New MRI Studies Show SSRIs Bring Rapid Changes to Brain Function

A story at the Los Angeles Times reports that researchers at the Max Planck Institute have found that Selective Serotonin Reuptake Inhibitors, various of which are widely used in anti-depressant medications, cause changes in healthy subjects' brain architecture just hours after ingestion. As the article mentions, one reason that this rapid change is surprising is that patients taking SSRIs to treat depression typically take considerably longer (weeks) to perceive a change in mood. A slice from the story: When more serotonin was available, this resting state functional connectivity decreased on a broad scale, the study found. This finding was not particularly surprising -- other studies have shown a similar effect in brain regions strongly associated with mood regulation. But there was a two-fold shock: Some areas of the brain appeared to buck the trend and become more interdependent. And all the changes were evident only three hours after the single dosage. ... The rapid connectivity shifts noted by the study might therefore be precursors to longer-term changes, perhaps starting with remodeling of synapses, the microscopic gaps where chemical neurotransmitters such as serotonin flood across to an adjacent brain cell, the study suggests. But this type of brain scanning can’t pick up changes at such a scale, so the hypothesis will have to be tested other ways[.] ... Study subjects did not have diagnoses of depression, so researchers will need to generate similar maps among those diagnosed with depression, and re-map them during and after depressive episodes, as well as after treatment, Sacher said. Comparisons might then show whether a certain initial architecture predicts treatment success.

Comments

mostly clarity

[Anonymous Coward]

I found that the SSRI that I took for a total of about 18 months (for diagnosed depression) was mostly helpful in allowing me some clarity to so that I could identify, build and grow the coping mechanisms that helped me maintain clarity without the SSRI. I've been free of needing the drug now for about 8 years and have found ways to cope on my own (changing my mind among others as Tim Leary used to say)...

Re:mostly clarity

[Anonymous Coward]

...was mostly helpful in allowing me some clarity...

Depression isn't just about feeling sad. It's a whole range of negative emotions including guilt, hopelessness, lack of motivation, lack of confidence, etc. The opposite of depression is being manic - where a person feels happy, supremely confident and motivated, that everything is possible, etc.

Now, you seem to be hinting that the SSRI made you smarter (i.e. gave you clarity). But that's unlikely for a variety of reasons. Instead, it most likely made you feel smarter, more confident, etc. And maybe that's what you meant - that you had a unrealistically pessimistic view of the world and the SSRI caused you to have a less pessimistic view of the world.

For many people, being able to biochemically feel more motivated and less concerned about the consequences of their actions is exactly what they need. Maybe someone lost their job in a particularly unpleasant way and they're having trouble getting back on the horse, so to speak, and looking for a new job - and then the fact that months are going by and they're still unemployed is making them even even less motivated, etc.

But consider someone who is so desperately unhappy that the thing they want more than anything is to not exist - but they're held back by lack of motivation and concern for the consequences on their family. If you biochemically alter such a person's brain to feel more motivated and less concerned about the consequences of their actions then you made an already dangerous situation much more dangerous. Now, SSRIs are often prescribed together with valium derivatives which could potentially take the edge off and make a person less unhappy - dulling the desire to cease to exist - and perhaps also dulling the motivation a bit. And then there's also depression caused by an external situation. If someone is depressed because they're in an abusive relationship then obviously SSRIs are the wrong solution (i.e. the right solution is to get out of the relationship).

Which is all consistent with this latest study. Depression isn't some simple biochemical imbalance that's cured as soon as the SSRI diffuses across the blood-brain barrier (i.e. a time scale of hours). And, to the extent that SSRIs do have a biochemical effect on mood (i.e. subtracting the massive placebo effect) it's important to be very careful that this biochemical effect is actually beneficial to the patient because if you get that wrong you end up with a dead patient.

Re:mostly clarity

[Bite The Pillow]

That's how it is supposed to work. It's a crutch to allow something like cognitive behavioral therapy to take hold.

Ideally, you would be seeing a psychologist to assist with identifying coping strategies, or problems with the way you filter input. Instead of triggering negative responses, everything you experience in a day should be more or less balanced. Not perfectly 50/50, but certainly not always negative.

Getting in a negative rut ("depression") makes it easier for a neutral stimulus to trigger a negative emotion, or something that should be positive to be misinterpreted.

