- Author: James Robert Brasic, MD, MPH; Chief Editor: Caroly Pataki, MD more...
The established therapies for autistic disorder are nonpharmacologic. These therapies may include behavioral, educational, and psychological treatment. No pharmacologic agent is effective in the treatment of the core behavioral manifestations of autistic disorder. However, medication may be effective in the treatment of comorbid disorders, including self-injurious behaviors and movement disorders.
The atypical antipsychotic agents risperidone and aripiprazole have been approved by the FDA for irritability associated with autistic disorders.
Risperidone is an atypical antipsychotic agent that is indicated for irritability associated with autistic disorder in children and adolescents aged 5-16 years. Risperidone is a mixed serotonin-dopamine antagonist that binds to 5-HT2 with very high affinity and binds to the dopamine D2 receptor with less affinity. Affinity for the dopamine D2 receptor is 20 times lower than that for the 5-HT2 receptor.
The combination of serotonin antagonism and dopamine antagonism is thought to improve negative symptoms of psychoses and reduce the incidence of extrapyramidal side effects in comparison with conventional antipsychotics.
Aripiprazole is indicated for irritability associated with autistic disorder in children and adolescents aged 6-17 years. Aripiprazole is thought to be a partial dopamine (D2) and serotonin (5-HT1A) agonist, and to antagonize serotonin (5-HT2A). Aripiprazole is available as a tablet, an orally disintegrating tablet, or an oral solution.
Ziprasidone, a second-generation antipsychotic drug, is used off-label to treat serious behavior disorders associated with autism, such as self-injurious behavior. It elicits its effects through antagonism of D2, D3, 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1D, and alpha1-adrenergic receptors. In addition, it has a moderate antagonistic effect for histamine H1. It moderately inhibits the reuptake of serotonin and norepinephrine.
SSRIs are widely prescribed for children with autism or a related condition. These agents are used off-label to help with intractable repetitive behaviors, such as compulsion.
Fluoxetine selectively inhibits presynaptic serotonin reuptake, with minimal or no effect on the reuptake of norepinephrine and dopamine.
Citalopram enhances serotonin activity by selective reuptake inhibition of serotonin at the neuronal membrane. Dose-dependent QT prolongation has been reported with citalopram.[149, 150] . This agent is contraindicated in patients with congenital long QT syndrome.
Escitalopram is an S-enantiomer of citalopram. The mechanism of action is thought to be potentiation of serotonergic activity in the central nervous system (CNS), resulting from the inhibition of CNS neuronal reuptake of serotonin.
Stimulants may be effective for treating hyperactivity associated with autism. The magnitude of response, however, is less than that seen in developmentally normal children with attention deficit hyperactivity disorder
Methylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. Methylphenidate is a racemic mixture composed of the d- and l-enantiomers. The d-enantiomer is more pharmacologically active than the l-enantiomer.
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