Caring for patients with autism spectrum disorder

When severe self-injury and aggression fail to improve with multiple medication trials, the next steps include combination treatment with multiple antipsychotics,³⁶ followed by clozapine, often as a last option.³⁷ Research suggests that clozapine is effective and well-tolerated in ASD^38-42; however, it has many potential severe adverse effects, including cardiomyopathy, lowered seizure threshold, severe constipation, weight gain, and agranulocytosis; due to risk of the latter, patients require regular blood draws for monitoring.

There is very little evidence to support the use of antiepileptic medications (AEDs) and mood stabilizers for irritability in ASD.⁴³ Placebo-controlled trials have had mixed results. Some evidence suggests that AEDS may have more utility in individuals with ASD and abnormal EEGs without epilepsy⁴⁴ or as an adjunct to SGA treatment.⁴⁵ One study found that lithium may be beneficial for patients with ASD whose clinical presentation includes 2 or more mood symptoms.⁴⁶

Anxiety

Anxiety is a significant issue for many individuals with ASD.⁴⁷ Anxiety symptoms and disorders, including specific phobias, obsessive-compulsive disorder (OCD), social anxiety, and generalized anxiety disorder, are commonly seen in persons with ASD.⁴⁸ Anxiety is often combined with restricted, repetitive behaviors (RBs) in ASD literature. Some evidence suggests that in individuals with ASD, sameness behaviors may limit sensory input and modulate anxiety.⁴⁹ However, the core RBs symptom domain may not be related solely to anxiety, but rather represents deficits in executive processes that include cognitive flexibility and inhibitory control seen across multiple disorders with prominent RBs.^50-54 Research indicates that anxiety is an independent and separable construct in ASD.⁵⁵

Studies of treatments for both RBs and anxiety have focused primarily on selective serotonin reuptake inhibitors (SSRIs), hoping that the promising results for anxiety and OCD behaviors seen in neurotypical patients would translate to patients with ASD.⁵⁶ Unfortunately, there is little evidence for effective pharmacologic management of ASD-associated anxiety.⁵⁷ Large, randomized controlled trials (RCTs) are lacking. A Cochrane Database review of SSRIs for ASD⁵⁸ examined 9 RCTs with a total of 320 patients. The authors concluded that there is no evidence to support the use of SSRIs for children with ASD, and limited evidence of utility in adults. Youth with ASD are particularly vulnerable to adverse effects from SSRIs, specifically impulsivity and agitation.^57,59 However, SSRIs are among the most commonly prescribed medications for youth with ASD. Because there is limited evidence supporting SSRIs’ efficacy for this indication and issues with tolerability, there is significant concern for the overprescribing of SSRIs to patients with ASD. In comparison, there is some compelling evidence of efficacy for modified cognitive-behavioral therapy (CBT) for patients with high-functioning ASD. Seven RCTs have shown that CBT is superior to treatment as usual and waiting list control groups, with most effect sizes >0.8 and with no treatment-associated adverse effects.⁵⁷

Risperidone has been shown to reduce RBs^17,60 and anxiety¹⁷ in patients with ASD. In young children with co-occurring irritability, risperidone monotherapy is likely best to address both symptoms. When anxiety occurs in isolation and is severe, clinical experience suggests that SSRIs can be effective in a limited percentage of cases, though we recommend starting at low doses with frequent monitoring for activation and irritability. Treatment of anxiety is further complicated by the significant challenges presented by the diagnosis of true anxiety in the context of ASD.

Continued to: Hyperactivity and impulsivity