How to answer when someone says drug tolerance is not just in psychiatry

[Mark840]

Hi,

 

From my understanding, psychiatric drugs thereupetic effect do not work in the long term because of compensatory adaptations (https://www.madinamerica.com/drug-info-how-psychotropics-act-on-the-brain/).

However, some point out it is common and occurs in non-psychiatric drugs and known as drug tolerance.

 

Can anyone explain if there is a difference in the drug tolerance in psychiatry and other medical fields? If you have links/sources, that would be great.

[InvisibleUnless]

no, drug tolerance is drug tolerance.  "tolerance" just means there are diminishing returns as a result of adaptations by the body, so a particular experiential effect of the drug is lessened over time, such as euphoria or.  it wont necessarily disappear completely.  however, not all tolerance works the exact same way.  the particular drug actions involved and the compensatory mechanisms the body responds with can vary somewhat.  so while all tolerance means a diminishment of particular experiential outcomes, not all tolerance is referring to the exact same process.

 

colloquially, "tolerance" is often used to more specifically refer to effects people were considering desirable, perhaps because this is the most common use of the term when discussing recreational applications.  in psychiatry, it is more common to hear "tolerance" in reference to intended effects rather than a reduction of 'side effects' over time even if the two work the same way.  this preferential usage may confuse people about what tolerance really is and how it works.  in reality, "tolerance" encompasses both the effects someone was wanting and the effects they werent.  many of these effects will be desirable to some patients and undesirable to others anyhow, for instance sedation.

 

there is no distinction between psychiatric drugs and all the other psychotropics out there other than popular use within psychiatry.  a 'non-psychiatric' drug can become a psychiatric drug, or a psychiatric drug can lose favor and no longer be prescribed in the mainstream.  psychotropics are psychotropics, period, so nothing sets apart drugs like zoloft or risperdal or lithium from anything not currently used psychiatrically.  what matters to tolerance reactions is the specific mechanisms of the drug rather than how popular it is in psychiatry.  those are what influence how the nervous system adapts to the presence of a continuously used drug.

 

an additional consideration here is tachyphylaxis, which overlaps with tolerance but is not necessarily the same thing.  tachyphylaxis is usually referring to a more sudden and enduring loss of particular experiential effects, and is sometimes called 'poop out' in psychiatric prescribing, most especially during the use of reuptake inhibitor antidepressants such as SSRIs.  because neither professionals nor the literature use these terms, "tolerance" and "tachyphylaxis", uniformly, what someone is meaning when talking about them may differ from other uses and we need to ask for clarification if we want to be sure we know what they mean.

 

tachyphylaxis is a term used outside of psychiatry as well, but a key distinction is that tachyphylaxis is typically referring to medical benefits in prescribing (or potentially other interventions) whereas within psychiatry there is no focus on medical benefits and the measure of tachyphylaxis is on the psychological and behavioral alterations caused by drug use.  because a sudden change in these experiential effects, for instance attenuated dysphoria, is not necessarily about the same processes mediating gradual tolerance, the ramifications of tachyphylaxis may differ from that of a tolerance that has built up.  other drug reactions which can interfere with desired outcomes can also be conflated with or mixed into tachyphylaxis.  nobody agrees on just what line to draw.

 

where does this all fit into ideas of effectiveness?  well, as you note, sometimes these dynamics can mean someone no longer experiences the reactions they were using a drug to experience, or the reactions have been so diminished that the downsides of drug use are no longer outweighed.  but, not all drug effects are going to be equally affected by the mechanisms which mediate tolerance, and not all individuals will be equally impacted by the processes of tolerance.  as such, we cannot universally say that all drug use has no potential for long-term upsides.  navigating the tolerance and rebound risks and other factors can be difficult, though, and most people are not responsibly and appropriately prescribed these drugs in the first place.  ongoing drug management can be a variable in tolerance and tachyphylaxis, too.

 

to read discussions of these topics, you can just put 'drug tolerance tachyphylaxis' or something like that into a pubmed search.  youll unearth a range of literature with contradictions aplenty.

[Mark840]

Thanks. Interesting insight. What about drugs for physical illnesses like hypertension? Does drug tolerance happen only with psychotropic drugs?

