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Risperidone use in children with autism carries heavy risks

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Emily Anthes
28 April 2014

Double edge: Risperidone can calm tantrums and aggression in some children with autism, but sleepiness is a common side effect.

Risperidone, the first drug approved for children with autism and the most widely used, improves some children’s behavior but can have severe side effects, suggests an informal analysis of the drug’s use.

The drug effectively treats the explosive and aggressive behavior that can accompany autism. “It has pretty big effects on tantrums, aggression and self-injury,” says Lawrence Scahill, professor of pediatrics at the Marcus Autism Center at Emory University in Atlanta, who has conducted clinical trials of risperidone. The change can be dramatic, he says, taking effect in a matter of weeks.

It has also been shown to reduce hyperactivity and repetitive behaviors, though the Food and Drug Administration has not approved it for those purposes1, 2.

Through these effects, risperidone allows children with autism to benefit from social services, educational programs and behavioral interventions, experts say.

“If you can’t sit still during speech therapy, you’re attacking the teachers, you’re not going to be able to take advantage of it,” says Christopher McDougle, director of the Lurie Center for Autism at MassGeneral Hospital for Children in Boston, who has studied risperidone use in children and adolescents.

But risperidone also has significant drawbacks and limitations. Not all people respond to it, symptoms often return when the drug is discontinued, and it doesn’t improve many of the core behaviors associated with autism.

In other words, risperidone is “not a cure for autism,” says Benedetto Vitiello, chief of the Child and Adolescent Treatment and Preventive Intervention Research Branch at the National Institute of Mental Health. “It doesn’t really go to the core symptoms of autism.”

More worrisome, however, are the side effects, the most significant of which is weight gain from an increased appetite. Children taking risperidone gain an average of 6 pounds within eight weeks of taking the drug1, 3. The drug can also cause drowsiness, hormonal changes and, in rare cases, involuntary movements.

If he were prescribing risperidone for a child with autism, says Scahill, “I would use as low a dosage as I possibly could and I would periodically see if I could take him off.”

Reducing irritability:

Although numerous studies have documented risperidone’s risks, efforts to find safer alternatives have so far come up short.

Aripiprazole, the only other drug approved to treat irritability in autism, has similar side effects. (The FDA approved it for children with autism in 2009.) And a clinical trial designed to evaluate the safety and efficacy of an extremely low dose of risperidone yielded disappointing results last year.

Risperidone is an antipsychotic that blocks the brain’s receptors for dopamine and serotonin. It was initially developed to treat schizophrenia. The U.S. Food and Drug Administration (FDA) approved risperidone for schizophrenia in 1993.

Older antipsychotics, most notably haloperidol, also work by dampening dopamine activity. Before risperidone came on the market, these drugs had often been prescribed to treat severe behaviors in some people with autism, such as temper tantrums and self-injury, symptoms often lumped together as ‘irritability.’

After risperidone’s approval for schizophrenia, researchers began to investigate its usefulness for autism. “The idea is that maybe we would be turning down the child’s tendency to overreact, to be able to give them another second or two before they erupt or become aggressive or self-injurious,” Scahill says.

In 2002, a randomized clinical trial of children with autism between 5 and 17 years of age showed a 57 percent reduction in tantrums, aggression and self-injury after taking risperidone, compared with a 14 percent reduction in children taking a placebo3. Among the children who responded positively to the drug, nearly 70 percent still showed improvements after six months of taking it.

In October 2006, the FDA approved risperidone to treat irritability in children with autism between 5 and 16 years of age.

This January, researchers published a new analysis of the 2002 data, in which they classified the participants by the type of aggressive behavior they showed — hotheaded aggression in response to provocation versus unprovoked aggression, for example. Risperidone significantly improved symptoms in all these subgroups, the researchers found4.

The challenge is to figure out how to maintain these benefits while minimizing the risks.

Last year, scientists at Janssen Research and Development — a sister company of Janssen Pharmaceuticals, Inc., which manufactures risperidone under the brand name Risperdal — published the results of a study designed to determine whether a low dose of risperidone reduces irritability in children with autism.

Researchers randomly assigned children with autism to one of three groups. Each day for six weeks, one-third of the children received a standard dose of risperidone, one-third got a dose lower than the FDA’s recommended minimum, and the final third received a placebo.

The lower dosage did decrease several side effects, including sleepiness and increased appetite, the researchers reported in a 2013 paper5. Unfortunately, the dose was no more effective than a placebo in alleviating irritability.

“It’s a tradeoff between what benefits you’re expecting [and] the risks for the specific patient,” says Gahan Pandina, senior director at Janssen Research and Development.

Weighty decision:

The researchers also found that after six weeks of taking a standard dose of risperidone, children had greater increases in insulin levels and insulin resistance than children taking a placebo. Weight gain and the resulting metabolic problems are side effects of nearly all antipsychotic drugs, but rapid weight gain can be especially worrisome in children.

