Friday, April 20, 2012

Do SSRI's Even Work? And if so, How?

Just in case you feel like reading Sunday's New York Times Magazine before it come out, over on "Post-Prozac Nation: The Science and History of Depression," Siddhartha Mukherjee will be writing about the history and efficacy of antidepressants.  Dr. Mukherjee writes:

Fast forward to 2012 and the same antidepressants that inspired such enthusiasm have become the new villains of modern psychopharmacology — overhyped, overprescribed chemicals, symptomatic of a pill-happy culture searching for quick fixes for complex mental problems. In “The Emperor’s New Drugs,” the psychologist Irving Kirsch asserted that antidepressants work no better than sugar pills and that the clinical effectiveness of the drugs is, largely, a myth. If the lodestone book of the 1990s was Peter Kramer’s near-ecstatic testimonial, “Listening to Prozac,” then the book of the 2000s is David Healy’s “Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression.”

He talks about depressed people in the 1950's being cured as a side effect of their treatment for tuberculosis (isoniazid was one of the first medicines to elevate mood in the depressed) and hyptertensive patients becoming depressed on Raudixin.

Mukherjee goes on:

In 2011, Hen and his colleagues repeated these studies with depressed primates. In monkeys, chronic stress produces a syndrome with symptoms remarkably similar to some forms of human depression. Even more strikingly than mice, stressed monkeys lose interest in pleasure and become lethargic. When Hen measured neuron birth in the hippocampi in depressed monkeys, it was low. When he gave the monkeys antidepressants, the depressed symptoms abated and neuron birth resumed. Blocking the growth of nerve cells made Prozac ineffective.
Hen’s experiments have profound implications for psychiatry and psychology. Antidepressants like Prozac and Zoloft, Hen suggested, may transiently increase serotonin in the brain, but their effect is seen only when new neurons are born. Might depression be precipitated by the death of neurons in certain parts of the brain?

He finishes off with the ideas:

The differences in responses to these drugs could also be due to variations in biological pathways. In some people, neurotransmitters other than serotonin may be involved; in yet others, there may be alterations in the brain caused by biological factors that are not neurotransmitters; in yet others, there may be no identifiable chemical or biological factors at all. The depression associated with Parkinson’s disease, for instance, seems to have little to do with serotonin. Postpartum depression is such a distinct syndrome that it is hard to imagine that neurotransmitters or hippocampal neurogenesis play a primary role in it. 

Nor does the theory explain why “talk therapies” work in some patients and not in others, and why the combination of talk and antidepressants seems to work consistently better than either alone. It is very unlikely that we can “talk” our brains into growing cells. But perhaps talking alters the way that nerve death is registered by the conscious parts of the brain. Or talking could release other chemicals, opening up parallel pathways of nerve-cell growth. 

But the most profound implications have to do with how to understand the link between the growth of neurons, the changes in mood and the alteration of behavior. Perhaps antidepressants like Prozac and Paxil primarily alter behavioral circuits in the brain — particularly the circuits deep in the hippocampus where memories and learned behaviors are stored and organized — and consequently change mood.


Sunny CA said...

It's lucky that some people still realize there is more to learn and continue to push forward to learn more about brain chemistry.

Kimberly said...

I've been on a few SSRI's over many years and am currently on Lexapro 20mg tab. I'd have to say something is working.. rather it be that specific one or the combination of meds I'm on (three total. My doctor says some times a combination works better, if one med seems to stop working as well.. after a period of time)

Meds work for me. No matter how you slice it, or hate to admit it.. or don't want to be someones lab puppy. Trust me I hate feeling controlled, but also MORE terrified of going backwards.

I have to admit though I'm now scared of being taken off of Lexapro.. because a year and half ago when I first started taking it, I had a rare side effect that didn't last two full days, but made me freak out pretty much in front of my family. It's the only med that has given me any real side effects. (I've been on mood stabilizers, antipsychotics, antdepressants.. all at once also)

Anonymous said...

i remember reading the original studies on SSRIs, the makers own, and being soundly disappointed by the poor results - 50/50. I'm glad if SSRIs work for some people but I believe very strongly that it's essentially a placebo affect. That said, I would be thrilled to get a placebo effect from an SSRI rather then partial response from a slew of antidepressants, mood stabilizers and antipsychotics all together.

moviedoc said...

