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New Studies Show Borna Disease Virus Infection in Psychiatric Patients

Hip

Senior Member
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17,824
New Studies Show Evidence of Borna Disease Virus Infection in Psychiatric Patients

Borna disease virus (BDV) infects a wide array of species, including: humans, horses, foxes, cats, dogs, cows, sheep and birds. It can cause Borna disease, a neurological syndrome involving viral infection of the limbic system and the brain stem. 1

Borna disease virus (BDV) has been associated with a range of human diseases, including ME/CFS, major depressive disorder, bipolar disorder, schizophrenia, anxiety disorder, multiple sclerosis, amyotrophic lateral sclerosis, dementia and glioblastoma multiforme. 1

But in 2012, Ian Lipkin, Mady Hornig et al published a major study examining the prevalence of BDV antibodies and BDV RNA in the blood (although they did not check the cerebrospinal fluid) of 198 schizophrenia, bipolar disorder and major depressive disorder patients, and found no association with Borna disease virus infection. They concluded that: "our results argue strongly against a role for BDV in the pathogenesis of these psychiatric disorders".

And back in 1999, a study by Lipkin et al found no evidence of Borna disease virus infection in Swedish patients with ME/CFS (although this 1997 Japanese study found BDV in 34% of ME/CFS patients).

So does that put paid to the idea that Borna disease virus could be involved in psychiatric disorders, or involved in diseases with psychiatric and physical symptoms such as ME/CFS?



Borna Disease Virus Circulating Immune Complexes (BDV CICs)

Not quite, it seems, because in the last few years, a couple of new studies have provided fresh evidence of Borna disease virus infection in psychiatric patients using a novel means of BDV detection, namely by looking for Borna disease virus circulating immune complexes (BDV CICs) in the blood of these psychiatric patients.

I'll get to these two new studies in a moment, but first we need to understand a bit about the nature of these BDV CICs.

In Borna disease virus research, there was an apparent problem of erratic and inconsistent BDV detection, with various epidemiological studies showing contradictory results. But in 2001, a German study (full paper here) claimed that BDV CICs are responsible for this problem of erratic and inconsistent detectability of the virus. They found that BDV CICs interact with free BDV antibodies and BDV plasma antigens, making detection by normal viral antibodies haphazard. So this German study seemed to explain the inconsistent results in BDV detection.

Furthermore, the German study found that high levels of BDV CICs in the blood correspond to a high presence of BDV antigens in the blood (antigenemia). So the authors suggest that finding Borna disease virus CICs is an easy and reliable way to detect BDV infection, more reliable than BDV antibody detection.

Additionally, the study authors demonstrated an association between BDV CICs and some psychiatric disorders: they found that 28 patients with major depressive disorder or bipolar disorder hospitalized due to severe depressive crisis nearly all had high BDV CIC levels, as did a further 28 patients with the same disorders who were just moderately depressed. Whereas in healthy controls, only 32% had high BDV CICs.

So BDV CICs are potentially a more reliable means of detecting BDV infection.



Two New Studies on Borna Disease Virus and Psychiatric Disorders

Two new studies used Borna disease virus CICs as a means to detect BDV, and discovered that BDV infections are more frequently found in psychiatric patients:

Primary psychosis and Borna disease virus infection in Lithuania: a case control study (2016)

This Lithuanian study looked at 106 patients with acute primary psychosis admitted to a mental hospital (these patients had no physical illnesses). They found BDV CICs in 40% of the psychosis patients (indicating a BDV infection), but only in 22% of the healthy controls.

Interestingly, this finding of BDV CICs in 22% of healthy controls is one of the lowest figures reported in Europe (the authors point out that in the Czech Republic, the figure is 37%).

This study also details how BDV CICs are formed:
The discovery of virus-specific circulating immune complexes (CIC) as the most prevalent variables of BDV infection in mammals provided both a better insight into infection dynamics and a new screening instrument which allowed comparability in epidemiological studies.

CIC are the result of a period of virus replication, release of abundant virus proteins (N and P; antigen [Ag]) into the plasma, and subsequent generation of antibodies (Ab) in the infected host, finally leading to Ag/Ab complexes which circulate in the blood (CIC). In accord to this dynamic process, most of Ab and Ag are bound into CIC, whereas unbound Ab as well as Ag are less frequent at the same time point.


