Saturday, August 24, 2019

Comments by janevs

Showing 4 of 4 comments.

  • As part of human diversity –necessary for the survival of the species – differing genotypes exist – fact.

    What we are saying is that people who have a genotype which compromises their ability to metabolise psychotropic drugs because of certain gene variations, are prone to suffer drug toxicities causing ADRs. Extra copies of genes with prodrugs will result in drug toxicities as will deletions in Intermediate and Poor Metabolisers.

    All people can be prone to toxic behavioural reactions to neuroleptics depending on dose, genotype, drug ½ life and withdrawal status.

    If 100 African or Asian people all had inefficient metabolising genes for a specific drug, all would suffer ADRs. However if all 100 African/Asian people had efficient metabolising genes, they would not suffer with ADRs. Likewise with Caucasian or any other people etc.

    We presented a reason for Psychiatric Intensive Care Units being over full of BME people in UK and suggest that the failure to recognise all peoples’ genotype, i.e. drug metabolism ability before using neurotoxic drugs is tantamount to clinical negligence.

    It is unfortunate that in today’s global arena of political correctness stating the obvious can be unpalatable.

    These “claims” are not ours – they are from solid pharmacogentics research – please see refs.

  • Oops sorry. I posted this reply to the wrong article. It’s supposed to be reply to the genetic marker article.

    By the way, SSRIs can cause haemorrhaging in the Gastrointestinal tract as well.
    Dalton SO, Johansen C, Mellemkjaer L, Nørgård B, Sørensen HT, Olsen JH. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med. 2003 Jan 13;163(1):59-64. http://www.ncbi.nlm.nih.gov/pubmed/12523917

    Alain Li Wan Po, Antidepressants and upper gastrointestinal bleeding BMJ. 1999 October 23; 319(7217): 1081–1082.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1116881/

    Gastrointestinal bleeding was added as a side effect on UK patient information leaflets (PILS) for Seroxat in June 2003, after the BBC Panorama programmes.

  • We think this article does not give a clear representation of how genetic markers do affect outcome of side effects which contribute to a non therapeutic response.
    This paper, sponsored by numerous pharmaceutical companies, is essentially flawed because –

    Firstly the article states, “… not all common genetic variants were directly genotyped…”
    Since 75% of psychotropic drugs, including antidepressants, are metabolised via the highly variable CYP450 2D6 gene (Arehart-Treichel 2005), encoding for drug metabolising enzymes, surely the researchers should have included it. Neither is the variable CYP450 2C19 gene, that also metabolises SSRIs, included in the study.
    Why were both these important genes, related to antidepressant response not included in the study?

    Secondly, “Individuals were excluded for… non-European ethnicity admixture…” i.e. people of mixed race were excluded from the study. Could this be because a high number of BME people have genetic polymorphisms incompatible for efficient metabolisation of antidepressants?

    Thirdly, a “Diagnoses of schizophrenia, schizoaffective disorder, or bipolar disorder… constituted exclusion criteria.” Individuals may have been given these diagnoses during the 6-12 week trial period due to toxic reactions (mania/ psychosis) because of an inability to metabolise antidepressants and subsequently excluded. Other people excluded prior to the trial may have also received their diagnosis following SSRI drugging for the same reasons. So these likely genetically diverse subjects of paramount importance as regards antidepressant drug metabolism are not reported in the study. There is lack of transparency re this issue.

    We are coming from a different slant. What we are looking at is human diversity and the different degrees of non reaction, (placebo – Irving Kirsch 2008), poisoning and adverse responses inflicted by SSRIs. Except it seems this study didn’t want to find any.
    Jan Evans & Catherine Clarke