Maybe it's not the talking in talk therapy that works. Maybe it's the doing differently as a result of the talking that makes the difference.

Anonymous said...

I believe SSRIs were effective for me. Until they made me hypomanic and my psychiatrist yanked me off them and on to a horrendous cocktail which eventually distilled itself down to several little pink capsules: lithium.

Anonymous said...

I was so frustrated with antidepressants not working that on the last one I tried to induce the placebo effect. I'd have given anything for them to work, even if it was false and they weren't really the ones doing anything.

Funny enough I flipped manic and now I'm on a drug cocktail that's actually doing something despite my protestations that this, like all the others, would do nothing.

I don't know if SSRI's work. I do believe, however, that if they work for you no matter what the reason, it's better than nothing working at all.

Anonymous said...

I have a cousin who's been medicated and treated for profound depression for around 30 years. He's in his early 50s now. Lately, he was re-diagnosed as bipolar, though without having exhibited any manic episodes, but as far as I can tell his treatment was unchanged.

I don't know what his untreated condition was like, but in treatment he sleeps 12 to 16 hours a day, is almost always tired and dopey, is hesitant to undertake any new task or hobby, and spends much of his waking time in his room, listening to music.

Oh, and he can't work, even if he was able to, and cannot move away from his county of residence, because then he would lose his medical disability coverage.

I just don't get it. It seems to me like the treatment for his depression is enough to make anyone depressed. What am I missing?

Minnesota Girl

Liz said...

ssri's have never benefited me, aside from illustrating to my family that we were "doing all we could" to treat my illness and help me recover. and provide me with a slew of dangerous pills with which i could overdose when my depression worsened in spite of the best modern medicine had to offer.

dialectical behavior therapy (you can check it out on wikipedia) is EXCELLENT, however, and has helped me tremendously. ***fingers crossed i continue to do well***

i have a brother who struggled with minor depression and visited his general practitioner, who placed him on paxil. he's been trying to get off that nastiness for years. when he complained to the doctor about withdrawal, he was told he was imagining things. he's still on a low dose and when he increases it, the withdrawal is horrifying.

Liz said...

sorry-- when my brother DECREASES the dose, not INCREASES it....

Anonymous said...

It's awfully hard to overdose (to suicide) on an SSRI. That is one reason docs don't prescribe the good old antidepressants because you really could off yourself on those. Even if you take lots of pills that should do you in if you mix with alcohol, you still have a chance of waking up in your own puke. It's hard to get an overdose right and then you get stuck in a psych ward.

Anonymous said...

So I just read that a woman in New Zealand (in her 30's, young mother) died due to a habit of drinking 10 liters of Coke per day. She barely ate food, smoked 30 cigs a day and had been puking for the past 6 weeks but her family didn't suspect anything was wrong. I think someone needs to write a post on that.Or not.

Anonymous said...

Liz, please tell your brother if he wants to get off the paxil to visit for support. It is independent and depends on financial donations.

The folks would help him taper by 10% of current dose every 4 to 6 which would greatly minimize withdrawal issues. Unfortunately, most doctors are not familiar with that tapering method and seem to scoff when it is suggested for some reason.

I got off of 4 psych meds by using that method.

I am so sorry to hear he is struggling. It is so not necessary.


PS - If he is taking Paxil at 10m, he can get it in the liquid form which would make it easy to taper slowly. But if he can't get the liquid form, there are other options.

Anonymous said...

I have a child with developmental disabilities/ processing difficulties and severe anxiety, which usually flares up for her with extreme stress.

She is a very skinny kid that eats very, very little when the anxiety is bad, and tends to lose weight that she doesn’t have to spare - resulting in some visible ribs. Sleep is of course poor during these times. Many, many times when severely anxious she would "lose it" in the car because it was too claustrophobic for her and she would try and open the door and jump out while the car was moving at high speeds. One of the hardest side effects of her anxiety to deal with, is when she has to use the bathroom every 5-15 minutes. These episodes would go on for a month or more with many trips to the ped. Yielding no results via testing. No UTI's, nothing.