An anti-depressant can't change the way you react to what you hear, read, or see. But it can give you enough of a lift that you have room to work on yourself.

As long as I'm typing - someone will probably mention cocaine. Similar caveat with cocaine - it doesn't help you change your mind. It actually gives you a positive feeling, which current anti-depressants don't really do. The need to change your mind goes away, temporarily, and users look to another hit to solve the problem. It's a great demonstration of how feeling good might feel, but serves no other useful purpose.

Re:mostly clarity

[Anonymous Coward]

...that you had a unrealistically pessimistic view of the world...

I seriously doubt that is possible.

Re:mostly clarity

[Anonymous Coward]

that you had a unrealistically pessimistic view of the world and the SSRI caused you to have a less pessimistic view of the world

You seem to assume that "depressed" means "unhappy" or "pessimistic". I've had depression for almost a decade while being happy and successful and an overall optimistic person who looked forward to his work day and time with friends and family.

I had a lack of energy and motivation, but I enjoyed being with people and doing stuff, but I relied on others to motivate me and I always wanted to sleep and do nothing. I also had anxiety, not a "fear" of anything, just my mind would race when I felt stress. I tried an SSRI, but I almost immediately got an adrenaline rush off of it with only a half dose that left me with almost no sense of pain, exaggerated movements, huge amounts of energy, and a 140 pulse that wouldn't let up for almost an hour. I eventually had to immediately see a doctor who gave me something else to counteract it. I had a few bruises and sore joints and tendons after that.

Eventually my doctor got me on Lorazepam for when I felt strong anxiety. After several months of using Lorazepam whenever I had my attacks, I noticed I got anxiety less and less. I have not had an anxiety attack in 6 months now and I now feel more energetic and I want to go out and do things, starting to exercise again, even taking up learning a new language. I'm also finding that I can think clearer and remember stuff distinctly easier. I'm just glad I haven't had to use Lorazepam in a long while.

I find it interesting that my ability to concentrate and remember is better than ever. I grew up with A.D.D. from kindergarten on, which continued to cause me issues up until very recently. A lot of my A.D.D. issues have subsided after my anxiety went away. No idea.I only used Lorazepam for a little bit, but it seems to have been a miracle worker in my case.

Re:mostly clarity

[bistromath007]

I have struggled with clinical depression basically for my entire life. I was diagnosed when I was eight. I have been on disability most of my adult life for it.

I know exactly what he means by "clarity." It's nothing to do with intelligence. That's not always the word I'd use to describe it, but that's only because just one word won't do.

Interesting

[DaMattster]

The study is interesting however, it is notable that no one studied had a diagnosis of depression. It so happens that I am autistic and have Autistic Spectrum Disorder and suffer from Major Depressive Disorder. Being autistic, I have certain stimuli that I am very sensitive to and others not so much. I noticed almost an immediate difference when I started to take Prozac. I've always been sensitive to medicines and I noticed some initial feelings along the lines of things seemed clearer somehow.

Re:Interesting

[Bite The Pillow]

That's a very good point. We know what happens to the chemicals in the brain, and we know that after some time people feel a bit better, and we know that is rarely permanent.

There was a great article in Newsweek or Time (I can't find it now...) that pointed out this delay. The chemicals happen immediately, but it is weeks before any effects are seen.

One idea was that the brain is damaged, and has to be repaired. It didn't make sense, but there are studies that report decreased brain tissue, or ridges, or various measures of physical properties.

I don't remember seeing any follow-up that showed reversal of brain tissue decline, which might prove this idea.

Anyway, I suspect that your sensitivity to stimuli would have made you aware of the chemical differences faster than most people. And it could be possible that the ASD makes you more susceptible to depression - *without* the physical atrophy that may or may not underpin most non-ASD depression. You did not have to endure the brain rebuilding that most people might.

All of this post basically points out that we don't know how the brain works, and if you have multiple differences from the norm maybe we super don't know how it works. If chemicals made you feel better, good. I don't think anyone can really explain why.

Re:Interesting

[ColdWetDog]

Although people are generally told that SSRIs take several weeks to work, many patients report that some effects are noticeable in the first few days. These are usually improvement in anxiety symptoms (depression and anxiety commonly coexist).

So this doesn't surprise me all that much. What will be interesting is to follow 'normal' and depressed people over time with and without treatment. However, given how annoying MRIs can be (confining and noisy and slow) I wonder if there will some sort of bias created with some people opting out of frequent testing.