Borna disease virus (BDV) infection in psychiatric patients and healthy controls in Iran (2014)

This Iranian study focused on a total of 114 psychiatric patients admitted to psychiatric departments: 64 bipolar disorder patients, 12 major depressive disorder patients, 18 schizophrenia patients, 15 schizoaffective patients and 5 obsessive compulsive disorder patients.

They found that in total, 40% of these psychiatric patients had BDV CICs, compared to 30% of healthy controls. In particular, in the bipolar, major depression and OCD patients, the BDV infection rates were high: 45%, 50% and 40% respectively.



Borna Disease Virus and ME/CFS

What all this means for ME/CFS is not clear. Although the1999 study by Lipkin et al found no evidence of Borna disease virus infection in ME/CFS, the study did not detect BDV infection by means of BDV CICs. So might BDV CICs exist in ME/CFS patients, indicating a BDV infection? I am not aware of any studies that have looked at this.



Borna Disease Virus Testing Laboratory

The following German laboratory tests for Borna disease virus infection by means of BDV CICs:

MVZ Diamedis Diagnostische Medizin Sennestadt
Dunlopstraße 50
33689 Bielefeld

www.diamedis.eu/Bornavirus.html (English translation here).

Info sheet in English here.

Note though that BDV CICs are found in around 30% of the general population, so it probably does not make much sense for individual ME/CFS patients to get tested. It would be more interesting to see if ME/CFS patients as a whole have a higher prevalence of BDV CICs, but that would require a study.



Borna Disease Virus Antiviral Treatments

The following drugs have efficacy against Borna disease virus:

Amantadine 200 mg daily. 1 (Though others claim amantadine does not work for BDV).
Ribavirin. 1
Ribavirin + interferon alpha synergistic for avian bornavirus in parrots. 1
Interferon gamma. 1
2'-fluoro-2'-deoxycytidine. 1
Favipiravir (Avigan) may have a strong antiviral activity against a broad range of bornaviruses. 1 Favipiravir has been approved in Japan for the treatment of influenza virus infections.



Bornavirus Taxonomy

Note that there are seven species of bornavirus identified, which each infect different animals, including humans. It is the mammalian 1 bornavirus species (which comprises two viruses: Borna disease virus 1 and Borna disease virus 2), that infects humans and other mammals and can cause Borna disease.

And it is specifically Borna disease virus 1 (BoDV-1) that has been associated with psychiatric disorders in humans.
 
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ebethc

Senior Member
Messages
1,901
@Hip

slightly off-topic question:
If you wanted to take a general test for CIC's, what is that test called?

one of the top 3 supplements I've taken is Wobenzym which is pancreatic enzymes, plus rutin and bromelain. the literature says it breaks down CIC's, so i'm looking for the pathway reverse engineer the problem..

thanks.
 

Hip

Senior Member
Messages
17,824
If you wanted to take a general test for CIC's, what is that test called?

I am not sure about such tests, but Quest, LabCorp and ARUP all offer CIC tests. I don't know if these would have any relevance for testing for borna disease virus CICs.
 
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Hip

Senior Member
Messages
17,824
Here is an information sheet from www.diamedis.eu about Borna disease virus (BDV) infection in humans:
FAQs on Human Borna Disease Virus Infection
for medical practitioners (family physicians, psychiatrists, pediatricians) and patients
by Dr. Hanns Ludwig
Professor of Virology at the Free University of Berlin, a University of Excellence​



What are Bornaviruses?
  • They are small, coated RNA viruses that infect preferentially brain-, but also blood cells, and are genetically related to measles and rabies viruses.
  • They have been found in many countries, globally, and comprise a separate family of viruses (Bornaviridae).
  • BDV (Borna disease virus) is persistently present in humans and many other mammals, and the recently discovered ABV (avian Bornavirus) infects exotic birds.
  • They have zoonotic potential, i.e., transmission to humans from infected pets or other domestic animals, such as horses, cats or dogs, is possible but not usual.

