Antipsychotics - Risperidone

Risperidone is an appalling drug. Complications include irreversible involuntary movements, and rapid weight gain with severe metabolic derangement.

But the most surprising aspect of its increasing use, in increasingly young kids, is that it has no real therapeutic effect in this age group.

I assume that antipsychotics are genuinely therapeutic, in psychosis. That's the indication - schizophrenia - for which this drug class was developed. Auditory hallucinations, persecutory delusions, and illusions of malign external control over one's thoughts and actions, can be horrific experiences; antipsychotics can provide relief from that suffering.

But this isn't the role which antipsychotics play for children and (non-psychotic) adolescents. In Australia, the main 'indication' for Risperidone prescription in young kids is challenging behaviours in autistic children. (It's also given to non-autistic, non-psychotic adolescents, with extreme challenging/aggressive behaviours.)

The use of Risperidone in autistic children has government authority behind it, quite literally. Australia's Pharmaceutical Benefits Scheme specifically authorises its prescription in 'severe behavioural disturbances' in patients with Autism spectrum disorder under 18 years of age, 'under the supervision of a paediatrician or psychiatrist'.  

Risperidone doesn't, however, promote any particular cognitive function or developmental ability, in autistic kids, or in kids of any sort. It blunts their thoughts and actions - it turns their overall cognitive-behavioural volume down. It does so very reliably, which is why it's so helpful in extreme, aggressive or self-injurious behaviours.

Its effectiveness in dampening down all undesirable thoughts, speech and actions, should in itself cause concern over the associated consequences for the young person's neurodevelopment and learning.

I see quite a few kids for whom someone started Risperidone a while ago, where it seems that the kid's ongoing ingestion of the antipsychotic hasn't featured as a major clinical issue for regular consideration, by the prescriber. A 'set and forget' approach. The change most often made, over the 6 months or 5+ years of repeat prescriptions, is a regular nudging up of the dose.

One question which has struck me, is - if an antipsychotic really is indicated for a child or adolescent, why is it almost never prescribed PRN (as needed)? Why does the current default plan seem to be to commence regular doses, as if these drugs have SSRI pharmacokinetics, which they don't? Olanzapine wafers have been used PRN with good effect in emergency departments, for years.

I assume that the reason that PRN use hasn't taken off, is that antipsychotics are just so reliably effective at controlling behaviours. Without adequate medical explanation and advice, it's natural for a parent or carer who sees an antipsychotic provide relief from extreme behaviours once, to wonder why that relief can't be sustained. This phenomenon of 'dosing creep' is common enough with stimulants for ADHD - initially judicious use, with breaks on weekends and holidays; but which over months-years slides steadily into daily administration of ever increasing doses. But with ADHD and stimulants, the problem behaviours targeted are often merely annoying to adults - disruptive wisecracks in the classroom, failure to comply with household chores etc. Whereas the behaviours for which antipsychotics are started are often extreme - punching, kicking, detailed death threats, property damage, you name it.

One trap is for a younger kid (6-10yo) to be started on Risperidone for extreme behaviours like this, but without adding either adequate parent/carer support and understanding, or expert clinician involvement, to look a bit deeper than the behaviours alone. Many parents in this situation will resort to purely physical containment strategies. But as the child grows up, that becomes less and less physically feasible - especially if the drug has caused massive weight gain. A particular warning is warranted - it's never a good idea for an adult parent/carer to sit on a child, to restrain or control them. 

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PBS authorisations follow the advice of expert committees, made up of thought leaders in the relevant medical specialties. A while ago I went looking for the 'evidence base' of Risperidone's PBS approval, for use in autistic kids.

I think the 2002 NEJM paper shown in this post's header probably really kicked things off. It has now been cited 1424 times. Abstract Conclusion: 
"Risperidone was effective and well tolerated for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder." 

A key outcome measure was the "Irritability subscale of the Aberrant Behavior Checklist, as rated by the parent... and confirmed by a clinician".  What more could an overworked paediatrician ask for?

But this doesn't look like good science to me. Antipsychotic use in profoundly autistic kids with severe self-injury might be justified, especially in the short term. But 'irritability'? That's not a core clinical concept in practice, it doesn't appear in DSM definitions either. It's a plain English word, as liable to motivated misuse as any other word.

I'm sure that Risperidone does reliably address any 'irritability' shown by autistic kids. Administration of adequate doses of a barbiturate, or of the anaesthetic agent Propofol, or for that matter of cheap brandy or gin, would also address irritability in any patient, in the short term. Handcuffs or a straitjacket would also be effective in most cases.

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The number of antipsychotic prescriptions to children continues to climb. Meanwhile, in the US, pharma firm Johnson and Johnson has paid over $10 billion in damages, between 2013 and 2019, for its marketing of Risperidone. I wonder how much of the drug's increasing popularity in Australia arises from the apparent respectability which PBS authority listing might evoke, in the minds of some practitioners.

I posted this image to Twitter once, a pharmacist accused me of misleading the hivemind by using a non-zero x-axis. So I referred him to the chart's author, Rupert Murdoch. I haven't heard from the colleague since.

There are intermittent signs of pushback against this trend. The peak Australasian developmental paediatric body, the NBPSA, is working on a policy paper on the use of psychotropic medications in children and adolescents; the draft looks good. It's hard to know how it'll all play out.

Would I argue for the current PBS authority indication for Risperidone to be rescinded? No - the antidote to misguided, simplistic, authoritarian control over clinical practice isn't just simplistic authoritarian control of a different flavour.

Real progress will come from better individual clinical practice, across the board. There are good reasons for optimism on this front.

Most commonly, in my experience, the problems which arise from the prescribing of psychotropics to kids have little to do with a doctor's ignorance or knowledge of noradrenaline receptor dynamics, or the drug's second-order pharmacokinetics, or any of that.

One basic but reliable clinical rule of thumb is to not start a kid on any psychotropic medication, until all the non-drug ducks are lined up for him/her (tonight's post is brought to you by Mangled Metaphors Pty Ltd). Most often this is a simple enough clinical concept, but a major real-life pain in the posterior. If you think an 8yo will benefit from stimulants, but he's already down on himself from getting in trouble all the time at school, then don't start the med trial until the kid has an appointment booked with a psych or OT who you know and trust.

Successful drug prescribing entails the provision of meaningful explanations to bamboozled parents, meaningful interdisciplinary collaboration, and deft management of one's own counter-transference. And most of all, it takes time.

Papers:

McCracken JT et al, "Risperidone in children with autism and serious behavioral problems" (2002) 347 New England Journal of Medicine 314.

Panagiotopoulos C et al, "First do no harm: Promoting an evidence-based approach to atypical antipsychotic use in children and adolescents" (2010) 19 Journal of the Canadian Academy of Child and Adolescent Psychiatry 124.  [ http://www.bcchildrens.ca/mental-health-services-site/Documents/First%20Do%20No%20Harm.pdf ]