Friday, 23 January 2015

NAC + risperidone = decreased irritability in autism?

It's been a while since I talked about NAC - N-acetylcysteine - on this blog with either autism or schizophrenia in mind (see here and see here respectively). Today I'm going to remedy that situation by bringing the paper by Nikoo and colleagues [1] to your attention, and their observation: "N-acetylcysteine can be considered as an adjuvant therapy for ADs [autistic disorders] with beneficial therapeutic outcomes." Adjuvant therapy by the way, refers to a sort of add-on therapy.
We have to call him, Havok. That's his name now.

Just in case you don't know, NAC among other things is the treatment of choice when it comes to paracetamol (acetaminophen) overdose through it's very important role in the formation of the glutathione (the big 'G' as I should start to call it). Glutathione already has something of a research interest when it comes to autism (see here); more recently increased following papers such as the one by Rahbar and colleagues [2] taking about some of the genetics of the glutathione system with [some] autism in mind, touched upon in a recent post.

Nikoo et al reported results based on a gold-standard randomised, double-blind trial whereby one group of children/adolescents with autism received the antipsychotic risperidone plus NAC and another group received risperidone plus placebo over the course of 10 weeks. Risperidone, as I just mentioned is an antipsychotic medicine which has some interesting history when it comes to [some] autism (see here). Irritability was the focus of the study, and what happened to scores on the "Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale" at baseline (start), 5 weeks and 10 weeks. 

The results suggested that NAC may well have some value as an add-on treatment when it came to scores of irritability in cases of autism as per the authors findings: "By week 10, the NAC group showed significantly more reduction in irritability (P = 0.02) and hyperactivity/noncompliance (P = 0.01) subscales scores."

This is not the first time that NAC + risperidone has been mentioned in the peer-reviewed autism research literature. The paper by Ghanizadeh & Moghimi-Sarani [3] (open-access) also reported significant positive effects albeit alongside a few adverse events such as: "constipation (16.1%), increased appetite (16.1%), fatigue (12.9%), nervousness (12.9%), and daytime drowsiness (12.9%)." This follows other research out of Iran looking at NAC + risperidone in relation to some of the negative symptoms of schizophrenia [4]. On all these research occasions, the experimental period of observation was relatively short (8-10 weeks).

Like many others, I'm always a tad reserved when it comes to the use of antipsychotics for cases/behaviours of/associated with autism. As per my recent discussions on weight gain and such pharmaceutics (see here), one always needs to be a little cautious about the use of such medicines and the application of good medicines management including continual health monitoring as a priority when used. The guidance from NICE here in Blighty advising that such medicines should not be used to manage the core symptoms of autism (see here) is testament to the research base on their effectiveness and their limited place in any management plan. That being said, such pharmaceutics do have a role for some people on the autism spectrum [5] even only if as a 'last resort' in the short-term.

I end by harking back to the paper by Hardan and colleagues [6] talked about in a previous post, which suggested that NAC on it's own might have something to add when it comes to irritability in relation to some autism.  I don't necessarily endorse NAC as being a cure-all for irritability in relation to autism - irritability as part of the so-called challenging behaviours is a very multi-faceted thing with lots of potential precursors [7] - but one might give some consideration to NAC as an intervention for some on the autism spectrum. The next question needs to be: how precisely does it work, and does it have any link back to 'the big G' findings with autism in mind?

Music then. Marvin Gaye and Heard it Through The Grapevine (and something funky is going down apparently).


[1] Nikoo M. et al. N-Acetylcysteine as an Adjunctive Therapy to Risperidone for Treatment of Irritability in Autism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Efficacy and Safety. Clin Neuropharmacol. 2015 Jan 9.

[2] Rahbar MH. et al. Interaction between GSTT1 and GSTP1 allele variants as a risk modulating-factor for autism spectrum disorders. Research in Autism Spectrum Disorders. 2015; 12: 1-9.

[3] Ghanizadeh A. & Moghimi-Sarani E. A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders. BMC Psychiatry. 2013 Jul 25;13:196.

[4] Farokhnia M. et al. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 2013 Nov-Dec;36(6):185-92.

[5] Dinnissen M. et al. Clinical and pharmacokinetic evaluation of risperidone for the management of autism spectrum disorder. Expert Opin Drug Metab Toxicol. 2015 Jan;11(1):111-24.

[6] Hardan AY. et al. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012 Jun 1;71(11):956-61.

[7] Guinchat V. et al. Acute behavioral crises in psychiatric inpatients with autism spectrum disorder (ASD): Recognition of concomitant medical or non-ASD psychiatric conditions predicts enhanced improvement. Research in Developmental Disabilities. 2015; 38: 242–255.

---------- Nikoo M, Radnia H, Farokhnia M, Mohammadi MR, & Akhondzadeh S (2015). N-Acetylcysteine as an Adjunctive Therapy to Risperidone for Treatment of Irritability in Autism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Efficacy and Safety. Clinical neuropharmacology PMID: 25580916