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McMAN'S DEPRESSION AND BIPOLAR WEEKLY

Posted by sjb on November 15, 2002, at 8:06:34

***********************************

McMAN'S DEPRESSION AND BIPOLAR WEEKLY (Nov 14, 2002 Vol 4 No 39)

***********************************

A GENOME PRIMER

According to an article in the New England Journal of Medicine: "We have
recently entered a transition period in which specific genetic knowledge is
becoming critical to the delivery of effective health care for everyone."
The authors are Alan Guttmacher MD and Francis Collins MD, PhD, deputy
director and director respectively of National Human Genome Research
Institute that mapped out a draft sequence of the human genome well ahead of
schedule in 2000. Whereas genetics is the study of single genes, genomics,
which only entered the lexicon 15 years ago, investigates the functions and
interactions of all the genes in the genome, including their causation on
different illnesses.

Single-gene conditions such as cystic fibrosis, the authors explain, are the
exception rather than the rule. More common are "multifactorial" disorders
such as Parkinson's, tuberculosis, HIV, and Alzheimer's, the result of the
interactions of multiple genes and environmental situations. We now know
that the human genome comprises 30,000 to 35,000 genes, far fewer than
originally thought, and mutations known to cause disease have been
identified in about 1,000.

Genes are distributed over 23 pairs of chromosomes, and "express" or turn on
or off the proteins that are responsible for everything from digesting food
to transmitting nervous signals. This is accomplished through DNA spelled
out in seemingly endless four-chemical sequences (A,T,C,G in various
arrangements) segmented along three-chemical amino acid bases called
"codons."

"A point mutation" involves the equivalent of a genetic typographical error,
say a C where an A should be. Since 98.5 percent of genes do not code for
proteins, most typos pass unnoticed. But then there are "functional
mutations" that can range from causing Huntington's to inducing a bad
reaction from eating fava beans. By the same token, mutations can also
decrease the risk of disease, including one that makes certain people almost
completely resistant to HIV type 1.

The illnesses that we have found genes for are highly "penetrant," ie their
mutations lead to diseases in a fairly large number of people who have them.
Breast cancer, diabetes, and Parkinson's are examples. Their "prevalence"
across the general population, however, is slight, one in several hundred to
one in several thousand. On the other side of the coin are genes less highly
penetrant but much more prevalent, such as those that increase the risk of
colorectal cancer and thrombosis.

Two unrelated people share more than 99.9 percent of their DNA sequences,
but since three billion base pairs constitute the human genome, we vary at
millions of bases. Researchers are looking to catalogue these variants,
called "single-nucleotide polymorphisms" (SNPs) and correlate them with
specific "phenotypes," or persons with certain clinical traits. An extension
of this effort is to correlate "haplotypes," ie a group of variants that may
be inherited together. The authors don't say it, but it is clear that these
are the types of cross-checks that will be used to tease out our thus-far
elusive mood genes.

After that, we may be able to find treatments that work rather than
half-work. As the authors conclude: "Genomics, which has quickly emerged as
the central basic science of biomedical research, is poised to take center
stage in clinical medicine as well." Here's hoping that psychiatry is part
of that change.

http://content.nejm.org/cgi/content/short/347/19/1512#F3

<a href="http://content.nejm.org/cgi/content/short/347/19/1512#F3">click
here</a>

MORE

The NEJM will continue to feature stories on genomics on its website. For an
article I wrote on the hunt for bipolar genes for the Depression and Bipolar
Support Alliance, please see:

http://www.ndmda.org/Research/ResearchUpdate8.html

<a href="http://www.ndmda.org/Research/ResearchUpdate8.html">click here</a>

CYMBALTA

According to two Eli Lilly studies involving more than 1,000 patients, its
new dual action antidepressant Cymbalta (duloxetine) showed efficacy in the
first week of treatment and continued to show "robust and sustained"
improvements. The drug has received conditional approval from the FDA,
pending resolution of manufacturing problems.

http://my.webmd.com/content/article/1674.53305

<a href="http://my.webmd.com/content/article/1674.53305 ">click here</a>

BIPOLAR DEPRESSION PILL

One day we may get a real bipolar depression medication, built from scratch.
In the meantime, Eli Lilly has announced it will seek FDA approval for
combination Zyprexa and Prozac (olanzapine, fluoxetine), OFC, for treatment
of bipolar depression. There are no medications approved to treat bipolar
depression. The company will also file for FDA and European approval for
Zyprexa to treat bipolar in the maintenance phase.

