McMAN'S DEPRESSION AND
BIPOLAR WEEKLY
April 17, 2002 Vol
4 No 14
Note: This
excellent newsletter is available weekly from:
http://mcmanweb.com/newsletter1.htm
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LOOKING DOWN THE PIPELINE
Consider this:
"The deficiency of noradrenaline and serotonin once believed to be the primary
cause of depression now appears to be secondary to disturbances in the
communication axis of biochemicals starting in a part of the brain, the
hippocampus, where noradrenaline, serotonin and many more neurotransmitters are
active. These compounds are influenced by and form a feedback mechanism with the
hypothalamus, the pituitary and the adrenal glands."
What's interesting about the above is it is published on the website of the
pharmaceutical company, Organon, which produces the antidepressant Remeron and
has another one, Ariza, on the launching pad. But the company is obviously
looking further ahead: "Several compounds that influence this system," it says,
"are currently being investigated."
Here, Organon goes unaccountably silent, but the narrative is picked up by
Neurocrine Biosciences, which is developing a "CRF antagonist" with
GlaxoSmithKline. "Corticotropin Releasing Factor (CRF)," says
Neurocrine's
website, "functions as a neurotransmitter in the brain and plays a critical role
in coordinating the body's overall responses to stress." Basically, stress and
depression are partners in an elaborate neuro-endocrine two-step. Recently, the
company completed a successful phase I trial to establish the safety and
tolerability of its drug, and phase II trials to test its efficacy are planned.
Then there are what might be called novel target drugs: In the 1990s, Merck
began looking at "substance P antagonists." Substance P is a neuropeptide that
co-exists with serotonin and is believed to play a role in modulating a host of
ills, including pain, nausea, inflamed bowel, migraine, anxiety, and depression.
Its test drug, MK-869, made it to phase III (the final trial phase) before it
was dropped, but late last year Merck entered into phase III with a successor,
aprepitant, though the company says it is too early to predict when it when it
will file for FDA approval.
Substance P acts on the brain's NK-1 receptor, and several drug companies are
calling their versions "NK-1 antagonists." According to a Pfizer press release
issued in Dec 2001, its "CP-122,721" has the efficacy of Prozac but with lower
sexual side effects.
Then we move back into serotonin country with Organon's Ariza, a "5HT-1A
agonist," meaning it triggers a response in one of the serotonin receptors.
Organon filed for FDA approval in May of last year, and is looking for a partner
to co-market the drug..
Finally, we're back into the reuptake blockade process with Eli Lilly's
anticipated son of Prozac, duloxetine, which targets serotonin and norepinephine
(noradrenaline), with FDA approval expected later this year. The company is also
seeking approval for its combination Prozac-Zyprexa for treatment-resistant
depression, which it hopes to have on the market in 2003. There is also Forest
Laboratories' Lexapro, which is a cleaner version of its Celexa, expected to
be released by the middle of this year.
This inventory of antidepressants in development is by no means complete, but it
does represent what the pharmaceutical companies are working on. The bad news is
the antidepressant we've all been waiting for - one that gets us to full
remission with no side effects - is probably another generation or two down the
pipeline, if at all. The good news is, over the next several years, we can look
forward to some real choices, arguably for the first time since Elavil came on
the market in 1961. Instead of, "if Paxil doesn't work, let's try Celexa,"
it could be, "if this NK-1 antagonist doesn't work, let's go with that new CRF drug." One of them,
let's hope, is bound to have your name on it.
DULOXETINE
A study funded by Eli Lilly found its nearly-ready-for-market antidepressant,
duloxetine, was "significantly superior to placebo" starting at week two.
Discontinuation due to adverse events (13.8 percent) compared favorably to SSRIs.
http://www.psychiatrist.com/abstracts/200204/ab040205.htm
REBOXETINE
A drug that is available in 50 countries, but has not yet received approval in
the US is Pharmacia and Upjohn's reboxetine (Vestra). Nancy writes:
I have been and am doing wonderfully on reboxetine, the only drug that has
worked for me in years. I have no side effects. My pdoc imports it from England.
Any pdoc can do the same. Reboxetine is the first of a new class called NARIs (noradrenaline
reuptake inhibitors). The FDA has been VERY slow on this drug.
