A Review of Complementary and Alternative Treatments for Autism Spectrum Disorders

Table 2

Randomized controlled trials of ingestible complementary and alternative treatments for autism spectrum disorders (ASD).

Tx	Author, year	N, age,; % male	ASD type and; DSM Dx	Control	Tx dose*,; duration	Results
Melatonin	McArthur et al. 1998 [117]	9, 4–17; 0%	Rett/N; (clinical dx)	PBO	2.5–7.5 mg; x-over; 4 wks each	Sleep latency^2,5  𝑃<0.05; Night waking^2,5: ns; Sleep time^2,5: ns
	Garstang et al. 2006 [118]	11, 5–15; 63%	ASD/N; (clinical dx)	PBO	5 mg; x-over: 4 wks each	↓ Sleep latency^2∗ ∗; ↓ night waking^2∗ ∗; ↑ sleep time^2∗ ∗
	Wasdell et al. 2008 [119]	51 (16 ASD); 2–18; 62%	ASD/N; (clinical dx)	PBO	5 mg; x-over; 10 days each	Sleep latency^5  𝑃<0.01; Night waking^5: ns; Sleep time^5  𝑃<0.01; Overall sleep^3  𝑃<0.01; Family stress^2: 𝑃<0.05
	Wirojanan et al. 2009 [40]	18 (12 ASD); 2–15; 89%	ASD/N; (ADOS; ADI-R)	PBO	3 mg; x-over; 2 wks each	Sleep latency^2,5  𝑃=0.02; Night waking^2,5: ns; Sleep time^2,5  𝑃=0.0001
	Wright et al. 2010 [120]	20, 4–16; 80%	ASD/N; (ICD-10)	PBO	2–10 mg; x-over; 3 months each	Sleep latency^2  𝑃<0.05; Night waking^2: ns; Sleep time^2: 𝑃=0.002; Disruptive behavior^2: ns; Communication^2: ns; Social^2: ns; Anxiety^2: ns
	B6/Mg	Martineau et al. 1985 [47]	16, 3–14; 63%	AD/Y	Mg only	B6: 30 mg/kg; Mg: 10–15 mg/kg; x-over; 2 wks each	Overall improved in both conditions^3∗ ∗
		Martineau et al. 1985 [47]	21, 3–14; 81%	AD/Y	PBO	B6: 30 mg/kg; Mg: 10–15 mg/kg; x-over; 2 wks each	Improved ASD^3∗ ∗
		Martineau et al. 1985 [47]	35, 3–14; 57%	AD/Y	PBO	Mg: 10–15 mg/kg; x-over; 2 wks each	No change ASD^3∗ ∗
		Martineau et al. 1985 [47]	37, 3–14; 57%	AD/Y	PBO	B6: 30 mg/kg/; x-over; 2 wks each	No change ASD^3∗ ∗
Lelord et al. 1981 [45]		21, 3–16; unk	Autistic Beh. N	PBO	625–1125 mg B6; 400–500 mg Mg; x-over; 2 wks each	Evaluated if response/nonresponse status from OL remain in DB 𝑃<0.01
		Findling et al. 1997 [46]	12, 3–17; 92%	AD/Y	PBO	30 mg/kg B6; 10 mg/kg Mg; x-over; 4 wks each	ASD^3: ns; Repetitive behavior^3: ns; ADHD^1,2: ns
B12		Bertoglio et al., 2010 [51]	30, 3–8,; 93%	AD/Y	PBO	64.5 mg/kg injection, every 3rd day, 12 wks	ASD^3: ns^∗ ∗; Language^5: ns**
Micronutrients		Adams and Holloway 2004 [53]	20, 3–8; 90%	ASD/N; (clinical dx)	PBO	3 mL/5 lbs; 3 months	Communication^2: ns; Social^2: ns; Sleep^2  𝑃=0.03; Gastrointestinal^2  𝑃=0.03
		Adams et al. 2011 [52, 54, 66]	141, 5–60; 91%	ASD/N; (clinical dx)	PBO	Formulated by Yahoo Health	ASD^2: ns; Expressive language^2: ns; Recep language^2: 𝑃=0.03; Gastrointestinal^2: ns; Sleep^2: ns; Social^2: ns; Hyperactivity^2: 𝑃=0.003; Disruptive beh^2: 𝑃=0.009