“It’s the cumulative impact,” says Jeremy Veenstra-VanderWeele, medical director of the Treatment and Research Institute for Autism Spectrum Disorders at Vanderbilt University in Nashville, Tennessee. “You may change the body shape or body fat distribution in a child for the rest of their life.”

Risperidone can also cause fatigue and drowsiness. In a 2011 paper, Shafali Jeste and her colleagues reviewed the medical records of 70 children with autism treated with risperidone6. They found that these records mentioned sleepiness less frequently than weight gain, but the former is often the reason that families take children off the drug.

“Unless it’s severe, most parents are willing to put up with some weight gain as long as their child’s behavior is better,” says Jeste, assistant professor of psychiatry and neurology at the Center for Autism Research and Treatment at the University of California, Los Angeles. Sleepiness, which can interfere with school and therapies, is “a pretty quick deal-breaker.”

Risperidone can also cause a less common side effect called tardive dyskinesia, or involuntary repetitive movements.

Like many antipsychotic drugs, it also increases levels of prolactin, a hormone secreted by the pituitary gland. High levels of the hormone can have a feminizing effect, causing breast development in boys and lactation in girls, as well as problems with menstruation and sexual dysfunction.

“When prolactin goes up, your body essentially thinks it’s pregnant,” McDougle says.

However, researchers caution, high prolactin levels don’t always cause clinical symptoms, and it’s not clear that elevated prolactin alone presents a health risk. There needs to be much more research on the effects of chronically elevated prolactin levels, especially in children and teens, they say.

Risperidone’s side effects have been the focus of several lawsuits. By the end of 2013, 500 plaintiffs had filed lawsuits alleging that the drug had caused personal injuries, according to Johnson & Johnson’s annual report. Johnson & Johnson is the parent company of Janssen Pharmaceuticals.

“Janssen intends to defend the company against the allegations made in these lawsuits,” says Greg Panico, spokesman for Janssen Research and Development. The company has “acted responsibly regarding informing physicians and the public about the risks and benefits of Risperdal.”

Last fall, Johnson & Johnson agreed to pay more than $2.2 billion to resolve claims that it had improperly marketed Risperdal and two other drugs.

In the final analysis, researchers say risperidone should be given with caution, only for children with the most serious symptoms and only after other treatments have failed.

“Is someone going to get hurt if we don’t intervene? And if I think the answer is yes, then I’ll be thinking about risperidone,” Veenstra-VanderWeele says. “If I think the answer is no, I’ll be thinking about doing other things.”

Disclosure: The reporter holds stock in Johnson & Johnson, the parent company of Janssen Pharmaceuticals.

News and Opinion articles on SFARI.org are editorially independent of the Simons Foundation.

References:

1: Shea S. et al. Pediatrics 114, e634-641 (2004) PubMed

2: McDougle C.J. et al. Am. J. Psychiatry 162, 1142-1148 (2005) PubMed

3: McCracken J.T. et al. N. Eng. J. Med. 347, 314-321 (2002) PubMed

4: Carroll D. et al. Child Adolesc. Psychiatr. Clin. N. Am. 23, 57-72 (2014) PubMed

5: Kent J.M. et al. J. Autism Dev. Disord. 43, 1773-1783 (2013) PubMed

6: Lemmon M.E. et al. J. Child Neurol. 26, 428-432 (2011) PubMed

Comments

Name: Emily L. Williams
28 April 2014 - 2:53PM

It would also be important to study long-term use of antipsychotics, like Rispderal, in people with autism. Given the Metabolic Syndrome that can crop up with use of drugs like this, it's vital to determine whether this permanently predisposes towards a Metabolic Syndrome or whether the endocrine system may recuperate after cessation of drug use. Information like this would be useful in guiding the decision for long-term use, especially in those cases in whom the decision to utilize these kinds of medications may not be essential. When using this kind of drug, it should also be standard practice for these kids and adults to be overseen by an endocrinologist who can keep a better eye on hormonal changes, i.e., a psychiatrist or GP is just not enough. Also, a dietician who specializes in working with people with insulin resistance or diabetes would be wise. Although, undoubtedly, sensory-derived dietary restrictions may make diet changes a real challenge.

Name: Autism Dad
28 April 2014 - 3:44PM

This is terrifying. Probably 40% of ASD children are on or have been given risperdal. Almost no parents receive a fully informed consent. So few are told of the extent of possible complications. Neurologists prescribe this drug as if it were a vitamin. What is more disturbing is the amount of ASD children on Medicaid given risperdal, probably the majority of those vulnerable children are on the drug.

More than ever researchers have to stop looking for the quick drug fix and instead look to address the underlying causes for aggression- GI pain, allergies for example.

Name: passionlessDrone
29 April 2014 - 2:30PM

The only thing I hate worse than giving my son anti-psychotics is how he acts when he doesn't get them.

Name: Pamela Feliciano
29 April 2014 - 5:56PM

I've been super hesitant to try risperidone with my ASD son. Thanks for the helpful writeup!

