Table 1.

Summary of the studies on the role of anti-inflammatory medications in the management of ASD.

Drug	Participants	Type of study	Treatment	Outcomes	References	Benefit based on strength of evidence
Amantadine
Amantadine	ASD (DSM-IV and ICD-10) N = 39 Age: 5–19 years	Double-Blind, Placebo-Controlled Trial Amantadine (n = 19), Placebo (n = 20)	Amantadine administered at 2.5 mg/kg/day for 1 week and then 5 mg/kg/day for 3 weeks.	Based on parent-rated ABC amantadine group had slightly higher (statistically non-significant) percentage of responders. However, based on the clinician-rated ABC, the amantadine group had significantly more improvement in absolute score of hyperactivity and inappropriate speech than placebo group. - Amantadine group had higher CGI score (not statistically significant) than placebo group.	King et al., 2001 (36)	Potential benefit
Amantadine plus risperidone	ASD (DSM-IV-R) and (6 or more DSM IV-TR symptoms) N = 39, Age: 4–12 years	Double-Blind, Placebo-Controlled Trial Risperidone plus Amantadine (n = 20) Risperidone plus placebo (n = 19)	Risperidone administered between 1 and 2.0 mg/day, Amantadine administered at 100 mg/d (if <30 kg) or 150 mg/d (if >30 kg), over 10 weeks	-Significant improvement in hyperactivity and irritability in the amantadine treated than the placebo group. - Significant improvement in the amantadine group on CGI	Mohammadi et al., 2013 (37)
Celecoxib
Celecoxib plus risperidone	Children with ASD ((DSM)-IV-TR)N = 40, Age: 4–12 years	Parallel-group, randomized, double-blind, placebo-controlled trial Risperidone plus Celecoxib (n = 20), Risperidone plus placebo (n = 20)	Celecoxib:100 mg/day to 200/300 mg/day Risperidone: 0.5 mg/day to 0.5 mg/week to 2–3 mg/day over 10 weeks	Significant improvement in: - Irritability -Lethargy/Social Withdrawal - Stereotypic Behavior as measured with ABC	Asadabadi et al., 2013 (40)	Potential benefit
Corticosteroids
Chronic oral prednisolone treatment	A 6-year-old boy with autoimmune condition plus ASD	Case study	2 mg/kg/day for 10 weeks followed by 0.5 mg/kg every other day for 12 months 2 mg/kg of daily for 4 weeks, measured monthly by 0.5 mg/kg from weeks 4 through 12. Between weeks 12 to 28, alternate-day dosing was quantified in 0.25 mg/kg steps every 4 weeks.	Significantly improved: -Spontaneous speech, greater responsiveness to verbal communications (Token Test for Children), and improved social relatedness. -Receptive (Peabody Picture Vocabulary Test) and expressive Vocabulary -Visuomotor abilities and Performance IQ(WISC-R) -Decreased Stereotyped utterances (Diagnostic Checklist for Behavior-Disturbed Children)	Stefanatos et al., 1995 (46)	Unknown benefit
Low-dose steroid therapy	Autism with autoimmune lymphoproliferative syndrome (ALPS) Age: 18 months old	Case study	2 mg/kg/day for 10 weeks. the prednisolone dose was further reduced to 0.4 mg/kg every other day. Finally, the dose of 0.5 mg/kg every other day was the effective maintenance dose for treatment of the ASD and autoimmune condition	- Increased social interaction - Improvements in speech, gesturing, non-verbal communication, and language expression and comprehension subjective improvement, followed by objective improvement in speech and developmental milestones	Shenoy et al., 2000 (47)
Steroid	Children with regressive Autism Spectrum Disorder (R-ASD) based on (DSM-IV) Steroid-treated R-ASD (STAR) (N = 20) Not-treated ASD patients (NSA) (N = 25), Age: 3–5 years	Retrospective Study	Oral prednisolone administered at 2 mg/kg/day. Treatment group: 4 Hz frequency modulated evoked response (FMAER) derived from language cortex of the superior temporal gyrus (STG)	-Significant increase in the 4 Hz FMAER spectral response and a significant reduction in response distortion compared to STAR group relative to the NSA group. - Significant improvement in STAR group subjects’ language ratings - Most STAR group children showed significant behavioral improvement after treatment. -STAR group language and behavior improvement were retained one year after treatment. - Groups did not differ in terms of minor EEG abnormalities. -Steroid treatment produced no lasting morbidity.	Duffy et al., 2014 (50)
