Wednesday, June 8, 2011

Our crappy health care system gave me depression

Yesterday I was tweeting a little about this fascinating article in the New York Review of Books about antidepressants. Understandably, this is a touchy subject for a lot of people; if you're not on or have never been on antidepressants yourself, chances are someone very close to you is, and it's uncomfortable to consider the possibility that their effectiveness is overstated. The question is not, however, whether they are completely worthless (they do have a positive effect), but how and why they work, because there's mounting evidence that they don't work as well as previously believed or for the purported reasons.

There's a section in the article about a classic correlation vs. causation mistake: Early researchers noticed that drugs like Zoloft increased levels of seratonin in the brain, so it was assumed that depression is caused by low seratonin levels, but this is a big leap and new research suggests we were totally wrong:
As Carlat puts it, “By this same logic one could argue that the cause of all pain conditions is a deficiency of opiates, since narcotic pain medications activate opiate receptors in the brain.” Or similarly, one could argue that fevers are caused by too little aspirin.
What's really scary is not the fact that antidepressants work only marginally better than placebos (which I've been hearing on and off for years), but the general corruption of drug companies:
If two trials show that the drug is more effective than a placebo, the drug is generally approved. But companies may sponsor as many trials as they like, most of which could be negative—that is, fail to show effectiveness. All they need is two positive ones. (The results of trials of the same drug can differ for many reasons, including the way the trial is designed and conducted, its size, and the types of patients studied.)

For obvious reasons, drug companies make very sure that their positive studies are published in medical journals and doctors know about them, while the negative ones often languish unseen within the FDA, which regards them as proprietary and therefore confidential. This practice greatly biases the medical literature, medical education, and treatment decisions.

Kirsch and his colleagues used the Freedom of Information Act to obtain FDA reviews of all placebo-controlled clinical trials, whether positive or negative, submitted for the initial approval of the six most widely used antidepressant drugs approved between 1987 and 1999—Prozac, Paxil, Zoloft, Celexa, Serzone, and Effexor. This was a better data set than the one used in his previous study, not only because it included negative studies but because the FDA sets uniform quality standards for the trials it reviews and not all of the published research in Kirsch’s earlier study had been submitted to the FDA as part of a drug approval application.

Altogether, there were forty-two trials of the six drugs. Most of them were negative.
Scarier yet is the fact that antidepressants can have lasting effects on the brain:
When, for example, an SSRI antidepressant like Celexa increases serotonin levels in synapses, it stimulates compensatory changes through a process called negative feedback. In response to the high levels of serotonin, the neurons that secrete it (presynaptic neurons) release less of it, and the postsynaptic neurons become desensitized to it. In effect, the brain is trying to nullify the drug’s effects. The same is true for drugs that block neurotransmitters, except in reverse ... Getting off the drugs is exceedingly difficult, according to Whitaker, because when they are withdrawn the compensatory mechanisms are left unopposed. When Celexa is withdrawn, serotonin levels fall precipitously because the presynaptic neurons are not releasing normal amounts and the postsynaptic neurons no longer have enough receptors for it. Similarly, when an antipsychotic is withdrawn, dopamine levels may skyrocket. The symptoms produced by withdrawing psychoactive drugs are often confused with relapses of the original disorder, which can lead psychiatrists to resume drug treatment, perhaps at higher doses.
Some thoughts:
  • I'm not trying to convince anyone to go off antidepressants. "It's complicated." I know a lot of people who take them. I've also seen antidepressant withdrawal firsthand and it isn't pretty.
  • A friend of mine who shall remain anonymous recently remarked that among a group of close friends, the ones on antidepressants are all doing well in terms of their careers and general life progress, while the ones who are not are semi-flailing. I wondered at the time if this might be a correlation effect, similar to what's been demonstrated through carefully controlled studies with multivitamins: The act of taking vitamins doesn't seem to actually improve health, but being the type of person who takes vitamins does. I wonder if being the type of person who would seek out therapy/elect to take antidepressants helps alleviate depression (it demonstrates self-awareness and a proactive stance toward your happiness)?
  • You've heard me bang my drum about saturated fat and salt intake before (like Stephan Guyenet I think America has been getting nutrition totally wrong for 30-40 years) but there's a bunch of other "common sense" health stuff that we all do blindly even though there's no convincing evidence to support it. Recently I read that it's actually unclear whether we should try to reduce a fever (it's your body trying to kill off an infection). Unless it's high enough to cause brain damage, some people think it's better to let the fever run its course. But there's never been a controlled trial to determine which is better. Some researchers once initiated a trial in which hospital patients with fevers were either treated with fever reducers or allowed to remain febrile. But midway through the trial, some number of the patients who were treated for fevers died. So the researchers panicked and stopped the trial! The upshot of course is that we keep on treating fevers. Now what kind of sense does that make?
  • There was an interesting article in a recent issue of Rice Magazine (my alumni magazine!) about the burgeoning field of "health economists," who research why health care costs are skyrocketing in the U.S. without actually improving outcomes. (Sometimes-nutjob Robin Hanson is also interested in this topic.) Key quote: "Costs continue to rise because doctors and hospitals are rewarded for performing more services, not for improving patient health." (You can read the article online here. Click the image and navigate through the magazine; you can click it again to zoom to full screen.) Am I the only one who finds this stuff endlessly fascinating/enraging?


