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Don't know if this is kosher but there's a really interesting thread on Reddit's "DepthHub" about a person who is scared to go on anti-depressants because he feels they will make him artificially happy. The really interesting part is the comment from Race-Hearse, which I'll copy here:


I'm very passionate about this, but I don't have enough time to write as thoroughly as I'd like. Just know that I can provide a citation for everything I say and will do so (later) if requested.

Here's a little background. My mom killed herself 10 years ago while taking antidepressant medication. I then developed depression myself. Eventually got on meds myself. In college I majored in neuroscience and decided to emphasize my study on depression (and it's treatment) in the brain. My senior thesis had to do with gauging beliefs on antidepressant medication and then weighing those beliefs against the current neuroscientific understanding. Currently I'm in pharmacy school.

With that out of the way, oh gosh where do I start. How about this? "Happy pill" is a bad way to think of it, in my opinion. They just simply don't make you happy, nor are they designed to. What's more accurate is that they bring you from bad to neutral. A specific doctor who was criticizing mental health in our nation once said that, he said meds are really good at bringing patients from bad to neutral, but we fall short of improving people's lives where they'd consider it good. And if you're only neutral, it's fairly likely meds alone will just keep you at neutral, and you'll fall back to bad without them.

I guess something important to consider is what they actually do. Now what I'm about to talk about, last I studied it, was in "strong hypothesis" status, it wasn't proven, but it seemed like it was headed in that direction. The whole "serotonin theory" just always seemed really weak to me. After taking the meds and studying how they worked, "increasing serotonin" seems to not be what is directly producing the "antidepressant effect" (I'm going to call that ADE from here on out). In depressed brains you notice some distinct things compared to non depressed brains. One of them is decreased neurogenesis in the hippocampus, another one is an overactivity of the HPA access (the thing that makes you stress out or go into fight or flight.) Now the hypothesis is this: hippocampus is a very plastic part of your brain. Short term memories live there, it's thought that maybe how we filter our day by day attitudes live there as well. In depressed people the plasticity is super low or non existent. Meanwhile, the stressy part of your brain is overfiring. Add these two things together and you have a stressy attitude and you're stuck in that attitude because the mechanisms a brain has to change the state it's in just aren't happening.

Now the meat of this hypothesis kinda hinges on this protein molecule called Brain Derived Neurotropic Factor (BDNF). Increased BDNF levels have been shown to increase neuroplasticity and neurogenesis in the hippocampus, as well as toning down the amygdala (fight or flight risk area of the brain.) The way I BELIEVE (but is not proven) antidepressant medication works is that eventually, for whatever reason, the effect of the drug increases BDNF gene expression (there is data that shows increases in BDNF after taking antidepressant medication)

Another reason I believe this to be true is because your doctor or pharmacist should have told you that antidepressants wont work for 4-6 weeks. Now consider that cocaine is a dopamine reuptake inhibitor and works instantly. I imagine serotonin reuptake inhibition occurs shortly after your first dose, but the antidepressant effect takes weeks and weeks. I guess there's many different reasons that this could be, but maybe one of them is just that it takes a while for serotonin reuptake to effect something downstream which effects something downstream which eventually effects BDNF reuptake. Maybe! 

Now, more support of this: There was a recent study that showed that exercise itself is shown to increase BDNF levels too. And we've all heard that exercise has helped end people's depression. Again, it's not proven, but I wouldn't be surprised if that's the mechanism. The newest novel treatment of depression is ketamine infusion. This has shown to increase BDNF production way faster than SSRIs do. Pretty cool stuff.

Anyway, I got carried away. So if that ends up being the actual mechanism for the ADE that shows us that depressed brains are physically malfunctioning and that medications can help fix these physical malfunctions. The "good to neutral" thing makes sense as well. If the drugs are working you're not being "artificially made to feel okay/good", you're repairing the parts of your brain that are keeping you depressed, giving you a new opportunity to get out of your rut. 

I believe that when people go off medications prematurely and are suddenly just as depressed as ever that isn't an indication that the medication doesn't work though. I believe the medication can actually be working but someone could still feel depressed. That's why I believe people really need to open up to the idea of therapy as well, and work on behaviors conducive to managing their depression.

