Ineffectiveness of pain killers and a depressed mind...
July 22, 2013 7:18 AM

Can someone who understands biology and brain chemistry please show me the (probably) glaring hole in my blinding flash of brilliance connecting my wife's mental health and her apparently abnormal responses to painkillers...? [ possible mental health triggers inside, I guess ]

Yesterday I had one of those flashes of inspiration that tend to hit people who only have a vague understanding of the topic they are considering. The facts are these...

1) My wife suffers from depression that doesn't seem to respond to antidepressants, mood stabilisers, or any of the other associated pills traditionally given to the depressed. She doesn't remember a time before depression. She often enjoys an event/stimulus but falls back into a depressed state almost the second the stimulus ends.

2) She has an odd response to painkillers / anesthetics / etc...
- a) She refuses painkillers because "they don't work" - even things like 30/500 co-codamol (Tylanol 3, I think). In case this sounds like a 'drug seeking' behaviour, she's never taken anything stronger, because she doesn't believe that will work either.
- b) She's had several local anesthetic minor ops where she has complained bitterly about the pain while doctors have (unsympathetically) told her that she can't possibly be feeling anything.
- c) She's just had a couple of more major ops under general anesthetic where the anesthetist has commented on how it's taken more anesthetic than expected to knock her out, and she's come back out more quickly than they expected.

My badly thought through logic is this...

It seems interesting to me that she doesn't seem to have the long lasting pleasure sensations (which my basic biology recollections say is an opiate-like response); doesn't get benefit from the opiate-like codeine; responds in a surprising way to local and general anesthetics.

I don't want to say "is my wife's brain failing to appreciate opiates" but that's probably the ultimate conclusion of my logic.

Is it possible that the same thing that is stopping her enjoying life is stopping her getting benefit from painkillers and anesthetics?

So, metafilter, just how clueless is my logic?
posted by anonymous to Health & Fitness (10 answers total) 3 users marked this as a favorite
I think a flaw in your logic is that she doesn't actually have any proof that painkillers per se don't work for her. Tylenol 3 may not work, but if she hasn't taken anything else, how does she know they are ineffective?

Is she a redhead? Redheads often need higher doses of anesthetic to achieve effectiveness.
posted by something something at 7:40 AM on July 22, 2013


I'm not at all an expert in this, but I think you are looking for the COMT gene, which has been associated with pain response, and also appears to have something to do with dopamine.
posted by Comrade_robot at 7:41 AM on July 22, 2013


Hey, OP, I don't have an answer per se, but I wanted to chime in and say that I am pretty similar to your wife, although I've never linked the two things. I too have a long history of depression (not linked to any incident or trauma) and local anaesthetic is often found to be ineffective on me.

I actually have to ask for a particular, stronger kind to be used at the dentist because they've given me like three times the usual dose of the usual stuff and it still does virtually nothing for what ought to be a simple numb job.
posted by greenish at 7:53 AM on July 22, 2013


I was depressed and unresponsive to treatment for most of my life, beginning as far back as I can remember, and I never experienced resistance to the effects of painkillers.

I HAVE experienced the inept ministrations of several individual asshole doctors who refused to believe that I was feeling things I was telling them I was feeling, but luckily they were enough of a minority that they haven't colored my judgment of the profession.

I probably wouldn't base any generalizations on my anecdata, though. I have this insane stoic high tolerance for pain that probably kept child protective services on my pediatrician's speed dial when I was a kid.
posted by The Underpants Monster at 9:32 AM on July 22, 2013


Seconding the question about whether she is a natural redhead-- there is a genetic mutation that causes red hair AND reduces the brain transmitters' ability to be affected by anesthetic. I always need about 3x the normal dose of novocaine when I get a filling, for example.
posted by joan_holloway at 9:37 AM on July 22, 2013


Genetic variations in the function of the enzyme CYP2D6 can inhibit a person's ability to metabolize certain types of drugs, among them opiates such as codeine and hydrocodone.

On the Wikipedia page I linked there is a whole list of drugs and they way they are affected by CYP2D6.
posted by Serene Empress Dork at 9:45 AM on July 22, 2013


I have bipolar disorder, and I actually am on lower dosages of my mood stabilizers and anti-depressants than most people with my disorder. HOWEVER opiates and other pain killers simply don't work for me. I've tried codeine, I've tried vicodin, I've tried morphine, and other such pain killers - it's like taking sugar pills. They simply have no effect on me at all. Going to the dentist is a nightmare. I distinctly remember starting to come to during my last c-section. I don't even get a runner's high. It sucks.

Anyway, I guess what I'm trying to say is that while pain meds have little to no effect on me, my psych meds work pretty well. I guess I should say the particular psych meds I'm on now do... It took me awhile to find this combo, but that's par for the course when it comes to psych meds. And as we say in this world your mileage may vary.

I'm a natural blonde, so if we're talking hair color, you can take that into account. Redheads run in my family, but I'm not one of them.
posted by patheral at 9:48 AM on July 22, 2013


I have FMS, a history of depression/anxiety, and a resistance to every OTC and prescription pain medications, anti-depressants, mood stabilisers, and anxiety meds I've ever tried. And I've tried just about everything there is out there (although I'm sure that the one magical thing I can't afford or don't have access to is the one for me). Anyway, people with FMS and/or CFS frequently are sensitive to medications and have adverse reactions to them, but it turns out I'm some kind of unicorn that I usually get no effect whatsoever, good or bad.
posted by sm1tten at 12:58 PM on July 22, 2013


Your post was not clear on this: is your wife in pain?

I'm a chronic pain person, fortunately well controlled, but before it was so I had to ponder a life in pain. And that was, well, ... on the other side of depressing. So your question made me wonder whether your wife is actively in pain, not controlled, and thus depressed.

Reactions to pain meds really vary, and especially post-surgery, your wife should by all means and rights expect her pain to be addressed, not just "well that should have done it ...."
posted by Dashy at 1:15 PM on July 22, 2013


OP, if you come back to this thread, I've been talking about this with someone who has knowledge on the subject, and got some interesting stuff out of it. MeMail me if you'd like, and I'll expand further - it's perhaps little too personal to go into here.
posted by greenish at 2:00 AM on August 2, 2013


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