	Case 1: 4.5-year-old boy with Childhood disintegrative disorder (CDD) and generalized tonic clonic seizure Case 2: 4.5-year-old girl with CDD who was mildly encephalopathic	Case series	Case 1: Prednisolone (40 mg; 2 mg/kg/day for 2 weeks and then weaned by 5 mg a week over 8 weeks). Prednisolone (2 mg/kg for 2 weeks, tapered over 1 week	-Remained seizure free on Sodium Valproate (30 mg/kg/day) and at 2-year follow-up his behavior remained normal. -Normal academic school progress at 30 months follow-up. -Slow improvement with fewer periods of agitation in the next 3 weeks -Clear understanding of some verbal commands and developed a little speech. - No periods of agitation or ataxia,	Mordekar et al., 2009 (49)
Adrenocorticotropic hormone (ACTH)
ORG 2766	ASD (DSM-III) N = 14, Age: 5–13 years	Placebo-controlled double-blind cross-over trial	20 mg/day over 4 weeks period	Significant Improvement in irritability, stereotypic behaviors, hyperactivity, and excessive speech) as measured with ABC	Buitelaar et al., 1990 (45)	Potential benefit
ORG 2766	ASD N = 14 Age: 5–13 years	Double-blind, placebo-controlled cross-over trial	20 mg/day over 8 weeks period	- Significant Improvement in stereotypic behaviors - Social interaction-, play behavior, and stereotypy (P < 0.05 for each) compared with placebo (ABC and CGI); -Adverse effects were minimal	Buitelaar et al., 1992 (44)
ORG 2766	ASD, N = 20 Age: 5–15 years	Controlled trial	40 mg/day for 8 weeks	-Significant improvement in the children’s play behavior and a significant increase in the social interaction between child and experimenter. -Gaze coordination between child and experimenter —Parents’ checklist ratings (ABC) as well as clinicians’ ratings (CGI).	Buitelaar et al., 1992 (43)
ACTH	Case 1: 8-year-old boy with ASD Case 2: 2-year-old girl with ASD	Case studies	Case 1: prednisone l0 mg/day followed by ACTH 10 IU/day Case 2: 10 mg of prednisone plus ampicillin as prophylactic treatment daily for two months which was replaced by ACTH 10 IU i.m. daily	-He was attentive and had no more echolalia, or stereotypies, -He was able to communicate using simple phrases, and to perform simple tasks; to correctly use toys and was willing to play with other children -Improvement in pronouncing a few words, understanding demands, -Improved attentiveness, calmness, and less isolatedness.	Matarazzo et al., 2002 (48)
Flavonoids
	Children with ASD N = 37, Age: 4–14 years, 29 boys and 8 girls	Case studies	-luteolin (100 mg) + quercetin (70 mg) + Flavonoid (200 mg) −2 capsules/20 kg/weight, or at least 400 mg total flavonoid	-Significant improvement in bowel color, form and habits in 2–3 weeks (75%) -Significant reduction in Allergic-like symptoms in their skin -Significant improvement in eye contact, and attention to directions (50%) -Significant improvement in retained learned tasks and social interactions (30–50% of patients) -Significant improvement in speaking skills (10%)	Theoharides et al., 2012 (52)	Unknown benefit
	ASD children N = 40, Age: 4–10 years; 42 boys and 8 girls	Prospective, open-label trial Two age groups: 4–6 years (n = 25), 7–10 years (n = 25)	luteolin (100 mg/capsule, from chamomile) and quercetin (70 mg/capsule), and the quercetin glycoside rutin (30 mg/capsule) for 26 weeks	-Significant improvement in adaptive functioning as measured by Vineland Adaptive Behavior Scale (VABS) age-equivalent scores in the communication domain, daily living skills, and the social domain -Significant improvement in overall behavior as demonstrated by the decline in ABC subscale scores. -Age had no significant effect on results	Taliou et al., 2013 (53)
	10-year-old boy	Case study	Co-Ultramicronized Palmitoylethanolamide/ Luteolin: 700 mg + 70 mg for 1 year	-Significantly decrease both total and subgroup scores, in particular; sociability, demonstrating improved behavioral outcome, in particular sociability (as per ATEC) -Significantly reduced most indexes of hyperactivity, as shown by reduction in motor stereotypies -Improved cognition as reported by parents and teachers (e.g. understanding of simple commands and accomplishing them easily; -Improved eye contact and the child’s behavior became more affectionate	Bertolino et al., 2017 (55)