What is different about Bornaviruses?
  • In evolutionary terms they are among the oldest viruses, reproducing in the host cell nucleus (the only negative-strand RNA viruses to do so), and have been finding their way into our and our ancestors’ genetic material for at least 40 million years.
  • They remain in the infected organism throughout their lifespan (no cell destruction).
  • They primarily attack the older portion of the brain (the limbic system) and contribute to behavioral and mood alteration (it can be assumed that viral proteins disturb the neurotransmitter equilibrium).

How dangerous are Bornaviruses to human health?

  • They are found in about one third (30%) of the adult population (as documented in Germany and Australia). In children the prevalence is about twice as high.
  • Most of those infected (>80%) show no symptoms.
  • Every sixth person infected (16-17%) has an increased risk of developing some form of mental illness during the course of his or her life. As a proportion of the overall population, one in twenty (5 out of every 100 persons, or 5%) is at increased risk of becoming ill.

What medical conditions are associated with a significantly higher rate of active Bornavirus infection than in the general population?
  • Acute depressive episodes (uni- and bipolar), in 80-90% of patients.
  • Chronic obsessive-compulsive disorders (OCD), in at least 50-60% of patients.
  • Chronic fatigue syndrome (CFS/ME), in at least 40% of patients.

What symptoms are common to the majority of these patients?

  • Cognitive deficits, bradylogia (abnormally slow speech).
  • Reduced intellectual capability.
  • Attention and concentration deficits (especially among children and young adults).
  • Memory loss (not age-related).
  • Learning disabilities (especially among children and young adults).

How can a Bornavirus infection be diagnosed?

  • From a small blood sample (5 -10 ml citrated blood or serum, children 1 ml) using special assays (ELISA formats). May be transported without refrigeration.
  • A screening test measures Bornavirus-specific circulating immune complexes (CICs) consisting of viral proteins and the patient’s antibodies, detectable only once the virus has replicated.
  • In the case of an acute illness, it is necessary also to test for the viral proteins (antigens) that together with the CICs signal an acute episode of viral activation.
  • The presence of antibodies is not an indication of viral activity. A negative antibody test does not rule out the possibility of infection.

Where can blood be tested for Borna virus infection?

  • Accredited medical laboratory: DIAMEDIS, Virus Diagnostics, Dunlopstr. 50, D-33689 Bielefeld-Sennestadt. http://www.diamedis.com Tel. +49 5205-7299-0
  • Consulting service: Prof. Hanns Ludwig, cell +49 171 754 2997; hanns.ludwig@web.de

Is there a therapeutic option for patients diagnosed with a BDV infection?

  • Yes, a drug that has been approved for the past 40 years for treatment of the influenza A virus (active ingredient: amantadine sulphate) has been shown both in vitro and in clinical studies to be highly effective against natural Bornaviruses (till now, off-label use).
  • Amantadine sulphate (AS) is a virostatic agent. It inhibits virus replication and thereby the formation of harmful viral proteins.
  • The majority (70 to 80%) of infected acute depressive patients derive a long-term benefit in the form of reduced symptoms (study results) in parallel with the disappearance of viral markers in the blood.
  • AS can be prescribed as an add-on medication to antidepressants (no undesirable interactions).
  • Dose level: 2-4 mg AS orally per day per kg of body weight. A patient weighing 75 kg would thus take 150 to 300 mg of AS daily. Initial dose of 1 mg AS per kg of body weight for the first three or four days.
  • Dosing interval: 1-1-0 or 1-0-0.
  • Treatment duration: normally 3 months; clinical improvement to be expected in the first month (laboratory testing of the blood markers adviced).
  • Tolerance: very well tolerated within the dosage range indicated. During the first week some restlessness and sleep disturbances are possible (in which case the dosing interval should be 1-0-0)

Which patients can expect to benefit from antiviral therapy?

  • In principle all patients who have been diagnosed with BDV infection and mental disturbances (but not dementia):
    • In uni-/bipolar patients who have developed a tolerance for antidepressants
    • In patients with obsessive-compulsive or anxiety disorders, such as ADH
    • In patients with chronic fatigue syndrome (CFS/ME)
    • In patients with chronic-stress-induced cognitive deficits

How often should therapeutic drug monitoring be carried out?
  • Optional after 6 weeks of therapy, in order to adjust the dosage if necessary.
  • Obligatory after 12 weeks of standard therapy or before discontinuing medication.

