Table 4.
Retrospective Reviews of Treatments for Aggression in Adults with Autism Spectrum Disorder
| Study | Diagnosis | Subjects (number, sex, mean age | Nature of aggression | Intervention | Measure of aggression | Adverse effects | Outcome |
|---|---|---|---|---|---|---|---|
| Hollander et al. (2001)112 | Autistic disorder (DSM-IV;21 10 subjects) Asperger’s disorder (DSM-IV;21 2 subjects) PDD NOS (DSM-IV;21 2 subjects) IQ range, 20–105, mean = 69.1 |
n = 14 12 male, 2 female 17.93 years (range, 5–40 years) 4 adults (3 male, 1 female) |
Aggression, self-injurious behavior, impulsivity (not specified) | Divalproex sodium 500–2500 mg daily (with blood levels from 65 to 92 μg/ml) for 2 to 27 months, depending on subject | CGI-I35 | Hair loss, weight gain, sedation, buccal numbness (1 subject) Elevated liver enzymes (1 subject) Difficulty waking in morning (1 subject) |
Substantial improvement (reflected by score of “much improved” or “very much improved” on CGI-I35) in 2 of 4 adult subjects (50%) in terms of overall clinical status; however, only 1 of 4 adult subjects actually demonstrated improvement in aggression 2 of other 4 subjects showed no improvement in these domains Another subject showed improvement in self-injurious behavior and impulsivity In both subjects with positive response, mood lability significantly improved |
| Corson et al. (2004)113 | Autistic disorder (DSM-IV21) and severe ID (1 adult subject) Autistic disorder (DSM-IV21) and mild ID (1 adult subject) PDD NOS (DSM-IV21) and mild ID (1 adult subject) |
n = 3 1 male, 2 female 25.67 years |
Aggression (not specified) | Quetiapine 25–500 mg daily for 32 to 54 weeks | CGI-I35 CGI-S35 |
Weight gain (2 of 3 adult subjects) | Modest effect on aggression Only 1 of 3 subjects had improved CGI-I35 score (“much improved”) pre- to post-treatment For entire sample (children + adults) of 20 subjects, CGI-S35 scores changed from mean of 5.1 (“markedly ill”) pre-quetiapine to mean of 4.2 (“moderately ill”) post-quetiapine |
| Cohen et al. (2004)39 | Autistic disorder (DSM-IV21) ID (profound in 9; borderline intellectual functioning in 1) |
n = 10 6 male, 4 female 43.8 years |
Assault (n = 5), self-injury (n = 5), agitation (n = 3), aggression (n = 1) (details not specified) | Ziprasidone at mean dose of 128 mg daily for 6 months (of note, 80% of subjects were previously treated with risperidone) | Maladaptive Behavior Scale39 | No concerning side effects of ziprasidone noted 80% of ziprasidone-treated patients lost weight (average = 9.5 pounds), 80% had decrease in cholesterol, and 60% showed decrease in triglycerides |
Improvement in Maladaptive Behavior Scale39 scores in 6 of 10 patients (60%), compared to 6 months prior to ziprasidone treatment In 1 of 10 patients (10%), scores remained same, and in 3 of 10 patients (30%) scores worsened |
| Janowsky et al. (2005)114 | Autistic disorder (DSM-III-R20 or DSM-IV21) | n = 8 6 male, 2 female 40.25 years |
Aggressive behavior toward others (including hitting, biting, kicking, shoving), self-injurious behavior (including self-hitting, self-biting, head banging, cutting one’s skin, skin picking), destructive behaviors (including overturning or breaking furniture) | Fluvoxamine 12.5–200 mg daily (5 subjects), paroxetine 10–40 mg daily (2 subjects), sertraline up to 200 mg daily (1 subject) for at least 6 weeks | Psychologist ratings of frequency of aggressive, self-injurious, and destructive behaviors based on staff observation Retrospective global behavioral ratings by one of authors roughly paralleling Severity of Illness component of CGI35 |
Overall well tolerated, although 1 subject experienced activation of target symptoms (e.g., aggression) on fluoxetine Weight gain in 7 subjects, but unclear how many of these had ASD |
Significant reduction in ratings of aggressive, self-injurious, and destructive behavior, with maintenance of gains over 6-month period |
| Beherec et al. (2011)115 | Autistic disorder (DSM-IV-TR;22 3 subjects) PDD NOS (DSM-IV-TR;22 3 subjects) All diagnoses corroborated by ADI-R24 and ADOS25 |
n = 6 2 male, 4 female 23.2 years |