  1. re: antidepressants - they sure saved my mind 10 years ago - but i'm slowly withdrawing from them; I find that no alchol intake and exercise is serving me better. But that's just me. As I said, they have helped me in the past, so I'm sure glad they're there. I don't want to think that I have ruined by brain by taking them, so I'm ignoring that part! ;)

  2. Hi B.F.! The withdrawal stuff is really unfortunate. I know some people end up taking them much longer than they want to because it's so hard to go off them.

    And yes, I know people who have lots of success with exercise, limiting alcohol and seeing a regular therapist.

  3. One can get "brain zaps" when withdrawing - oddly I find them interesting.

  4. What exactly is a "brain zap"?

  5. It feels in my head like an electric shock or buzzzzzzzzzzzzzzzzz.

  6. Depressed Man 1: How is your wife like Zoloft?

    Depressed Man 2: I don't know. How is my wife like Zoloft?

    Depressed Man 1: I popped them both this morning.

    (Sorry. I wasn't ready to give up on your last post just yet.)

    Seriously, though, I wouldn't trust the efficacy of anything prescribed by any arm of the current U.S. health care system, whether it was a new drug, "universal" coverage, or the new food "plate" which replaces the pyramid that replaced the other pyramid just a couple years ago.

    While they may claim altruistic motives, what both Corporate America and the federal government are doing is essentially nothing more than exploiting the citizenry's greatest fear -- that of death -- for profit.

  7. I assume you've read the much-discussed old Atul Gawande piece on costs,

    I find this topic pretty interesting as it's a great example of a lot of issues in "political economy" (or maybe economics-of-politics, the study of how incentives interact with power when power is seen as a means to self-enrichment, which it rarely is by 1st world politicians but always is by corporations). I've always found it pretty hard to get particularly angry just because people are wasting money, though.

  8. I like Atul Gawande but not sure I've read that one. Earmarked.

    It's not just money, though, when it comes to health care -- it's, er, health. Few medications have no negative side effects.

  9. Also, I dislike the tendency to (attempt to) treat symptoms rather than address real causes. But it's obviously more infuriating if you have real health problems (as I do). It's easy to shrug it off when you're basically healthy (as I was for years).

  10. What's really scary is that drugs of a whole class, like, say, anti-cholesterol drugs, are prescribed at a really high rate and basically are not only dangerous but have been proven in many studies not to work at all to lessen the risk of any heart problems. But, as you point out here, the pharmaceutical companies don't care as long as they make a buck. And then you try to show your folks who are damaging their livers taking statins that eating, say, a cup of blueberries or a handful of almonds is just as effective as taking a statin, and they wave you off as crazy. My pre-med degree isn't going to waste - but it does make me more annoyed!

  11. Right! And a lot of people think that current nutrition advice is actually harmful as well -- for instance, by stressing low-fat, low-fat all the time, people have cut their omega 3 intake really low, and usually their fat comes from less-good omega-6 sources like processed vegetable oil. Too much omega 6 and not enough omega 3 might lead to heart disease.

    I also think low-fat diets fail because even if you feel "full" after eating a bunch of vegetables, you don't feel satisfied, so your appetite is raging all the time.

