Antipsychotics can be very effective for irritability in autism, but they are often unnecessary, and the side effects are truly problematic. Don’t be the prescriber who hears irritability in autism and immediately prescribes antipsychotics. There are usually multiple steps to try before using the FDA-approved antipsychotic medications.

Published On: 04/17/2023

Duration: 15 minutes, 56 seconds

Transcript:

Dr. Feder: Irritability can be a significant challenge for autistic individuals, as well as their families. While there are FDA-approved medications for treating irritability in autistic children, such as risperidone and aripiprazole, they can come with some undesirable side effects, including weight gain, neurotoxicity, tardive dyskinesia, and even worsening of catatonia.

In this podcast, Mara and I will delve into the topic of irritability in autistic children, and explore alternative approaches to minimizing the use of antipsychotic medications. 

I’m Dr. Josh Feder, The Editor-in-Chief of The Carlat Child Psychiatry Report and co-author of The Child Medication Fact Book for Psychiatric Practice and the brand-new book, Prescribing Psychotropics.

Mara: And I’m Mara Goverman, a Licensed Clinical Social Worker in Southern California with a private practice.

So, one of the first things we can do to tackle irritability in autistic children is to set functional goals. Now, you might be wondering, what's the difference between functional goals and behavioral goals? Well, with behavioral goals, the focus is on changing specific behaviors, kind of like what's done in applied behavioral analysis. But functional goals are more about promoting meaningful interaction.

Dr. Feder: Think about it this way: if we just tell an autistic person to "stop screaming," we're not really getting to the root of the problem. Maybe they're overwhelmed by a busy household, or having trouble processing requests from their parents. By setting functional goals, we can work together to brainstorm ways to address those underlying factors. And that can actually help reduce the need for medications.

Mara: Some examples of functional goals might include finding ways to sustain meaningful interactions, managing sensory differences, or learning how to respond adaptively to social problems like teasing. The idea is to focus on what really matters to the autistic individual, and help them live their best life possible.

Dr. Feder: Definitely! Another approach to tackling irritability in autistic individuals is by addressing co-occurring conditions that may be driving the irritability. It's important to start with non-pharmacologic approaches for conditions such as sleep problems, ADHD, depression, and anxiety. This can involve things like exercise and cognitive behavioral therapy for insomnia, modified for autistic patients by using visualization techniques. For ADHD, breaking down tasks can be helpful. For anxiety, depression, or everyday problem-solving, parent-implemented developmental relationship-based intervention or some forms of modified CBT can be effective. It's also important to collaborate with occupational therapists, speech and language pathologists, and special educators to address challenges related to sensory processing, motor planning, communication, and learning that may be contributing to irritability. By taking this comprehensive approach, we can minimize the use of medications and improve the quality of life for autistic individuals and their families.

Mara: Okay, so we’ve tried all the non-pharmacologic treatments and the irritability is still an issue. What's next?

Dr. Feder: It might be time to think about medications. But before jumping to prescription drugs, there are some non-prescription alternatives you can consider, like valerian, omega-3 fatty acids, melatonin (for daytime use), and lavender. There's not a ton of data to support their use, but some people have found them helpful.

If those options don't do the trick, it might be time to consider prescription medications. It's important to note that most studies on medication treatments for autistic individuals are open label studies and don't have control groups or measure effect sizes either. But with that in mind, here are some off-label options that have shown varying degrees of effectiveness, ranked from most to least evidence within their categories.

Mara: Starting with the category of neurotransmitter related medications, we have stimulants. Despite negative clinical lore, a recent study suggests stimulants work as well in autistic individuals as anyone else. They have no additional side effects, and at similar dosages for ADHD they may help with irritability and aggression. 

Dr. Feder: Next up, we have SSRIs. These medications may help with irritability by treating co-occurring depression or anxiety. They tend to work better for anxiety than depression in neurotypical kids and teens, but there's limited research on their effectiveness in autistic children. A recent controlled trial of sertraline for language outcomes in young autistic children ages 24–72 months showed no effect but no significant side effects either. So they may be worth considering for anxiety, depression, OCD, and repetitive behaviors after naturalistic approaches. Just make sure to titrate carefully to avoid behavioral activation.

Mara: Moving on to memantine, which targets NMDA glutamate receptors. The idea here is that decreasing glutamate activity may reduce irritability. Three controlled trials have shown that memantine is well-tolerated and helps with receptive language in autistic children. The maximum dosing varies depending on weight with 3mg daily for kids under 20kg, 6mg daily for kids between 20-39 kg, 9mg daily for kids between 40-59 kg, and up to 15mg daily for those over 60kg.

Dr. Feder: Lastly, there's bumetanide, which targets GABA receptors. Autistic animal models have shown increased GABAergic activity, so the thought is that decreasing GABA tone with bumetanide could help with irritability. However, in the only controlled human trial, bumetanide didn't show any effect on irritability or other autistic symptoms. So, our recommendation is to skip it and focus on other options.

Mara: Next up we have autonomic medication approaches using guanfacine and propranolol. 

Dr. Feder: Guanfacine, is a central alpha-agonist that helps reduce sympathetic tone, promoting calmness, but might cause occasional dizziness or paradoxical irritability and even sometimes stomach problems. In a 2015 study, it was found that about half of autistic children showed improvement in ADHD symptoms with guanfacine, and with few side effects. 

Mara: How should guanfacine be prescribed?

