Tuesday, June 08, 2004

Another Oddity of Medical Science

From time to time, I post abstracts or excerpts that illustrate the fact that many aspects of medical science are not straightforward.  It has been known for a long time that there is a strong correlation between sleep disorders and mood disorders, as well as a less robust, but still significant, correlation between sleep disorders and anxiety disorders.  Furthermore, it has been observed that there is a nonlinear relationship between the severity of a sleep disorder as measured on objective tests, and the degree of dysfunction that a patient experiences.  There also is a nonlinear relationship between the improvement seen of objective tests after treatment, and the degree of improvement in a patient's daily function.  These demonstrations of nonlinearity indicate that there is something going on that we do not understand. 

Now, we see an indication that surgical treatment of sleep apnea can result in measurable improvements in anxiety and depression -- and the degree of psychiatric improvement is not strongly associated with the changes in objective tests. 

In this study, the objective tests included measurements of the frequency of apneas (periods of interrupted breathing), and measurement of blood oxygen saturation (how much oxygen is present in the arterial blood.)  Overall sleepiness was assessed using the Epworth Sleepiness Scale.  (See link in sidebar.)

Mood Improvement after Surgery for Obstructive Sleep Apnea.
Laryngoscope. 114(6):1098-1102, June 2004.
Li, Hsueh-Yu MD; Huang, Yu-Shu MD; Chen, Ning-Hung MD; Fang, Tung-Jen MD; Liu, Chia-Yih MD; Wang, Pa-Chun MD, MSc

Objective: Patients with obstructive sleep apnea (OSA) may experience unfavorable psychologic symptoms such as depression and anxiety. The aim of this study was to confirm this hypothesis and to investigate whether the psychologic symptoms among OSA patients can be relieved by surgical intervention.

Study Design: Prospective, longitudinal intervention study.

Methods: The 5-Item Mental Health scale (MH-5) was used to evaluate the postoperative changes of mood after extended uvulopalatal flap (EUPF) surgery on 84 Taiwanese patients with OSA. The preoperative and postoperative MH-5 data obtained from these patients were compared with a Taiwanese population norm. 

Results: Before surgery, the MH-5 scores of the OSA patients were significantly worse than the Taiwanese population norm of 72.8 (P < .0001). Postoperatively, mean MH-5 scores significantly increased from 61.8 +/- 16.0 to 70.0 +/- 15.8 (P = .0006). The effect size of this score change was 0.51, indicating a moderate degree of mood improvement. However, this score was still inferior to that of the population norm (P = .0045). The mood improvement was not significantly associated with the changes in either sleep apnea events or the level of sleepiness. Neither the changes in respiratory disturbance index (P = .4382), maximum arterial oxygen saturation (P = .4866), nor the change in Epworth Sleepiness Scale scores (P = .4951) were predictive of the MH-5 score improvement (R2 = 0.07).

Conclusions: This study demonstrated that patients with OSA had a higher level of anxiety, depression, and probable behavior or personality changes than the population norm. EUPF surgery could significantly improve the mood status among OSA patients; the effect of surgery was mild but clinically relevant. However, the extent of mood improvement experienced by OSA patients receiving operations may not simply be attributable to the changes in sleep apnea events or a reduced level of sleepiness.

(C) The American Laryngological, Rhinological & Otological Society, Inc.

It makes sense to speculate that interruptions in sleep and decreases in blood oxygen could result in anxiety and/or depression.  However, if it were that simple, one would expect there to be a more or less linear correlation between the two.   At the very least, we would expect to see a relationship between the overall level of sleepiness and the psychiatric symptoms.  However, the Epworth scale improvements were not related to the improvements in anxiety and depression. 

I am not familiar with the instrument they used to assess psychiatric symptoms: the MH-5.  It is not widely used in psychiatry, so there is a chance that it is not really a valid measure of clinical syndromes.  Taking it at face value, though, assuming the MH-5 actually means something, it would be of great interest to look at the individual patients, see which ones got the greatest mental health boost from the surgery, and try to figure out what is different about them, as compared to the patients who had the surgery but did not have improvements in mood and anxiety. 

