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Why you don't do well under Amitriptyline (Mitochondria, CYP2C19, CYP2D6)

Discussion in 'General ME/CFS Discussion' started by pattismith, Aug 23, 2017.

  1. pattismith

    pattismith Senior Member

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    I had a comatose reaction under Amitriptyline years ago (prescribed to fight my pains), and now know why:

    not only is Amitriptyline toxic for Mitochondria activity, but it shouldn't be prescribed to people who have CYP2C19 increased activity (fast or ultrafast metabolizer) and furthermore if you have CYP2D6 decreased activity. (I have both)

    "In 2016, the Clinical Pharmacogenetics Implementation Consortium (CPIC) made dosing recommendations for tricyclic antidepressants based on CYP2C19 and CYP2D6 genotypes"

    For CYP2D6 intermediate metabolizers, CPIC recommends considering a 25% reduction of the starting dose, and for CYP2D6 poor metabolizers, to avoid the use of tricyclics because of the potential for side effects. If a tricyclic is still warranted for CYP2D6 poor metabolizers, CPIC recommends considering a 50% reduction of the starting dose while monitoring drug plasma concentrations to avoid side effects.

    For CYP2C19 ultrarapid metabolizers, CPIC recommends avoiding the use of tricyclic antidepressant tertiary amines (e.g., amitriptyline) due to the potential for a sub-optimal response, and to consider an alternative drug not metabolized by CYP2C19"

    "The CYP2C19 enzyme metabolizes tertiary amines to active metabolites, which include desipramine (the active metabolite of imipramine) and nortriptyline (the active metabolite of amitriptyline). Both the tertiary and secondary amines are metabolized by CYP2D6 to less active metabolites."

    "Because standard doses of amitriptyline may lead to an increased risk of adverse events in individuals who are CYP2D6 poor metabolizers, CPIC recommends avoiding the use of amitriptyline or other tricyclic antidepressants, and to consider using an alternative drug that is not metabolized by CYP2D6. If a tricyclic is warranted, CPIC recommends considering a 50% reduction of the recommended starting dose, and they strongly recommend therapeutic drug monitoring to guide dose adjustments"

    Here you will find all the recommandations for this drug class according to your CYP2C19 and CYP2D6 status:

    https://www.ncbi.nlm.nih.gov/books/NBK425165/
     

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