Existing Studies and Potential Research on Psychiatric Drugs for the Treatment of Autism Spectrum Disorder (ASD)

The atypical antipsychotics, risperidone (Risperdal) and aripiprazole (Abilify), are recommended by the Food and Drug Administration (FDA) since they are "well-established" in the research literature for the treatment of irritable, aggressive, and self-injurious behaviors often associated with children who have autism spectrum disorder (ASD; see U.S. Department of Health and Human Services et al, 2019). They are also FDA-approved and often prescribed for schizophrenia and bipolar disorder (also called manic-depression), as well as off-label to promote nightly sleeping in children with ASD.

Further, it is considered best practice to typically augment the antipsychotic to a SSRI antidepressant, as antipsychotics usually enhance the effectiveness of the SSRI. However, antipsychotic medication often results in undesirable side effects of increased appetite and significant weight gain.

There have been large RCT studies on the SSRI antidepressants, fluoxetine (Prozac), fluvoxamine (Luvox), and paroxetine (Paxil) for children and adolescents with ASD, but no large vigorously designed study on sertraline (Zoloft), which is the most prescribed antidepressant in the country for individuals of all ages who have anxiety, obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and depression (Grohol, 2018).

Some studies have already revealed significant progress in adolescents and adults on the autism spectrum who were prescribed sertraline for anxiety, depression, and even mild forms of irritability (Hellings et al, 1996; LeClerc & Easley, 2015; McDougle et al, 1998). Since a number of large RCT studies show the effectiveness of this drug in the treatment of OCD for typically developing children and adolescents, there should be several large RCTs conducted on the use of it for the repetitive and ritualistic behaviors in children and adolescents with ASD.

Guanfacine (Tenex, or Intuniv—the long-acting form) was originally designed to control high-blood pressure, but is frequently prescribed and FDA-approved for the treatment of attention deficit hyperactivity disorder - hyperactivity impulsive (ADHD-HI) subtype. It has also been prescribed off-label as a sedative to enhance nightly sleep and better manage tic disorders. A recent RCT study has indicated that guanfacine was highly effective in decreasing hyperactivity and impulsivity in children and adolescents with ASD, but not for improving their quality of sleep (Politte et al, 2018; Scahill et al, 2019).

A current survey study even revealed similar results of another antihypertensive, clonidine (Kapvay), which is also a popular FDA-approved drug for ADHD-HI (Coleman et al, 2019). An earlier open-labeled retrospective study on the drug indicated that it was effective for promoting and maintaining sleep in children with ASD, but not as beneficial for their co-morbid ADHD symptoms (Ming et al, 2008).

A large RCT, as well as a survey study on lamotrigine (Lamictal), an anticonvulsant medication that is commonly prescribed and FDA-approved for bipolar disorder, substantially reduced irritability and improved the overall mood in children with ASD who were between the ages of 3 and 11 (Belsito et al, 2001; Coleman et al, 2019). According to Psych Central, in 2016, lamotrigine was the second-most prescribed mood-altering drug in the United States, right behind the atypical antipsychotic, quetiapine (Seroquel; see Grohol, 2018).

More research is also needed on these other three drugs (guanfacine, clonidine, and lamotrigine) because like the antipsychotics, guanfacine and clonidine both have a sedative effect that can promote sleeping throughout the night while lamotrigine can also stabilize mood swings, yet each contrast in that they do not cause weight gain (despite lamotrigine having somewhat of an overeating side effect for some; it is still not as significant compared to the antipsychotics).

Stimulant medications, such as methylphenidate (Ritalin, or Concerta) and mixed amphetamine salts (levoamphetamine and dextroamphetamine; often branded as Adderall), are FDA-approved and widely prescribed for ADHD - predominantly inattentive (ADHD-PI). Nevertheless, studies on their use for the co-morbid inattentiveness in children and adolescents with ASD has revealed not only to be ineffective, but also results in agitation and anxiety. This is not to imply that all individuals on the autism spectrum do not show improvement in their attention or have a bad reaction when taking stimulant medication—considering it can sometimes be very helpful for those who have milder forms of ASD (Myers & Johnson, 2007).

