Yeah I understand that, what I mean is that from our perspective a person should be able to walk into a government office and be safe from extra-judicial sanctions. So a Saudi national may not feel that safe themselves, but it is harder for someone from a Western-style liberal democracy to intuitively understand and is therefore horrifying.
Reminds me of a Nathan For You episode that lampoons the idea of ranking something as subjective as a burger.
Nathan convinces the owner of a burger joint in LA to go on a popular local radio station and promise that he has the best burger in LA, and offer $100 to anyone who eats there and disagrees. The comedy in this is apparent to pretty much anyone, but people will still refer to different restaurants as 'the best'.
My mood has more effect on the pleasure I get from many things than their intrinsic nature. The first beer on holiday in a new country is the best beer you've ever tasted. A meal eaten in silence when you've been looking forward to it tastes divine.
Hell - my own narcissism even overrides most things. My own cooking is often my favourite thing in the world.
And on the other side of things - high expectations or rote habit often kill pleasures for me. If I try too hard to enjoy something it blows away like dust.
Context is king. Back when I was a consultant and flew all over the place a lot, there were more than a few times I landed at O'Hare sometime after midnight, got off the plane starving, and immediately beat it to the "open 24 hours" McDonalds in the food court and had a box of Chicken McNuggets that were, at that moment, the best meal I could dream of. I mean, who knew that damn mcnuggets could be absolutely heavenly under the right circumstances...
>"We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression."
Wikipedia defines treatment resistant depression as "cases of major depressive disorder that do not respond adequately to appropriate courses of at least two antidepressants."
Maybe I'm unfamiliar with study methodology, but doesn't this undermine the study's conclusion? It's essentially stating that forms of deppresesion that respond well to antidepressants respond well to antidepressants.
Please don't repost across threads. It makes merging them much more of a pain. If there are two discussions going on about the same thing, you're welcome to let us know at hn@ycombinator.com.
>"We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression."
Wikipedia defines treatment resistant depression as "cases of major depressive disorder that do not respond adequately to appropriate courses of at least two antidepressants."
Maybe I'm unfamiliar with study methodology, but doesn't this undermine the study's conclusion? It's essentially stating that forms of deppresesion that respond well to antidepressants respond well to antidepressants.
SSRIs are generally indicated for what's called mild/moderate depression, the most common form, not for the serious conditions that you highlighted.
There were some older meta-studies that called into question their general efficacy vs. placebo even for mild/moderate depression but this new meta-study (with the additional previously unpublished data from their initial approval trials) looks like it has finally settled the matter.
Reading this paper I'm amazed at the increased efficacy of some of the newer SSRI's despite not having a novel mechanism of action. This is similar to how effective some of the newer statins are at lowering LDL cholesterol despite the drug class being around for decades.
edit: It looks like I'm a bit out-of-date in my knowledge but the general point still stands. DSM V has a definition of 'major depressive disorder' which seems to have replaced the old mild/moderate categorization and this study looked at all anti-depressants that treat this type of depression, not just SSRIs.
> Reading this paper I'm amazed at the increased efficacy of some of the newer SSRI's despite not having a novel mechanism of action.
There are huge differences in the mechanism of action, quantitatively speaking, even within a class of antidepressants. As a particularly striking example, you're allowed to call your drug an SNRI as long as it has any detectable N effect at all -- even if the N effect is too small to practically make any sort of difference, and the drug is practically an SSRI.
Right, so since a common problem with anti-depressants are the varied side effects of different classes (insomnia, weight loss/gain, sexual dysfunction, etc.. and etc..) a big part of going on an anti-depressant is you and your doctor finding a drug and a dose that shows both efficacy and a tolerable side effect profile.
This study generalizes this process by discussing both efficacy (how well the drug helps with depression) and the tolerability of the treatment, as measured by how long people tend to stay on the drug (the site is down right now so I forget the actual term used). Once the paper is accessible again have a look at some of the graphs that chart both of these measures. Generally, the drugs in the upper-right quadrants are better, showing both good efficacy and tolerability.