Name: Rick Colosimo
29 April 2014 - 8:28PM

The last few sentences were extremely helpful in putting this treatment in perspective with other alternatives. Doing this helps improve, rather than replace, communication with doctors.


>In the final analysis, researchers say risperidone should be given with caution, only for children with the most serious symptoms and only after other treatments have failed.

>“Is someone going to get hurt if we don’t intervene? And if I think the answer is yes, then I’ll be thinking about risperidone,” Veenstra-VanderWeele says. “If I think the answer is no, I’ll be thinking about doing other things.”

Name: Donna Creasy
7 May 2014 - 1:28PM

Current research on using neurofeedback to treat autism is showing a 40% reduction in symptoms with 1 year of training. The problem is cost. It meets the criteria to qualify as an ABA training and needs to be in the schools. Permanent results, no side effects.

Name: felo
24 May 2014 - 7:59AM

my main problem with my almost 4 year old autistic son is his repetitive behaviour ,i can't manage it anywhere also he is always moody,he started talking few months ago ,i just need to know if i give resperidal is it sure to stop these sterotype behaiours??also what is the duration for treatment with such drug??please need a reply

Name: lee
3 July 2014 - 7:03AM

7.5 year old son been on risperdal 0.5mls twice a day for 8 weeks still showing signs of aggression has the medication been in his system long enough we should be seeing positive results??.Son has a typical poor diet-fussy eater.

Name: adam
15 July 2014 - 3:37AM

today I stared the medication with my son, he is 12 and is the first time taking medication. I'm really afraid of side effects. I know all psychotic drugs have serious side effects, but my questions its... what its ,,, to deal with the problem or the consequences of the medication side effect??? really i don't know what to do at this point. also I'm researching about cannabis for children and side effects. thanks for this researching, because it shows the pros and cons.

Name: Allison
15 July 2014 - 7:46AM

My girl is 9 and has asperger and ADHD. She always has a bad temper and likes to throwing things or hit me. She recently use a hammer to destroy everything in the house and hurt me. Doctor now suggested her to take risperidone 0.5 once a day before sleep. I have been struggling to give her this med cos I searched and found that it's some kind of med for biopolar people. Can any mummy's out there can give me more advise or sharing the effect or consequence for the med. thank you so much and may God blessing to all our special child.

Name: Fee
20 July 2014 - 10:16PM

My son is 8 years old. He is downs syndrome and autistic. He does not speak and we are una le to put him into a school. His does not concentrate. He hurts himself by banging himself with his fists on his face and his head. He hurts us by banging, scratching, pinching and biting us. He throws vicious temper tantrums. The paediatrian has now prescribed Rispersdal. I have not started the meds as yet as I have read all the side effects and am terified. I need help desperately. Please can anyone that is using the drug answer if they are currently on rispersdal of your success or problems you may have had.

Name: mj
29 July 2014 - 9:09PM

reading all this i am convinced we parents desperately want someone to provide us positive answers but unfortunately all i can gather is unless there super emergency we shall avoid using these meds. What you all say?

Name: Sam
5 August 2014 - 12:17PM

My son has been on this medication for 2 years now since he was 7yrs old. He has high functioning Autism, with behavioural problems. The meltdowns at home and out-and-about were becoming more frequent and longer in duration, and very threatening to himself and others. We've been very happy with the way this medication has helped to decrease the intensity and frequency of the aggression over the last 2yrs. We are always worried about the long-term side effects of the drug and lately, we're seeing a return in the frequency of the tantrums - maybe the dosage needs to be increased (he's on 0.75mg per day), but we're actually considering taking him off the drug to see how he is. I feel after 2 years that I don't know what to do for the best. Afraid of long-term effects

Name: Anja
17 August 2014 - 6:11AM

At 12 1/2 years of age our son lochie was put on risperadone as we were at our wits end with the self abuse ie punches to the head banging his head into desks making holes in walls throwing anything or tipping over anything in his way and of course attacking us...the ones who love and care for him. 85% of the time he was this passive sweet little angel ....but the rest of the time he was the devil incarnate . So risperadol was a god send to our family ,it literally changed our lives we started at .25 no change
Then at .50 then to 1mg saw the change after a couple of weeks we wnt to 2 mg and he was on this dose for quite some time he then got older and bigger and yes there was weight gain but I'd definetely prefer a bit of excess weight to having a television hurtled at my head.He is now 16 years of age on 4 mg but now he seems to have developed some very wierd behavior jerking of the head his tougue sticking out really distorted facial twists and mask and long periods of this type of behavior and of just zoning out in the process of finding something else to help him through the next few years ......our quality of life and the happiness we have shared as a family has been a real gift but now I see thi young mans twitching and jerking and distorted face and it truly breaks my heart ......your given a present with one hand and in the other hand the Indian giver is ready and waiting to tear it away
I know life wasn't meant to be easy BUT why does it have to be SO damn hard at other times x

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