What risk factors predispose to an activation of Bornavirus infection?

  • Significant risk: chronic stress, which weakens the immune system over time and allows dormant Bornaviruses to become active:
    • Chronic stress can be brought about by a systematically over- or underdemanding work life, psychosocial stressors (unresolved conflicts, loss of close friends or relatives) and poor coping strategies.
  • A weakened immune system, whether medically induced (by corticosteroid therapy, for example) or as a result or illness, likewise increases the risk of virus activation:
    • At particular risk are adult oncology patients and children with leukemia, and patients with auto-immune diseases.

What preventive strategies could be put in place to combat Bornaviruses?
  • Infection not easily prevented because:
    • Transmission occurs early and unnoticed (generally vertical, intrauterine or perinatal; sometimes horizontally through nasal secretions and probably saliva)
    • The prevalence of symptom-free carriers is relatively high (30% among adults, 60% in children on average).
  • Disease quite preventable because:
    • Increased risk is testable from blood samples (high CIC values are an indicator)
    • Prophylactic antiviral therapy is a short-term (4 weeks) option for patients in long-term care, and also for stressed healthy persons with high CIC values (and who do not respond to stress reduction).
 

pattismith

Senior Member
Messages
3,931
I am not sure about such tests, but Quest, LabCorp and ARUP all offer CIC tests. I don't know if these would have any relevance for testing for borna disease virus CICs.


CIC test is also available in France in the main reference laboratory.

Here what they say about it:

"High levels of CIC are present in systemic lupus erythematosus, various autoimmune diseases and in some chronic infections including bacterial endocarditis.The specificity of a positive result is poor."
and:
"High concentrations of CIC are found in various pathological, autoimmune, infectious or neoplastic situations"


"Circulating immune complexes (CICs) are antigen-antibody aggregates of variable size, non-covalently bound to the corresponding antigens. Their formation results from a classical reaction of protection of the immune system against the introduction of a foreign antigens. These CICs normally need to be rapidly cleared by the macrophage system. In certain pathological conditions, it is poorly eliminated and deposited at the level of the vascular endothelium causing damage by activation, including a complement system. High concentrations of CIC were found in various pathological, autoimmune, infectious and neoplastic conditions. The nature, size, and concentration of the antigen and antibody in the immune complex influence its ability to eliminate, and thus its pathogenicity. The antigens involved may be exogenous (whole microorganisms, toxins, viruses, allergens) or endogenous (rheumatoid factor, enzymes or circulating proteins). The complement system and the erythrocyte CR1 receptors are involved in the elimination of CICs: the activation of the proteins of the classical pathway allows the solubilization of the complexes and the erythrocyte CR1 receptors allow their transport to the phagocytic cells. The persistence of CIC may be due to a deficiency of C2 or C4 complement protein, often observed in systemic lupus erythematosus, or a decrease in the density of erythrocyte CR1 that can be observed in different situations (systemic lupus erythematosus, rheumatoid arthritis, hematology, etc.). CIC tissue repository can activate complement and trigger a series of destructive events."
 

Hip

Senior Member
Messages
17,824
CIC test is also available in France in the main reference laboratory.

Circulating immune complexes (CICs) are the issue in type III hypersensitivity autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus.

Under the Coombs and Gell classification, the various types of hypersensitivity reactions found in autoimmunity and allergy are given in here.

Circulating immune complexes consist of an antibody which has attached to its antigen.


But in the case of Borna disease virus, I believe they test for a special type of CIC, caused by Borna disease virus antibodies attaching to their antigens.
 

pattismith

Senior Member
Messages
3,931
But in the case of Borna disease virus, I believe they test for a special type of CIC, caused by Borna disease virus antibodies attaching to their antigens.

Do you have any evidence that any laboratory offers a Borna virus specific CIC test?
 

CFS_for_19_years

Hoarder of biscuits
Messages
2,396
Location
USA
Do you have any evidence that any laboratory offers a Borna virus specific CIC test?
In the FAQs on Human Borna Disease Virus Infection that Hip posted, the complete PDF is here:
http://www.diamedis.eu/uploads/_download/FAQs, BDV, Human BDV, engl. 2010.pdf

On Page 2 it says:
How can a Bornavirus infection be diagnosed?