[InvisibleUnless]

great question.  any drug mechanisms where the body changes in response to or adapts around the influences of a drug in a way that lessens the effect being experienced may well qualify as "tolerance" of one sort or another.  heartburn drugs (PPIs) cause an increased proliferation of proton pumps which counteract the suppressing influence on acid secretion, antibiotics can lead to a surge in resistant pathogen strains, and stuff like that.  the nervous system is extremely plastic and thus routinely adjusting to drug alterations, but most other parts of the body have their own plasticity which can affect drug responses over time.

 

there can be lines to draw about what mechanisms are involved, so it may not be most clear to say anything involving this reduced effectiveness is "drug tolerance".  there can be preferences in how particular dynamics are termed, though i cant delineate them all because im not a medical professional and havent studied it.  however, it is not always clear exactly how an adaptation or other kind of change comes about, and there is not necessarily an overarching coherence to what terms are in popular use for each situation.  the fact of changes caused by chronic use reducing drug effectiveness is what to hold on to; how to term it is negotiable.

 

drugs which try to change how the body would normally be functioning in some way will often entail this risk in a way drugs which simply supplement natural processes experiencing some sort of deficit often dont.  using steroids to soup up certain functioning beyond the bodys normal homeostatic range can produce tolerance, for example, whereas giving daily insulin to insulin-dependent diabetics ('type 1') should not cause diminishing returns in dose effectiveness over time.  for all medical actions, there are bodily reactions.  not all will lead to reduced effectiveness of an intervention, but there is always some sort of reaction.

[whatisbrain]

Hey, at one point, 2020 to 2021 I think, I was a listener and sometimes Q and A asker on a bunch of the Zooms offered by madinamerica.com and there was one that started with a discussion of pills that lower blood pressure, just to show that it is a mechanism that is common to many substances, whether supposedly psychoactive or supposedly purely physically active. I wish I could find that video, to show to my friends and acquaintances that take blood pressure pills...but I really would have to do a lot of searching.

 

In just a few minutes, the doctor explaining the blood pressure stuff said there was three ways those pills lower pressure, one is to relax the walls of the blood vessels, another is to change the amount of fluid volume in the system, and the third, I forget. The first way, well, your body reacts by stiffening the walls of the blood vessels. The second way, your body reacts by countering the change to try to restore the previous volume of fluid. The third way, similarly, your body tries to get back to what it knows.  In all three of these, the result is that your body tries to undo what the pill is doing, and you get to a point where your blood pressure is still not great, and if you stop the pill, your body gets even more confused and you might feel out of sorts, no surprise there. Then of course, the cardiologist or general practitioner says, see, you don't want to have heart attack, right, go on and get that refill right away, and we can prescribe another one of these for a total of four, enjoy. Of course, they never ask, how many cups of coffee or cola or red bulls do you drink a day, or anything of that sort, because they believe that a caffeine addict can never stop drinking coffee so the only way to help is with some pills.

 

I will go ahead and look for the recording of that Zoom, not just for this forum, but because I always wanted to have it as a reference for folks in my life that get on these lower blood pressure substances and then are afraid to stop. Only the first five minutes of the video are about that, then the rest are more standard mental pills content.

 

I have always had low blood pressure, just like my father and just like his mother, my grandmother. The medical helpers always want to get me on something called midodrine, to increase blood pressure, but, holy robots, if I want to, I can just drink a cup of coffee, or have some salty potato chips, get the heck away from me, you nonconsensual helpers. Or if you want to help, can you get me a cup of coffee and some salty potato chips, or at least a quart of water to drink? Huh, you don't have any of those here, and the water in the tap is for washing, not for drinking, you can only give me a midodrine, two spoonfuls of water to wash it down, and a bill for $2000 US dollars. Got it, thanks.

 

 

[whatisbrain]

OK, I wrote the staff of madinamerica to ask for help in searching the old Zoom recording archives, and hope to have some updates later on. The explanation already in this thread is great, but the video is also great, very brief and concise, as well as accurate and simple.

[Mark840]

Thanks @whatisbrain. Interesting insight. I look forward to the the recorded Zoom video once it's available.