Apologies for not being clearer and thanks for the opportunity to clarify.
Tolerance is something you hear about so often but see so rarely that it’s not something I take into account at work. If a patient tells me they’re experiencing loss of effect my approach is to triple check everything else. For example off the top of my head:
Have they changed their diet? Methylphenidate is absorbed much more if taken with lipids but also delayed, and amphetamines are excreted much faster depending on the kidney acidity output. Likewise exercise impacts amphetamine duration. Maybe they’ve eaten organic chemistry fruits that wreak havoc on cytochromes. Maybe they finally stop coffee but didn’t tell you. Those things are not subtle and have a double digit percentage impact on pharmakinetic characteristics.
Have they changed sleep patterns? Methylphenidate works less effectively when sleep deprived while amphetamines seem much better at hiding sleep deprivation feelings, also meaning it can get pretty chronic.
Change of mood? Depression is so common that anhedonia alone is much more likely than tolerance.
Wrong diagnostic? Bipolar and we changed season?
Menstruation? They might have gone vegan and went anemic.
Maybe their pharmacist changed the pill with an unbranded one? They have woefully different tail ends for OROS delivery vs unbranded ones (they have to guarantee the same area under the curve within 25% but there’s no requirements on tail or spikiness IIRC)
And of course patients are not reliable for figuring this out on their own and it takes quite a bit of time to lower the uncertainties on those question (but doc, what’s a lipid?). Especially patients suffering from ADHD.
Let me know if I can clarify this or other stuff or criticism.
Thanks for the clarification! So basically you’ve prescribed stimulants to a lot of patients and find that they very rarely complain about a loss of effect without one of these confounders being present and without the problem being resolved once it gets fixed?
I wouldn’t say I’ve prescribed it to a lot, but i’ve talked about this with a lot of more senior doctors than me.
Those doc that talk about tolerance are either just talking from a theoretical risk (as in they never saw it), and when they talk from experience they never thought of checking the above factors I mentionned.
The thing is this tolerance idea is so ingrained in France that they’re ready to stop prescribing at the very first sign of a loss of effect without further investigation so we can’t even know. We are historically very underprescribers of methylphenidate because of psychoanalysis and amphetamines are available since only like 2 years and still out of pocket.
I do have other arguments to support my convinction that tolerance is that rare but am not comfortable sharing them here out in the open as they relate to my own chemistry. I could be biased sure, but let’s say I’m much more convincing when I mention those other points.
Edit: i also advised about 5 friends about their ADHD medication, they all take it daily without tolerance. And all doctors I know that are treated for ADHD take their meds daily and without holiday breaks.
What made you conclude that?
Apologies for not being clearer and thanks for the opportunity to clarify.
Tolerance is something you hear about so often but see so rarely that it’s not something I take into account at work. If a patient tells me they’re experiencing loss of effect my approach is to triple check everything else. For example off the top of my head:
Have they changed their diet? Methylphenidate is absorbed much more if taken with lipids but also delayed, and amphetamines are excreted much faster depending on the kidney acidity output. Likewise exercise impacts amphetamine duration. Maybe they’ve eaten
organic chemistryfruits that wreak havoc on cytochromes. Maybe they finally stop coffee but didn’t tell you. Those things are not subtle and have a double digit percentage impact on pharmakinetic characteristics.Have they changed sleep patterns? Methylphenidate works less effectively when sleep deprived while amphetamines seem much better at hiding sleep deprivation feelings, also meaning it can get pretty chronic.
Change of mood? Depression is so common that anhedonia alone is much more likely than tolerance.
Wrong diagnostic? Bipolar and we changed season?
Menstruation? They might have gone vegan and went anemic.
Maybe their pharmacist changed the pill with an unbranded one? They have woefully different tail ends for OROS delivery vs unbranded ones (they have to guarantee the same area under the curve within 25% but there’s no requirements on tail or spikiness IIRC)
And of course patients are not reliable for figuring this out on their own and it takes quite a bit of time to lower the uncertainties on those question (but doc, what’s a lipid?). Especially patients suffering from ADHD.
Let me know if I can clarify this or other stuff or criticism.
Thanks for the clarification! So basically you’ve prescribed stimulants to a lot of patients and find that they very rarely complain about a loss of effect without one of these confounders being present and without the problem being resolved once it gets fixed?
I wouldn’t say I’ve prescribed it to a lot, but i’ve talked about this with a lot of more senior doctors than me.
Those doc that talk about tolerance are either just talking from a theoretical risk (as in they never saw it), and when they talk from experience they never thought of checking the above factors I mentionned.
The thing is this tolerance idea is so ingrained in France that they’re ready to stop prescribing at the very first sign of a loss of effect without further investigation so we can’t even know. We are historically very underprescribers of methylphenidate because of psychoanalysis and amphetamines are available since only like 2 years and still out of pocket.
I do have other arguments to support my convinction that tolerance is that rare but am not comfortable sharing them here out in the open as they relate to my own chemistry. I could be biased sure, but let’s say I’m much more convincing when I mention those other points.
Edit: i also advised about 5 friends about their ADHD medication, they all take it daily without tolerance. And all doctors I know that are treated for ADHD take their meds daily and without holiday breaks.