From a small blood sample (5 -10 ml citrated blood or serum, children 1 ml) using
special assays (ELISA formats). May be transported without refrigeration.

A screening test measures Bornavirus-specific circulating immune complexes
(CICs) consisting of viral proteins and
the patient’s antibodies, detectable only
once the virus has replicated.

In the case of an acute illness, it is necessary
also to test for the viral proteins
(antigens) that together with the CICs signal an acute episode of viral activation.

The presence of antibodies is not an
indication of viral activity. A negative
antibody test does not
rule out the possibility of infection.

Where can blood be tested for Borna virus infection?

Accredited medical laboratory: DIAMED
IS, Virus Diagnostics, Dunlopstr. 50,
D-33689 Bielefeld-Sennestadt.
http://www.diamedis.com
Tel. +49 5205-7299-0

Consulting service: Prof. Hanns Ludwig, cell +49 171 754 2997;
hanns.ludwig@web.de
 

pattismith

Senior Member
Messages
3,931

Hip

Senior Member
Messages
17,824
If you see @NotThisGuy's comment above, he says www.diamedis.eu are no longer providing this CICs Borna disease virus test, and that a new lab that plans to offer the test is https://dedimed.com.

From this (Google-translated) page of the dedimed.com website, it seem that they are now offering this CICs Borna disease virus test by ELISA.

But as I mentioned above, they say that 30% of the population have these BDV CICs anyway, so I am not sure that testing for BDV CICs would provide an individual patient with much information. But I don't understand the ins and outs of testing fully.

Dedimed.com also have a FAQ document about BDV very similar to the original one from www.diamedis.eu I posted above.
 

Lisa108

Senior Member
Messages
675
they say that 30% of the population have these BDV CICs anyway, so I am not sure that testing for BDV CICs would provide an individual patient with much information

Differentiated evidence of infection

Our ELISA-format screening test measures Borna virus-specific immune complexes (CICs), which are made up of viral proteins and patient antibodies and can only be detected if the viruses have multiplied. In order to detect an acute illness, the virus proteins (antigens) are additionally determined, which indicate an acute activation thrust together with the CIC. However, antibodies (AK) say nothing about virus activity. Therefore, an additional antibody test is omitted.
[https://dedimed.com/borna-virus/]
(Translation by Google, bold by me)

Costs: Borna AG (antigens?): 16,76 €; Borna CIC: 73,73€ (plus 5,20 € for blood sample tubes and shipping)
 

Hip

Senior Member
Messages
17,824
In order to detect an acute illness, the virus proteins (antigens) are additionally determined

That is for acute illness, which I presume means the initial infection when you first catch Borna disease virus. But what about chronic BDV infection, which is linked to various neurological diseases?
 

Lisa108

Senior Member
Messages
675
Hi @Hip! As I understand this, Bo-DV1 infection is a bit like herpes virus infection in that it stays with you once your are infected (= chronic persistent infection).

So anyone infected should show CICs in the test by Diamedis.

You can be infected with Borna virus and be asymptomatic, meaning your immunesystem sufficiently suppresses the virus. The test should show CICs.
You can be infected with Borna virus and have symptoms, meaning your immunesystem can't suppress the virus suffiently. The test should show high CICs and AGs.

You don't have to have an acute outbreak of symptoms in initial infection. The reaction to initial infection seems to depend on the strain of Borna virus you caught and the strength of your immunesystem at time of infection.

Well, at least that is my opinion of today. I'm reading more into this, so sorry if I change my point of view tomorrow... ;)
 

Hip

Senior Member
Messages
17,824
Thank you for that explanation, @Lisa108. The cost of the Borna disease virus (BDV) tests at dedimed.com is not very much, so it may be an interesting test for ME/CFS patients to take, especially patients who also have depression, bipolar or OCD, which are apparently linked to BDV infection.

I'd like to better understand how this lab tests for BDV; it might be an idea to email dedimed.com at some point, and ask for a more detailed explanation.

I wonder also if there is any controversy about the reliability of the BDV test provided by dedimed.com (the sort of controversy that you find with some Lyme testing labs like ArminLabs or IGeneX). When tests are not validated by a central medical authority (like the CDC in the US), then there can be concerns about whether the test results are really meaningful.


