Category: mood disorders

The Parable of the SAMe

Seth Roberts4 Comments

SAMe is a drug well known to help depression. For example, “a popular dietary supplement called SAMe may help depressed patients who don’t respond to prescription antidepressant treatment, a new study shows.” But there’s something important few people know about SAMe.

While talking to a Seattle woman about how Vitamin D3 first thing in the morning helped her with depression, she told me the following story:

When I was 47, I just wanted to be healthier. I kept gaining weight. I knew what foods are healthy. I just didn’t seem to eat them. A naturopath suggested SAMe. I tried it — Twin Labs SAMe. That was really fabulous for me. For the first time I got a glimpse of what being not depressed was like. Cravings weren’t there any more. Went from a size 24 to a size 14. Lost 70 pounds. I’m 5′ 8″. I didn’t feel deprived. I was eating plenty of food. going to yoga. Feeling really great.

Then Twin Labs discontinued it. It was made in Japan. I tried every other SAMe out there, eight different brands. None of them worked. I gave each of them a month. I tried different dosages.

I started slipping back into depression. Not being able to cope. I was sleeping more. Sugar cravings returned.

[why did Twin Labs stop making it?]

It wasn’t a good seller for them. So fucking wrong. I wrote letters to try to get them to start making it again. I did a campaign. People found pockets of what was left in the country and sent it to me. But it finally ran out.

The moral(s) of the story? 1. So much for word of mouth. You might have thought it would make the good SAMe sell well, better than the bad SAMe. Apparently not. 2. So much for the placebo effect. 3. Clinical studies (e.g., of SAMe) may higher-quality versions of what they are testing than the versions available to the rest of us. 4. So much for quality control in the supplement industry — except maybe in Japan. There can be substantial quality variation among supplements, undetected by the industry. I have to believe the companies selling the useless SAMe didn’t realize it. Surely they thought that good SAMe would be a better product for them than bad SAMe.

This resembles the Vitamin D3 story I have been telling. Tara Grant said she’d heard countless times that Vitamin D is good. She hadn’t heard once that it must be taken in the morning. I’ve heard countless times that SAMe is good. This was the first time I heard about huge quality control issues. In both cases individual self-observation uncovered a crucial truth that an industry had overlooked. They didn’t want to miss it. The Vitamin D Council didn’t want to miss the time-of-day effect. They just did.

This also resembles what I said about ultrasound machines: A lot of them are broken, unbeknownst to their operators and the people (often pregnant women) being scanned. The countless “experts” (doctors) who recommend ultrasound don’t seem to know this.

Which is why personal science (trusting data, not experts) is more valuable than experts want you to think.

Ten Interesting Things I Learned From Adventures in Nutritional Therapy

Seth Roberts13 Comments

A blog called Adventures in Nutritional Therapy (started March 2011) is about what the author learned while trying to solve her health problems via nutrition and a few other things. She usually assumed her health problems were due to too much or too little of some nutrient. She puts it like this: “using mostly non-prescription, over-the-counter (OTC) supplements and treatments to address depression, brain fog, insomnia, migraines, hypothyroidism, restless legs, carpal tunnel syndrome, and a bunch of other annoyances.” In contrast to what “the American medical establishment” advises. Mostly it is nutritional self-experimentation about a wide range of health problems.

Interesting things I learned from the archives:

1. Question: Did Lance Armstrong take performance-enhancing drugs? I learned that LiveStrong (Armstrong’s site) is a content farm. Now answer that question again.

2. “If you return repeatedly to a conventional doctor with a problem they can’t solve, they will eventually suggest you need antidepressants.”

3. “When I mentioned [to Dr. CFS] the mild success I’d had with zinc, he said it was in my mind: I wanted it to work and it did. When I pointed out that 70% of the things I tried didn’t work, he changed the subject. Dr. CFS’ lack of basic reasoning skills did nothing to rebuild my confidence in the health care system.” Quite right. I have had the same experience. Most things I tried failed. When something finally worked, it could hardly be a placebo effect. This line of reasoning has been difficult for some supposedly smart people to grasp.

4. A list of things that helped her with depression. “Quit gluten” is number one.

5. Pepsi caused her to get acne. Same here.

6. 100 mg/day of iron caused terrible acne that persisted for weeks after she stopped taking the iron.