It's important to remember that these drugs are ranked in term of efficacy vs placebo at reaching a specific outcome threshold (greater than 50% reduction in depressive symptoms). So best in terms of efficacy just means the highest ranked has the best statistical chance of working. It does not mean that it works x% better than another drug (i.e. Drug A reduces symptoms 60% and Drug B only 50%. It also means that the drug ranked #1 might not work for you at all; the "best" for you could be drug ranked #16.
This is basically a ranking to use in when trying drugs to statistically maximize your chance of finding one that works.
"Best" is a complicated concept. Yes, amitriptyline has the greatest efficacy, i.e. response rate in a clinical setting. It may still have poor effectiveness (how well it works in the real world) because it belongs to a class of medications which, if you use them, you have to exclude many types of common foods from your diet. It also has less safety margins in terms of overdosing than many modern alternatives.
And then there's also the odd fact that earlier trials of antidepressants show better effect than recent ones -- even for the same treatment and all else held equal. We don't know why.
Basically, the foods you need to avoid are any that might cause constipation, because Amitriptyline kind of does that for you already. The parent post was possibly confusing Amitriptyline with a different drug.
It is very weird to be mixing two different antidepressants. Depending on what your other antidepressant is, it could be dangerous. Were your two medications prescribed by the same doctor, and if not, have the two doctors talked to each other? A very simplistic view is that some antidepressants cause the body to make more serotonin, and others prevent the body from destroying serotonin as quickly. Doing one is fine, but doing both at the same time can lead to serotonin syndrome.
Amitriptyline does have higher risk from overdose than SSRIs, but has much gentler withdrawal symptoms.
Being on more than one antidepressant is not unusual, and can even sometimes be optimal. Even ones acting on the same neurotransmitter often target different receptors and hence different symptoms. More often it's because doctors are better at adding drugs rather than taking away ones prescribed by other doctors "just in case."
Serotonin syndrome can be an issue with all kinds of things (most people aren't warned about being on a SSRI and having cough syrup for example), but is not very common in practice, and because it coincides with a change/increase in medication, often sorted out quickly, even if it's characterized as a "side effect" or "tolerability" problem and not actually recognized for what it is.
Thank you for your concern. Yes, both medicines were prescribed by the same doctor, and there are others in the mix as well that mean Serotonin Syndrome is something I'm very aware of (Tramadol, Immigran). It's been a fixed dosage for a long time and I'm regularly seen by my GP, have LFT's twice a year etc. Just to note, the Amitriptaline isn't perscibed in my case for depression, it's taken in a smaller dose for it's neurapathic pain properties.
I find the ZoMorph blocked me up quite a bit, Fibrogel works well in this case.
It was anything but sly. He occasionally writes "I, I mean, Horselover Fat..." and never once concretely states that he and Fat weren't the same person.
Valis was part of Dick's attempt to interpret and come to terms with that experience
>“I’ve heard that there are colors that are too bright for our eyes to see,”
I don't know about brightness, but psychedelic drugs routinely cause visuals of colors that are too saturated for the eyes to see. This is because the responsivity spectra of the eye's cone cells have a lot of overlap, especially between the red and the green types. See: https://commons.wikimedia.org/wiki/File:Cones_SMJ2_E.svg
Psychedelic drugs affect the nervous system directly, so they can trigger one color channel without triggering the others. Presumably religious experiences can do the same thing.
You can approximate this effect without drugs by tiring out the overlapping channels before viewing the one you're interested in. Fill your screen with pure cyan (#00FFFF), and set up another tab full of pure red (#FF0000). Turn your display brightness up and switch off the room lights. Stare at the cyan screen for several minutes, and then immediately switch to the red screen. I suspect this color is close to what Dick and West saw.
I think this sort of "divine light" experience happens to a lot of people. In the Burmese school of Buddhism started by Mahasi Sayadaw, there is a stage of insight called the "Arising and Passing Away" that teachers identify when their students report phenomena like this. If you go to a Buddhist internet community like dharmaoverground.org, you will find a lot of people reporting and discussing this sort of thing.
Although I no longer consider myself Buddhist, I don't know what to make of it.
https://en.wikipedia.org/wiki/Legal_system_of_Saudi_Arabia