Presence of depression and anxiety with distinct patterns of pharmacological treatments before the diagnosis of CFS 2023 Chen et al

Full title: Presence of depression and anxiety with distinct patterns of pharmacological treatments before the diagnosis of chronic fatigue syndrome: a population-based study in Taiwan

Abstract

Objective
An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan.

Methods
An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls.

Results
Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04–1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59–2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09–1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs. A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women.

Conclusion
This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs.

Open access, https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03886-1

 

I wanted to know for quite some time whether comorbidities of mental disorders existed before MECFS and this confirms what I always believed. It is no coincidence that psychiatrists also got involved with MECFS.

Does this mean that MECFS is psychosomatic? Far from it. But if we hypothesise that metabolic/mitochondrial dysfunction could be responsible for some mental disorders then we can suddenly see mental disorders through a completely different perspective : That they could be attributed to key biological causes.

 

A simpler explanation would be that patients who go on to be diagnosed with CFS are given diagnoses of anxiety or depression beforehand because of their unspecific but disabling symptoms (fatigue, pain etc) that stand in contrast with their routine blood tests showing normal results. This is supported by the finding that these diagnoses were associated with increased use of trazodone (SARI that is often used off label for insomnia), analgesics, benzodiazepines and muscle relaxants.

 

@cassava7

I am not sure this is the only explanation. I had my first panic attack when I was 7. It came out of nowhere for no apparent reason. I just felt very anxious and I felt I couldnt breathe. No MECFS then. After that the next Anxiety attack came when I was 17. I got MECFS when I was 30.

I believe that me having GAD since a child can be attributed to metabolic/mito dysfunction

EDIT : SARI are also given for anxiety disorders if I am not mistaken

 

There may or may not be a biological link between ME/CFS and psychiatric disorders, but the study was not designed to answer this question. It should have compared the prevalence of anxiety and depression among people who have gone on to be diagnosed with CFS versus those who presented with overlapping symptoms of similar duration (e.g. fatigue for more than 6 months) but went on to be diagnosed with well recognized chronic illnesses for which the diagnosis required a comparable amount of medical investigation (e.g. differential diagnoses).

Perhaps looking at the prevalence of anxiety and depression in patients referred to an internal medicine department, at their first appointment, would have been a better approach.

 

The study itself maybe sound but the cohort identification is based on Taiwanese diagnoses 2000 - 2010 which looks to have some conflation with chronic fatigue (criteria is Fukada 1994), study says:

"With regard to the prevalence of comorbidities, participants with CFS had higher numbers of psychiatric disorders (depression, anxiety disorder, and insomnia), irritable bowel syndrome, inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), autoimmune disorders (rheumatoid arthritis, and Sjogren’s syndrome), metabolic disorders (type 2 diabetes mellitus, gout, and dyslipidemia), and renal disease (all p < 0.005)."

Renal disease, RA and SS would be considered exclusive of ME/CFS in later criteria. Note also the 53/47 ratio F/M (Table 1), I think this tells us more about how CFS has been diagnosed in Taiwan than actually anything very helpful about pre ME/CFS health status.

 

I was degrading for years before it got really bad. I assume this is mostly the prodromal phase. That medicine hasn't clued in on this yet is frankly absurd, as a consequence they're doing this to everyone and this is likely the main reason diagnosis for many neurological and autoimmune diseases can take years.

All this means is this is how those things were labeled, they tell us absolutely nothing about the patients themselves.

 

I was personally diagnosed GAD due to neurocognitive symptoms from PEM, mild depression due to the grief of having an incurable disease, and then somatic symptom disorder, before getting an ME diagnosis.

 

I suffered from depression in the first years of the illness. I think it had a lot to do with my life falling apart, people not believing me, people demanding I push through, repeated crashes.

Despite this I would likely regard a diagnosis of depression as being a harmful misdiagnosis, even if the experience sort of aligns with what the general public think depression is.

A more accurate description would have been extreme stress due to the combination of everything going wrong that could have gone wrong, with the root cause being the nonrecognition of PEM. It was mismanaged badly.

There were probably also biochemical changes that made me more susceptible to this, and these might be as simple as heightened stress intolerance due to underlying illness causing it. If you're stress intolerant, it can be harder to rationally engage with difficult problems and find solutions.

The best intervention early on would have been to have some way to get students who are showing reduced school attendance assessed by someone capable of recognizing PEM. That would have led to a proper diagnosis and with better pacing I might not have crashed as much. If we believe that crashing too hard or often leads to permanent deterioration, it might have prevented progression of the illness too.

 

I suspect that this paper will be cited quite a lot by proponents of the psychosomatic approach to ME/CFS because it seems to confirm their views. Therefore, I think it's worth having a closer look at it.

This group has been publishing several papers based on the data of the Taiwanese health insurance database. It looks like they are going over each potential risk factor and then publish a separate paper on it. They have reported an increased risk of CFS following dry eye syndrome, psoriasis, atopy, herpes zoster etc. This has obvious implications for their statistical analyses (who knows how many risk factors they looked for but didn't report on because the results did not reach statistical significance?).

A second issue is that the database used ICD-9-CM code 780.71 for CFS cases. Previous studies have shown that CFS registrations in health insurance databases in the US are not very reliable or comparable to how ME/CFS is defined in diagnostic criteria or expert studies. Doctors seem to use the code for all sorts of (unexplained) fatigue. Taiwan isn't exactly known for their ME/CFS clinical expert centres so I expect the same issue here.

The data showed that 'CFS' patients had higher numbers of psychiatric disorders (depression, anxiety disorder, and insomnia) but the same was true for irritable bowel syndrome, inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), autoimmune disorders (rheumatoid arthritis, and Sjogren’s syndrome), metabolic disorders (type 2 diabetes mellitus, gout, and dyslipidemia), and renal disease (all p<0.005). So it's not really that psychiatric diagnoses stood out.

Then they also looked at treatments patients received and whether these increased the risk of CFS. Antidepressants increased the odds of having CFS but the same was true for benzo's, muscle relaxants and analgesics. The odds ratio for SSRI also wasn't very convincing: 1.21 (95% CI 1.04–1.39). The authors note that it was mainly trazodone that was a predictor. This drug is often prescribed, not as a treatment of anxiety or depression, but at lower doses as a sleeping aid. That would explain that why it remained a predictor for CFS after controlling for anxiety and depression.

So this is far from strong evidence that depression or anxiety are a risk factor for CFS but I predict that the paper will nonetheless be cited frequently because the abstract seem to support that conclusion.

 

Friends with MS were told they had depression and/or anxiety before they became sick enough to be tested and diagnosed. Women get told they have anxiety if they complain about period pains!

There is no reason why someone with anxiety, depression, schizophrenia or psychosis can't get ME but there is no evidence it is a risk factor or a big part of the disease.