To get a bit anecdotal about it. I was suicidal once, extremely depressed, every day was suffering. It's like the feeling of pure dread and worry on a day to day basis. I took medication, it got me out of that rut, went off medication, and then became a new flavor of depressed: I had anhedonic depression. Didn't care about anything, didn't really do anything, it was blah-incarnate. I was in neuroscience at the time so I was very reflective on my depression because I was learning about it in school, so I realized I had to see a therapist. Through her I learned how to identify my behaviors, do things counter to what my instincts told me too to stay out of a rut, etc. I learned that depression is something one doesn't have to suffer with forever, but you likely DO have to manage it for the rest of your life in order for it to stop coming back bad and effecting you greatly. It still sneaks up on me sometimes, but I identify it, I have strategies for dealing with it, and it doesn't effect me anymore. (I would have failed first quarter of pharmacy school if I didn't learn how to manage it, guaranteed.) I also don't have to take medication anymore.

With all that in mind, the way I like to think of antidepressant medication nowadays is this: It's a tool. It'll help you in your battle if you need it. There's many different tools out there though. Other tools work for other people. But many people do need it as a tool and they shouldn't be afraid of that or think they're damned to have to rely on it for the rest of their life. Depression has physical manifestations though, and I imagine for many people nothing they will ever do will solve those issues except medication. The trick though, is to not rely on it as an easy fix. Depression is hard as **** to fix. It requires embracing the source of your suffering, the ability to admit your brain is thinking bad thoughts due bad hardware, the ability to reality check yourself and admit your braindidn't is just straight up wrong (which can be hard as ****), and constant behavior changes to make sure you're setting yourself up for a good life. (Exercise, eat right, sleep well, and being nice to others will do wonders for your soul.) 

There's three more big issues I won't get into due to the already-wall of words I've typed. Side-effects. Treatment resistant depression. and Diagnosing depression. Maybe if there's more interest I will tomorrow, but for now I gotta go.

Hope this helped, good luck.

TL;DR: There are physical differences in a depressed brain that antidepressant medication has shown to fix. I believe depression is, to put simplistically, a brain being simultaneously stressed out (fight or flight) and stuck in a rut so that one doesn't have a means to change it. Medication can break the rut. It doesn't produce false feelings, it grants an opportunity for one to heal the physical parts of the brain that may be keeping them in their depression. This won't necessarily make someone happy, but may create a new path towards happiness that wasn't there before, and treatment should be coupled with therapy. Unfortunately there's no cure to depression, it's something you manage, and medication is a tool to help you with that if you need it. But I'm evidence that management eventually get's easy and no big deal.


Full thread: https://www.reddit.com/r/changemyview/comments/51uv12/cmv_depressed_people_on_antidepressants_are/



2012 - Started on 50mg Pristiq 2013 - Increased to 100mg Pristiq in 2012 under Drs orders 

2013 - 2016 Decreased to 50mg Prisiq and increased to 100mg Pristiq as I felt was required. No major withdrawal symptoms noticed.

August 24th 2016 Started tapering from 50mg Pristiq last week, started 3 day washout as doctor wanted me to change to Prozac

Horrible withdrawals from Day 2 - night sweats, nightmares, foggy head, headaches, brain zaps

August 26th 2016 Decided to start tapering of AD altogether instead of switching to Prozac.

Got 25mg of Pristiq compounded. Some withdrawals the first three days but has stabilised as of day 4.

Plan is to taper by 5mg per month if tolerated. If not, will revert to 10% per month formula.

September 24th 2016 - Next taper, down 5mg to 20mg for a month. Pattern seems to be ok on first day of taper, totally rubbish (exhausted, brain zaps, visual processing changes) the next day, a bit rubbish day 3 and then stabilise. Will watch for this pattern in the next taper. Some night sweats two weeks in. Next taper in two weeks. 

October 21st, 2016 - Horrendous fatigue for the last two weeks. Debilitating up to the point of sleeping every day and being physically unable to get out of bed. Pretty concerned about next taper beginning this weekend due to this fatigue. 

October 24th 2016 - Started next taper, down 5mg to 15mg for a month. First day good, second day better than previous month. 

November 27th 2016 - Decided to go cold turkey to 0mg in an effort to be well before the start of uni in Jan 2017. Have been struggling with fatigue, sensory changes (auras etc.) hair-trigger neuro-emotions and general feelings of unwellness. I would not recommend this course of action. 

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