[harbie]

>"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.

[tyu100]

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general efficacy vs. placebo even for mild/moderate depression but this new meta-study (with the additional previously unpublished data from their initial approval trials) looks like it has finally settled the matter.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edit: It looks like I'm a bit out-of-date in my knowledge but the general point still stands.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.

[kqr]

> 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.

Don't remember well enough to cite exactly but this may have been it: https://link.springer.com/article/10.1007/s11920-013-0370-7?

[nerfhammer]

treatment-resistant doesn't mean severe, it means treatment resistant.

[icantdrive55]

I am obviously confused, as usual. I'm not used to reading these studies.

I'm looking at the study. I'm looking at the #3 graph under Tables and Functions Tab.

It says amitriptyline is the best drug? Isn't that an older drug, or am I misreading the chart?

[tyu100]

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.

[gehwartzen]

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.

[kqr]

"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.

[alex_hitchins]

What foods should I avoid? I'm been taking Amitriptaline for 8 years now for pain management and wasn't given any advise on substances to avoid.

Although I'm on another Anti-Depressant, I certainly notices a positive effect from Amitriptaline that outweigh the bad effects.

[mnw21cam]

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.

[markroseman]

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.

[alex_hitchins]

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.

[markroseman]

Amitriptyline is a tricyclic; it's MAOI's that require a special (low-tyramine) diet.

[kqr]

I stand corrected. I was indeed thinking of the wrong class.

[nerfhammer]

relevant: http://slatestarcodex.com/2015/04/30/prescriptions-paradoxes...

[alz]

Right! They exclude cases where they don’t work, then conclude ‘All antidepressants were more efficacious than placebo’. This is highly misleading