Antipsychotics and Autism: Weighing The Benefits, Eyeing The Risks

Marina Sarris
Interactive Autism Network at Kennedy Krieger Institute

ian@kennedykrieger.org

Date Published: December 13, 2016

Children and adults with autism are sometimes prescribed an array of psychiatric drugs for hyperactivity, poor attention, or challenging behaviors. One type of medication, called antipsychotics, has become something of a "go-to" treatment for the most severe behaviors. According to the latest studies, one in five or six youth with autism has taken them,^1,2 along with 43 percent of adults with autism, on average.³ Antipsychotics are the most frequently used type of psychiatric drug in autism.³

That may be because two antipsychotics are the only drugs approved specifically for certain behaviors in children and teens with autism.¹ The U.S. Food and Drug Administration gave its stamp of approval to aripiprazole (brand name Abilify) and risperidone (brand name Risperdal) for "irritability" in autism – namely self-injury and aggression – almost a decade ago. More recently, the U.S. Agency for Healthcare Research and Quality weighed the scientific evidence on those medications. It found significant benefits and also "harms," or bad side effects.⁵ The drugs reduce challenging and repetitive behaviors when compared to no treatment. They also are associated with significant weight gain, sedation, tremors and movement disorders, it noted.⁵

Another scientific review of aripiprazole came to similar conclusions. On the plus side, children and teens "showed less irritability and hyperactivity and fewer ... repetitive, purposeless actions. However, notable side effects, such as weight gain, sedation, drooling and tremor, must be considered," concluded reviewers from the Cochrane Collaboration, an independent network of scientists and researchers.⁷

In fact, those side effects are serious enough to limit the type of patient who should take these drugs, according to a 2011 article in the prestigious medical journal, Pediatrics. Those researchers said antipsychotics should only be used in youth with "severe impairment or risk of injury."¹⁸

Some families wish they had more options for treating severe behavior.

A Parent's View of Antipsychotics for Autism

As a little girl she was hyperactive and underweight, and now we have the opposite problem....

Jane Wickstrom said her teenage daughter with autism has struggled with impulsivity and aggression. When her daughter was younger, she would bolt from safe places, a somewhat common and dangerous behavior in children with autism.¹¹ She once escaped and boarded a New York City subway. Fortunately, a rider found her unharmed and got help. Her doctor prescribed a newer generation of antipsychotic, which helped reduce unsafe behaviors. She also experienced unwanted side effects. "As a little girl she was hyperactive and underweight, and now we have the opposite problem, where she's borderline obese in the medical sense," her mother said.

A doctor is monitoring her daughter's health to guard against pre-diabetes, and her diet is regulated. "The major reason why I dislike these medications is because of the weight gain. I wish there were more options," said Ms. Wickstrom, a participant in the Simons Simplex Collection (SSC), an autism research project. About 14 percent of 1,605 youth in the Simons project have taken an antipsychotic or mood stabilizing drug.¹²

A History of Antipsychotics

What are antipsychotics, and how did they become as widely used as they are in autism?

Typical antipsychotics, also called neuroleptics, were introduced in the United States in 1950s. Doctors hailed their ability to curb the hallucinations and delusions of schizophrenia and other psychotic disorders. These drugs included the generics haloperidol, molindone and chlorpromazine. They carried a significant risk of extrapyramidal symptoms, which are drug-induced movement problems. One such side effect, tardive dyskinesia – uncontrollable facial movements – could become permanent.

In the 1990s, a second generation, called atypical antipsychotics, came on the market. These drugs, which include Abilify and Risperdal, were less likely to cause movement disorders than their older cousins. Doctors began prescribing them "off-label" – or without specific approval by the U.S. government – for challenging behaviors in autism, as well as other conditions.⁴ The Food and Drug Administration formally approved Risperdal to treat irritability in children with autism ages 5 to 16 in 2006, followed by Abilify three years later.

