Autism’s repetitive behaviors and restricted interests interfere with adaptive functioning, social interactions, and learning. No medications are FDA-approved for autistic disorder, but some selective serotonin reuptake inhibitors (SSRIs) and atypical antipsychotics and an anticonvulsant have reduced repetitive behaviors in controlled trials. We discuss how that evidence shapes our approach to patients with or without a comorbid family history of bipolar disorder.
Evidence for SSRIs
Repetitive behaviors and restricted interests are autism’s third core domain, as defined by DSM-IVTR criteria.1 For an autistic disorder diagnosis, a patient must show at least one of these behaviors:
- encompassing preoccupations with stereotyped or restricted patterns of interest
- inflexible routines or rituals
- stereotyped, repetitive motor mannerisms
- or persistent preoccupation with parts of objects.
As in obsessive-compulsive disorder (OCD), rituals and restricted interests are thought to decrease anxiety in autism, whereas self-stimulatory behaviors and stereotypy may regulate arousal. The behaviors persist2,3 but may change across the lifespan.
Because SSRIs improve OCD’s repetitive behaviors, clinicians have also used them to treat autism’s repetitive behaviors, though without supporting data. Recently, however, fluoxetine and fluvoxamine have shown efficacy for autism’s repetitive behaviors in randomized, controlled trials. Results indicate:
- In children, fluoxetine is probably better-tolerated than available dosing forms of fluvoxamine.
- In adults, fluvoxamine is well-tolerated and can improve repetitive behavior.
SSRIs and suicidal ideation in autism. The increased risk of suicidality reported with SSRIs when treating depression and OCD has not been seen in children with autism. But because fewer children with autism have been treated with SSRIs, we recommend that you try to assess suicidal ideation during SSRI treatment in those able to express such concerns (Box). Starting with low SSRI dosages (Table 1) and increasing slowly may help prevent behavioral activation, a possible risk factor for suicidality.
How to assess suicidality with SSRIs in patients with autism
Suicidal ideation has not been reported in studies of selective serotonin reuptake inhibitors (SSRIs) in autism. Even so, children and adolescents with autistic disorder are not excluded from the FDA black-box warning of increased risk of suicidality with SSRIs.
Children with obsessive-compulsive disorder (OCD) treated with SSRIs have shown evidence of suicidal thoughts. Thus, higher-functioning children and adults with autism might think about suicide when they become aware of their deficits.
For lower-functioning patients (generally, those who receive medication), we need markers of possible suicidal ideation other than their reports of symptoms. In clinical trials, investigators measure behavioral activation symptoms as risk factors for suicidality.
Thus, when you start an SSRI in a patient with autistic disorder, educate the caregivers to watch for agitation, increased energy, poor sleep, disinhibition, or new hyperactivity. Encourage them to contact you immediately if these signs of activation occur.
Ask higher-functioning patients taking SSRIs about suicidal thinking in a step-wise fashion: thoughts of death, thoughts of their own death, intent, plan, and finally possible attempts.
Table 1
4 drugs with evidence of benefit for autism’s repetitive behaviors*
| Medication | Suggested target daily dosage |
|---|---|
| Fluoxetine7 | Children: Start at 2.5 mg/d; maximum 20 mg/d |
| Adults: Start at 10 to 20 mg/d; maximum 60 mg/d | |
| Fluvoxamine10 | Children: Not first-line; start at 12.5 mg/d; maximum 150 to200 mg/d |
| Adults: Start at 25 mg/d; maximum 300 mg/d | |
| Risperidone13,16 | Children: Start at 0.25 mg/d; maximum 3 mg/d |
| Adults: Start at 2 mg/d; maximum 4 mg/d | |
| Valproate20 | Children: Start at 125 mg (sprinkles); titrate to clinical effect and blood levels of 50 of 120 mcg/mL |
| Adults: Start at 250 mg; increase by 250mg/week to clinical effect and blood levels of 50 to 120 mcg/mL | |
| *Data from randomized, placebo-controlled trials | |
Fluoxetine. In the first open-label study of fluoxetine in children and adults with autistic disorder, global functioning improved significantly in 15 of 23 patients, as measured by the Clinical Global Impressions (CGI) scale.4 Autism symptoms also improved in follow-up, open-label trials, but these did not target repetitive behaviors specifically.5,6
Our group conducted the first randomized, placebo-controlled study of fluoxetine’s effect on repetitive behaviors in children with autism.7 We measured obsessions and compulsions in 45 children, ages 5 to 16, with the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS). This 10-item, clinician-rated questionnaire uses a 5-point scale to rate repetitive behaviors by time spent, distress, interference, resistance, and control.
Using a crossover design—two 8-week phases of active or placebo treatment separated by a 4-week washout—we started liquid fluoxetine at 2.5 mg/d and slowly increased the dosage to clinical effect or a maximum of 0.8 mg/kg/day. Mean final dosage was 9.9 (±4.35) mg/d.
Repetitive behaviors improved, even though we used relatively low dosages to avoid side effects. The mean baseline CY-BOCS compulsion score of 13.15 dropped to 11.6 with fluoxetine and to 12.9 with placebo. Fluoxetine’s effect size was moderate to large, and we found no suicidal ideation with this SSRI.