Where am I going with this? I finally got her into a child psych. a few months back and the Dr. prescribed a low dose of Zoloft. Two weeks later it was like night and day. Stress? It didn't phase her as much and she deals with it better. I am over the moon with what a difference it has made. Weight back up to normal ranges. Placebo effect in a 10 year old whose cognitive functioning is 2 years behind? I think not – no placebo. She is too young to understand.

Our brains (each one of our individual brains) are such complex things with so many factors!

It is fantastic to see how helpful an SSRI has been for my child whose brain does not function normally. I realize this is not the norm as many times several different types of drugs/doses and combinations have to be tried before relief is reached for each individual.

Thank heavens that we live in an era where those of us that do need psychotropic drugs, have access to them.

K said...

Thoughts about Mukherjee's article:

1. It's a shame he doesn't discuss the phenomenon of loss of effectiveness of an antidepressant over time and why that may happen. In my n=1 study (myself) of severe depression over many years, that "poop-out" first happened within the SSRI class, then the tricyclics, then the SNRIs with ECT bridging the gap when changing drugs. I am now on an "old-fashioned" MAOI (with an antipsychotic, thyroxine and fish oil) which is actually working well (long may it continue since there are no more antidepressant options).

2. It would've been illuminating to review the theoretical basis of the effectiveness of the other classes of antidepressants (i.e. tricyclics, SNRIs and MAOIs) and how that compares to the SSRI model.

Perhaps the Shrink Rappers could discuss one or both of these topics in future?

K said...

P.S. The ECT was needed by the time I changed drugs because I'd become persistently suicidal.

Kimberly said...
This comment has been removed by a blog administrator.
L said...

Also relevant to note that SSRIs tend to be signifiacntly more effective in treating anxiety then depression.

Simple Citizen said...

I would write a lengthy response - but I've already written two

First: The publication bias with SSRI's is a huge problem:

Second: It's true that the majority of the effect of SSRI's can be obtained with placebos:

Sophia said...

Late to the party, but this topic always gets me going on tangents.

People who end up with the "psych meds are useless" conclusions - atleast the ones who write books and articles on the topic - probably don't have three generations of suicides in their families. If it weren't for psych meds, I wouldn't have met my grandparents. I probably wouldn't be typing this, either. I'm one of those weirdos who gets a paradoxical reaction to antidepressants (I also become alert on opiates, don't get tired from benzodiazepines, can drink a pot of coffee and sleep like a baby, and didn't gain weight on Seroquel). Antidepressants tend to keep me fairly depressed. I've tried around five of them, and I've gotten similar results from each one despite really-really-really wanting them to work. Still, I'll rant for your right to take the things.

Yes, pharmaceutical companies are evil. Yes, insurance companies would prefer you take pills over seeing a therapist. For the most part, though, no one really cares whether or not you take pills unless you're in the "danger to self or others" category.

One thing I wonder is how many people actually take their antidepressant prescriptions. I couldn't tell you how many times I have heard, "Oh, I have depression." "Yeah?" "Yeah, I don't take drugs, though. I took two and felt nauseous, so I stopped. I prefer to treat things naturally." "Really now." Fairly certain that studies reviewed for pro/con antidepressants actually checked for compliance, but the pill-popping culture is practically mythical. Unless the drug works in the immediate (opioids, amphetamines, antihistamines, etc.), you'll die, or something really embarrassing will happen, you probably won't stick with meds. People don't even finish their antibiotic prescriptions half the time, for crying out loud. Why are we assuming they take their antidepressants?

Brains are complex. As for therapy's affect on the brain, it seems like it would do something structural. The brain changes as we learn things. The brain changes if we see someone shot in front of us. The brain changes if we take up kick boxing. Not sure how therapy would be much different. Do something enough, and the brain will react. The thought that your brain is more or less a static entity seems silly. Not really sure why every other body part would be subject to change in reaction to sun, food, exercise, etc. but not the brain (just a musing there).

Anyway, I have a lot of thoughts related to this that cannot be contained to a blog response. Topic irritates me so much...