Galantamine
	Autism (DSM-IV-TR) Case 1: 21-year-old male Case 2: a 32-year-old male Case 3: 42-year-old male	Case series	Case 1: Initial dose of 4 mg each month to a maximum of 12 mg as an adjunct treatment to his asthma medications Case 2: 4 mg daily Galantamine followed by a trial of donepezil due to side effects Case 3: Initial does of 4 mg per day for a month to a maximum of 16 mg	Case 1: Improved speech and cognition: active speech sound production -Spontaneous articulation, proper to the context and complex verbalizations Case 2: -Improvements in verbalizations, which were restricted to one- or two appropriate word responses to the questions asked Case 3: -Slight improvement in spontaneous speech and drooling -Significant improvement in aggressive behavior within the first month of treatment.	Hertzman et al., 2003 (57)	Potential benefit
	Children with autism N = 13, Mean Age: 8.8 +/- 3.5 years	12- week Open-label trial		-Significant improvement in irritability and social withdrawal subscales of ABC -Significant progresses in inattention and emotional liability (Conners’ Parent Rating Scale-R) -Improvement in the anger subscale of the Children’s Psychiatric Rating Scale.	Nicolson et al., 2006 (58)
	ASD (DSM IV-TR) N = 40, Age: 4–12 years	Parallel-group, placebo-controlled, and double-blind trial Risperidone plus galantamine (n = 20) Risperidone plus placebo (n = 20)	Galantamine administered up to 24 mg/day or placebo, plus Risperidone administered up to 2 mg/day, for 10 weeks	-Significant improvement in the Irritability and Lethargy/Social Withdrawal subscales in the galantamine treated patients than the placebo group as measured with ABC	Ghaleiha et al., 2014 (59)
Intravenous immunoglobulin (IVIG)
	ASD (DSM-III-R) and immunological abnormalities N = 10, Age: 3–12 years	Open-label Study	400 mg/kg/month for 6 months at 4 weeks intervals	-Improvements in speech (better articulation and improved vocabulary) -one child almost completely recovered speech -Improved social behavior, better eye contact, loss of echolalia, and response to commands. - Mild improvement on spontaneous meaningful speech	Gupta et al., 1996 (60)	Potential benefit in individual with concurrent immunological disorder
	ASD (DSM-IIIR) N = 10, -Age: 4–17 years	Open-label study	4 infusions of (154 to 375 mg/kg), every 6 weeks	Mild improvements in attention and hyperactivity (n = 4) -No improvements (n = 5) - Almost total amelioration of autistic symptoms (n = 1)	Piloplys et al., 1998 (61)
	ASD (DSM IV) N = 7 -Age: 3–6 years (6 male, 1 female),	Pilot Open Clinical Trial	400 mg/kg/month- for 6 months	Not beneficial for behaviors or severity	Delgiudice-Asch et al., 1999 (62)
	Outpatient male children with autism (ICD-10), N = 12, Age: 4.2–14.9 years	Double-blind and placebo-controlled crossover study	0.4 g/kg at once	Significant improvement in Irritability, hyperactivity, Inadequate eye contact, and Inappropriate speech as measured with ABC	Niederhofer et al., 2003 (63)
	ASD N = 26, Age: 3–17 years	Open retrospective study	400 mg/kg/month IVIG for 6 months	-Significant decrease in irritability, social withdrawal, stereotypy, hyper- activity, inappropriate speech as measured with ABC -Regressing to pre-IVIG level within 2 to 4 months of termination of IVIG (n = 22)	Boris et al., 2005 (64)
	Children with ASD, N = 31	Open-label case series	Initiated with 2 g/kg monthly with 1 g/kg/day for 2 days monthly	Reports from parents: -Improvements in communication and/or language with fewer reporting -Improvements in aberrant behavior, repetitive behavior, and academics, social interactions, tics, motor function, and seizures -Significant Improvement in cognition and mannerisms on Social Responsiveness Scale, SRS) -Mild significant improvement in communication and motivation (SRS) -Significant improvement in irritability, lethargy/social withdrawal, hyperactivity, and inappropriate speech as measured with ABC	Connery et al., 2018 (65)
Lenalidomide
