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A tricky Question that my Prof. can't give the exact answer

Mr Blonde said:
To be honest, the only advantage the fentanyl analogues offer is potency and that isn't an advantage unless the dose of the original compound is so large as to be a burden to take. Doctors back in the day (and maybe even today) seemed to have this notion that 'greater potency means better in general', without considering things like the efficacy or therapeutic index of a new compound.
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Doesn't fentanyl have a greater therapeutic index than morphine, and carfentanil a greater therapeutic index than fentanyl? :/
 
^ It does indeed, but the the therapeutic index of morphine is still fairly high (~400 for fentanyl and 70 for morphine). Some opioids may offer advantages over others for anesthesia... I will post more about this later.

shoo-bop said:
Yep, that's what I meant by ECT. Can't say I expect it to be a particularly promising project even if it ever gets through the various approval processes!

Another thing to consider is the possible dissociation between anticipatory anhedonia and consummatory anhedonia. We tend to assume that we look forward to what we find pleasurable, and vice versa, but this is not actually always the case - recent schizophrenia research for example suggests that schizophrenics have impaired expectancy of pleasure and/or ability to take pleasure in the expectancy of something good, but normal pleasure when something good actually happens (this may be as much do to the meds as due to the illness, as this research was conducted only in medicated patients, and most of those medications block dopamine receptors). My impression is that this may also apply to so-called "atypical" depression - not feeling like anything's going to be good, not deriving pleasure from knowing of something good coming up, but still being able to take pleasure when it happens. Anhedonia in melancholia, however, is much more profound: it's both anticipatory and consummatory anhedonia.

There's at least a few people out there who will say dopaminergic dysfunction is involved in anticipatory anhedonia and opioid and/or serotonergic dysfunction is involved in consummatory anhedonia. That's probably a massive over-simplification, perhaps to the point of being largely incorrect, but if it even vaguely approximates reality, it also adds to the explanation of why some medications that help some people with depression don't help others. Last I heard, though, around a third of people treated for depression with the "standard" classes of antidepressants don't have an adequate response even after multiple trials of different classes of those medications.
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Very interesting post there, and some interesting ideas on depression that I will have to look into.

Part of the problem with the efficacy of antidepressants is that they are over prescribed. I might try and find more information later, but antidepressants are most effective when used for severe clinical depression; mild to moderate depression is much less likely to respond to these agents and is probably better treated with psychological counselling, teaching of behavioral techniques and perhaps even dietary modifications when necessary.
 
Very interesting thread team, I literally have nothing I can add to it though as so much has been covered.
I will say that I whole heartardly agree that there needs to be further research into whats causing the depression Exogenously or Endogenously.
Ultimately the causes of depression can be so different that it's important to explore what is the cause.

For about 12 months I believe I was depressed, I had virtually no reason to be, I didn't really speak to anyone about it but I found myself being miserable when everything in my life was going well. I would find times to be happy but most of the time I was depressed and when I would think about it I could find no reason for me to be. Maybe it was a chemical imbalance that some how has worked itself out because now I'm happy as Larry.

@Deathdomukun
I loved your comment, I never knew that talking about depression could make me feel so happy haha. Gold.
 
Mr Blonde said:
^ It does indeed, but the the therapeutic index of morphine is still fairly high (~400 for fentanyl and 70 for morphine). Some opioids may offer advantages over others for anesthesia... I will post more about this later.
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Just to add to this: the reasoning behind using fentanyl for ECT and other surgeries or traumas involving the brain is that morphine raises intracranial brain pressure (ICP). Fentanyl has the advantage of not increasing the ICP, and also being a shorter acting narcotic.

The reason for the increased ICP comes down to respiratory depression and increased levels of carbon dioxide in the blood, measured as paCO2. This increased CO2 level, known as hypercarbia, leads to anoxia and ischemia in the brain which then causes swelling of the brain.
 
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I'm not sure that differences between drugs in respiratory depression would be relevant to ECT, at least as it's practiced in Australia and most industrialised countries for 2 reasons:

- the muscle relaxant they give ECT patients (suxamethonium, I think the name is, to prevent the electrically-induced convulsions from causing spinal injuries) stops their lungs from working for a few minutes anyways, regardless of what anaesthetic is used, and the seizure itself involves a brief period of total respiratory depression anyways.