  12. Dear Elisa,
    I think you're right! As soon as I cut wheat, I noticed I replaced carbohydrates mostly with protein - and lost a ton of weight almost instantly. (I've always been big on fruits and veggies, so that didn't really change.) Haven't gained back a pound yet. So that pretty much supports the whole low-fat/high carb diet as not so great, at least it wasn't for me.

  13. I used to eat a pretty low-fat, high-carb diet and I was basically the same weight I am now, but I had to pay a lot more attention to how much I ate to maintain that weight. If I ate whatever I wanted I'd gain weight. Now I eat when I'm hungry, stop when I'm full and maintain the same weight pretty easily. I think calories in/out matters but it's just much easier to eat fewer calories when they're coming from fat and protein.

  14. One of the best books I've ever read is The Noonday Demon by Andrew Solomon, a 900 page atlas of depression. He looks at so many facets (alcoholism, diet and exercise, depression in different countries, medication), and he himself suffers from depression. Even more interestingly, he's the son of some super $$$ Eli Lilly guy, so he has a huge pharmaceutical fortune. He's very upfront about it, and I think that makes his story even more interesting.

    I've been on anti-depressants on and off for half my life, and I've also been in therapy. I know that without them, I would have at least attempted suicide. I resent the idea that I would take drugs just as a cop out...I've also seen mental illness run rampant on both sides of my family, and the serious consequences of stopping medication. Anyway, you're right about the touchiness of the subject, and I look forward to reading that article.

  15. Thanks for sharing and for the book rec Leigh! Sounds very interesting.

  16. "...while the ones who are not are semi-flailing"

    sounds like me alright

  17. I dunno. I don't want to sound insensitive but I think s lot of people who classify themselves as "clinically depressed" are just emotional namby-pambies. Day-to-day life becomes too difficult for them so, as a means of avoiding having to deal with it, a medical condition is fabricated and mind-/mood-altering medications are consumed.

    I have all the classic symptoms of a "major depressive disorder" -- constant low mood, inability to experience pleasure in formerly enjoyed activities, lack of self-worth, sleep problems, and so on and so on -- but, guess what? I'm underemployed, broke, middle-aged, and have already resigned myself to the inevitability of dying alone. If I didn't feel like shit all the time considering my circumstances, then I would think something was wrong with me.

    People need to come to the realization that life is not going to be all perfume and poetry all the time. In fact, I think it's safe to say that, historically, it's been pretty cruel for most which is why man-/womankind created things like art, love, and myths -- to help minimize the pain of existence.

    Suck it up, people. Just deal with your depression. And if you're too weak, then do what you can to escape from it. Become an artist. Take drugs. Or not. I really don't care what you do. I have problems of my own.

  18. well then.

    travis, I understand where you are coming from...who would Lincoln have been if he was on anti-depressants - was he a better president because he sucked it up?

    it was difficult for me to go on meds - but given that I was raising my son alone, and I had to bring in the bacon and I would lose my job if I took too many sick days...well, it helped me and my son.

    Different strokes for different folks.

  19. While I agree that "historically, it's been pretty cruel for most" in the world, I think depression is more of a disease of civilization. Like, when you're fighting for your life in a warzone (or trying not to starve to death) you don't have time to be depressed. But that doesn't make unhappiness feel any less real. It's extraordinarily difficult to reason yourself out of unhappiness (or reason someone else out of it). Plus, when assessing our lives, we tend to compare ourselves to our peers, not people who have it way worse.

  20. Frida. I applaud you for working and raising a child alone. I'm guessing your circumstances at the time were big contributing factors in your mental and physical health. If you don't mind me asking, would you still have gone on the meds if you didn't have the pressure of bringing home the bacon?

    Elisa. Agreed. If I could exist without being constantly bombarded with images of happy, beautiful, and successful people then I probably wouldn't feel so bad. Sure, I'd still be broke, old, lonely, etc., but with no points of reference.

    If the Media had to present a true cross section of humanity all the time, I'd probably realize I was doing pretty good after all. I have to share this stage with the asshole in the convertible Porsche who cut me off this morning AND that sub-Saharan kid with the flies landing on his eyelids.