	ASD (DSM-IV-TR) N = 7, Age: 6–12 years	Open-label (Pilot Study)	2.5 mg/day for 12 weeks	-Significant improvement in socialization, expressive, and receptive language (CGI) -Significant decreased symptoms of autism based on the CARS scores in six children who completed the 6-week follow-up	Chez et al., 2007 (67)	Unknown benefit
Memantine
	Children with ASD (DSM-IV-TR) N = 40, Age: 4–12 years	Double-blind, placebo-controlled study Risperidone plus Memantine (n = 20) Risperidone plus placebo (n = 20)	Risperidone was administered up to 3 mg/d and memantine was administered up to 20 mg/day Initiate Risperidone with dose of 0.5 mg with subsequent dose increase in 0.5 mg increments weekly Initiate Memantine with dose of 5 mg/day with subsequent dose increase in 5 mg increments weekly for 10 weeks	Significant improvement in irritability, stereotypic behavior, and hyperactivity as measured with ABC	Ghaleiha et al., 2013 (69)	Unknown benefit
	Autistic disorder, or Asperger disorder ((DSM-IV-TR) plus Moderate to severe ASD based on Social Responsiveness Scale-Adult Research Version (SRS-A), and the clinician-rated CGI N = 18, Age: 18–50 years	12-week, open-label treatment trial	Initiated with a daily dose of 5 mg that was increased by 5 mg weekly up to a maximum daily dose of 20 mg twice daily. (average dose, 19.7 ± 1.2 mg/day; range, 15–20 mg)	-Significant improvement in the severity of core features of autism based on (SRS) and (CGI) -Significant improvement in impaired reading and nonverbal communication based on Diagnostic Analysis of Nonverbal Accuracy Scale test and in executive function per self-report (Behavior Rating Inventory of Executive Functioning–Adult Self-Report Global Executive) -Significant improvement in cognitive dysfunction in particular executive areas of emotional control, task initiation, cognitive flexibility, self-regulation, planning and organization, response inhibition, and working memory; -Significant improvement in global functioning -Significant improvement in anxiety and ADHD symptoms	Joshi et al., 2016 (70)
	ASD ((DSM-IV-TR), Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) N = 121, Age: 6–12 years Study 2: ASD (DSM-IV-TR) N = 66 (completed the study) Age: 5–16 years	Study 1: 12- week, randomized, double-blind, placebo-controlled, parallel-group. Placebo (n = 61), Memantine (n = 60). Study 2: 48-week open-label extension trial (enrolled participants n = 102; n = 66, completed the study) Placebo/Memantine (n = 35), Memantine/Memantine (n = 31)	Memantine doses were administered based on bodyweight and ranged between 3 and 15 mg/day	Study 1: -No significant between-group difference on the efficacy outcome of caregiver/parent ratings based on the Social Responsiveness Scale (SRS), -A Significant improvement as compared to baseline at Week 12 in both groups Study 2: -A tendency for improvement at the end of the extension period (48 weeks). -No significant improvements in the active group - Significant worsening of one communication measure in memantine group relative to placebo after 12 weeks.	Aman et al., 2017 (71)
Minocycline
	ASD (Autism Diagnostic Interview - Revised (ADI-R)), DSM-IV, or the Autism Diagnostic Observation Schedule N = 10 Age: 3–12 years	Open-label trial	1.4 mg/kg over 6 months	No clinical improvement noticed	Pardo et al., 2013 (73)	Unknown benefit
	ASD (DSM-IV-TR) N = 46	Randomized, double-blind placebo-controlled trial Risperidone plus minocycline (n = 23), Risperidone plus placebo (n = 23)	50 mg twice per day for 10 weeks plus Risperidone titrated up to 2 mg/day	-Significant improvement of irritability and hyperactivity/noncompliance	Ghaleiha et al., 2016 (74)
N-acetylcysteine
	Children with ASD (DSM-IV-TR), N = 29, Age: 3–12 years	Double-blind, randomized, placebo-controlled study NAC (n = 14) Placebo (n = 15)	Initiated with 900 mg/daily for 4 weeks, followed by 900 mg/twice daily for 4 weeks and then 900 mg/three times daily for 4 weeks	-Significant reduction in irritability in the treatment group as measured with ABC -Significant improvement on stereotypies as measured with RBS-R - Significant improvements in social cognition and autism mannerisms as measured with SRS	Hardan et al., 2012 (80)	Potential benefit
