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Re: ADs: Overshooting the optimal dose? undopaminergic

Posted by Mtom on December 28, 2020, at 11:55:03

In reply to Re: Dose increase recommendations vs time for effect?, posted by undopaminergic on December 27, 2020, at 15:55:49

> I agree with your concern about "over-shooting" the optimal dose.
> -undopaminergic

Yes undopaminergic, that is my concern and I've changed the heading to show your comment in order to invite further discussion. The rush to get to an "effective" dose, without really knowing what that dose is for each individual, may be contributing to lack of efficacy, adverse effects, and drop-outs.

Other factors that are increasingly being written about dosing include:

- Pharmacogenomics-Pharmacogenetics: Variant and mutant alleles, for example those that code for the various liver P450 enzymes involved in drug metabolism are increasingly being researched in the context of dosing, efficacy and adverse effects. I had Genetic Testing for medications 2 1/2 years ago - the data was more limited than anticipated (not quite ready for prime time was how my Doctor put what she had heard about these tests). However it did find that 1 of my 2 alleles for CYP2D6, involved in the metabolism of many drugs including most ADs is non-functional making me an Intermediate metabolizer for drugs metabolized by this enzyme. Other enzymes and genes are also involved in drug distribution and metabolism and I'm betting there are a significant number of people for whom this might be relevant (as indicated by growing research into this).

- Drug, and even supplement and food pharmacokinetic interactions. Food, supplements and other drugs can impact how a drug is metabolized - and variants-mutations such as the above can increase these interactions. A well known example: Grapefruit juice can block the action of the P450 enzyme CYP3A4 which metabolizes many drugs, so more of the drug enters the blood and stays in the body longer. The result: too much drug in your body. Other drugs, supplements and foods can also either increase or decrease the activity of various metabolizing enzymes resulting in too little or too much of a drug in the body with a standard dose. Again there is increasing research on this being published. (But not enough, likely due to lack of funding.)

- Sex Differences: A number of papers have been written on this. Doses prescribed do not typically account for differences in size, weight, body fat composition. In addition it has been found that females metabolize many drugs differently than males, a variety of examples have been written about. In general and on average, it has been noted that females develop more adverse effects than males for many drugs.

I see "Personalized Medicine" being written about as the wave of the future to address some of these issues. However this will be expensive and take much time per individual, I don't see it happening any time soon.

I don't think Dr. Bob comments frequently, if at all, on posts however it would be interesting to hear his thoughts on this.....




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