7. “ In September 2008 I started a journey that serves as a good example of the limits of the American health care system, where you can go through three months, 15 doctor visits, $7,000 in medical tests, three prescriptions and five over-the-counter medications trying to treat your abdominal pain, and after you lose ten pounds due to said pain, you are asked by the “specialists” if you have an eating disorder.” I agree. Also an example of the inability of people within the American health care system to see those limits. If they recognized that people outside their belief system might have something valuable to contribute, apparently something awful would happen.

8. Acupuncture relieved her sciatica, but not for long. “By the time I left [the acupuncturist’s office] the pain was gone, but it crept back during my 30-minute drive home.”

9. Pointing out many wrongs does not equal a right. She praises a talk by Robert Lustig about evil fructose. I am quite sure that fructose (by itself) did not cause the obesity epidemic. For one thing, I lost a lot of weight by drinking it. (Here is an advanced discussion.) In other words, being a good critic of other people’s work (as Lustig may be) doesn’t get you very far. I think it is hard for non-scientists (and even some scientists) to understand that all scientific work has dozens of “flaws”. Pointing out the flaws in this or that is little help, unless those flaws haven’t been noticed. What usually helps isn’t seeing flaws, it is seeing what can be learned.

10. A list of what caused headaches and migraines. One was MSG. Another was Vitamin D3, because it made her Vitamin B1 level too low.

She is a good writer. Mostly I found support for my beliefs: 1. Of the two aspects of self-experimentation (measure, change), change is more powerful. She does little or no self-tracking (= keeping records) as far as I could tell, yet has made a lot of progress. She has done a huge amount of trying different things. 2. Nutritional deficiencies cause a lot of problems. 3. Fermented food is overlooked. She never tries it, in spite of major digestive problems. She does try probiotics. 4. American health care is exceedingly messed-up. As she puts it, “the American medical establishment has no interest in this approach [which often helped her] and, when they do deign to discuss it, don’t know what the #%@! they’re talking about.” 5. “Over the years I’ve found accounts of personal experiences to be very helpful.” I agree. Her blog and mine are full of them.

Thanks to Alexandra Carmichael.

More Her latest post mentions me (“The fella after my own heart is Seth Roberts, who after ten years of experimenting . . . “). I was unaware of that when I wrote the above.

Is Health Data Ever Harmful?

Seth Roberts16 Comments

In yesterday’s post I described how searching the medical literature helped me avoid a dangerous surgery with no obvious benefit. The surgeon I consulted, who recommended the surgery, said that published evidence backed her up. I could not find that evidence, however. Others found evidence that contradicted her recommendation.

Among the comments on that post were similar stories: Searching/reading the medical literature had been helpful. Learning what had happened (in research studies) was better than relying on an expert (a doctor). Here is an example:

A little over two years ago, I was “depressed”. My psychiatrist wanted to prescribe an SNRI [serotonin-norepinephrine reuptake inhibitor]. I related, once again, my poor experience with an SSRI and asked for evidence that an SNRI would be any more effective. He said there was evidence that SSRIs [selective serotonin reuptake inhibitors] worked. I pointed out the 2004 meta-analysis that showed no meaningful difference between SSRIs and placebos. Then I asked whether there was any better evidence for SNRIs. Since he wasn’t able to provide any, I told him that since we know that extremely low Vitamin D blood levels, poor diet, no exercise, and no social life can cause depression (all things I had at the time), I’ll try fixing those things first and then resort to drugs if that fails. It did not fail and I quit seeing him.

None of the stories in the comments described the opposite outcome: Knowing the data made things worse.

Are there exceptions? Is it always helpful (or at least not harmful) to know what happened (i.e., know research outcomes)? Has anyone reading this had an experience where knowing health research data was harmful?

Poor Replication Rate in Psychiatric Genetics Research

Seth Roberts3 Comments

With the ability to measure individual genes has come interest in learning what they do. Perhaps Person X is depressed and Person Y is not depressed because Person X’s genes differ from Person Y’s. A whole generation of psychiatry researchers now believes this is plausible. There are “general reasons to expect that GxEs [gene by environment interactions] are common,” says a new review paper in the American Journal of Psychiatry. By “common” they mean large enough and common enough to do research about.