PAX-ILLS

A University of Toronto study has found that of 55 women who had taken Paxil
during their third trimester 12 of their babies experienced complications
(mostly respiratory illness) necessitating longer hospital stays vs only
three of 54 in the control groups. Third trimester Paxil babies were also
much more likely to be born prematurely, 20 percent vs 3.7 percent.

http://www.reutershealth.com/archive/2002/11/11/eline/links/20021111elin019.
html

<a
href="http://www.reutershealth.com/archive/2002/11/11/eline/links/20021111el
in019.html ">click here</a>

PSYCH WARS - THE ARIPIPRAZOLE MENACE

These guys are worse than politicians. The latest ...

Bristol-Myers Squibb, makers of the soon-to-be-marketed Abilify
(aripiprazole), has sponsored a study published in the Archives of General
Psychiatry that found those on Eli Lilly's Zyprexa ran a five-fold increase
in the odds of developing hyperlipidemia (excess fat or lipids in the blood)
over the general population.

Stay tuned for The Empire Strikes Back.

http://archpsyc.ama-assn.org/issues/current/abs/yoa20354.html

<a href="http://archpsyc.ama-assn.org/issues/current/abs/yoa20354.html
">click here</a>

ANGER

An article in the NY Times reports that "the human brain comes hard-wired
for anger and rage." One can induce rage in animals by stimulating the
amygdala, part of the brain's limbic system. In humans, destruction of the
amygdala leads to docility. A preliminary study of brain scans comparing
impulsive with premeditative murderers found that impulsive murderers had
significantly lower activity in the prefrontal cortex than the premeditative
murderers (whose brain activity was no different than the controls). The
prefrontal cortex processes information and inhibits emotional impulses from
the limbic system, suggesting impulsive killers are less able to resist
their own impulses.

According to Maurizio Fava MD of Harvard, up to 40 percent of depressed
patients experience anger attacks. Significantly lower serotonin levels have
been found in some violent and impulsive patients.

http://www.nytimes.com/2002/11/12/health/psychology/12BEHA.html

<a href="http://www.nytimes.com/2002/11/12/health/psychology/12BEHA.html
">click here</a>

UNIFORM STRESS

An Army report into the four spousal murders (in which two of the men
committed suicide) at Fort Bragg this summer attributed the killings to
likely marital strife made worse by frequent family separations. The report
recommended early intervention and for mental health workers to be put in
combat battalions so ''the troops can access us casually.'' According to the
report, marital strife was high at Fort Bragg, but none of the families
surveyed sought help at any level. The report also said that the antimalaria
drug, Lariam, given to overseas troops, was unlikely to have been at fault.

http://www.boston.com/dailynews/312/nation/Army_report_Mental_health_work:.s
html

<a
href="http://www.boston.com/dailynews/312/nation/Army_report_Mental_health_w
ork:.shtml ">click here</a>

STILL A LONG WAY TO GO

A UnitedHealth Foundation survey ranks the following states in the top 10 to
live in, healthwise: New Hampshire, Minnesota, Massachusetts, Utah,
Connecticut, Vermont, Iowa, Colorado, North Dakota, and Maine.

The bottom 10 are: West Virginia, New Mexico, Florida, Tennessee, Alabama,
Oklahoma, Arkansas, South Carolina, Mississippi, and Louisiana.

According to UnitedHealth, the health of the US has improved 15.5 percent
since 1990, with a 32 percent drop in infant mortality (from 10.2 to 6.9
deaths per 1,000 live births), 27 percent drop in infectious diseases (from
40.7 to 29.7 cases per 100,000 population ), 23 percent decline in child
poverty (20.6 percent to 15.8 percent of persons under age 18 ), 22 percent
drop in smoking (from 29.5 percent to 22.9 percent of the population), and
17 percent drop in violent crime (from 29.5 percent to 22.9 percent of the
population).

http://www.unitedhealthfoundation.org/shr/index.html

<a href="http://www.unitedhealthfoundation.org/shr/index.html">click
here</a>

BIPOLAR NOTES

An article in Medscape by Charles Bowden MD of the University of Texas
Health Science Center at San Antonio reports on a number of presentations on
bipolar given at a conference in Barcelona in October. Highlights include:

* A cohort of one-sixth of the Swiss population followed since 1959 showing
that one to three days of hypomanic activity is more characteristic of
bipolar II than the four or more days required by the DSM-IV. The
restrictive criteria yielded a prevalence of 0.5 percent vs 5.3 percent for
the one to three day criteria.