When it comes to regular ME/CFS viruses (like enteroviruses and herpesviruses), it is usually high IgG antibody titers that suggest a chronic active infection, and ME/CFS specialist doctors will typically treat patients with antivirals or immunomodulators when they have such high titers.
 

Cipher

Administrator
Messages
838
@Hip After doing some research, I would make the case that borna disease virus infection is common among ME/CFS patients. It's not clear if it's something that can cause ME/CFS, or if ME/CFS patients just have a higher risk of acquiring borna disease virus as a consequence of the disease. I would guess it's the former. Here's all the research I've found regarding borna disease virus (BDV) and CFS:

Kitani et al. (1996) [1] found that 33,7% of CFS patients had BDV-p24 antibodies, which was significantly higher than in healthy controls (P<0.001). They didn't specify the exact percentage of healthy controls that they deemed positive, but from what I can ballpark from figure 1, it seems to be around 4 %. They also found BDV RNA in peripheral blood mononuclear cells (PBMC) in 12,3 % (7/57 patients) of CFS patients, compared to 4,7% in healthy controls.

They also describe unpublished research done at the CDC supporting the notion that borna disease virus infection is more common among CFS patients:
Dobbins et al (Centers for Disease Control and Prevention, Atlanta, Ga., U.S.A.) also found antibodies to BDV p40, p24, and p18 at a significantly higher rate in CFS patients (11.5%) than in normal controls (0.0%) (personal communication)

Nakaya et al. (1996) [2] also looked at BDV-p24 antibodies and BDV RNA in PBMC in CFS patients. They found positive BDV RNA in PBMC in 12 % (3/25 patients), and BDV-p24 antibodies in 24% of patients.

Nakaya et al. also published a case-report (1999) [3] describing two family clusters of CFS. All patients were deemed infected (presence of antibodies to viral p40, p24 and/or gp18 and BDV p24 RNA in PBMC), whereas all but one of the healthy family members tested negative for all BDV tests.

In contrast to these studies, Evengård et al. published a paper (1999) [4] where they looked for antibodies to different BDV proteins, and used PCR for detection of BDV N- and P-gene transcripts in PBMC in CFS patients. They didn't detect any antibodies in 169 patients or 62 controls. No BDV N- or P-gene transcripts were found through RT-PCR analysis of PBMC from 18 patients with severe CFS. They did not use the same analysis methods as the other researchers, and the fact that they didn't even find one positive sample indicates that the methods used didn't have the sensitivity to detect chronic BDV-infections.

In a review-paper published by Bode et al. (2003) [5], they describe unpublished research detecting activated BDV infection (CICs and plasma antigen) in about one-third of CFS patients with depression comorbidity. They also describe a single CFS patient that had high CICs and plasma antigens. There was a slow but continuous decrease of plasma antigen after starting amantadine treatment (300mg) over a two and a half year period. During this period, the patient improved significantly to the degree that the patient could return to daily work but still with reduced energy compared to previous skills. They explain that human borna disease virus strains are sensitive to amantadine treatment in vitro, in contrast to laboratory strains.

Yong-jie et al. (2003) [6] tested 61 CFS patients and 73 healthy controls for BDV-p24 antibodies using western-blot analysis. Of the CFS patients 11.48% tested positive, whereas 0% of the controls tested positive.

In another paper, Yong-Jie et al. (2005) [7] report that the prevalence of anti-BDV-p24 antibody was 20.73% among CFS pateints, and 0% among controls.

Zhang et al. (2014) [8] tested 63 CFS patients, and found positive BDV RNA in PBMCs in 12.70% of patients, compared to 0,78% among healthy controls.
 
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Hip

Senior Member
Messages
17,824
@Hip After doing some research, I would make the case that borna disease virus infection is common among ME/CFS patients. It's not clear if it's something that can cause ME/CFS, or if ME/CFS patients just have a higher risk of acquiring borna disease virus as a consequence of the disease.

Borna disease virus (BDV) was actually one the first viruses I first investigated when in 2003 I caught a mysterious infection that triggered mental health symptoms as well as ME/CFS. BDV was linked to schizophrenia, and that's how I became aware of it.