By 2010, one in five children with autism was taking an atypical antipsychotic, according to a study of 7,900 children in the Kaiser Permanente Northern California and other health care networks.²

Trends in Antipsychotic Use in Autism

To learn more about antipsychotic trends, a group of researchers analyzed 39 studies, involving more than 350,000 children and teens, conducted from 1996 to 2011. They found that antipsychotic use increased in youth with autism and/or intellectual disability in the latter years.¹ They speculated that an increase in autism diagnoses, as well as FDA approval of Risperdal and Abilify for ASD in the late 2000s, contributed to that trend.

Scientists are investigating the side effects, particularly increases in body weight and cholesterol, in children and teens taking antipsychotics. In one major study, youth ages 4 to 19 gained one to 1.5 pounds per week, on average, over 11 weeks while taking one of four atypical antipsychotics for the first time.⁶ The patients on olanzapine (brand name Zyprexa) had the largest increases in weight and cholesterol, while those on aripiprazole (Abilify) had the least weight gain and no cholesterol changes. Children and teens on quetiapine (Seroquel) and risperidone (Risperdal) fell in between.⁶ That research was led by New York psychiatrist Christoph U. Correll, MD, who has studied antipsychotics extensively.

Two other antipsychotics are worthy of mention, although they were not included in that study. Clozapine (brand name Clozaril) has a greater risk of weight gain, diabetes and high cholesterol, similar to Zyprexa. And ziprasidone (Geodon) is less likely to cause those side effects, similar to Abilify, according to a 2004 article by professional associations representing American psychiatrists, endocrinologists and others.¹⁴ As with any medication, some patients will not experience any side effects.

Managing Weight, Monitoring Risks During Antipsychotic Treatment

Weight is an important concern in autism. In general, children with autism are more likely to be overweight or obese than other kids.⁹

People of all ages may experience increases in weight, cholesterol, or blood sugar from taking antipsychotics, but children and teens appear to be most susceptible.^{6, 8, 15, 19} Obesity "can set the stage" for the development of serious medical problems, including diabetes, heart disease and strokes. That warning came from the same researchers who called the antipsychotics "indispensable in the treatment of a variety of symptoms in autism."⁴ Fortunately, Type 2 diabetes "seems rare" in children and teens who take antipsychotics.¹⁶ However, they do face a higher risk for diabetes than their peers who don't take the medication, particularly if they take olanzapine (Zyprexa). A research review found about three additional cases of diabetes per 1,000 youth who took antipsychotics, compared to those who didn't.¹⁶

Doctors should order blood tests to check for diabetes and, in youth who gain a lot of weight, high cholesterol, according to the American Academy of Child and Adolescent Psychiatry.¹⁷

As adults, people with autism experience more cardiovascular disease and diabetes than adults who don't have autism, according to a huge study by Kaiser Permanente Northern California.¹⁰ That study did not pinpoint the reasons for heart disease, but it noted that antipsychotic medications, a limited diet, and lack of exercise may play a part. People with autism may be picky eaters, due to sensory problems. They also may not have access to sports and exercise programs suited to their needs. Those factors could make it harder to keep a healthy weight.

Once a patient gains weight, it can be challenging to lose. "Unfortunately, it's a major problem with this class of medication," said child psychiatrist Elise M. Sannar, MD, of the Neuropsychiatric Special Care Program at Children's Hospital Colorado, part of the Autism Inpatient Collection research project. For example, the mother of a young adult told her that risperidone has changed his life for the better, she recalled. But "over the course of a year, he's gained 45 pounds. He can't keep gaining weight like this. It's a big challenge."

Dr. Sannar routinely treats youth with autism. When choosing a medication, she looks for a lower-risk drug first, even though it is not approved for treating irritability in autism. A blood pressure pill such as clonidine may not have the evidence behind it, but could reduce the impulsivity and anxiety that's fueling irritability, she said. "I'm weighing what are the potential long-term side effects."

Finding Other Solutions to Aggression in Autism

Medication is rarely going to be enough, or the only answer, for a child.