More recently, a large RCT study conducted by the late Tristram Smith, a renowned behavior analyst and psychologist—who was a graduate student of Lovaas' at the UCLA Young Autism Project in the 1980s—and his colleagues at the University of Rochester Medical Center (URMC) indicated that atomoxetine (Strattera), an antidepressant well-established for treating the hyperactivity and impulsivity in children and adolescents with ADHD, was ineffective for ASD (Rameshwari et al, 2019).

Regardless of such common overeating side-effect, antipsychotic medication—such as risperidone and aripiprazole, as well as quetiapine and olanzapine (Zyprexa)—are still needed to treat individuals on the autism spectrum if they are aggressive, self-injurious, or still irritable (and when positive behavior support (PBS) is just not enough). Yet, as I mentioned before, alternatives to the antipsychotics should be considered first.

With additional research, more drug options for individuals on the autism spectrum could become a reality.

References

Belsito, K. M., Law, P. A., Kirk, K. S., Landa, R. J., & Zimmerman, A. W. (2001). Lamotrigine therapy for autistic disorder: A randomized, double-blind, placebo-controlled trial. Journal of Autism and Developmental Disorders, 31(2), 175-181.

Coleman, D. M., Adams, J. B., Anderson, A. L., & Frye, R. E. (2019). Rating of effectiveness of 26 psychiatric and seizure medications for autism spectrum disorder: Results of national survey. Journal of Child and Adolescent Psychopharmacology, 29(2), 107-123.

Grohol, J. M. (2018, July 8). Top 25 psychiatric medications for 2016. Retrieved on Psych Central from https://psychcentral.com/blog/top-25-psychiatric-medications-for-2016/

Hellings J. A., Kelley L. A., Gabrielli W. F., Kilgore E., & Shah P. (1996). Sertraline response in adults with mental retardation and autistic disorder. Journal of Clinical Psychiatry, 57, 333–336.

LeClerc, S., & Easley, D. (2015). Pharmacological therapies for autism spectrum disorder: A review. P&T: A peer-reviewed journal for formulary management, 40(6), 389-397.

McDougle C. J., Brodkin E. S., Naylor S. T., Carlson D. C., Cohen D. J., & Price L. H. (1998). Sertraline in adults with pervasive developmental disorders: A prospective open-label investigation. Journal of Clinical Psychopharmacology, 18, 62-66.

Ming, X., Gordon, E., Kang, N., & Wagner, G. C. (2008). Use of clonidine in children with autism spectrum disorders. Brain and Development, 30(7), 454-460.

Myers, S. M., & Johnson, C. P. (2007). Management of children with autism spectrum disorders. Pediatrics, 120(5), 1162-1182.

Politte, L. C., Scahill, L., Figueroa, J., McCracken, J. T., King, B., McDougle, C. J. (2018). A randomized, placebo-controlled trial of extended-release guanfacine in children with autism spectrum disorder and ADHD symptoms: An analysis of secondary outcome measures. Neuropsychopharmacology, 43(8), 1772-1778.

Rameshwari, V. T., Corbett-Dick, P., Aman, M. G., Smith, T., Arnold, L. E., Xueliang, P. ... Handen, B. L. (2019). Adverse events of atomoxetine in a double-blind placebo-controlled study in children with autism. Journal of Child and Adolescent Psychopharmacology, 27(8), 708-714.

Scahill, L., McCracken, J. T., King, B. H., Rockhill, C., Shah, B., Politte, L. ... McDougle, C. J. (2015). Extended-release guanfacine for hyperactivity in children with autism spectrum disorder. The American Journal of Psychiatry, 172(12), 1197-1206.

Steingard R. J., Zimnitzky B., DeMaso D. R., Bauman M. L., Bucci J. P. (1997). Sertraline treatment of transition-associated anxiety and agitation in children with autistic disorder. Journal of Child and Adolescent Psychopharmacology, 7(1), 9-15.

U.S. Department of Health and Human Services, National Institute of Health, & National Institute of Child Health and Human Development. (2019). Medication treatment for autism. Retrieved from https://www.nichd.nih.gov/health/topics/autism/conditioninfo/treatments/medication-treatment