Re:Interesting

[jasno]

I've tried taking SSRIs a few times over the years for depression/anxiety/OCD. I haven't been able to last longer than 36 hours. I feel like I am experiencing all of the anxiety and uncontrolled mental energy of LSD without any of the good feelings or positive emotions. I think I have a wacko serotonin system. Tramadols get me reallly high(like taking an E pill) and I am very sensitive to serotonin-system drugs like LSD and psilocybin.

Re:Interesting

[slaker]

My experiences with Zoloft and Paxil suggest that side-effects, most especially related to my physical appetite and sleep schedule, occur within 12 hours of starting medication or a change in dosage. I can't say I ever experienced any positive impact from either medication in the couple of years I spent at various dosages, but do know that all three of the physicians I was seeing swore up and down that SSRIs don't work like that.

I likewise found that a mental fog settled over me within a few days of starting each SSRI that I try. I felt more like I was controlling a video game character than experiencing any part of my own life, to the point that I would at times find myself sitting in the passenger seat of my own car, wondering why it wasn't moving.

I eventually decided that the pharmacological aspect to my treatment for depression was doing far more harm than good. I have to say that I have a strong distrust for purported utility of SSRIs, and a vastly lower opinion of mental health providers in general as a result of my experiences.

Prementrual Dysphoria

[godel_56]

SSRIs are also the preferred treatment for PMDD and in small doses, about 5% of the usual dose for depression.

In this application it also works almost immediately, no waiting 6 weeks for something to happen. The original article I saw speculated that it affects the amount of GABA in the brain.

http://en.wikipedia.org/wiki/Premenstrual_dysphoria

Re:Now all they need to do...

[Anonymous Coward]

SSRIs can increase suicidal tendencies when initially starting treatment. This is because SSRIs improve motivation before mood, and it is the reason you start a dose under close observation. Additionally, SSRIs can have a whiplash effect when stopped cold turkey, potentially increasing anxiety and depression. SSRIs MUST be tapered in order to safely withdraw from them. This are all well-known, studied effects of this class of drugs. Though these effects don't occur in all patients, it's frequent enough to warrant caution.

http://www.mentalhealth.umn.edu/medication/pdfs/antidep_bro.pdf
http://www.mhra.gov.uk/PrintPreview/DefaultSP/CON146583

Study subject not depressive

[manu0601]

Tthe summary says:

Study subjects did not have diagnoses of depression

If they do not have the problem, how could we hope to see something about the problem improvement?

Re:Study subject not depressive

[uvajed_ekil]

Because our understanding of how SSRIs operate on the most basic level is still very poor, and the research in question has found some clues about how to proceed. It makes sense to eliminate the variable of serious mood disorders, since the mechanisms behind them are poorly understand and differential diagnoses are a huge problem. Before fixing your car that runs rough you have to have some idea of how it works and what your tools do, and that's what this study was about. Hopefully some day soon we'll have a more thorough understanding of depression and similar ailments, as well as why some drugs help some people, but we are a long way off.

Re:Study subject not depressive

[ColdWetDog]

It's obviously the beginning of a research project. Take a drug - see what it does to 'normal' people with the testing platform you are using (in this case functional MRI), then try it on different clinical diagnoses. Remember, most medical diagnoses and especially psychiatric ones are not binary events - they lie on a continuum. We really don't know how to diagnose most patients with complex psychiatric problems. We typically give them several overlapping diagnoses that really don't explain the patient's problems and medicate them accordingly. I've always thought there should be a 'just plain nuts' category. It would be more objective and honest.

Treatment of psychiatric issues with medications is still in it's infancy and it's still akin to using hand grenades instead of scalpels. Studies like this one are trying to pin point areas of regulation and dysregulation with the eventual idea of finding more specific treatments.

Of course, that means more specific ways of controlling someone's mind. Which has its upsides. And it downsides.

Re:Now all they need to do...

[Moridineas]

I, on a personal level, am skeptical about the usage--or at least the possible over-usage--of mood-altering medications primarily because we know so little about the way they work. See TFA as an example. I'm doubly skeptical on using SSRIs and other drugs on childrens, adolescents, and even young adults, as there are even more uncertainties about these drugs on still-developing brains!