The reason this is important is that psychiatric disorders are defined by symptoms, not by underlying causes.  This is a known problem in psychiatric research.  Everyone in the field wants to come up with so way of subdividing the population of depressed patients into groups that would correlate with treatment responses.  That way, we would not end up given treatments that are not likely to work, to patients who really need some other kind of treatment. 

With the exception of atypical depression (which responds preferentially to MAOI's) and psychotic depression (which responds preferentially to a combination of an antidepressant and an antipsychotic), we have not had much success in subdividing the types of depression into clinically relevant groups.  There is hope that functional neuroimaging  -- fMRI and PET -- could be useful in this regard.  So far, however, all we have is tantalizing clues; nothing really useful has come of it so far.  If there is a relationship between sleep architecture  and subtypes of depression, that would be good to know. 

(Note: The Rest of the Story/Corpus Callosum has moved. Visit the new site here.)
E-mail a link that points to this post:
Comments (0)

Monday, June 07, 2004

More Facts About Antidepressants and Suicide

From the newsletter, Psychiatric Times, here is a summary of recent findings from analysis of data pertaining to the association between antidepressant use and the incidence of suicide.  I wrote a flurry of articles on this subject back in April.  (previous CC posts: 1  2  3  4  5  6  7  8  9)

Now, however, the interest in the topic has waned; people just aren't talking about it so much any more.  Despite the fickle nature of the sensational-news-consuming public, the scientific community has retained an interest in the topic. 

Yes, there was an article  in the NYT last week, regarding a study that showed a positive effect using fluoxetine to treat depressed adolescents.  This article did not attract much attention, which, in fact, was appropriate.  Few few individual studies deserve front-page coverage in a major newspaper.  Although the results of the study were encouraging, any such study must be viewed in a wider context in order to be interpreted properly.

Because of the need for a wider context, it was with interest that I read the recent article in the Psychiatric Times.  The article reviews the findings of five population-based studies of the association between antidepressant prescribing and suicide rates. 

The entire report is fairly short, so it would be almost as easy to ask readers to just go read the entire thing, as opposed to providing excerpts here.  However, the article is rather technical, enough so that I imagine it would take a sustained effort of will to plow through it. 

This is one of those articles that starts out by reviewing studies that reported negative findings, then goes into the ones that show positive findings, then shows why we should believe the positive findings and not the negative ones.  Therefore, persons who have already made up their minds should not bother reading it.  If you have decided already what you believe, this article will not change your mind.  If, on the other hand, you are willing to be open-minded about it, you may find it sways you one way or the other.

Is Antidepressant Prescribing Associated With Suicide Rates?

by Philip B. Mitchell, M.D., MB, FRCPsych

Psychiatric Times May 2004 Vol. XXI Issue 6

First, the negative findings:

In 2003, the eminent European mood disorder researcher Herman van Praag lamented what he has termed the "stubborn behaviour" of the failure of antidepressants to reduce suicide rates, arguing that the majority of evidence does not support any reduction in such outcomes related to the increased volume of prescribing. Van Praag highlighted two major issues. First, there have been few countries reporting sustained reductions in suicide rates, despite the substantial increase in antidepressant prescribing. Second, randomized, controlled trials of antidepressants have failed to demonstrate any effect on suicide. In a most telling report, Khan et al. (2003) analyzed U.S. Food and Drug Administration summary reports of controlled clinical trials for nine recently marketed antidepressants. Similar suicide rates were seen in those randomly assigned to each SSRI, comparator antidepressant or placebo, failing to provide any evidence of a suicide-reducing effect of antidepressants.

Next, the limitations of the negative findings:

There are, however, limitations as to how much one can infer from such trials. Suicide is a rare event, and even in the FDA trials, which comprised over 48,000 patients with depression, only 77 committed suicide, making comparisons between treatment groups difficult. Moreover, such trials exclude entry to those with prior significant suicidal risk.