I don’t agree with this conclusion. Sure, twin studies show that genes matter for psychiatric diagnoses. Identical twins are more likely to be concordant (= have the same diagnosis) than fraternal twins, for example. But this is a very long way from indicating that single genes matter. Twins results are entirely consistent with the possibility that a large number of genes each matter a little. If this is true — and I find it far more plausible, when it comes to psychiatry, than the single-gene idea — then searching for one gene that does this or that is a waste of time. Individual genes are too weak. To do psychiatric gene research you have to dismiss or ignore the many-tiny-effects possibility, because if true it would mean what you are doing is bound to fail. The new review paper I mentioned ignores it.

The new review paper surveys all of the research papers about GxEs during the first decade of research (2000-2009) in this area — about 100 papers. It asks (a) if initial findings have been repeatable and (b) how much we should trust the repetition attempts. To answer the first question, they found that only a third (10 of 37) of initial findings were repeated when tested a second time. If things were working well, all of the initial findings would have been repeatable. The low replication rate doesn’t mean that two-thirds of the initial findings were false. Perhaps the replication attempts were poorly done and all of the initial findings would have held up if they were better done (e.g., larger samples). Or perhaps the replication attempts were biased toward positive results and none of the initial findings would have held up if they were better done.

The review paper also found that positive replication attempts had much smaller samples (median sample size about 150) than negative replication attempts (median sample size about 380). This suggests that the negative replication attempts are more trustworthy than the positive ones. The true replication rate is probably lower than one-third.

The findings, in other words, support my initial belief that the whole field is a waste of time. Amusingly, the authors of the review (one at Harvard, the other at the University of Colorado) conclude the opposite. Here’s what they say:

This review should not be taken as a call for skepticism about the G×E field in psychiatry. . . . True progress in understanding G×Es in psychiatry requires investigators, reviewers, and editors to agree on standards that will increase certainty in reported results. By doing so, the second decade of G×E research in psychiatry can live up to the promises made by the first.

Of course their findings support skepticism about GxE research. This isn’t slanting your conclusions to be more convenient, this is bending them backwards. And failure to mention the many-tiny-effects possibility, a plausible explanation for all the results they describe, is another sign that this area of research is not to be trusted.

Van Gogh Defense Project: Rationale

Seth Roberts2 Comments

A colleague I’ll call John has decided to start tracking his mood for a long period of time (years). He explains why:

A few years ago, after a severe manic attack, I was diagnosed with bipolar disorder. The attack was preceded by an intense period of stress, then two weeks of elevated mood, increased social activity (hanging out and meeting people), and racing thoughts (hypomania). Then I skipped a few nights of sleep, wandered down roads in the middle of the night, and eventually became psychotic, in that I could no longer distinguish between reality and imagination. I was chased by cops on several occasions, and was involuntarily committed to the mental health wing of a hospital for a month. It put a massive dent in my life.

Family, medicine, and time helped me recover. Being out of control like that was fun only for the first two weeks. Having my life turned upside down was not fun either. As I recovered I became increasingly interested in finding ways to prevent a relapse. One doctor said: You have a vulnerability. You need to protect yourself. I agreed.

Looking back on the experience, I realized there was a rise in odd behaviors two weeks before I started to skip nights of sleep and fell into psychosis. There was an even longer buildup of stress, anxiety, and fear in the months before the mania hit. During the last two weeks before the mania, my behavior was different from what is normal for me. I felt elated and had a sense of general “breakthrough”. I suddenly felt no fear and anxiety. I felt on top of the world. I was constantly taking notes because ideas and thoughts were running through my head. I scheduled meetings and social activities almost constantly throughout these two weeks and shared my experiences as my new self. As I started to sleep less and skip nights of sleep, others later told me I seemed agitated and down.

Maybe it is possible to catch these early warning signs and take counter measures before they worsen into mania or depression. This is why I have started to track my behavior starting with mood and sleep. If I can get a baseline of my behavior and know what is ‘normal’ for me, it will be easier to notice when I am outside my normal range. I can alert myself or be alerted by others around me who are monitoring me. Long-term records of mood will also help me experiment to see which things influence my mood. This may give me more control over my mood.

Mood tracking might be a good idea for anyone to do, but it may be especially helpful for people with a bipolar diagnosis. Everyone has mood variation. For bipolars, however, mood swings can be more extreme (in both directions, up and down) , have far worse consequences (psychosis on one end and suicide on the other), change more rapidly, and be more vulnerable to environmental triggers like stress. The good news is that the first changes in mood can happen hours or days before more extreme changes. This gives people a chance to take countermeasures to prevent more extreme states.