Aggressive behavior (assaulting others, destroying property, self-injury) | Clozapine for 4 to 6 months (dose unspecified) | For each subject, proportion of days with aggression was measured during 4–6 months preceding initiation of clozapine and during 4–6 months following clozapine initiation, based on daily behavioral reports completed by nursing staff | Weight gain in most subjects, with average weight increase of 14.3 kg Constipation (5 subjects) Metabolic syndrome (1 subject) Tachycardia (1 subject) No patients developed agranulocytosis or extrapyramidal symptoms |
Proportion of days with aggression decreased from average of 19.1% during period preceding clozapine treatment to average of 10.7% during period following clozapine initiation (approximately 2-fold decrease) Reduction in number of antipsychotic medications used and in total antipsychotic dose from pre- to post-clozapine initiation |
| Ishitobi et al. (2012)116 | Autistic disorder (DSM-IV-TR;22 16 subjects) Asperger’s disorder (DSM-IV-TR;22 3 subjects) PDD NOS (DSM-IV-TR;22 4 subjects) |
n = 23 16 male, 7 female 15.1 years (range, 9–24 years; unclear how many adult subjects) |
Aggression (not specified) | Aripiprazole at mean dose of 2.8 mg daily for average of 14.9 weeks (after being switched from risperidone due to tolerability issues, including increased appetite and weight, hyperprolactinemia, somnolence, amenorrhea) | CGI-S35 CGI-I35 |
Improvements in excessive appetite/weight gain in 7 of 11 patients (64%) who had experienced this side effect on risperidone Improvement in hyperprolactinemia in 3 male subjects |
Aripiprazole at mean dose of 2.8 mg/day as effective as risperidone at mean dose of 0.7 mg/day at treating aggression and impulsivity (mean CGI-S35 scores pre- and post-aripiprazole were 4.7 ± 1.4 and 4.6 ± 1.3, respectively; mean CGI-I35 score was 3.4 ± 0.8), suggesting efficacy of risperidone for treating behavioral problems was maintained by aripiprazole Aripiprazole associated with improvements in excessive appetite/weight gain in 7 of the 11 patients (63.6 %) who had experienced this side effect on risperidone, and with improvement in hyperprolactinemia in 3 male subjects |
| Sajith (2017)117 | ASD (unclear which criteria used, but subjects were admitted to specialist inpatient unit for adults with ID and autism associated with severe behavioral problems) | n = 3 All male 25.67 years |
Aggression (destroying property, assaulting others, poking others’ eyes, severe self-injurious behavior) | Clozapine 400–550 mg/day for 2 months | Staff observation of frequency of aggressive incidents | Tachycardia, drooling, and sweating (1 patient), which improved over time Transient sedation and constipation (1 patient) Generalized tonic-clonic seizure treated with levetiracetam and dose reduction of clozapine to 400 mg/day, with no further seizure recurrence (1 patient) No instances of neutropenia or agranulocytosis |
Substantial reduction in frequency of aggression for all 3 patients |
| Wink et al. (2017)118 | Autistic disorder (DSM-IV-TR;22 44 subjects) Asperger’s disorder (DSM-IV-TR;22 3 subjects) PDD NOS (DSM-IV-TR;22 14 subjects) ID (41 subjects) |
n = 61 53 male, 8 female 15.1 years (range, 4.2–26 years); unclear how many adults |
Physical aggression (82%), self-injury (23%) | Daily doses of 2 or more antipsychotics concurrently for at least 2 clinic visits; most common initial combinations were risperidone + quetiapine (10 subjects), risperidone + aripiprazole (9 subjects), and aripiprazole + quetiapine (7 subjects); most common combinations at final visit were risperidone + quetiapine (10 subjects), aripiprazole + quetiapine (8 subjects), and risperidone + aripiprazole (5 subjects) | CGI-S35 CGI-I35 |
Weight gain and sedation most common | Antipsychotic combinations found to be associated with small, nonsignificant reductions in agitation/irritability, aggression, and self-injury, reflected by modest decrease in CGI-S35 scores from pre- to postintervention (mean = 4.7 pretreatment to mean = 4.6 posttreatment; p = .45) and mildly improved CGI-I35 scores pre- to posttreatment |
ADI-R, Autism Diagnostic Interview–Revised; ADOS, Autism Diagnostic Observation Schedule; ASD, autism spectrum disorder; CGI-I/S, Clinical Global Impression Scale–Improvement/Severity; DSM, Diagnostic and Statistical Manual of Mental Disorders; ID, intellectual disability; IQ, intelligence quotient; PDD NOS, pervasive developmental disorder not otherwise specified.