	8-year-old boy with ASD (DSM-IV)	Case study	800 mg per day over 6 weeks	- Significant reduction in his nail-biting behavior - Significant reduction in his autistic symptoms 1 month after the onset of treatment -Significant improvement in: social interaction ( visual analog scale), verbal skills and communication (visual analog scale), aggressive behavior, hyperactivity and limited interests, and severity and frequency of his blinking tic (parents report)	Ghanizadeh et al., 2012 (78)
	Children and adolescents with ASD (DSM-IV-TR), N = 40, Age: 3.5–16 years	Randomized double blind placebo controlled trial NAC plus Risperidone (n = 17) Placebo plus Risperidone (n = 14)	1200 mg/day NAC + Risperidone or placebo + Risperidone for 8 weeks	Significant improvement in irritability as measured with ABC	Ghanizadeh et al., 2013 (81)
	4-year-old boy with self-injurious behavior	Case study	Initiated with 0.45 g/d and titrated up to 1.8 g/day over 3 weeks	Improvement in frequency and severity of self-injurious behavior	Marler et al., 2014 (77)
	17 years old with ASD	Case study	Administered 20% acetylcysteine oral solution started at 600 mg twice daily as an add-on to Quetiapine therapy for six weeks. continued acetylcysteine with 900 mg twice a day plus Quetiapine 200 mg twice a day	Significantly improved tantrums, irritability, and aggressive behavior	Stutzman et al., 2015 (79)
	Children with autism spectrum disorder (ASD) N = 40, Age: 4–12 years	A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Risperidone plus NAC (n = 20) Risperidone plus placebo (n = 20)	Risperidone administered up to 1 and 2.0 mg/d, NAC dosage was 600 to 900 mg/day over 10 weeks	-Significant interaction of time and treatment on irritability, and hyperactivity/ Noncompliance subscales. -By the end of trial, the treatment group had more improvement in irritability and hyperactivity/ noncompliance subscales scores as measured with ABC	Nikoo et al., 2015 (82)
	Children with Asperger’ s disorder, PDD NOS, ASD ((DSM-IV, (ADI-R))) N = 31, Age: 4–12 years	Randomized, double-blind, placebo-controlled trial NAC (n = 16), Placebo (n = 15)	Regular daily dose was 56.2 mg/kg over week 12, with dose varying between 33.6 - 64.3 mg/kg. Initiated with the dose of 300 mg/day for weights between 15 to 30 kg Initiated with the dose of 600 mg/day, > 30 kg	- No significant difference between the treatment and placebo groups on the CGI test	Wink et al., 2016 (83)
	Children with ASD (DSM-IV-TR) N = 98, Age: 3–9 years	Placebo-controlled, randomized clinical trial NAC (n = 48) Placebo (n = 50)	500 mg/day orally administered over 6 months	-No significant differences between treatment and placebo-treated groups for, scores on the SRS, Children’s Communication Checklist and the RBS -No significant difference found on the three global impression scales: DBC-P, CGI, and PGI-I	Dean et al., 2017 (84)
Palmitoylethanolamide
	Case 1: 13-year-old male with autism Case 2: 15-year-old male with autism	Case series	Case 1: Oral administration of 1/2 tablet (300 mg) twice daily, followed by (600 mg) tablet twice daily for a month Case 2: 600 mg tablet for 3 months	Case 1: -Improvement in his behavior and expressive language (parents and school teacher’s reports) -Decrease in tantrums, outburst, self-talking, and stereotypies. -Improvement in skin eczema, nose-picking, asthmatic cough, and allergy stigmata Case 2: -Improvement in speech, sociability, sensory/cognitive, and overall behaviour -Improvement in aggression and cognitive and behavioral skills, and Language	Antonucci et al., 2015 (87)	Potential benefit
	Autistic children (DSM-V) N = 62, Age: 4–12 years	Randomized, parallel group, double-blind placebo-controlled trial Risperidone plus PEA (n = 31), Risperidone plus placebo group (n = 31)	Children in both groups received Risperidone equally with initial dose of 0.5 mg and stepwise 0.5-mg weekly increases for the first 3 weeks plus 600 mg PEA twice daily over 10 weeks	-Significant improvement on ABC irritability and hyperactivity/noncompliance, and inappropriate speech symptoms related to risperidone plus placebo group	Khalaj et al., 2018 (88)
Pentoxifylline