  21. Travis, if I had a good partner at the time which would have enabled our financial situation to have been stable without me having to work full-time (or if all), truth to tell, I'm not sure. Having a depressed parent is not all fun and games, as my son could attest to as I didn't go on meds until 2000 (when he was 12 years old) I'm thinking would I have gone on them, or given the time available, would I have been able to push through without? Good question!

    But now that he's on his own, I'm weaning myself off of them.

  22. I found the excerpts from the article on drug "research" fascinating, and (unfortunately) not much of a surprise.

    I've never been diagnosed as clinically depressed, though there have been a couple of times in my life when I likely would have been, if I'd sought out a diagnosis. Each of the times I'm thinking of, I was unemployed and had a lot of anxiety about my future. In general, I've found that I'm a little prone to depression (as it's commonly described) when I've been under high stress or high uncertainty for a while.

    I've never taken anti-depressants or other psych meds, and I can't speculate whether they would have helped. Ultimately I've found other ways to cope, mostly just talking about whatever was going on in my life (in support group settings of various kinds).

    I do know people who have been on anti-depressants and other prescribed psychoactive drugs, and who felt they were helped by them. As suspicious as I am of the medical-industrial complex, I don't feel qualified to be anyone else's doctor or healer.

    I've had generally good health so far, and I've tended to go to the doctor only when I've been at death's door. If I have a fever I'll usually take Tylenol to bring it down, because otherwise my mind gets into a weird semi-dream-hallucinatory state and my body perceptions get strange. And if I have a head cold I'll usually take something over-the-counter for that, just to help me sleep at night.

    Many years ago, I saw an interview with Jonathan Miller, a British doctor who was also a writer. He commented at one point that the term "side effects" is somewhat misleading, because it makes a false distinction between whatever helpful or therapeutic things a drug does, and the more detrimental or potentially harmful things it can do. The negative or harmful effects of the drug, he said, aren't "side effects," they're part of the effects of the drug, as such.

    The description of what can happen when a psychoactive drug is discontinued -- neurons fail to bring serotonin levels back up to normal level, or dopamine level suddenly skyrockets -- sounds highly similar to what (as I've understood it) happens in the process of addiction:

    You take a drug or alcohol or whatever, and it temporarily either suppresses or stimulates some part of the body chemistry (depending on the particular substance), then as the drug wears off the body chemistry either crashes or jumpstarts, which you might experience as feeling vaguely ill, hungover, etc., and the body "learns" to experience this is a craving or need for more of the drug.

  23. Hi Lyle,

    I feel like most people I know are prone to temporary/circumstantial depression when under "high stress or high uncertainty" -- I know I am. I think if it's not a chronic condition, therapy is probably a better route, because, as you note, antidepressants seem to be addictive. No one ever talks about that.

  24. In response to Travis: if you don't want to sound insensitive, don't say insensitive things. That's what's so frustrating about the stigma attached to depression. Would you say someone with leukemia is just being a "namby-pamby"?

    My depression doesn't stem from me being a sad sack who feels sorry for herself. I have two very rewarding jobs, I love working with children, I'm in school full time, and I write. I also have a good relationship with my family and friends. And yet I still, sometimes, have severe depression and anxiety that is so crushing I'm literally unable to function (I'm talking about eating and bathing), and it feels like aliens take over my brain and want to destroy all that's good. There's no "sucking it up." That's such an ignorant position to take. I'm sorry you're depressed, too, but you can at least acknowledge that your depressive symptoms may be different from someone else's.

  25. Hey, great. Now people I don't even know think I am insensitive and ignorant. As if I wasn't already lacking in self-worth...

    Ms. Stein, in my earlier comment I wrote "I think a lot of people who classify themselves as 'clinically depressed' are just emotional namby-pambies." I didn't mean to suggest that all clinically depressed people were a bunch of wusses. Clearly, some experience depression-like symptoms due to physiological abnormalities in the brain. I was addressing my rant to those whose problems were purely emotional and likely self-inflicted, not physical (like leukemia).

    I used to experience debilitating panic attacks. It took every bit of strength I had to leave the house and, when I did, I had to keep reassuring myself that I was not going to freak out or pass out. These episodes lasted for about a year and a half until I realized that nobody really cared if I made an idiot out of myself in public, so I shouldn't care either. I had been putting undue pressure on myself to be "normal" and it was a physically exhausting experience. Coincidentally, this all happened when I was holding down two jobs and attending school full-time.