Treatment of 95 post-Covid patients with SSRIs, 2023, Rus et al.

SNT Gatchaman

SNT Gatchaman

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Treatment of 95 post-Covid patients with SSRIs
Rus, Carla P.; de Vries, Bert E. K.; de Vries, Ingmar E. J.; Nutma, Idelette; Kooij, J. J. Sandra

After Covid-19 infection, 12.5% develops post-Covid-syndrome (PCS). Symptoms indicate numerous affected organ systems. After a year, chronic fatigue, dysautonomia and neurological and neuropsychiatric complaints predominate. In this study, 95 PCS patients were treated with selective serotonin reuptake inhibitors (SSRIs).

This study used an exploratory questionnaire and found that two-thirds of patients had a reasonably good to strong response on SSRIs, over a quarter of patients had moderate response, while 10% reported no response. Overall, patients experienced substantial improved well-being. Brainfog and sensory overload decreased most, followed by chronic fatigue and dysautonomia.

Outcomes were measured with three different measures that correlated strongly with each other. The response to SSRIs in PCS conditions was explained by seven possible neurobiological mechanisms based on recent literature on PCS integrated with already existing knowledge. Important for understanding these mechanisms is the underlying biochemical interaction between various neurotransmitter systems and parts of the immune system, and their dysregulation in PCS.

The main link appears to be with the metabolic kynurenine pathway (KP) which interacts extensively with the immune system. The KP uses the same precursor as serotonin: tryptophan. The KP is overactive in PCS which maintains inflammation and which causes a lack of tryptophan. Finally, potential avenues for future research to advance this line of clinical research are discussed.

Link | PDF (Nature Scientific Reports)
 
Patients who were interested in treatment with an SSRI and their general practitioners (GP) were informed by e-mail about the experimental nature of the treatment, the possible response to SSRIs in PCS, which SSRIs could be used, the dosage, the titration and the possible side effects.
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We did not treat the patients ourselves but advised them to consult with their own (primary) physician about treatment with an SSRI. It was always important to emphasize that the SSRI in PCS was advised for other working mechanisms than for depression or anxiety symptoms.
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The questionnaire also contained a score for the severity of 8 common PCS complaints in both part A and part B (see below). Participants were requested to complete part A immediately upon receipt. The open question about PCS complaints gave the patients the opportunity to report previously undescribed PCS symptoms. Existing questionnaires such as the Chalder Fatigue Scale or the Canadian Consensus Criteria, both developed for ME/CFS, were deemed less suitable for this purpose.
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61 patients—who under our guidance—had already started an SSRI before November 1, 2022, were asked to complete part A of the questionnaire retrospectively.
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In response to the open question about outcomes, 93 out of 95 patients described the therapeutic outcomes of the SSRI in their own words. We developed a guideline for rating the answers to this Open question outcomes. Answers were rated in 5 categories: strong improvement (4), good improvement (3), reasonably good improvement (2), moderate improvement (1) and no improvement (0). Two independent researchers not involved in the study applied this guideline to the open-ended question, in addition to one of the authors. Based on these 3 applications, the inter-rater reliability of the guideline showed "good reliability" (ICC = 0.74; Cronbach’s alpha = 0.89). We refer to this first effect measurement as ‘Open question outcomes’.
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63.4% of patients (n = 93) reported decrease in symptoms after treatment with an SSRI with an improvement that was reasonable good (26.9%), good (29%), and strong (7.5%) (see Fig. 2). 29 patients (31.1%) reported improved sleep. 67 patients (72.0%) described a decrease in PEM. Four patients reported decreased gastrointestinal symptoms. In one patient, fever had disappeared, and one patient was able to chew better again. In one patient, PCS had caused her only functioning adrenal gland to fail, for which she was treated with hydrocortisone. After an SSRI, her adrenal gland recovered and she was able to taper off the hydrocortisone dosage.
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No. They state in limitations —

The main weakness of this study is that it is not a randomized controlled trial (RCT). We had no control group. Therefore, a placebo effect cannot be ruled out. However, it is known that 85% of patients who have symptoms two months after Covid-19 infection still have them after one year. ME/CFS and dysautonomia are usually lifelong. So without treatment with an SSRI, many PCS patients may suffer from these conditions in permanently.
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It's probably worth quoting further given that this is an unblinded study with subjective outcomes. The authors try to work with what they had, though I'm sure we will all agree that this does not represent good quality evidence in comparison to an actual DBRPCT.