Dr. Feder: People should start by taking 1 mg daily probably at night since it is a bit sedating and slowly increase to a total of 4 mg daily, possibly all at night, or possibly spread throughout the day depending on how it affects that particular individual. For kids who weigh less than 90 pounds, the recommended top dose is 2 mg.

Mara: So, another medication that we can consider is propranolol, which is a beta-blocker. It's often used to reduce racing heart rate to lower anxiety in people. However, it's important to note that it may also lower exercise tolerance or exacerbate asthma in some individuals.

Dr. Feder: That's right. A 2016 controlled pilot study showed that a single dose of propranolol improved conversational reciprocity in autistic kids. And if effective, it would presumably help with problem-solving abilities, which could in turn help with irritability.

Mara: And how should propranolol be prescribed?

Dr. Feder: Patients should start by taking 5-10 mg daily and increase by 5 mg weekly until a maximum of 20 mg daily is met. However that is not always enough, and in fact you can sometimes safely prescribe a couple 100 milligrams a day and even start using the extended release versions 60mg XR or 80mg XR.

Mara: Next up we have hormonal medication options which include balovaptan and oxytocin. 

Dr. Feder: Balovaptan is a medication that blocks central vasopressin activity. A preliminary double-blind placebo-controlled study in autistic children ages 6–12 years showed improved social function and reduced anxiety. However, even though these results are exciting, we still need more research before we can recommend it as a treatment option. It's always important to thoroughly evaluate any medication before deciding to use it.

Mara: How does oxytocin compare to balovaptan?

Dr. Feder: Oxytocin also known as the “bonding hormone” is actually a ­non-starter since multiple trials in autistic adults have failed. There was a lot of excitment about it a number of years ago, but it really has not panned out. 

Mara: I guess that takes us to low-dose naltrexone, an opioid antagonist.  Small older studies show that low-dose naltrexone may help irritability in autistic individuals. If you're interested in trying it, it's recommended to start with a low dose of 3-5 mg per day and closely monitor your liver function tests (LFTs).

Culture and other social determinants can have an impact on the use of off-label medications in autistic children. Sometimes certain medications may be too expensive, or getting prior authorization for them may be difficult without clear research evidence to support their use. Families may also have concerns about off-label experiments due to past historical injustices and may not trust the medical system as a result.

Dr. Feder: To address these concerns, it's important to listen to families and offer neutral information so that they can make informed decisions. As a healthcare provider, you can offer options based on your clinical judgment and the existing research, and then let families choose what's best for them based on their culture, values and circumstances.

Mara: After examining several alternative treatments and off-label medications, what steps should we take if the person still experiences significant irritability? Should we then consider the potential use of antipsychotics?

Dr. Feder: Well not quite yet, if the person is still feeling extremely irritable or acting that way, there are a few options we can try. First, we might consider antiepileptic drugs like gabapentin, oxcarbazepine, valproate, or topiramate. If the irritability is really persistent or severe, we could think about using antipsychotics, especially the ones that are less likely to cause metabolic problems - like ziprasidone or lurasidone. Just keep in mind that insurance is more likely to cover lurasidone for patients over 10 years old who meet criteria for bipolar depression. And a lot of times when kids are that dysregulated, they actually meet that criteria.

We should save stronger options like risperidone and aripiprazole for really tough cases, and maybe start patients on metformin early to help prevent metabolic issues, especially weight gain. And of course, we'll want to monitor for abnormal involuntary movements, metabolic parameters such as hemoglobin A1C, and for any unusual side effects. We also like to think about stopping the medication when it's no longer needed. If somebody is stable for 6 months or so and you've got a lot of other things in place and working pretty well, thats a time to start easing away and seeing if you can do without whatever medication the child is on. 

Also, it's worth noting that only Risperidone and Abilify have been approved by the FDA for treating irritability associated with autism. So every other approach we have discussed in this podcast is considered off-label. 

Mara: When it comes to irritability in autistic people, there can be a lot of different things going on behind the scenes. So our first priority is to try to figure out what's causing the irritability and tackle that issue directly, before we jump straight to using antipsychotics. We want to focus on setting goals that really matter to the person and finding non-medication strategies that can help them meet those goals. 

And if we do decide to use medication, we should start with milder off-label options or ones that are less likely to cause metabolic problems before we consider using FDA-approved antipsychotics. For a handy visual guide, you can check out the diagram in our latest edition of the Child Medication Fact Book.

Dr. Feder: The clinical update is available for subscribers to read in The Carlat Child Psychiatry Report. Hopefully people check it out. Subscribers get print issues in the mail and email notifications when new issues are available on the website. Subscriptions also come with full access to all the articles on the website and CME credits. 

And we have some exciting news for you! The podcast now has CME credits of its own. To get your credits for listening, follow the Podcast CME Subscription link in the show notes. It will link you to a CME post-test for this episode and for future episodes. 

Mara: And everything from Carlat Publishing is independently researched and produced. There’s no funding from the pharmaceutical industry. 

Dr. Feder: Yes, the newsletters and books we produce depend entirely on reader support. There are no ads and our authors don’t receive industry funding. That helps us to bring you unbiased information you can trust. 

Mara: As always, thanks for listening and have a great day!

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The Carlat CME Institute is accredited by the ACCME to provide continuing medical education for physicians. Carlat CME Institute maintains responsibility for this program and its content. Carlat CME Institute designates this enduring material educational activity for a maximum of one quarter (.25) AMA PRA Category 1 Credits^TM. Physicians or psychologists should claim credit commensurate only with the extent of their participation in the activity.