The project name refers to the fact that Van Gogh had bipolar disorder.

Assorted Links

Seth Roberts1 Comment

The Rules of the Tunnel by Ned Zeman

Seth Roberts1 Comment

I loved Ned Zeman’s new book The Rules of the Tunnel, which I read during a long plane flight. Not only does it combine three of my favorite subjects — high-end magazines, bipolar disorder, and the crappiness of modern psychiatry — but it’s very well-written and revealing. I haven’t enjoyed a book so much in a long time.

Zeman once wrote for Spy, as did I. Long ago, I met him at a Spy party. I suppose I could have gotten a free copy of his book but I bought it. I wanted something great to read on the plane.

Morning Faces Therapy For Bipolar Disorder: A Story (Part 2: First Two Months)

Seth Roberts3 Comments

In the 1990s, I discovered that if I see faces on TV early in the morning, I feel better (happier, more eager, more serene) the next day, but not the same day. Faces Monday morning, for example, make me feel better on Tuesday but not Monday. I studied this effect extensively. The results suggested that a circadian oscillator controls our mood and sleep and needs morning face exposure to work properly. Absence of morning face exposure, this theory says, increases your risk of depression — a view not compatible with the “chemical imbalance” explanation of depression but one supported by the strong association between depression and insomnia.

I told friends about this. One of them had devastating bipolar disorder. As he describes here and here, he got great benefit from looking at faces in the morning. After I posted his account of his experience, a man I’ll call Rex wrote me that he was going to try it. At 29, he was diagnosed with bipolar disorder. At 32, he slit his wrists. He is now 37.Since then he’s been in and out of mental hospitals. Now he lives at home. I wanted to follow his use of morning face therapy “prospectively” — before knowing what would happen. I posted this, about his background, around the time he started.

Treatment details. He began about two months ago. He gets up naturally (no alarm) at about 8 am. He starts watching faces on TV — Squawk on the Street (CNN) — soon after he gets up. He watches for 1-2 hours on a 43-inch high-definition TV; the faces are roughly life-size. He sits 10 feet away.

Mood. Before starting the faces, he was in a depressed mood 5-7 days per month. During those days he had low energy, low motivation, and a bad attitude. The low phases would last a few days, then he’d start feeling better. Now, he says, “my mood is better first thing in the morning. I feel ready to go, turn the TV on, watch something. I feel a little lighter. I no longer feel the early morning doom that I used to feel. I’ve never been a morning person, but I feel that way more now than any time I can remember. I haven’t had any depressed moods since I started the faces. I haven’t had any really adverse or negative emotions. Things are going very smoothly. I have less worries, I feel a more uplifting, upbeat tempo throughout the day. Everything seems better.” (Note: Morning faces likewise shifted me toward being a morning person.)

Medication. He used to take an antidepressant every day (Simbalta, 60 mg/day). Now he takes 30 mg once every 3 to 4 days. He’s tried to stop taking it entirely but gets withdrawal symptoms (headache, nausea) when he does that. Note that he still had 5-7 days/month of depressed moods every month even when taking the antidepressant. In the spring his depression was better so he cut back slowly on the medication.

Sleep. For a long time he has had great difficulty falling asleep. He would lie in bed for an hour without falling asleep. He took sleep medication, usually Lunesta or Ambien, very often. “Lots of times in the past I would give up [after lying in bed a long time] and go watch TV. Or start to read, stay up to 2:30. That’s always been a problem — ever since I was in college. In college, my sleeping schedule went nuts. When I got into the working world, it continued to where I would stay up late and couldn’t sleep.” Since he started the morning faces, his sleep is much better. He usually falls asleep within 20 minutes of lying down, a very noticeable difference. He has taken much less sleep medication — about 20% of what it was before. (He still takes it when he knows he has to get up early or he feels wired.) At one point, when he took antipsychotics, he did fall asleep quickly “but the side effects were awful,” he said. “Grogginess, foggy head all day. I didn’t have as much mania and depression but I would sleep 11 hours per night and I couldn’t get out of bed in the morning. I couldn’t concentrate. I couldn’t go back to college, because I couldn’t think clearly.”