THIRD-GENERATION ANTICONVULSANTS
A multi-center review published in the Journal of Clinical Psychiatry reports
that Lamictal is the best studied of the newer mood stabilizers, with efficacy
in acute bipolar depression and longer term treatment of bipolar depression, as
well as rapid-cycling, but not for acute mania. Open trials suggest the
usefulness of Neurontin as an add-on, but double-blind trials failed to confirm
its efficacy in acute mania and treatment-resistant rapid-cycling. Open studies
have found Topamax effective in acute mania and rapid-cycling, but it failed a
double-blind study in acute mania. Zonigran warrants further investigation while
Gabitril does not appear to be useful in acute mania.
http://www.psychiatrist.com/abstracts/200204/ab040201.htm
DEPAKOTE
Women taking Depakote may want to discuss the following with their doctor or
psychiatrist:
A Dalhousie University/ QE II Health Sciences Centre (Halifax) study of 32 women
with bipolar, 17 taking Depakote and 15 not on Depakote compared to 22 healthy
controls found: 47 percent of the women on Depakote reported menstrual
abnormalities vs 13 percent of those not on Depakote vs zero in the control
group. Forty-one percent of the Depakote group had polycystic ovary syndrome.
http://www.psychiatrist.com/abstracts/200204/ab040207.htm
BIPOLAR WOMEN
A University of Arizona/University of Cincinnati survey of 50 women with bipolar
has found 32 percent incurred bipolar prior to the onset of menstruation and 18
percent experienced bipolar within a year of menstruation. Most women did not
receive an accurate diagnosis or get treatment until after they had children. Of
those with children, 67 percent experienced a postpartum mood episode. Those who
had postpartum episodes after their first child all had episodes after
subsequent pregnancies. Postpartum episodes were "almost exclusively
depressive." Women not using hormone replacement therapy were "significantly
more likely" to report worsening of symptoms during perimenopause/menopause.
http://www.psychiatrist.com/abstracts/200204/ab040202.htm
NUMBER ONE?
A widely publicized study published in Dec JAMA last year concluded that Paxil,
Prozac, and Zoloft were similar in efficacy and improvement in health-related
quality of life. A letter to the editor in this week's JAMA by Richard Elliott
MD, PhD and Francis Dane PhD of Mercer University (Georgia) disputes that
finding, arguing Zoloft ranks number one on several different measures using the
same data, with the other two drugs equally second.
http://jama.ama-assn.org/issues/current/ffull/jlt0417-1.html
NO END IN SIGHT
"We are witnessing a race to the bottom in terms of respect for human rights and
international humanitarian law, with the danger that both communities will come
to support continual violence as normal and acceptable."
Physicians for Human Rights, on the West Bank crisis, made at the end of last
month, reported in The Lancet.
http://www.thelancet.com/journal/vol359/iss9314/full/llan.359.9314.editorial_and_review.20750.1
THINKING POSITIVE
From an article by Michael Craig Miller MD Harvard Mental Health Newsletter on
the benefits of positive psychology:
"In several studies, optimists have been found to live longer, while pessimists
suffer what some researchers call ‘excess mortality,' not a good thing by
anyone's standard. The evidence suggests that avoiding pessimism is more
important than boosting optimism. Pessimistic, anxious, and depressed people are
more likely to develop high blood pressure. Their immune systems are not as
effective, and they recover from surgery more slowly and less completely ... In
a study of 300 heart patients, researchers found that optimists were less likely
than pessimists to need rehospitalization after coronary bypass surgery."
http://www.health.harvard.edu/article.cfm?id=40
BROKEN PROMISES
Similar stories are playing out in states throughout the US:
Last year, New York's governor and legislative leaders promised mental health
workers cost-of-living adjustments, 10 percent increases in Medicaid
reimbursement fees, and funding transfers from the closures of facilities to
community care. Instead, the legislature passed a stripped down budget that has
resulted in the closing of more beds. Meanwhile, there is a turnover rate of 54
percent among the state's mental health workers, who have not had a pay
increase in 10 years.
http://nycitizens.org/2002/news/0413-1.html
THE PRICE OF SUCCESS
"If I was making $100,000, I wanted to be making $200,000. If I was making
$200,000, I wanted to make $300,000." - a Wall Street broker.
