A randomised controlled trial of the monoaminergic stabiliser (-)-OSU6162 in treatment of ME/CFS (2017) Nilsson et al.

[Hutan]

SciHub link

In the present study around 60% of the patients receiving placebo improved according to CGI-C, a remarkably high figure, and clearly a more pronounced placebo response than observed in previous clinical studies with (−)-OSU6162 con- ducted in patients with mental fatigue following stroke/head trauma and Huntington’s disease patients (2,10). In part this could be due to a shorter duration of the present study (2 rather than 4 weeks). Further, ME patients are very research-minded and as there is at present no evidence-based pharmacological treat- ment for ME, the patients are eager to assist in identifying a new, effective drug. Another possible explanation could be the different nature of the conditions studied – it is probable that for the disorders included in the previous trials there was a greater number of patients with obvious brain damage.

Note this improvement on the placebo, versus the 30% reported improvement in the fatigue of patients in the recent open-label Ablify study. Certainly, the short time period will have been a factor, as it is fairly easy to hope that you have improved over just a 2 week period. But still, it shows that open label trials with subjective outcomes are not very helpful in determining efficacy.

 

[J.G]

I revisited this paper with recent insights into apipiprazole (Abilify) in mind. Both OSU6162 and Abilify are dopamine system stabilisers that also exercise serotonergic effects. They work as partial agonists on some of the same receptor subclasses. If I have my facts straight, both were originally developed to treat schizophrenia.

A couple of things about the OSU6162 trial jumped out at me.

First there's dosage. Gottfries and colleagues had patients build up to the OSU "schizophrenia dosage" of 30mg/day. Which was great for establishing the safety of OSU6162 in MECFS but less than ideal from a treatment standpoint.

Schizophrenia is thought to be characterised by dopamine excess. Like Abilify for schizophrenia, the comparatively large dosage of OSU aims to "bat away" the excess and guarantee a steady signal. By contrast, dopamine drought is thought to occur in MECFS so there's no need for such high doses.

As others have pointed out, this clinical trial spanned only two weeks. This short timeframe is extra jarring in light of what we (think we now) know about Abilify in MECFS, ie. that beneficial effects tend to become apparent *from* approx. 2 weeks onwards after starting low and going slow as the drug concentration reaches a steady state. I've not closely investigated the exact pharmacological properties of OSU6162, perhaps it works similarly.

Long story short, I'd love to see a variation of this trial happen, double-blinded once more with strict CCC patient selection, but this time employing OSU6162 doses of up to max. 2mg/day for a duration of 8 weeks. This can't be difficult to set up, can it?

Edit: I completely missed this 2021 open label study by the same group! They're still working on OSU6162 for MECFS; I'm relieved.

 

[mango]

I revisited this paper with recent insights into apipiprazole (Abilify) in mind. Both OSU6162 and Abilify are dopamine system stabilisers that also exercise serotonergic effects. They work as partial agonists on some of the same receptor subclasses. If I have my facts straight, both were originally developed to treat schizophrenia.

According to the interviews with Arvid Carlsson I've read (here and here, for example), OSU6162 was first tested in l-dopa dyskinesia and Huntington's disease.

His company Carlsson Research also developed the antipsychotic ACR16 (Huntexil), which has sometimes been compared to Abilify.

 

[J.G]

According to the interviews with Arvid Carlsson I've read (here and here, for example), OSU6162 was first tested in l-dopa dyskinesia and Huntington's disease.

His company Carlsson Research also developed the antipsychotic ACR16 (Huntexil), which has sometimes been compared to Abilify.

I see. Good to know!