At the same time he started the faces, he started getting blue light exposure in the morning from a blue light box called the Apollo Health goLITE. He started with 20 minutes of exposure. It did seem to improve his mood and make him feel tired earlier. However, it also made him feel anxious and tense. To try to get rid of this effect, he reduced the exposure: 10 minutes, 5 minutes, 2 minutes. After a week, he stopped using it altogether.

“I’m just ecstatic about the results,” he said.

 

Harvard Psychiatrist Joseph Biederman and Parents: “Should Be Left in a Room Together”

Seth Roberts4 Comments

Joseph Biederman is a professor of psychiatry at Harvard. He recently received a far-too-mild sanction for behavior that included this:

Biederman was then placed in charge of the institute and began a study of 40 children between 4 and 6 years old who were given Risperdal [made by Johnson & Johnson] and Lilly’s Zyprexa, another antipsychotic. At the time, Harvard and MGH [Massachusetts General Hospital] rules forbid researchers from running trials with [drugs] if they receive more than $10,000 from a company that makes the drug.

It was eventually revealed that Biederman had received at least $1.6 million from drug companies, including far more than $10,000 from Johnson & Johnson and far more than $10,000 from Lilly. One comment on the quoted article made the excellent point that bipolar disorder had a usual onset age of onset of 18 years or more and had never been found in young teenagers (e.g., 14-year-olds). Yet Biederman suddenly claimed it appeared in 6-year-olds. In a good expression of how I feel about Biederman’s behavior, another comment said he should “be left alone in a room with the parents of the children [he] treated”.

Welcome to the Sausage Factory: Multiple Fraud in a Paxil Study

Seth Roberts2 Comments

Dr. Jay Amsterdam, a professor of psychiatry at the University of Pennsylvania, recently lodged a very interesting complaint against five authors of a 2001 study that compared Paxil to another drug and placebo for treatment of bipolar disorder. The paper reports research paid for by SmithGlaxoKline, the makers of Paxil. For a subgroup of patients, it says, Paxil worked better than the other drug and better than placebo. Paxil supposedly had fewer side effects than the comparison drug. Amsterdam accuses the five academic authors of plagiarism — meaning they put their names on a paper they didn’t write (like a student who buys a paper). He also says the paper grossly misrepresents the results (because the subgroup analysis was completely ad hoc and the side effects description utterly wrong). So if they did write it . . .

The paper has been cited hundreds of times. Given the actual results — Paxil had worse side effects than the other drug, and the subgroup result means little — this is no small matter.

As Spy magazine has said, if you cheat your customers, don’t fire anyone. Email included with Amsterdam’s complaint suggests he was upset because he was not an author on the paper. Why? Well, the study was done at many sites and there could be only one author per site — according perhaps to SmithGlaxoKline. At Penn, the work (enrolling subjects) was first given to a junior faculty member named Laszlo Gyulai. However, Gyulai couldn’t enroll enough subjects. Amsterdam was asked to help and paid for doing so. He ended up enrolling more subjects (12) than Gyulai (7). Yet Gyulai was an author and he was not! This greatly bothered him. He considered it “misappropriation” of his data, said Gyulai had engaged in “the theft and publication of a professor’s data”, and wanted Gyulai censured. Perhaps Gyulai had considered Amsterdam’s non-authorship okay because many professors who contributed subjects were not authors. Whatever the reason, it appears that authorship was determined by the firm that did the ghostwriting, Scientific Therapeutics Information, presumably following orders from SmithGlaxoKline.

I don’t know why Amsterdam waited ten years to complain. Since 2001, however, the ghostwriting problem has become much clearer. In 2001, Amsterdam complained to his department chair, Dr. Dwight Evans, about the situation. In 2010, Amsterdam learned that Evans had benefited from ghostwriting. That’s how common it was.

There’s also this:

POGO [Project on Government Oversight], in a letter to President Obama [related to Amsterdam’s complaint], asked that he remove Amy Gutmann, president of the University of Pennsylvania, from her position as chairman of the Presidential Commission for the Study of Bioethical Issues, until the two cases involving Dr. Evans are fully investigated and resolved.

Chairman! Another indication how common and tolerated ghostwriting is. It is as if an obesity expert, appointed head of the most important obesity committee in the country, charged with recommending how to stop the obesity epidemic . . . is fat.

Perhaps British journalistic phone-hacking has been more common than misrepresentation of results by med school professors but the latter, I’m sure, has done more damage.

Attachments to the Amsterdam complaint. Pharmalot weighs in. Some of the accused defend themselves.