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

https://www.ncbi.nlm.nih.gov/pubmed/29212562

 

Thanks. Only looked at the abstract: "superior to placebo in counteracting fatigue in a subgroup of ME patients who received concomitant pharmacological treatment for depression." - Could just be a chance finding? Or maybe it's helpful for counter-acting a side effect of anti-depressants? Or maybe it's useful for fatigue, but only for those with depression.

The same group reported positive results for this drug for post-TBI fatigue in 2012, but I don't know if this has been replicated by others: http://onlinelibrary.wiley.com/doi/10.1111/j.1601-5215.2012.00678.x/abstract

 

Not sure if I understand that right. I thought it was the case that people who suffer from depression on its own, experience symptoms of fatigue anyway. So if someone suffers from both ME and depression, does that mean they potentially experience two clinically distinct forms of fatigue? An ME fatigue component, due to their scuppered energy availability; and a depression-related fatigue component. So if they take tablets to help fix the depression, then that might also help sort the depression-related component of the fatigue; and it might be no more than that. What might seem an improvement in perceived fatigue, may simply be that all they are left with, is the true ME fatigue component.

 

I had a look at the paper, and it's definitely a null result. It appears they did some post hoc analyses. These found that the subset of patients on antidepressants did show an effect of treatment. But even that was not very convincing because the treatment effect was only evident at 1 and 2 weeks, it had disappeared at six weeks. They were just fishing and got lucky, I think.

They seem to believe that those patients on antidepressants form some sort of special group, that might behave differently. But this sounds ridiculous to me. We know the way doctors hand out antidepressants to us, there is no precision science involved at all. It is very unlikely that the "antidepressant" subgroup differ in any systematic way from the other patients. They might have been a bit more severe I suppose (the more severe cases might get fed more antidepressants than the less severe), but that's all.

The level of credulousness shown in this paper about depression and the effectiveness of antidepressants at treating it is quite extraordinary.

Just thinking aloud here, but the idea of having a dual diagnosis of ME and depression is kind of nonsensical in a way. Its not really possible because the criteria for diagnosing the two conditions massively overlap. Its a technicality, but its more correct to say that people diagnosed with ME can also experience persistent low mood states.

I think its better to say it in those terms, because it forces you to unpack what people mean when they say "depression".

 

This is just a personal perspective but I don't associate depression with fatigue, although it's a little difficult to tell since I already had ME long, long before the depression and I was working full time and permanently fatigued.

My depression was of the 'utter gut wrenching despair' kind which stemmed from the absolute conviction that nothing good was going to happen to me ever again. It was in no way similar to ME, in fact it helped me to understand that the concentration problems people with ME and depression have are radically different and it would only require a little probing from a doctor to differentiate them if they knew what to look for.

A more vague low mood state is something that I don't have experience of (or at least not in a pathological sense) but I would question whether or not it's helpful to have a dual diagnosis. It's seems a slippery slope to say a dual diagnosis is nonsensical because of the symptom overlap, but as it's too easy to flip and assume co-morbid depression because of the overlap.

Not related to ME but I witnessed a brief exchange (there was clearly history) between my brother's friend, an academic psychologist, and the psychologist's daughter, a GP. In summary, the psychologist proposed that depression was being vastly over diagnosed but, in reality, people lives were just "shit"; the GP countered that it was irresponsible to take that chance so they had to hand out the antidepressants.

 

I am very, very familiar with real clinical depression, as a close family member suffered with it relentlessly most of her adult life. It is of course as massively different from "feeling depressed", as ME is massively different from "feeling tired" - such comparisons are absurd and nonsensical.

ME, so far as we know, can strike anyone, regardless of what other illnesses they may have. In which case there would inevitably be some people already suffering from clinical depression prior to their ME onset, in which case they would then unequivocally suffer from both conditions. There may be others who succumb to both conditions in the reverse order. Some symptoms may be difficult to segregate, but that doesn't mean they don't each have their own origin; I don't think it is right to treat that as just a technicality, because it is fundamental to what is really going on.

So if we take real clinical depression as a diagnosis, and ME as a diagnosis, I think it would be nonsensical to not have a dual diagnosis. However (big however), I do very much agree that if doctors are using "depression" as an umbrella diagnosis (i.e. more a non-diagnosis), then things get much more confused and complicated - as if they weren't anyway.

 

"Depression" in a study like this is likely classified using the Montgomery-Asberg Depression Scale.

But I've not read the paper (due to a currently slow and easily strained brain).

 

I wasn't trying to say that the phenomenon - intense sadness/numbness, despair, loss of joy/pleasure - isn't real. I just think the word "depression" encourages us to think about it in the wrong way.

What @Scarecrow experienced is certainly real and awful. But I also got a diagnosis of depression too in the early days. And I was just upset that I was so sick. So "depression" as the term is used currently, is very vague.

What I'm suggesting the word itself is maybe not helpful, because it assumes certain things form a coherent entity that actually don't.

 

They used the BDI. But they didn't define their subgroup on this basis. They define it according to whether the person was on antidepressants.

 

Oh dear - I see what you mean!

 

Might not be the right place to say this but I have been thinking more and more that depression is a symptom and not a diagnosis.
There are various mechanisms for it to occur and one of them might be that thing people refer to as Real Clinical Depression (someone here will have the best name) but others will be strange physiological effects (I'm thinking about how some people with epilepsy have short bouts of severe suicidal depression in one stage of their seizures which passes as quickly as it comes on, or the feeling of impending doom as one possible symptom of heart attack etc), and others will be sadness, grief, and... etc etc. so I think it helps to see depression as a symptom like diarrhoea which does not refer to mechanism, cause or specific disease but only to the symptom itself. Sure, most people will only experience diarrhoea as a symptom of a tummy bug but there are plenty of other scenarios.

 

I agree completely, @Subtropical Island. The collection of problems is real, but something about giving that name implies that its a single entity, with one cause.

Diarrhoea is a good analogy. You wouldn't have a comorbid diagnosis of ME and diarrhoea, would you? The diarrhoea would be considered to be a probable symptom of the ME (unless an other explanation came forward).

 

I wonder if this drug would be superior to something like Selegiline or Rasagiline.

 

I generally tolerate meds and supplements very well, but amitriptyline (a tricyclic antidepressant) was absolutely awful.

 

Same.

For me it caused morning drowsiness, POTS etc.

 

I also generally tolerate meds well. Amitriptyline (Elavil) had no effect whatsoever. However, I had a terrible reaction to another tricyclic, Protriptyline (Vivactil), that required hospitalization.

 

I've been using a dopamine stabilizer drug (very low dose amisulpride) for years to treat my ME/CFS and comorbid symptoms, with some beneficial effects. Works well for reducing the ME/CFS sound sensitivity. See this post.

 

Am I completely misreading the study design? To me the major design flaw in this study and possibly a huge reason why they had a null result is because they only gave the drug for 2 weeks.

They did a follow-up 6 weeks after starting the trial but patients did not take the drug or placebo for 6 weeks, only the first 2 weeks. I think this was major mistake.

Two weeks is a really short time to dose and evaluate efficacy for drugs of this class (dopamine and serotonin stabilizers), especially given the more recent findings on a similar drug Abilify, where anecdotally patients only started experiencing benefits at around 2 weeks and reported those benefits continued to increase for weeks afterward.