Delivering medicines in psychiatry the transdermal way: application to autism

The real iron man

Pharmaceutical technology, and specifically the various research strategies looking at the way that medicines are delivered to the body, is probably not a topic high on most people's list of interests. This area is generally not 'sexy' research insofar as producing headlines about almost miracle interventions for condition X or label Y. Instead, we take for granted that the tablet or capsule we have been given has been formulated and tested or that the nicotine patch that you may be wearing includes some pretty comprehensive physics, chemistry and biology behind its development.

In order to raise the profile - even champion the role - of pharmaceutical technology, I'm briefly bringing the paper from Jonathan Stevens and colleagues [1] to your attention, reviewing the literature "related to transdermal delivery systems from the perspective of clinical practice and research related to their use in the treatment of psychiatric conditions." Transdermal delivery by the way, refers to the various ways and means that medicines can be formulated to pass through the skin and into general circulation. This method has significant advantages insofar as bypassing the gastrointestinal (GI) tract and the first pass effect among other things. This might also be important from the point of view of those trillions of wee beasties that call our gut home [2].

I've covered some of the ways and means that transdermal drug delivery might impact / has impacted on conditions like autism before on this blog. This has included the very preliminary suggestion that transdermal nicotine patches might impact on individual cases of aggression comorbid to autism (see here) and some of my own research (see here) looking into the now controversial suggestion that dermal preparations of low dose naltrexone might be useful for various conditions [3].

Insofar as some of the other research talking about transdermal preparations and autism, there are a few studies to quickly direct you towards. The trial by Kern and colleagues [4] is worth mentioning in view of their use of transdermal glutathione with autism in mind and effects "improving some of the transsulfuration metabolites." Glutathione is something of an elephant in the room when it comes to at least some cases of autism (see here). There is also the older study by Fankhauser et al [5] to consider, describing the use of transdermal clonidine in cases of autism. I'm not necessarily advocating clonidine for autism (despite there being some indications for some use) but what this research does suggest is that various medicines currently used to manage some core and peripheral aspects of autism are perhaps ripe for re-formulation in order to better control drug delivery and potentially increase important issues such as compliance to specific medication  regimes. Dare I also mention the use of transdermal secretin [6] when it comes to autism too?

I do think we are going to see more and more about transdermal drug delivery systems being used when it comes to autism and beyond in future times. Coupled to other drug delivery methods such as via the nasal route (think oxytocin and autism... carefully) and the days of pill-popping and even painful injections (all hail micro-needles) may well be numbered.

Music: The Cure - Boys Don't Cry. Well, only at the football (soccer) match and/or when watching Watership Down.

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[1] Stevens JR. et al. The Use of Transdermal Therapeutic Systems in Psychiatric Care: A Primer on Patches. Psychosomatics. 2015 Apr 1. pii: S0033-3182(15)00060-2.

[2] Swanson HI. Drug Metabolism by the Host and Gut Microbiota: A Partnership or Rivalry? Drug Metab Dispos. 2015 Aug 10. pii: dmd.115.065714.

[3] Bouvard MP. et al. Low-dose naltrexone effects on plasma chemistries and clinical symptoms in autism: a double-blind, placebo-controlled study. Psychiatry Res. 1995 Oct 16;58(3):191-201.

[4] Kern JK. et al. A clinical trial of glutathione supplementation in autism spectrum disorders. Med Sci Monit. 2011 Dec;17(12):CR677-82.

[5] Fankhauser MP. et al. A double-blind, placebo-controlled study of the efficacy of transdermal clonidine in autism. J Clin Psychiatry. 1992 Mar;53(3):77-82.

[6] Ratliff-Schaub K. et al. Randomized controlled trial of transdermal secretin on behavior of children with autism. Autism. 2005 Jul;9(3):256-65.

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Stevens, J., Justin Coffey, M., Fojtik, M., Kurtz, K., & Stern, T. (2015). The Use of Transdermal Therapeutic Systems in Psychiatric Care: A Primer on Patches Psychosomatics DOI: 10.1016/j.psym.2015.03.007

Transdermal nicotine for aggression comorbid to autism?

The paper from Gerrit Van Schalkwyk and colleagues [1] caught my eye recently and a potentially interesting case report on the use of "transdermal nicotine as an adjunctive medication to treat aggression in a hospitalized adolescent with ASD [autism spectrum disorder]."

Transdermal, by the way, refers to passage through the various and complicated layers of the skin, and reflects an important way of getting medicines into the body other than via the more traditional oral route. I'm more than a little interested in the various ways and means that science is coming up with to bypass the mouth - gut - general circulation route as per other discussions on this blog (see here) with some of my own peer-reviewed contributions in mind [2]. In terms of how this might translate into autism and beyond, think about the processes for example, involved in swallowing a tablet or capsule and whether more could be done to 'ease' the mechanics of getting medicines into the body as well as improving things like adherence to a particular regime...

Anyhow, Van Schalkwyk et al reported that transdermal nicotine use - "a 21 mg nicotine patch" - seemed to have something of a positive effect on aggression in their particular case. Said young man presented with various issues with aggression against himself ("headbanging and biting... continuously re-opened old wounds") and others ("violently attacked staff at school") in the context of "a diagnosis of non-verbal ASD... requiring support with each of his activities of daily living." Various behavioural and pharmacological options were tried to alleviate aggression when he was hospitalised with seemingly little effect.

The idea to use a nicotine patch stemmed from some previous research interest from some of this authorship group on a role for nicotinic acetylcholine receptors in relation to mood and anxiety [3]. Their idea that: "smokers may use the nicotine in tobacco products as an attempt to self-medicate symptoms of affective disorders" potentially taps into some interesting research questions on the role of smoking in light of diagnoses where 'affective disorders' may be prominent.

Further research is of course indicated as to whether nicotine patches may be useful for some people and some behaviours associated with the autism spectrum. I say this bearing in mind that the rates of tobacco smoking tend to be quite a bit lower in autism compared with the general population [4] and the desire not to see such figures increase bearing in mind the adverse effects smoking can have for a person. Remember also, that nicotine is classified as addictive...

Music: The Clash - Complete Control.

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[1] Van Schalkwyk GI. et al. Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder. JADD. 2015. May 16.

[2] Dodou K. et al. Ex vivo studies for the passive transdermal delivery of low-dose naltrexone from a cream; detection of naltrexone and its active metabolite, 6β-naltrexol, using a novel LC Q-ToF MS assay. Pharm Dev Technol. 2014 May 2.

[3] Picciotto MR. et al. Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states. Neuropharmacology. 2015 Jan 9. pii: S0028-3908(14)00479-1.

[4] Bejerot S. & Nylander L. Low prevalence of smoking in patients with autism spectrum disorders. Psychiatry Res. 2003 Jul 15;119(1-2):177-82.

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Van Schalkwyk, G., Lewis, A., Qayyum, Z., Koslosky, K., Picciotto, M., & Volkmar, F. (2015). Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-015-2471-0