	Omega-3	Amminger et al., 2007 [64]	13, 5–17; 100%	AD/Y	PBO	840 mg EPA,; 700 mg DHA; 6 wks	Irritability^3: ns; Hyperactive^3: ns; Repetitive beh^3: ns
Bent et al. 2011 [65]		27, 3–8; 89%	ASD/Y	PBO	700 mg EPA,; 460 mg DHA; 12 wks	Hyperactivity^2: ns; ASD^2: ns; Language^5: ns; Repetitive behavior^2: ns
Probiotics		Munasinghe et al.; 2010 [67]	43, 3–8; 84%	ASD/Y	PBO	Up to 9 caps; x-over; 3 months each	ASD^2: ns; Language^2: ns; Gastrointestinal^2: ns; Sleep^2: ns; Food variety^2: 𝑃=0.02
L-Carnosine	Chez et al. 2002 [72]	31, 3–12; 68%	ASD/Y	PBO	800 mg; 8 wks	ASD^2  𝑃=0.01^∗∗∗; Receptive vocab^5  𝑃=0.01^∗∗∗; Expressive vocab^5: ns***
Ascorbic Acid	Dolske et al. 1993 [73]	18, 6–19; 72%	AD/Y	PBO	90 mg/kg; x-over; 10 wks each	Repetitive beh^4  𝑃=0.01; Language^4: ns; Social^4: ns; Sensory^4: ns
Cyproheptadine	Akhondzadeh et al., 2004 [74]	40, 3–11; 60%	AD/Y	Haloperidol + PBO	0.2 mg/kg Cypro + Haloperidol 0.5 mg/kg; 8 wks	ASD^2  𝑃=0.004
Gluten-Free/ Casein-Free Diet (GFCF)	Knivsberg et al. 2003 [121]	20, M = 7.4; unk	AD/N; (clinical dx)	No Tx	GFCF diet; 12 months	Social^2  𝑃<0.003; Language^2  𝑃<0.004; Repetitive beh^2  𝑃<0.007
	Elder 2006 [122]/Seung et al. 2007 [123]	15, 2–16; 80%	ASD/Y	Typical diet	GFCF diet; x-over; 6 wks each; food provided, blinded	ASD^3: ns; Language^4: ns; Social^4: ns
	Whiteley et al. 2010 [124]	72, 4–10; 89%	ASD/N; (ICD-10)	No Tx	GFCF diet; 12 months	Social: ns^2,4, 𝑃<0.0001^2; Communic: ns^2, 𝑃=0.002^4; Repetitive beh^2,4: ns; ADHD^2: 𝑃<0.05
	Johnson et al.; 2011 [125]	22, 3–5; 82%	ASD/Y	Healthy diet	GFCF diet; 3 months	ADHD^2: 𝑃<0.05; Communication^4: ns; Social^4: ns

Note: AD: Autistic Disorder, ASD: Autism Spectrum Disorder; ASP: Asperger’s Disorder; unk: unknown; Tx: treatment; dx: diagnosis; DSM dx: Y: yes (children diagnosed according to DSM-III or DSM-IV symptoms of ASD) and N: no (children not specifically diagnosed by DSM criteria; ADOS: Autism Diagnostic Observation Schedule; ADI-R: Autism Diagnostic Interview Revised); PBO: placebo; wk: week; x-over: cross-over; WL: Wait List; ns: nonsignificant; *treatment dosages are per day, unless otherwise specified; OL: open label; beh: behavior; vocab: vocabulary; communic: communication; results superscripts indicate the method of assessment: ¹teacher/staff, ²parent, ³therapist/clinician, ⁴observation, ⁵psychometric/standardized testing; **significance values not included in the text; ***P values only provided for pre-post comparison for active treatment, not compared to placebo. M: mean.