* Two 18-month trials of patients on lithium, Lamictal, or a placebo found
Lamictal worked best for extended treatment of bipolar depression without
intervention while lithium worked best for extended mania treatment without
intervention. The patients in the two studies had 50 percent more recent
depressive episodes than manic, hypomanic, or mixed episodes, with the first
depressive episode preceding the first manic or mixed episode by 3.6 years.

* Rapid cyclers had earlier onset of illness than non-rapid cyclers (19
years vs 30 years), with more manic, depressed, and mixed episodes. Lamictal
is the only treatment studied in a placebo controlled trial for rapid
cyclers, showing significant superiority over the placebo. For rapid cyclers
where mania predominates, Depakote may be the choice.

* A debate on the merits of treating bipolar depression was resolved with
voters overwhelmingly favoring treatment combining a mood stabilizer with an
antidepressant.

* Bipolar II is not mild bipolar when considered in terms of functional
impairments, which can be equal or worse than bipolar I.

http://www.medscape.com/viewarticle/443970

<a href="http://www.medscape.com/viewarticle/443970 ">click here</a>

SEDATING INSTEAD OF TREATING

A Royal College of Psychiatrists (UK) one-day audit of 3000 patients has
found one in five admitted for severe mental health problems are prescribed
antipsychotics in excess of official guidelines, often without the patient's
knowledge and without proper monitoring. According to the study's authors,
there is little evidence that high doses or two drugs at the same time are
more effective, but there is strong evidence of the dangers of their side
effects. In half the cases, the decision to increase the doses was left to
nursing staff.

http://www.medscape.com/viewarticle/444468

<a href="http://www.medscape.com/viewarticle/444468 ">click here</a>

DEATH SENTENCE

The Canadian Medical Association Journal reports that of 308 inmates who
died in custody in Ontario between 1990 and 1999, 283 of the deaths involved
men, 90 were due to suicide by strangulation, 48 to poisoning or toxic
effect, and 16 to homicide. Natural causes accounted for 115 of the deaths.

http://www.cmaj.ca/cgi/content/full/167/10/1109

<a href="http://www.cmaj.ca/cgi/content/full/167/10/1109">click here</a>

OUTREACH OR OUTRAGE?

A column in the Boston Globe by Alex Beam blasts away at Wyeth's latest
promotion aimed at the college market, including forums to be presented at
four campuses featuring a video with Cara Kahn of MTV fame. " How insidious
is this?" Smith writes. "Millions of college students feel lousy, for any
number of reasons ... God knows we all have been there. Do they need a
$120-a-month Effexor fix to see them through these tough years? Probably
not. But who could be more suggestible, or vulnerable, than a boy or girl
making the transition to adulthood?"

TUESDAY NIGHT DEPRESSION CLUB

A cover story in Parade magazine reports that singer Sheryl Crowe spent
seven months in bed with depression. "I've had this thing with depression
since I was little," she confesses. "I wound up downwardly spiraling into a
place that I couldn't see my way out."

CONGRATULATIONS

... to subscriber Bryce Miller, for the 26 years of tireless advocacy that
has resulted in his receiving this year's Lionel Aldridge Award, NAMI's
highest consumer award.

SUPPLEMENTS

Last week, I asked readers to share their experiences either with the EM
Power supplement reported in last week's newsletter or any other supplement
programs. Several detailed replies came in, so without further ado ...

DISAPPOINTMENT

Adam writes:

My experience with the Synergy supplement was a very poor one by all
accounts, and their support hotline just kept on pushing me to take the
supplement despite its lack of effectiveness and rather serious side effects
when I was too depressed to even move about my house and was confined to my
bed most of the day. I took the supplement, 32 capsules a day for over two
and one half months and experienced nothing but GI problems, and a worsening
of my condition as I slowly removed my more traditional meds. The staffers
told me at the time that the supplement had a 99 percent "cure rate", and
that all of my GI problems were being caused by staying on common
medications such as Synthroid which I cannot stop taking and Klonopin which
has never caused any side effect for me other than some mild tiredness. I
nevertheless stuck with the program encouraged by the hope of their
impressive statistics.

The removal of my more traditional meds soon led to two successive
hospitalizations due to my increased suicidality. It was not until I went
back on a cocktail of antidepressants, Lamictal, and stimulants that I began
to recover and feel more normal. I notified the Synergy staff about the lack
of effectiveness of their product and the GI problems I experienced which
were quite severe. They again told me that the two and a half month trial
was not enough and the GI complaints were from my other meds, even when I
was completely off them with the exception of my thyroid supplement.