	Behavioral anomalies of biological basis or autism N = 36, Age: 3–15 years	Open-label study	150–600 mg/day over 1 month	-Remarkably effective in (N = 10) Fairly effective in (N = 8) Slightly effective in (N = 3) No effect (N = 2) -Improvement in sameness maintenance syndrome as well as in increasing the understanding of language and human relations and in their self-image to the extent (based on authors observations)	Sogame et al., 1978 (90)	Potential benefit
	ASD N = 30 Case reports: aged 12, 13, and 15 years	Open-label study	Not specified	-Marked improvement (n = 6) -Slight amelioration of symptoms (n = 14) -three out of six patients reported marked improvement	Nakane et al., 1980 (91)
	Male autistics N = 20, Age: 3–22 years	Open-label study	200 mg/day for 3 months	–35% improvement in behavior and mental development	Shimoide et al., 1981 (92)
	Psychotic (N = 18) and autistic children (N = 2): a 5-year-old boy and a 7-year-old girl	Open-label study	Dose of 50 mg/day to 200 mg/day Over 4–10 months	-Significant improvement in pronunciation of syllables and words -Significant improvements in behavior and in language -Significant Increased in attention to others and speech -Improvement in pronunciation of syllables and words	Turek et al., 1981 (93)
	ASD (based on DSM IV-TR) N = 40, Age: 4–12 years	Randomized double-blind, placebo-controlled Risperidone plus pentoxifylline (n = 20), risperidone plus placebo (n = 20)	Pentoxifylline: 200- 600 mg/day Risperidone: 0.5- 3 mg/day Over 10 weeks	Significant improvement in: -Irritability, social withdrawal, and stereotypic behavior -Hyperactivity and inappropriate speech As measured with ABC	Akhondzadeh et al., 2010 (94)
Pioglitazone
	ASD (DSM-IV) N = 25, Age: 3 –17 years	Open-label study	30 mg/day for individuals with age range of 3 to 5 years 60 mg/day for individuals with age range of 6–17 years -Over 4 months	-Significant decrease in hyperactivity, Irritability, lethargy, and stereotypy as measured with ABC	Boris et al., 2007 (98)	Potential benefit
	Outpatients with ASD N = 40, Age: 4–12 years	Randomized, double-blind, parallel-group, placebo-controlled trial Risperidone plus Pioglitazone (n = 20) Risperidone plus placebo (n = 20)	Risperidone: initial dose of 0.5 mg/day which was titrated in 0.5 mg increments every week over 10 weeks Pioglitazone: dose of 30 mg/day (15 mg two times daily) in one group	-Significant reduction in irritability, lethargy/social withdrawal and hyperactivity/non-compliance	Ghaleiha et al., 2015 (99)
Riluzole
	ASD (DSM-IV-TR), N = 40, Age: 5–12 years	Double-Blind, Placebo-Controlled, Randomized Trial Risperidone plus Riluzole (n = 20), Risperidone plus placebo (n = 20)	Riluzole administered up to 50 or 100 mg/day according to bodyweight. Risperidone administered up to 2 or 3 mg/day (according to bodyweight) for 10 weeks.	-Significant improvement in the irritability, lethargy/social withdrawal, stereotypic behavior, and hyperactivity/non-compliance subscale in Riluzole-treated patients - 11 individuals in Riluzole group and 5 individuals in the placebo group were categorized as responders according to their CGI scores	Ghaleiha et al., 2013 (110)	Potential benefit
Spironolactone
	12-year-old boy with well-established autism, immune dysregulation, and food allergies	Case Report	2 mg/kg/day for 4 weeks	-Significant improvement in irritability, social withdrawal, stereotypy, hyperactivity, inappropriate speech as measured with ABC -Significant improvement in receptive language (as measured with Peabody Picture Vocabulary Test III)	Bradstreet et al., 2007 (103)	Unknown benefit
Topiramate
	Autistic children (DSM IV), N = 40, Age: 3–12 years	Double-blind, placebo-controlled trial Risperidone plus Topiramate (n = 20) Risperidone plus placebo (n = 20)	Risperidone was administered up to 2 mg/d for children between 10 and 40 kg and 3 mg/day for >40 kg. Topiramate was administered up to 100 mg/day for individuals <30 kg and 200 mg/day for individuals >30 kg) over 8 weeks	Significant improvement on irritability, stereotypic behavior, and hyperactivity/non-compliance subscales as measured with ABC	Rezaei et al., 2010 (107)	Potential benefit