Next, the positive findings:

Despite such negative findings, a potential beneficial effect of antidepressants on suicide rates has become apparent in a recent series of national population-based reports. The first studies came from countries that had observed overall reductions in their suicide rates. Isacsson (2000) and Carlsten et al. (2001) both investigated the Swedish experience, where there had been a gradual reduction in suicide rates over the period from 1977 to 1997. They found that the decline in suicides accelerated after 1990 when the SSRIs were introduced. The rate of suicides in the 1990s was significantly inversely related to the rate of antidepressant prescribing in most age and gender groups. Similarly, in Hungary, rates of suicide declined in parallel with a rapid growth of antidepressant usage, despite steep increases in unemployment and per capita alcohol consumption (Rihmer, 2001, as cited in Hall et al., 2003). The same phenomenon was, however, not observed in all European countries, with no such association being seen in Italy (Barbui et al., 1999).

Next, the author's own findings, which, in their view, indicate that the positive findings are the ones we should pay attention to:

We examined the association between changes in antidepressant prescribing in Australia for the period 1991 to 2000 (Hall et al., 2003).

One of the complexities that faced us, however, was that the total suicide rate for Australian men and women did not change between 1991 and 2000, because marked decreases in suicide rates in older men and women were offset by increases in younger adults, especially young men. A similar phenomenon has been observed in the United Kingdom, where suicide rates doubled in males younger than 45 between 1950 and 1998, but rates declined in older males and females of all ages (Gunnell et al., 2003). Because of this phenomenon, we analyzed differences in suicide trends between men and women in different age groups to assess whether age and gender rates in suicide were related to differences between these groups in exposure to antidepressant medication (Hall et al., 2003).

[...] We found strong evidence of a beneficial impact of antidepressant prescribing on suicide rates. Among both men and women, the largest declines in suicide occurred in the age groups with the highest exposure to antidepressants across the study period (males, r=-0.91; females, r=-0.76; both significant) (Figure 1). Furthermore, as detailed in Figure 2, there was also a significant inverse correlation between change in the defined daily dose/1,000 for women (r=-0.74), with a trend toward significance for males (r=-0.62).

Then, more supporting evidence:

The validity of our findings has been supported by two other studies published in 2003. In the United States, Olfson et al. (2003) evaluated the relationship between geographical regional changes in antidepressant prescribing and suicide in adolescents from 1990 to 2000. A significant negative relationship (after adjusting for potential confounds such as gender, age, income and race) was found between regional change in antidepressant medication treatment and suicide during the study period. They calculated that a 1% increase in adolescent use of antidepressants was associated with a decrease of 0.23 suicides per 100,000 adolescents per year. The clearest benefits were found in males, youths aged 15 to 19 and those with lower family incomes. In the United Kingdom, Gunnell et al. (2003), examining the period 1950 to 1998, found that the dramatic reductions in suicide rates in older people were associated with increases in gross domestic product, the size of the female work force, marriage and the increased prescribing of antidepressants. This report highlighted that the population trends in suicide appeared to be associated with a range of social and health-related factors, with antidepressants comprising one of the latter.

The author is careful to point out that such corellations do not establish causation.  They do, however, argue against the proposition that antidepressant medication is more likely to cause suicidal behavior than it is to prevent it. 

It is therefore apparent from these studies of five different national data sets that the recent phenomenon of a substantial increase in the recognition of depression and greater rates of treatment with antidepressant medications and psychosocial interventions appears to be one of the significant contributants to reduced suicide rates in either total populations, older people or adolescents.

Note that the studies cited by the author are studies of adult populations.  The recent controversy had more to do with the risks of using antidepressant medication in children and adolescents.  It looks as though we will have to wait for more definitive information on that issue.

(Note: The Rest of the Story/Corpus Callosum has moved. Visit the new site here.)
E-mail a link that points to this post:
Comments (0)

Sunday, June 06, 2004

The Passing of another American Icon

This afternoon, my beautiful redheaded wife and I were driving out to the hardware store to get some stuff for the barn.  We heard on the radio that Ronald Reagan died.  Later, we went to Barnes & Noble to sit around and read and drink good coffee.  As usual, I spent some time in the photography section.  On the way out of the bookstore, we noticed that they already had put up a sales exhibit with books about Mr. Reagan. 

This got me to thinking: I feel bad that I missed the opportunity to commemorate the death of another great American Icon.

