Can antidepressant tachyphylaxis lower mood in the long-term?

[WiseOne]

This is not an anti-psychiatry motivated question, but a question I've genuinely been curious about. Antidepressant tachyphylaxis ("poop out") is well documented in the literature and usually the patients never regain their original sensitivity to the medication. This implies some permanent change to the brain (and that antidepressants are capable of permanently changing the brain). Does it thus follow and could one then conclude that they could permanently decrease sensitivity to serotonin?

I was surprised about this phenomenon because I've often been told in lectures that the effects of antidepressants completely reverse themselves after stopping the medication.

Anyone mind enlightening me a bit on this? Does my speculation make sense? It seems that other psych meds are able to cause adaptations that the brain does not fully reverse after stopping, so is that not possible with SSRIs? if not, then why.

Thanks!

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[witzelsucht]

bump for interest

 

[MacDonaldTriad]

The concept of tachyphylaxis implies that the chronic use of an antidepressant would require an increase in dose over time to sustain an equivalent effect. The reuptake inhibition provided by antidepressants doesn't lessen over time given the same dose. In my opinion, applying the term "poop out" to a chronic cycling illness like depression is foolish and wrought with folly. It is much better to describe this as break through depressive symptomatology. Who is to say that the antidepressant is working "less well", or is it just that the disease requirements have overwhelmed our poor ability to help with pharmacology. The literature you cite hasn't been universally accepted, or at least no one has included it in any major text or test.

 

[smalltownpsych]

I have never heard the term tachyphylaxis so googled it. It sounds like an extremely steep tolerance curve to me something like what you might see with opiates or maybe decongestants, for example. That doesn't fit with anything that I have seen with SSRIs. They don't even tend to have a very rapid response not to mention a rapid tolerance and loss of efficacy. It seems that your view might be a bit oversimplified. Here are some of the patterns that I have seen. Some patients recover with just a medication and can independently address or cope with some of the causal factors and do well. They might even stay on the SSRI for years at the same dose. Some patients take the SSRI, continue to use maladaptive strategies and then look for more medicines to fix them. Some patients get medicine to get them from a point where they are too low to benefit from psychotherapy and then they begin learning and implementing adaptive coping. Some patients just use psychotherapy and recover without any medications. Some patients recover without any intervention. Then there are all of the patients who have comorbidities and complex presentations. You know the ones who aren't in the clinical trials, but are the ones who are always showing up to my office.

 

[WiseOne]

Tolerance would have been a better word to use. Tachyphylaxis is used in the literature for some reason though.

But it's not totally unfathomable to me that antidepressants could have effects that are not totally reversible. We already know this is true for antipsychotics (adaptive changes that don't reverse), so why is it not fathomable for antidepressants? True, there is not much literature on the topic, but there is a lot of anecdotal evidence. And the same was true for tardive dyskinesia where it took the literature a bit of time to catch up to what patients were actually saying. But anyways, I'd like to think that antidepressants don't cause this effect, but mechanistically I just can't see why not.

edit: seems like this has been looked into by a few people
The mechanisms of tolerance in antidepressant action. - PubMed - NCBI

Can long-term treatment with antidepressant drugs worsen the course of depression? - PubMed - NCBI

 

[Promethean]

I don't know that anyone has rigorous data to quantify precisely how much adaptation in the presence of an SSRI will be persistent versus what will dissipate. And I disbelieve that anyone can say with certainty that mechanisms of tolerance/tachyphylaxis play a meaningful role with SSRIs, or at least not one analogous to say, habituation to opiates. Maybe it works that way, but I'm betting that the story isn't quite that simple.

We like simple explanations, that "make sense" because they square with what we think we know and understand. Be careful about telling yourself stories about what must be true based on how it fits with your current (possibly flawed) understanding of mechanisms. It is really easy to get diverted away from evidence by compelling conjecture.

Unrelated: Someone once used the phrase "without concomitant tachyphylaxis" in a love note that she sent me. Instant commitment.

 

[smalltownpsych]

Tolerance would have been a better word to use. Tachyphylaxis is used in the literature for some reason though.

But it's not totally unfathomable to me that antidepressants could have effects that are not totally reversible. We already know this is true for antipsychotics (adaptive changes that don't reverse), so why is it not fathomable for antidepressants? True, there is not much literature on the topic, but there is a lot of anecdotal evidence. And the same was true for tardive dyskinesia where it took the literature a bit of time to catch up to what patients were actually saying. But anyways, I'd like to think that antidepressants don't cause this effect, but mechanistically I just can't see why not.

edit: seems like this has been looked into by a few people
The mechanisms of tolerance in antidepressant action. - PubMed - NCBI

Can long-term treatment with antidepressant drugs worsen the course of depression? - PubMed - NCBI

As far as the point of permanent changes to brain chemistry and/or function. Quite possible. What we can't see is not easy to measure. We can see tardive dyskinesia so we know about it. My patients with TBIs experience this frustration everyday. Their injury is not visible so friends and family don't understand. Also, keep in mind that there could be changes in a positive direction from the use of the SSRIs. A brain that is depressed is causing permanent or lasting changes to neurological functioning as well. I seem to recall some evidence of linkage to hippocampus in particular. Theoretically it makes sense that since the brain is always changing in response to the environment and the depressed person has a different external and internal environment that a depressed state would adversely affect it. Think of the rats raised in the impoverished environment vs the rats raised in the rich environment and which brains were more developed.

 

[birchswing]

I recently asked my psychiatrist about permanent changes to my brain and in particular the HPA-axis from Paxil use, and also several abrupt discontinuations (when I was taken off abruptly over the summers in high school with no weaning, and would then go back on the next school year). She really dislikes Paxil. She said she couldn't answer my questions with certainty (an answer I, as a patient, LOVE—I love when people say they don't know rather than make something up), but that she suspected there were changes. I wish more were known about this. I feel like it could be a factor in my testosterone issue (secondary hypogonadism, low lh/fsh), autonomic issues (POTS type symptoms along with strange respiratory issues and hypoventilation), and lack of sexual interest issues. But there's no way of knowing. I do know that something completely changed about how Paxil affects me. When I was taken off cold-turkey I had brain zaps and awful side effects. But I recently went off it rapidly for suspected mild serotonin syndrome and had no side effects going off except improvement of symptoms. No brain zaps at all. Also over time, the way it affected me sexually changed significantly, which is probably TMI, but suffice it to say the original side effects I had for many years changed into completely different side effects.