Aggression in autism spectrum disorder: presentation and treatment options

Figures & data

Table 1 Pharmacologic management of aggression in ASD, selected controlled trials

Medication	Author	Study design	N	Age (years)	Details	AEs
Antipsychotics/selected controlled trials
Haloperidol	Campbell et al^Citation92	12-week, RPCT	42	2.6–7.8	Haloperidol superior to placebo on stereotypy and social withdraw subscales of CPRS	Sedation, acute dystonic reaction in two subjects
	Anderson et al^Citation94	14-week, RPCT	45	2.3–7.9	Haloperidol superior to placebo on all subscales of CPRS	Sedation, increased irritability
Risperidone	McDougle et al^Citation50	12-week, RPCT	31	18–43	Risperidone superior to placebo on CGI-I and SIB-Q	Abnormal gait (n=1), sedation
	McCracken et al^Citation46	8-week, RPCT	101	5–17	Risperidone superior to placebo on ABC-I and CGI-I	Weight gain, increased appetite, fatigue
	Shea et al^Citation51	8-week, RPCT	79	5–12	Risperidone superior to placebo on ABC-I	Somnolence, weight gain
	RUPP^Citation52	Part 1: 16-week open-label extension of 2002 trial Part 2: 8-week DB placebo-substitution study	Part 1: 63 Part 2: 32	5–17 5–17	Sustained improvement on ABC-I 62.5% relapse rate in placebo group	Weight gain Increased aggression in placebo group
	Aman et al^Citation53	Naturalistic 21-month follow-up	84	5–17	Improved scores on ABC-I; significant rate of continued use	Weight gain, excessive appetite, enuresis
Aripiprazole	Marcus et al^Citation58	8-week, RPCT (fixed dose)	218	6–17	Aripiprazole superior to placebo on ABC-I	Weight gain, sedation, EPS
	Owen et al^Citation47	8-week, RPCT (flexible dose)	98	6–17	Aripiprazole superior to placebo on ABC-I and CGI-I	Weight gain
	Marcus et al^Citation59	52-week open-label extension of 2009 trial	330	6–17	Aripiprazole superior to placebo on ABC-I and CGI-I	Weight gain, increased appetite, vomiting, insomnia
Olanzapine	Hollander et al^Citation73	8-week RPCT	11	6–14	Olazapine superior to placebo on CGI-I, but not on CY-BOCS or OAS-M	Weight gain, sedation
Lurasidone	Loebel et al^Citation90	6-week RPCT (fixed dose)	150	6–17	Lurasidone not superior to placebo at either dose	Vomiting, somnolence
Antiepileptic medications/selected controlled trials
Valproic acid	Hellings et al^Citation99	8-week RPCT	30	6–20	Valproic acid not superior to placebo on ABC-I	Skin rash, weight gain, elevated ammonia
Other medications/selected controlled trials
N-acetylcystei e (NAC)	Hardan et al^Citation109	12-week RPCT	29	3.2–10.7	NAC superior to placebo on ABC-I	Minimal gastrointestinal symptoms
Naltrexone	Campbell et al^Citation114	6-week RPCT	41	2.9–7.8	Improved hyperactivity on CPRS but no improvement in self-injury	Well tolerated

Abbreviations: AEs, adverse events; ASD, Autism spectrum disorder; RPCT, randomized placebo-controlled trial; CPRS, Children’s Psychiatric Rating Scale; CGI-I, Clinical Global Impressions-Improvement scale; SIB-Q, Self-Injurious Behavior Questionnaire; ABC-1, Aberrant Behavior Checklist Irritability subscale; RUPP, Research Units on Pediatric Psychopharmacology; DB, double-blind; EPS, extrapyramidal symptoms; CY-BOCS, Children’s Yale-Brown Obsessive Compulsive Scale; OAS-M, Overt Aggression Scale modified.

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