Back on April 22, 2004, it was the twentieth anniversary of the death of Ansel Easton Adams.  (born 2-20-1902 in San Francisco, California
died 4-22-1984 in Monterey, California, at  age 82)

In this post, I explain why Ansel Adams was an American icon, and why I still have some respect for Ronald Reagan. 

From David Hume Kennedy's article

I met Ansel when I was the official photographer during President Gerald Ford's administration. I had admired his work, and we had started a correspondence. I arranged for Ansel to come in and meet with President Ford, and to give the president his views on the national parks. Even though some members of the press joked that Ansel was the first environmentalist the president had ever met, Ford was in fact a strong supporter of the national parks, and had been a park ranger at Yellowstone when he was a young man in 1936.

[...] Ansel was a big bear of a man, hearty and good natured. But during the meeting with Ford, despite the bluntness of his words, he spoke in soft tones, and the president responded in kind, often leaning in to hear more clearly. I think that one of the things that attracted Ansel to the president was that, like himself, Ford was a very modest, self-effacing man.

As a result of the meeting, President Ford wrote to Ansel agreeing with him that the policies of the Park Service "needed a fresh look," and reported to him that he had commissioned a task force to redefine the priorities of the service. He also reiterated in the letter his commitment to the national park system, and among other things, supported Ansel's desire to preserve open space close to large urban centers, which would serve local recreation programs.

The 74-year-old photographer's letter and proposals struck a deep chord within the president. On Aug. 29, 1976, against the backdrop of Yellowstone National Park, Republican President Gerald R. Ford stunned the environmental world. He announced that he would be submitting to Congress the "Bicentennial Land Heritage Act," a 10-year, $1.5 billion commitment to double the present acreage for national parks, recreation areas and wildlife sanctuaries.

"Moon and Half Dome"
Yosemite National Park, 
California, 1960

Copyright © 2000 Ansel Adams 
Publishing Rights Trust/CORBIS

If you are interested in Presidential history, I urge you to read Kennedy's article about Ford and Adams.  It is an interesting study of personalities.  As a clinical aside, both personalities were psychologically healthy, although very different.
 Given the rapprochement between Adams and Ford, one would be tempted to assume that a subsequent meeting between Ansel Adams and Ronald Reagan would have a amicable and positive outcome.  Not so. 

"This visage meek and humble,
and hear this confidential plea
voiced in reverent mumble:
give me Shylock, give me Fagin
but, oh God, spare me Ronald Reagan!"
 - Ansel Adams

This quote appears on timmareca.com; I cannot vouch for its validity.   Getting back to Kennedy's article:

After Ansel met with President Reagan in July of 1983 he sent me another of his trademark typed notes, this one on the back of a card that featured an Edward Weston nude from 1936 on the front. He said:

"The meeting with RR was not funny; it was very discouraging. He is very gracious and persuading, but it was like confronting a stone wall . . . I was told I had '15 or 20 minutes' but I ended up with 50! He talked for a time at first and I was scrambling for my priorities. I said most of what I had to say. I think it is a marvelous country when a citizen can talk with the President and tell him he (the citizen) thinks he is seriously misinformed. I felt with a sinking feeling that this country is in very poor hands. The subsequent interview might do some good; it has been published all over the world. WAKE UP, AMERICA (AND KENNERLY!!) We are facing disaster! ALL BEST, as ever!"

Ansel never got another chance to try and make Reagan come around to his passionate point of view about the environment. He died nine months later on April 22, 1984. When I got word of Ansel's passing, I was in the People's Republic of China covering President Reagan.

A different perspective, but with the same conclusion, is found on the Housatonic Museum of Art's website

In subsequent years, he was invited to discuss American environmental policy with several Presidents, including Lyndon Johnson, Gerald Ford and Jimmy Carter, and received from the latter the Presidential Medal of Freedom. By way of contrast, Adams conducted a war of words with President Reagan. He described Reagan's Secretary of the Interior James Watt's policy of allowing strip mining and timber harvesting in the national parks as an indefensible policy of "rape, ruin and run!" 12

12 "Playboy Interview: Ansel Adams - candid conversation,"; Playboy vol. 30, no. 5 (May 1983).
I went to the Playboy.com website to try to get the interview, but for some reason they don't keep an archive of such things.  (Note to beautiful redhead: If you look through my browser history and see something you don't like, there's a perfectly good explanation.  Really.)
I was able to find places that would sell me an old copy, but I guess I'm not that interested.  You can't see it on the little copy of the cover, but one of the articles in the May 1983 issue of Playboy was:  "The Targeting of America: A Special Report on Terrorism" by Laurence Gonzales.  Some things never change.  And won't change, no matter how may hundreds of billions of dollars we spend. 