And there is more evidence that a placebo effect may not fully explain the positive results. A placebo effect usually occurs shortly after the start of an intervention and diminishes again after a few weeks, unless a positive expectation is given again. However, 72 patients (n = 95) still had no response in the first weeks, but instead suffered side effects. The 24 patients who used the SSRI for more than six months reported that the effect was maintained, while they were not asked by us to do so, as we had no treatment relationship with the patients. A cohort study without a control group also does not exclude natural recovery. However, because the participants had been seriously ill for 1.5 years and deteriorated over time, it seems highly unlikely that, if they had received an SSRI and recovered after a few weeks, this would have been due to natural recovery.
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Working with self-reporting is always vulnerable to biases. However, self-report often expresses the experience of patients better. In psychiatry not all physiological parameters can be measured. We also asked the patients to rate their complaints on a scale of 1 to 10. By inviting them to compare the severity of their complaints, we introduced more structure into the self-report.
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The Bell score before Covid-19/PCS and the Bell score during PCS before starting an SSRI were completed retrospectively by all patients. This may have led to some bias. The complaint of PEM was not part of the 8 complaints in the Score list; patients had to list and score this on their own under "other complaints". This may have led to underreporting of this important symptom. LinkedIn gave an overrepresentation of patients with a higher level of education, but perhaps also of a group of initially healthy people who were fully employed. It is precisely in this group that the impact of PCS as well as the outcomes of an SSRI may be well observed.
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So, not controlled or randomized, and retrospective. How does this even get approved and published? Medicine has to rein in the mass of low quality studies, this is not the way to do this.

And their weird framing of this being a placebo only reinforces the fact that for the most part, the "placebo" is just what goes on when you do a poor study and have biased and inaccurate results.
 
Given the study was carried out by online recruitment and the patient's GP prescriblng the medication and questionnaire being submitted online, and lots of the before questionnaires being filled in retrospectively, and Bell scores only showing small levels of improvement which could equally well be explained by patients pacing better and hopium, I can't take this study seriously.

It's not a clinical trial in the normal sense as far as I can see. If it were carried out in exactly the same way and the treatment was homeopathy or GET by app, or drinking pumpkin juice while standing on your head, we would not take such results seriously, so I don't think we should with this study.
 
3/5 of the authors are “independent researchers”

That’s pretty unusual for a medical type study.
 
My PCP put me on SSRI’s to help my LC even though my mood was fine and I was feeling as mentally good as you can given the circumstances. My symptoms worsened, she kept on dismissing it until testing showed I developed serotinin syndrome. Only time will tell but i think that permanently worsened me, and I was already very severe.
 
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yannlk said:
My PCP put me on SSRI’s to help my LC even though my mood was fine and I was feeling as mentally good as you can given the circumstances. My symptoms worsened, she kept on dismissing it until testing showed I developed serotinin syndrome. Only time will tell but i think that permanently worsened me, and I was already very severe.
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Hi @yannlk, I'm really sorry to hear that. I think this shows up the importance of trials like the one on this thread being done properly with protocols, ethics approvals, expert oversight and watching for side effects etc. SSRI's might be commonly handed out by GP's but they can cause harm, especially probably when used off label and not for the main indication of depression.
 
yannlk said:
I honestly don’t understand why researchers are so obsessed with SSRI’s in LC (and ME/CFS), as with GET/CBT if they made a large positive impact we would definitely know by now.
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It seems to give them the illusion of doing something that they consider harmless, because the harms of SSRIs have been dismissed for decades. Basically it's win-win as long as you simply don't count the losses.

For decades it's been argued that even though it only helps a few, it's worth it for those it helps. They just never consider the broader implications, or the harms, or anything really. Few things have contributed to the lazification of medicine, although much of it is mostly a problem of massive mismatch between supply and demand.

And of course calling this class of drugs antidepressants, even though in many cases the mechanism of action seems to affect the immune system. It has distorted the whole thing. And mislabeling chronic illness and a whole lot of health issues they don't have a real explanation for as depression, where it makes sense to give antidepressants. If you don't think about it.

Classic "yes two wrongs don't make a right but what about many, many wrongs?"
 
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