Both researchers and doctors say antipsychotics are not the only solution to severe, challenging behavior in autism. Before writing a prescription, doctors should consider using "psychosocial interventions" for irritability and aggression, according to a 2016 article in the Journal of the American Academy of Child and Adolescent Psychiatry.¹ Those interventions include behavior and social skill therapies, and parent training.

"Medication is rarely going to be enough, or the only answer, for a child," Dr. Sannar explained. She considers other factors: Could an undiagnosed physical problem, such as constipation or pain, be triggering aggression? Are sensory problems, common in autism, contributing to severe behavior? A sound-sensitive child, for example, could benefit from wearing noise-cancelling headphones. Also, does a child have access to behavioral (non-drug) therapy to address his challenges?

A behavioral therapist may help uncover the triggers of aggression, self-injury and tantrums, and can develop a plan for changing those behaviors. Behavior is a form of communication, so people with limited spoken language can be taught to communicate their needs in other ways. A picture exchange system or mobile communication device (such as an iPad) can help. In the United States, an Individualized Education Program (IEP) at school can address both communication and behavioral problems in students with disabilities from birth to 21. Ideally, a team of experts in speech pathology, behavior, psychiatry and education would address these problems together.

Unfortunately, some communities or families may not have access to child and adolescent psychiatrists, behavior therapy programs, or other resources for autism. In those instances, "is there an opportunity for a primary-care doctor to be in touch with a psychiatrist?" Dr. Sannar asked. "We want to figure out a way to support the doctors in the community dealing with super-complicated children."

What to Ask When An Antipsychotic is Considered

Dr. Sannar said parents can take an active role in treatment. "If a doctor mentions that an antipsychotic might be the right medication for your child, you can ask, 'Why this particular medication? Are there alternative medications that are just as good? What non-medication interventions might also help the problem?' Abilify and Risperdal are helpful medications. There is a role for them, for sure, but they're not the only answer."

Jodi Tewelis found help for her son's challenging behavior in a different type of medication. An antipsychotic did not work well, and it caused him to gain weight. His doctor instead prescribed fluoxetine (Prozac), an anti-depressant that also can reduce anxiety. "The Prozac has helped immensely because he's not so anxious, and there's no more aggressive behavior in public or at home," said Ms. Tewelis, who participates in IAN Research.

But, as she pointed out, "every child with autism is different."

Additional Resources: 

• National Institute of Mental Health article on antipsychotics and other "Mental Health Medications"
• IAN article: Challenging Behavior in Autism: Self-injury
• IAN article: Diagnosing and Treating Extreme Behavior in Children with Autism
• IAN series: Behavioral Therapies: Key Interventions in ASD
• To learn about U.S. special education: The Short-and-Sweet IEP Overview from the Center for Parent Information and Resources

References: 