I tried to find other references to the meeting between Ansel Adams and Reagan, but was not able to do so.  There were newspaper articles at the time, but that was before newspapers started using the Internet.   In fact, 1983 could be considered the year the Internet was born, because that's when ARPANET converted entirely to TCP/IP, and the Domain Name System was introduced.   The WWW, though, was not established until 1992. 

The newspaper reports about the meeting between Ansel Adams and Reagan were not extensive, and I recall only the overall negative tone, not the specific content.  Perhaps the only transcript of the meeting, if there is one, is in the Ronald Reagan Presidential Library.  The library, however, does not have much on line. 

So far, my patient readers have learned that Ansel Adams was an American icon, that Gerald Ford was not a bad guy, and that Adams said, of Reagan's leadership, that "I felt with a sinking feeling that this country is in very poor hands."

Reagan did some good things.  His defense spending, while extravagant almost beyond belief, contributed to the fall of the Soviet Union.  Never mind that he ran up deficits so enormous that George H. W. Bush had to break his "no new taxes" pledge, which, by the way, is what opened the door to the Clinton Presidency; Bush 41 lost the support of the "Reagan Democrats" when he succumbed to the economic reality that classic tax-and-spend Republican policies simply are not sustainable. 

I believe that RR was genuinely patriotic, and that he really thought that his economic and foreign policies made sense.  He wanted the United States of America to be a good place.  He wanted people to be nice to each other, and he set a good example with his own behavior.  He did not start any wars, and he did not have any intention of using bizarre political doublespeak to justify taking taxpayer money and handing it over to huge corporations, thereby transforming rich people into filthy rich people (reference to Halliburton and KBR.) 

If RR knew that "reducing the size of government" would lead to private contractors getting paid over one hundred thousand dollars a year to do what used to be done by an E-3 for eighteen thousand, he would have put a stop to it.  If he had known about the Iran-Contra scandal, he would have put a stop to it.  If he had understood that the Strategic Defense Initiative would be a colossal waste of money, he never would would have proposed it.  If he had been in office when the Abu Ghraib scandal broke, he would have shut it down immediately, not months later. 

The anniversary of the passing of Ansel Adams should be a time for reflection upon the importance of artistry in the advancement of political causes.

The passing of Ronald Reagan, likewise, should give us pause to reflect on the virtues that contribute to a great President.  As reported on Netscape, in the words of Bill Clinton:

"Hillary and I will always remember President Ronald Reagan for the way he personified the indomitable optimism of the American people, and for keeping America at the forefront of the fight for freedom for people everywhere."

And from Jacques Chirac:

"A great statesman who through the strength of his convictions and his commitment to democracy will leave a deep mark in history."

And finally, from George W. Bush (as reported  in WaPo):

"This is a sad hour in the life of America," Bush said after speaking with Nancy Reagan by telephone. "A great American life has come to an end. Ronald Reagan won America's respect with his greatness and won its love with his goodness. He had the confidence that comes with conviction, the strength that comes with character, the grace that comes with humility and the humor that comes with wisdom."

Both Adams and Reagan were artists: Adams a great photographer; Reagan a mediocre actor.  Both had political agendas: Adams with little influence; Reagan with tremendous influence.  Both were nice guys.  Both were American Icons.  Only Ronald Reagan got a Nimitz-class aircraft carrier named after him.  Nobody is going to name a warship after Adams, but perhaps we could rename the Alaska National Wildlife Refuge the Ansel Adams National Wildlife Refuge. 

(Note: The Rest of the Story/Corpus Callosum has moved. Visit the new site here.)
E-mail a link that points to this post:
Comments (0)