000; Schulz et al. 1995). Small trials may also overestimate treatment effects by approximately 30% (Moore et al. 2003). Four of the included trials employed an intention-to-treat analysis. Most of the included trials also suffered from a high risk of bias for incomplete outcomes and sequence generation. One was an unpublished thesis (Wong 2008). Two were published only as abstracts (Wong and Sun 2002, 2007) and lacked essential details. These studies had not undergone formal peer review. One could question the rationale behind including the data from abstracts and theses; however, we chose to include them to identify all of the eligible trials and summarize the available information. Two RCTs employed a sham control procedure (Wong and Chen 2010; Wong and Sun 2010); however, the authors failed to check the success of the blinding. One

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RCT used supercial needling penetrating non-acupuncture points without electric stimulation for sham control (Wong and Chen 2010). The other RCT used sham TAC with rough needling on non-acupuncture points for the placebo controls (Wong and Sun 2010). To reliably account for the placebo effect, it is crucial for the sham procedure to be indistinguishable from the real treatment. Therefore, the success of the blinding procedures should be assessed, reported, and accounted for. Culture-specic assessment and diagnosis of ASD might continue to be an issue in these studies. Although the CCMD-3 has been found to have a reasonably high correlation with the ICD-10 and DSM-IV, there are still discrepancies in some diagnostic criteria, including that for ASD. One study based diagnoses on the ABC, which has not been validated for ASD diagnosis (Yan et al. 2007). Self-reported subjective questionnaires completed by patients and specialists are the most convenient method for collecting data on ASD. Two of the included RCTs assessed ADOS symptoms using questionnaires that had not been tested for validity and reliability (Wong and Chen 2010; Wong 2008), while others used validated inventories for ASD. However, it seems important that only validated questionnaires be used. Unless the reliability and validity of outcome measures have been established, the data derived from them are subject to bias, and it is difcult to compare different studies results. Three RCTs, which compared acupuncture plus conventional therapy with conventional therapy only, generated favorable effects for at least one outcome measure (Allam et al. 2008; Wang et al. 2006; Yan et al. 2007). These RCTs results suggested the effectiveness of several acupuncture methods. Due to their design (A ? B vs. B), these RCTs were unable to demonstrate specic therapeutic effects (Ernst and Lee 2008). It is conceivable that with such a design (A ? B vs. B), the experimental treatment can seem effective even if it is, in fact, purely a placebo effect (i.e., the nonspecic effects of A are likely to generate a positive result, even in the absence of the specic effects of A). In principle, this also applies to trials that compare acupuncture with no treatment. In this case, we have an A ? B versus B design, in which B represents no therapy at all instead of a conventional therapy. Needle stimulation that causes a typical needle sensation has been claimed to be important for producing maximum effects. This form of needle sensation (de-qi) was considered in only one of the included RCTs (Wang et al. 2006). The higher validity of acupuncture was shown in ve trials (Allam et al. 2008; Wang et al. 2006; Wong 2008; Wong and Chen 2010; Yan et al. 2007) from our points of view, the other six trials seemed to employ different acupuncture techniques (Chan et al. 2009; Liu and Yuan 2007; Wong and Sun 2002, 2007, 2010; Yuan et al. 2007). However,

this does not mean the original authors used incorrect acupuncture techniques. The lack of proper information about optimal acupuncture dosages means that questions remain about the absence of acupunctures effects on ADS symptoms. For instance, the number of treatment sessions could have been too small to generate a signicant effect; treatment could have been suboptimal; or the protocol applied in the acupuncture group might not have been suitable for treating ASD symptoms. One concern is that ethical approval was reported in only four of the included trials (Allam et al. 2008; Chan et al. 2009; Wong and Chen 2010; Wong and Sun 2010). Considering the importance of protecting patients rights, acupuncture researchers must develop an awareness of ethical issues similar to their awareness of other aspects of research work. Moreover, the reporting of clinical trials should follow CONSORT procedures (Schulz et al. 2010). A serious issue is the fact that most studies fail to mention adverse effects. Although acupuncture is generally considered safe, serious complications have been reported (Ernst et al. 2010). Thus, the nonreporting of adverse effects may contribute to a falsely positive picture of acupunctures safety. In any case, all researchers are ethically obligated to report adverse events. The nonreporting of such events could be seen as a violation of medical and publication ethics. Our review has a number of important limitations. Although strong efforts were made to retrieve all RCTs on the subject, we cannot be certain that we succeeded. Moreover, selective publishing and reporting are other major causes of bias that must be considered (Egger and Smith 1998; Ernst and Pittler 1997; Pittler et al. 2000; Rothstein et al. 2005). It is conceivable that several negative RCTs remain unpublished; thus, the overall picture may be distorted (Ernst and Pittler 1997; Pittler et al. 2000). Most of the included RCTs originated from China. It is therefore relevant to mention that Vickers et al. have shown that no acupuncture study from China has ever reported negative results (Vickers et al. 1998). In our view, this phenomenon further limits the possibility of drawing reliable conclusions. An additional limitation is the preponderance of studies (5 of 11 included studies) from one team including the only two trials judged to be of acceptable quality. Further limitations include the paucity and the often suboptimal methodological quality of the primary data. In total, these facts limit the conclusiveness of this systematic review considerably. In conclusion, the results of our systematic review provide limited evidence of acupunctures effectiveness in treating ASD for functional independence. The total number of studies included in the analysis, their total sample sizes and their methodological quality, however, were too low to draw rm conclusions for other ASD

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symptoms. Further rigorous RCTs are warranted, but need to overcome the limitations of the current investigations.
Acknowledgments Myeong Soo Lee and Tae-Young Choi were supported by KIOM (K11111). Conict of interest None declare.

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