Having said that, SSRIs are common medications today. The kind of people who are suicidal or have such a mood-disorder that going on a shooting rampage seems like a good idea are exactly the people for whom you would expect SSRIs to be prescribed! In other words, are SSRIs causing these issues (and earning your blame), or were the problems there to begin with?

I don't know, and I don't know of any studies or other medical evidence that points either way. IMH(and not not scientifically grounded)O, I would, like you, suspect some causal relationship.

Re:Now all they need to do...

[Charliemopps]

Is figure out why so many who are on SSRI's or had recently stopped taking them, become suicidal or go on shooting rampages, or both.

Seriously, what the fuck? What an idiotic, close minded, asshole of a comment. 13% of the population are on anti-depressants, and go off them regularly. They do not shoot anyone or get suicidal. Sometimes, the mentally deranged end up shooting people or committing suicide. Is it any wonder that they had been medicated prior to going off the rails?!?! It's not the drugs, it's the asshole that took them. He had a general 13% of had take them even before you counted the fact they were crazy enough to commit murder.

Now stop making rude and insensitive comments about a group of people you clearly have no knowledge of what-so-ever. I took these drugs for over 15yrs and did not kill anyone, especially not myself, when I stopped taking them. If there is any one worst thing about SSRI's its the stigma people like you have put on people who take them.

Re:Now all they need to do...

[Charliemopps]

Not much is known about how they work, but plenty is known about their effects. Millions of people take them safely and effectively. I'd avoid newer drugs for a time... I like the buffer of a few hundred thousand people ahead of me in line... That said, I've taken them in the past. Make no mistake, they change who you are. Sometimes that's required though, so you should think logically about the situation.

An SSRI turned me into a sadomasochist for a decad

[Anonymous Coward]

A long time ago, I took an SSRI called Luvox in order to treat OCD. Within a month, the drug had turned pain signals into pleasure. Headaches, burning myself via a hot water faucet--I would literally feel pleasure from these normally painful experiences. I stopped right away, and those effects lingered for a decade. Prior to that, I had taken Prozac and Zoloft without significant effects that I remember. But after seeing an SSRI make my particular brain sadomasochistic, I never popped another SSRI pill and I never will again. They really do change the brain, and I'm convinced that the outliers (read: really smart people with non-normal brain chemistry perhaps--at that time, I was pretty damn smart :)) have brain chemistries that react in vastly different ways than the baseline. I know this isn't exactly on topic, but it was shocking how much my brain changed from what should have been just the early trial period of the drug and for how long that lasted, and frankly how much it pushed me into brand-new areas of being f'ing crazy. I would heartily recommend against using these things, especially to the types of people that are going to read 0-level comments on slashdot. :) I'm also convinced that even if it seems kinda normal, it could very well not be and be royally messing up other parts of your consciousness that just aren't as apparent as suddenly pain=pleasure. And I highly suspect this kind of thing is happening when kids who see psychiatrists and are on drugs, smart loners, go f'ing nuts and kill people. Random rewiring of the brain because they have unique chemistries. That's just my theory though, just knowing how "crazy" I got. I figure it more or less follows from giving these things to so many people and knowing how drastically wrong they can go. And sadomasochism may not be the right term as it didn't involve sexual feelings or anybody else. It's just like my wires got crossed and stayed that way, tapering off, for a decade.

Re:Now all they need to do...

[TheRealMindChild]

We know how they work. We don't know why they work. It is right there in the name "Selective Serotonin Reuptake Inhibitor". It causes excess amounts the neurotransmitter Serotonin to be not reclaimed

Re:SSRI effect times...

[Anonymous Coward]

Posting as AC -- the effect is to interfere with the ability to "finish." For those with premature "issues," this can be a benefit. For those of us with "normal" "stamina," it may cause an inability to "finish," essential providing infinite, though very frustrating stamina.
 

Re:Behavior changes

[God Of Atheism]

I've been on various SSRIs, and I must add to this that even on the same person some SSRIs have different effects than other SSRIs. The first one I took (I don't remember the name atm) made my situation far worse in the beginning and I was given valium (or another -zepam) to mitigate the sideeffects in the beginning. However, later it turned out that same medication took my bloodpressure through the roof (250/150 instead of 120/80) and changed medication. I have changed medication a few times since. However, the best antidepressant I've added is bupropion, which is not a SSRI.