Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study, 2022, O'Kelly et al

[LarsSG]

Highlights

• Low dose naltrexone (LDN) is safe to use in patients with long covid (LC).
• In patients with LC for a median 11 months, LDN reduced symptoms at 2 months.
• In this cohort, LDN also improved well-being in 6 of 7 parameters at 2 months.

Abstract
Background
Up to 37.7% of patients experience symptoms beyond 12 weeks after infection with SARS-CoV-2. To date care for people with long covid has centred around multidisciplinary rehabilitation, self care and self pacing. No pharmacotherapy has been shown to be beneficial.

Methods
In this single centre interventional pre post study, the safety of Low Dose Naltrexone (LDN) was explored in patients with Post COVID-19 Syndrome (PCS), defined by NICE as patients with ongoing symptoms 12 or more weeks after initial infections with SARS-CoV-2 where alternative explanation for symptoms cannot be found. Patients were recruited through a Post COVID clinic, had a baseline quality of life questionnaire in symmetrical Likert format, were prescribed 2 months (1 mg month one, 2 mg month two) of LDN and repeated the same questionnaire at the end of the second month. Patients were monitored to adverse events.

Findings
In total 52 patients participated of whom 40(76.9%) were female. The median age was 43.5 years(IQR 33.2–49). Healthcare workers represented the largest occupational cohort n = 16(34.8%). The median time from diagnosis of COVID-19 until enrolment was 333 days (IQR 171–396.5). Thirty-eight participants (73.1%) were known to commence LDN, two of whom (5.3%) stopped taking LDN post commencement due to new onset diarrhoea and also described fatigue. In total 36(69.2%) participants completed the questionnaire at the end of the two-month period. Improvement was seen in 6 of 7 parameters measured; recovery from COVID-19, limitation in activities of daily living, energy levels, pain levels, levels of concentration and sleep disturbance (p ≤ 0.001), improvement in mood approached but was not significant (p = 0.054).

Conclusions
LDN is safe in patients with PCS and may improve well-being and reduce symptomatology in this cohort. Randomised control trials are needed to further explore this.

https://www.sciencedirect.com/science/article/pii/S2666354622000758

 

[LarsSG]

Not much to take from this one, I don't think. Small N, no controls, very low naltrexone dose, vague questionnaire.

 

[Hoopoe]

Not liking the positive spin in the abstract. The questionnaire results don't look impressive and are uninterpretable due to lack of controls. I suppose the purpose of the study is to show LDN isn't causing any obvious serious harm so that a proper clinical trial becomes easier to get funding for.

 

[rvallee]

The more I look at how it's structured, the more I am convinced that evidence-based medicine is a useless process here. It simply cannot yield anything useful without a valid starting point for what to test, it fully depends on understanding the underlying process as otherwise it's nothing but a very limited brute force approach. It's just too expensive. The idea works, but not at the scale we need. It's like trying to brute force a password where you can only make one guess per second. If the encryption key is high enough it would take billions of years.

How much more would we learn from a larger trial, for example? Still safe, still mildly effective for a few. So what? Trivial benefits for some, stalled progress for everyone else.

The entire paradigm is wrong, a failure, and probably explains why so few new effective treatments are found anymore. The million monkeys on typewriters approach to things leads mostly to feces on the wall, along with people employed to decipher any meaning out of it.

 

[Amw66]

Oh for a better process.
I know many who have put down their improvements to LDN.
It would be good to have some meaningful data.

 

[Hutan]

An explanation including a combination of peripheral, central, and psychological components may best explain these symptoms, more research is needed to better define this syndrome.

Hmm. 'Psychological' gets thrown in there, even though no evidence for that view is specifically cited.

Approaching long covid in a similar way to other conditions like chronic fatigue syndrome or myalgic encephalomyelitis with graded exercise therapy and cognitive behavioural therapy may be beneficial but is not supported by evidence(Crook et al., 2021).

Hmm

At present long covid clinics have been established in the UK and elsewhere(Care, 2021). To date there is no pharmacotherapy approved for long covid at present. A number of drug classes have been proposed as potential therapies including antihistamines and antidepressants. A Phase II pilot study (NCT04604704) exploring low dose naltrexone(LDN) and nicotinamide dinucleotide(NAD) effectiveness for symptoms of long covid is also underway.

Given what we know about the problems of some antidepressants, the suggestion that they are potential therapies is concerning. Note mention of a UK study of LDN that is currently underway.

LDN has been shown to be beneficial for a number of conditions including crohn's disease; induction of remission and reduction in need for anti-inflammatory medications, chronic fatigue syndrome, reduction in use of disease modifying drugs in rheumatoid arthritis, fibromyalgia, multiple sclerosis and complex regional pain syndrome although studies are small (Bolton et al., 2020; Lie et al., 2018; Raknes et al., 2018; Raknes and Småbrekke, 2019; Younger et al., 2014).

It seems a stretch to say that LDN has been shown to be beneficial for CFS.

Baseline blood tests on initial clinic visit including full blood count, urea and electrolyte panel, liver blood tests, C-reactive protein, and up to date X-ray chest were done routinely. Additional tests including troponin, d-dimer, fibrinogen, echocardiography, spirometry or computerised tomography of the thorax, sleep studies were done if clinically indicated.

Three patients had anaemia (Hb 10.9, 10.4, 11.2 mg/dL), two of whom had shortness of breath and fatigue, although other symptoms were found in these patients not explained by anaemia. No patients had neutrophilia, CRP was raised in five patients (range 10–24 mg/L), creatinine is raised in two patient 92,94μmol/L, alanine aminotransferase was raised in 5 (range 59–140 IU/L). Of those that had additional tests 3/18 d-dimers were raised(range 0.61–1.09 mg/L), 0/18 troponin levels were raised, ferritin was raised in 5/28 (range 313-609μg/L), and fibrinogen was within reference range for 0/14.

I thought it was interesting that none of the 14 people tested for fibrinogen had results that were within reference range. The tests however were allocated according to 'clinical indications', so it's hard to know what it tells us.

In summary larger more robust studies are needed to explore the safety and efficacy of LDN in long covid patients.

Perhaps this group will seek to do such a study. If they do, they could use some help e.g. in how they assess changes in symptoms.

 

[rvallee]

may be beneficial but is not supported by evidence

That's what's called saying the quiet part out loud. So much for "evidence"-based medicine. I mean technically evidence to the contrary is evidence, all you have to do is not care what it says because you always meant your cruise ship to get to the destination it planned to get to.

 

[Hutan]

That's what's called saying the quiet part out loud. So much for "evidence"-based medicine. I mean technically evidence to the contrary is evidence, all you have to do is not care what it says because you always meant your cruise ship to get to the destination it planned to get to.

Yes, it's something that could legitimately be said about a treatment that hasn't been researched well yet. But to say that for something like CBT or exercise aiming to improve ME/CFS, things that have been researched again and again for years, in all sorts of permutations, is a just a triumph of bias over logic.