1. Park, S. Y., Cervesi, C., Galling, B., Molteni, S., Walyzada, F., Ameis, S. H., . . . Correll, C. U. (2016). Antipsychotic use trends in youth with autism spectrum disorder and/or intellectual disability: A meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 55(6), 456-468.e4. doi:10.1016/j.jaac.2016.03.012. Abstract.
2. Madden, J. M., Lakoma, M. D., Lynch, F. L., Rusinak, D., Owen-Smith, A. A., Coleman, K. J., . . . Croen, L. A. (2016). Psychotropic medication use among insured children with autism spectrum disorder. Journal of Autism and Developmental Disorders, doi:10.1007/s10803-016-2946-7. Abstract.
3. Jobski, K., Hofer, J., Hoffmann, F., & Bachmann, C. (2016). Use of psychotropic drugs in patients with autism spectrum disorders: A systematic review. Acta Psychiatrica Scandinavica, doi:10.1111/acps.12644. Abstract.
4. Posey, D. J., Stigler, K. A., Erickson, C. A., & McDougle, C. J. (2008). Antipsychotics in the treatment of autism. The Journal of Clinical Investigation, 118(1), 6-14. doi:32483 [pii] Abstract.
5. Agency for Healthcare Research and Qualifty. (2014). Comparative effectiveness of therapies for children with autism spectrum disorder [Abstract]. AHRQ Pub No.14-EHC036-3
6. Correll, C. U., Manu, P., Olshanskiy, V., Napolitano, B., Kane, J. M., & Malhotra, A. K. (2009). Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA, 302(16), 1765-1773. Abstract.
7. Hirsch, L. E., & Pringsheim, T. (2016). Aripiprazole for autism spectrum disorders (ASD). The Cochrane Database of Systematic Reviews, (6):CD009043. doi(6), CD009043. doi:10.1002/14651858.CD009043.pub3. Abstract.
8. Maayan, L., & Correll, C. U. (2011). Weight gain and metabolic risks associated with antipsychotic medications in children and adolescents. Journal of Child and Adolescent Psychopharmacology, 21(6), 517-535. doi:10.1089/cap.2011.0015. Abstract.
9. Hill, A. P., Zuckerman, K. E., & Fombonne, E. (2015). Obesity and autism. Pediatrics, 136(6):1051-1061. doi: 10.1542/peds.2015-1437. Abstract.
10. Croen, L. A., Zerbo, O., Qian, Y., Massolo, M. L., Rich, S., Sidney, S., & Kripke, C. (2015). The health status of adults on the autism spectrum. Autism : The International Journal of Research and Practice, 19(7), 814-823. doi:10.1177/1362361315577517 [doi] Abstract.
11. Anderson, C., Law, J. K., Daniels, A., Rice, C., Mandell, D. S., Hagopian, L., & Law, P. A. (2012). Occurrence and family impact of elopement in children with autism spectrum disorders. Pediatrics, 130(5), 870-877. doi:10.1542/peds.2012-0762; Abstract.
12. Mire, S. S., Nowell, K. P., Kubiszyn, T., & Goin-Kochel, R. P. (2014). Psychotropic medication use among children with autism spectrum disorders within the simons simplex collection: Are core features of autism spectrum disorder related? Autism : The International Journal of Research and Practice, 18(8), 933-942. doi:10.1177/1362361313498518 [doi] Abstract.
13. American Academy of Child and Adolescent Psychiatry. (2013). Workforce issues. Retrieved from http://www.aacap.org/aacap/Resources_for_Primary_Care/Workforce_Issues.aspx
14. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, & North American Association for the Study of Obesity. (2004). Consensus development conference on antipsychotic drugs and obesity and diabetes. The Journal of Clinical Psychiatry, 65(2), 267-272.
15. Correll, C. U., & Carlson, H. E. (2006). Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. Journal of the American Academy of Child and Adolescent Psychiatry, 45(7), 771-791. doi:10.1097/01.chi.0000220851.94392.30. Abstract.
16. Galling, B., Roldan, A., Nielsen, R. E., Nielsen, J., Gerhard, T., Carbon, M., . . . Correll, C. U. (2016). Type 2 diabetes mellitus in youth exposed to antipsychotics: A systematic review and meta-analysis. JAMA Psychiatry, 73(3), 247-259. doi:10.1001/jamapsychiatry.2015.2923. Abstract.
17. American Academy of Child and Adolescent Psychiatry. (2011). Practice parameter for the use of atypical antipsychotic medications in children and adolescents. Retrieved from https://www.aacap.org/App_Themes/AACAP/docs/practice_parameters/Atypical_Antipsychotic_Medications_Web.pdf
18. McPheeters, M. L., Warren, Z., Sathe, N., Bruzek, J. L., Krishnaswami, S., Jerome, R. N., & Veenstra-VanderWeele, J. (2011). A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics, 127(5), e1312. Abstract.
19. Stigler, K. A., Potenza, M. N., Posey, D. J., & McDougle, C. J. (2004). Weight gain associated with atypical antipsychotic use in children and adolescents. Pediatric Drugs, 6(1), 33-44. doi:10.2165/00148581-200406010-00003 Abstract.