Needless to say, I was incredibly disappointed. I don't want to discourage
people from finding a combination that works for them even if it includes
the Synergy Supplement, but I also don't feel that their claims are all
true, and that in their zeal to help others, they may overlook serious
problems with their supplement.

ORTHOMOLECULAR MEDICINE

Bob Sealey writes:

I am bipolar II with migraines, had a horrible time for years before finally
finding competent care.

Consulted eight mental health pros over 20 years - the usual medications
made me worse, talk "therapy" with a depressed brain added pain to the pain.
Self-esteem shredded and wanting to be dead - I started learning about
orthomolecular medicine. Trying regimens of vital amines - trace minerals,
amino acids - read many books, met patients who recovered, met
orthomolecular health professionals. Tried various supplements and soon got
a lot better - still taking them, consider them brain "fuels". I also take
gingko biloba extract - for me that is an excellent antidepressant and
anxiolytic.

In the same way that a diabetic needs insulin supplement to keep well,
mental patients can restore normal levels by taking biochemical
supplements - a different regimen depending on their diagnosis.

Orthomolecular medicine was founded about 50 years ago by Linus Pauling PhD
and Abram Hoffer PhD, MD. There are orthomolecular health professionals
around the world. The next international conference - Nutritional Medicine
Today - is in Toronto, April, 11-13, 2002.

[Bob Sealey is author of "Finding Care for Depression." You can check out
his website at: http://www.searpubl.ca ]

NO LUCK

Jan writes:

I have tried mega vitamin therapies, but many did not have any profound
effect on the way I felt. I got a little boost from taking a multivitamin
that was rich in B6-B12, and many other nutrients such as ginko biloba,
zinc, echinacea, garlic and many others.

The problem is that many of these "vitamin quick fix anti-depressant"
supplements are not regulated by the FDA, and there have not been
significant case studies done over 10-20 year periods.

I think it is absolutely absurd to think you can wean yourself off of
medication, and exchange meds for supplements instead. You are asking for
trouble when you play God, and I have tried it and ended up right back in
the psych ward. My heartfelt conclusion is there may be a better solution if
this blend of elements and minerals is custom blended on an individual
basis, is monitored
weekly, and the patient reports how he feels back to the person doing the
vitamin therapy.

PERSONAL TREATMENT

George writes:

I tried EM Power alone for months with little luck. I liked the basic idea,
though, of approaching my BP nutritionally and looked around for a pdoc who
took that approach. Our Dr Hedaya (Georgetown University) has been doing
that kind of work for a long time and it works. I just barely need meds
anymore and lost 50+ Zyprexa pounds with a 40-30-30 (zone) diet. He works to
control immune response via allergy control etc ... does live cell analysis
of blood to figure out just what you are deficient in and has a program to
make sure you absorb the supplements you take. It's not a cure but I'm 500
percent better. You don't even need to see him because he has books that
tell your MD how to do it. Of course the bastard insurance companies won't
often pay, but they'd rather have us suffer sudden death and suicide and
save on the costs that increase as we age.

[McMan's note - An early Newsletter carried a report of Dr Hedaya's book,
"The Antidepressant Survival Program: How to Beat the Side Effects and
Enhance the Benefits of Your Medications." You can check out his website at:
http://www.wholepsych.com/public/index.html ]

FINAL NOTE

Your own experiences are virtually the only source we have for therapies
involving supplements. Please feel free to share your story by emailing me
at jmcmanamy@snet.net Confidentiality ensured.

MCMAN'S WEB

Check out more than 240 articles on all aspects of depression and bipolar,
plus a bookstore, readers' forum, message boards, and other features at:
http://www.mcmanweb.com

SUBSCRIBE

If someone has passed this on to you:

You are invited to subscribe for US $29 a year for 48 issues. You can pay by
credit card online at: http://mcmanweb.com/newsletter1.htm

<a href="http://mcmanweb.com/newsletter1.htm">click here</a>

Or you can mail your check to:

McMan's Weekly

PO Box 331

Southington, CT 06489

USA

Please be sure to include your email address on your check or money order.
For those of you who wish to write larger checks, the surplus will be
applied toward subsidizing subscriptions to those in need. For those in
need, subscriptions are $10 contingent on the generosity of other readers.

You can also pay by credit card via PayPal and credit to the account of
jmcmanamy@snet.net

Non-US readers can subscribe using PayPal.

For change of address, email jmcmanamy@snet.net with your new email address.

For three free sample issues, email jmcmanamy@snet.net and put "Sample" in
the heading and your email address in the body.

John McManamy

"Knowledge is necessity."


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