In a review-paper published by Bode et al. (2003) [5], they describe unpublished research detecting activated BDV infection (CICs and plasma antigen) in about one-third of CFS patients with depression comorbidity. They also describe a single CFS patient that had high CICs and plasma antigens. There was a slow but continuous decrease of plasma antigen after starting amantadine treatment (300mg) over a two and a half year period. During this period, the patient improved significantly to the degree that the patient could return to daily work but still with reduced energy compared to previous skills. They explain that human borna disease virus strains are sensitive to amantadine treatment in vitro, in contrast to laboratory strains.

I did try taking amantadine, but did not notice much, though it does have a mild antidepressant effect. But I only took amantadine for a short period of one or two months I think.

The trouble with amantadine is that Dr David Bell found low doses of up to 50 daily seem to help ME/CFS symptoms a bit, whereas higher doses make ME/CFS worse. And this is what I found myself. So if taking amantadine for antiviral purposes, you are limited to low doses, unless you want to suffer worsened symptoms.
 

Cipher

Administrator
Messages
838
The trouble with amantadine is that Dr David Bell found low doses of up to 50 daily seem to help ME/CFS symptoms a bit, whereas higher doses make ME/CFS worse. And this is what I found myself. So if taking amantadine for antiviral purposes, you are limited to low doses, unless you want to suffer worsened symptoms.

I wonder if different forms of amantadine have different side-effect profiles. In the US, amantadine hydrochloride seems to be the only approved amantadine variant. A newly published double-blind placebo-controlled randomized clinical trial found amantadine sulphate (100mg twice daily) effective in the treatment of borna disease virus associated major depression. No significant side-effects were reported:

Amantadine at a daily oral dose of 200 mg was very well tolerated confirming previous open trials
Neither serious adverse events (SAEs) nor significant differences between amantadine and placebo periods were observed. No patient discontinued the treatment due to an adverse event (AE). Notably, none of severe side-effects, such as psychotic symptoms, severe anticholinergic effects or restlessness, and sleeplessness, were reported. Those events, however, had been solely described in the context of intravenous application of amantadine in patients with Parkinson’s disease.

Furthermore, the symptoms-check-list SCL-90R [45], which was used to screen especially for possible somatic symptoms, did not disclose any major differences of the global severity index (GSI) and of eight out of nine subscales. Only the subscale “interpersonal sensitivity” demonstrated a significant difference between the groups (p = 0.033), however, related to a reduction of symptoms in the amantadine group (two-sided t-test).

An interesting side note; the trial actually took place in 1997-1999:
The core part of the clinical trial including preparatory parts and basic virology was conducted
between 1997 and 1999. A pilot virological screening phase started on 27 th of January 1997.
The date of first enrolment was on 28 th of April 1997. Post-phase virological testing periods as
well as clinical and virological evaluation updates were extended up to 2002. Final statistical
analysis updates were done until 2010. The trial was retrospectively registered on 4 th of March
2015 (see Additional file 1). The discontinuity in post-study evaluation of clinical and
virological study parts, study statistics and manuscript versions up to the current final form
was on the one hand due to shifting of workplace and/or area of activity of study authors. On
the other hand, completion and publication was significantly impeded through doubts raised
in the scientific community about human infection until final incontrovertible proof of human
infection by BDV-1 caused encephalitis cases published in 2018.


Do you know if you tried amantadine hydrochloride or amantadine sulphate?
 

Hip

Senior Member
Messages
17,824
I wonder if different forms of amantadine have different side-effect profiles. In the US, amantadine hydrochloride seems to be the only approved amantadine variant. A newly published double-blind placebo-controlled randomized clinical trial found amantadine sulphate (100mg twice daily) effective in the treatment of borna disease virus associated major depression. No significant side-effects were reported:

According to this article on pharmaceutical salts:
Does the salt form add any therapeutic effect to the drug, in addition to the main active ingredient?

It depends. Usually, the salt form of a drug does not lend therapeutic qualities to the active ingredient. It’s primary purpose is to enhance pharmaceutical characteristics like dissolution, absorption, and onset of action.



Do you know if you tried amantadine hydrochloride or amantadine sulphate?

I tried amantadine hydrochloride. I still have the old packet.