- As a result of the above, the anaesthetist and/or nursing staff always artificially ventilate the patient from the time that the suxamethomium is administered until the time that the patient is breathing voluntarily again and their blood oxygen saturation has stabilised in the safe zone.

So, while this may apply to other surgical procedures, I can't see how the choice of anaesthetic, as long as it was short acting (which I think is why fentanyl would be one they'd consider) would make much of a difference to ICP, if that's simply a function of respiratory depression. Most commonly, though, ECT anaesthetists seem to use propofol, thiopentone, or ketamine.
 
^ Thanks for the info on ECT there, I don't know much about it myself. Didn't even know they used the neuromuscular blocker suxamethonium either. I've always heard it called succinylcholine
as well so had to think for a moment what it's mechanism is. :)

I wasn't actually discussing the drugs used for ECT though, just more generally talking about the drugs in clinical use. And although the artificial ventilation will prevent the respiratory depression aspect, I should have mentioned in my post that many opioids cause ICP even when there is adequate oxygen intake. Morphine is one such drug; if you look at the contraindications and precautions for it, head trauma and ICP are both listed on most charts.
 
^ It's usually called suxamethonium in Aus. I'm not 100% sure but I think succinylcholine is the American name
 
^ Just had a look at Wikipedia, and suxamethonium is the International Non-proprietary Name and so is more correct then succinylcholine. Must be an old Americanism I picked up from one of my text books. ;)
 
wow this thread is one of the best discussions i have ever read on ADD, shoo bop you made some good points that i was going to bring up. we do tend to take ourselves out of the environment and cut the head from the body when thinking about these issues. i have done counselling for paitients with depression and gotten some results, seen medication get some results, and seen just a lifestyle focus no medication get some results, but when you add all three interventions together you get more than the sum of the parts... for me this would suggest a complex relationship between a person and their environment.

Im a big critic of the pharmacetical system and the belief that drugs will fix everything, the more im reading into health systems the more i am convinced that there actually is a big death when it comes to physical and mental health... we have been trained to believe that doctors can fix everything... but even their knowledge is limited significantly to their training. diagnosis and application of medication as remedy.

im not sure we are thinking or conceptualizing the 'problem' correctly to get a decent answer, i know that a fair amount of research is starting to happen with buphrenorphine for treatment resistant depression... opioids are great at affect supression but still my view is that is treating the symptoms rather than the underlying cause. im sure it wont be too long before as a society we find out that out way of living is not sustainable or healthy and move back to a less economic based way of living (or consuming). the recent decline in life expectancy for future generations has already shown this to a degree.

also some things are so highly individually environmentally associated that mass diagnosis of a cluster of symptoms may actually not be the proper way to think about treatment. biological functioning relies on a complex interaction between the person and the environment that its pretty hard to determine a true cause/effect pathway from what ive read. not exercising or doing pleasurable things, no sunlight, too much white light, not enough balance in the diet, impulsivity and other personal traits also play into this which means a life course perspective is also needed... neuro adaptation may actually occur due to environmental variables... there was some reserach done on monks who meditate for exceptionally long periods of time (months) where the body would overwhelmingly produce heaps of serotonin... go figure for doing nothing but emptymind!! maybe the way we respond to this world is the reason for soo much depression, i witness that more and more people are less willing to tolerate any normal ranges of emotions and tend to reach for quick fixes, or are so overstimulated by life that any but ramping up the stimulation leads to boredom and depressed affect...

as usual the answer is ... its complex and we still dont know much about humans and knowledge changes so rapidly that who knows where we might be in say 15 years- lobotomies were once the go to treatment for mental illness irrespective of the outcome!!!

i always fall back onto a great saying i once heard i think harold kalant a psychopharmacologist said-"if the human brain was simple enough to understand, we would be too simple to understand it" :)
 
You seem like a very smart and switched on individual, madmick19! Thank you for your post. I also agree, one of the best and more informative posts in ADD I've seen a quite a long while!
 
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