Psychotropic medications are commonly prescribed to treat maladaptive behaviors such as depression, repetitive behaviors, epilepsy, psychosis in ASD children. The presence of maladaptive behaviors can diminish the benefits of other social and language interventions. Most medications which are prescribed for treatment in those with ASD have not been tested for effectiveness in this population, but many safety and efficacy studies are underway. Experienced clinicians note that those with ASD tend to have side effects more often and of a more severe nature than the typically developing population.
Antidepressants are the most commonly prescribed medications for those with ASD. Usually, antidepressants prescribed are serotonin selective re-uptake inhibitors (SSRIs). One randomized, placebo-controlled, double-blind study which looked at effects of fluvoaxmine in 30 adults found improvements in repetitive behaviors, aggression, language use, and overal maladaptive behavior ratings. However, subsequent studies which tried to replicate these findings failed to find an effect.
Antidepressants should be used with with increased caution for children with ASD because of the current FDA warning for increased suicidal thinking and behavior for children taking antidepressants, as well as the tendency for children with ASD to experience side effects more frequently and more severely than the typically developing population. Side effects include nausea, sedation, activation, agitation, insomnia, and sometimes increased activity, increased anxiety, or mood lability. ASD children tend to have greater disinhibition when taking antidepressants. Activation also happens more frequently in ASD children (one study had a 20% activation rate among ASD subjects).
The best management strategy to avoid activation in this population is to use the lowest effective dose and to slow the titration schedule (much less than the schedule used in adults).
Medications which have neurological side effects such as Clomipramine should be used with caution in ASD patients because children with ASD may be at higher risk to experience neurological side effects since many in this population also suffer from seizures.
At this time, studies of antidepressant use in children with ASD do not show evidence of benefits from use in this population.
Stimulants are prescribed for up to 15% of the ASD population for hyperactive, inattentive, and impulsive behaviors. A large controlled study of methylphenidate use in ASD children found that approximately half of the subjects had reduced hyperactivity. However, 20% of enrolled subjects did not complete the trial because of adverse side events such as social withdrawal and decreased appetite. Methylphenidate was associated with increases in measures of joint attention and self regulation, but this association must be further tested.8 Atomoxetine has been suggested as possibly beneficial for hyperactivity and impulsivity in those with ASD, but many experience adverse effects.9 Alpha-2 adrenergic agonists/antihypertensives, such as clonidine and guanfacine possibly affects alpha-2-receptors, which betters performance on measures of cognition.However, more research needs to be done to assess utility because of the frequency of adverse side effects. 10, 11
Controlled studies suggest that there is an elevated risk of adverse events such as confusion, possible psychosis, and treatment emergent tic disorder occurring for children with ASD who take stimulants compared to typically developing children with other disorders including ADHD. Studies involving children with ASD to test the safety and efficacy of stimulants in this population show a much higher dropout rate than for the typically developing population. Reasons cited for dropping out are usually from negative mood effects. Additionally, children with ASD report a higher rate of insomnia in studies when taking medium ( 0.25 mg/kg/dose) and high doses (0.5mg/kg/dose) as well as a reduction in appetite.
Some suggestions for management in this population include extended-release preparations for medications rather than those that are rapidly releasing. Patients prescribed stiumulants should be monitored closely for side effects using a structured measure, such as growth in height. If growth drops off too quickly, the clinician should reconsider using stimulants.
Second Generation Antipsychotics
Although there are warnings about possible adverse effects of long term use, the short term benefits of second generation antipsychotics have propelled this class of medications to become the second most commonly prescribed medications for those with ASD. The FDA has specifically approved two medications in this class for irritability and aggression in those with autism.
Adverse effects from using second generation antipsychotics include sedation, increased appetite, weight gain, disrupted sleep, prolactin elevation, and extrapyramidal symptoms. However, some side effects such as sedation seem to fade with time. Low doses appear to be highly effective from studies and they also tend to have a lower risk of side effects than higher doses.
Second Generation Antipsychotics are diverse, but most medications affect serotonin and dopamine systems. Most antipsychotics can also affect other neurotransmitter receptors including histaminic, adrenergic, and cholinergic receptors.5 Risperidone and aripiprazole have both been investigated in large placebo controlled studies and results suggest that these medications improve agitation, aggression, irritability, and self-injury in those with autism6,7.
Serotonin Reuptake Inhibitors
Fluoxetine is a FDA approved drug for the treatment of OCD and depression in children. In the only double-blind placebo-controlled crossover study of using this drug in children with autism, they decided that Fluoxetine was superior to the placebo in reducing repetitive behaviors when measured by the CY-BOCS. Low-dosages of fluoxetine was slighly superior to placebo in reducing global autism severity when measured by the GACIM scale. Further analysis of this drug in another study showed that positive fluoxetine response in autistic children correlated with family history of major affective disorders, unusual intellectual achievement, and hyperlexia, which may suggest that this drug works best for a genetically defined subtype of autism. 2
Fluvoxamine is a FDA approved drug for the treatment of OCD in adults and children. In an open label study to assess the overall effectiveness and tolerability of fluboxamine, the effect of puberty on drug response, an the relationship of changes in platelet serotonin to behavioral response in 18 children. The drug had no statistically significant improvement for autistic children in global functioning, repetitive behaviors. or anxiety symptoms. Side effects were notable from the drug. Different ethnic groups also display different responses to this drug. 2
Escitalopram is often given to children to improve repetitive behaviors in those with ASD, although a recent large study has questioned its efficacy3.Response to the drug may depend on the individual's genotype of the serotonin transporter, which could explain the lack of efficacy in a large group sample. A minority of the children experienced drug-induced insomnia, hyperactivity, and or general disinhibition, even at low doses.4
Many people with ASD take antiepileptic drugs to manage seizures. Moreover, interest in investigating the use of mood stabilizers and antiepileptic drugs has increased due to reports of associations between ASD and mood swings. However, efficacy for using Levetiracetam, an anticonvulsant, to alleviate maladaptive behaviors has not yet been established from studies despite hopeful anecdotal accounts.12
Studies have been done to test if acetylcholinesterase inhibitors reduce symptoms of autism because of reports from post mortem tissue analysis of those who had autism, which suggested that those with ASD had reduced nicotinic receptors. Recent studies report modest improvement in some behavioral measures.13
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