A Reuters article reports on a 1999 study by doctoral candidate Alan Cass of 26
male brokers, aged 22 to 32, 23 percent who met the criteria for depression. The
brokers spent an average 12 hours a day at work, smoked on average two packs a
day, and downed almost two drinks daily. They also suffered from flu or virus
four times a year.
http://story.news.yahoo.com/news?tmpl=story&u=/nm/20020413/bs_nm/bizstress_dc_1
BRAIN REPAIR
The following was reported in the context of Alzheimer's and Parkinson's:
Researchers at the Salk Institute of Biological Studies isolated stem cells from
the hippocampus of adult rats and modified the gene to produce glowing proteins,
which were cloned and took on the properties of adult neurons as they matured,
including the ability in some to make synaptic connections with other neurons.
http://www.healthscout.com/template.asp?page=newsdetail&ap=1&id=506736
SOBERING STATISTIC
According to the Connecticut Department of Mental Health and Addiction Services,
56 percent of individuals with bipolar are estimated to have a lifetime history
of substance abuse or dependence.
http://www.medscape.com/viewarticle/431186
PSYCHIATRIZATION?
"The number of diagnostic categories has increased in the Diagnostic and
Statistical Manual of Mental Disorders of the American Psychiatric Association
from 106 in DSM-I in 1952 to 357 in DSM-IV in 1994."
From an article in the British Medical Journal by psychiatrist Duncan Double
advocating psychiatry to "temper and complement a biological view with
psychological and social understanding, thus recognizing the uncertainties of
clinical practice."
http://bmj.com/cgi/content
CLINICAL TRIALS
"Until last year, in fact, when the agency's budget tripled, OHRP had just two
full-time investigators to monitor more than 4,000 federally funded research
institutions. Since 1980, the agency has audited, on average, just four sites a
year. The FDA is somewhat more vigilant, making site visits to about 200 of the
approximately 1,900 IRBS that oversee research on FDA-regulated products."
From a Time magazine cover story on clinical trials in the US. A sidebar to the
article advises those considering participation in a clinical trial to ask: 1)
What is the primary purpose of the trial (to help cure patients or advance
medical knowledge)? 2) Is the trial in phase I, II, or III (the earlier the
phase, the more experimental the treatment)? 3) What are the known risks (and
potential side effects)? 4) Is your doctor the only one conducting the trial (if
other centers are further along in the trial, ask for a synopsis of the
experience of those patients)? 5) What procedures are there for reporting
problems (is the contact person available 24 hours a day)? 6) What is the track
record of the primary investigator (how long has he or she been conducting
trials)?
http://www.time.com/time/covers/1101020422/story.html
NOT THE PARTY LINE
From the Toronto Sun:
A Centre for Addiction and Mental Health (Canada) study reports that only six
percent of the homeless had spent any time in a psychiatric hospital in the year
preceding their homelessness. Two-thirds of the 300 people had mental health
issues, the study found, but most of these were "non-severe."
The study has drawn flak from shelter workers, who say mental illness among the
homeless is far more prevalent.
ADDING INSULT TO INJURY
An article in the St Louis Post-Dispatch reports that many times parents are
forced to relinquish custody to get proper treatment for their mentally ill
children. In many cases, the article reports, these parents are put on Missouri's
child abuse and neglect registry, even when there is no evidence of abuse.
GUNS
Newsletter 4#12 posed the question of firearms ownership for those with mental
illness. Charlene writes:
Regarding the issue of firearms for those who have experienced/are experiencing
mental illness: I am from Texas, where we have a right to carry concealed
handguns. I believe that people with mental illness have just as much right to
defend ourselves as anyone else and that we are more likely to be victims of
crime than perpetrators of it. While I do not personally own a handgun since I
have had suicidal tendencies in the past, that is my choice. If someone else
wants a gun for their own protection, that is their choice and their right under
the US Constitution. Let us not forget, also, that people who want guns will get
them, legal or not.
VEGGIE VIEWPOINT
Two articles in Newsletter 4#13 referred to fish oil while another article
reported on experiments with lab rats. Nancy writes:
For people who avoid fish and fish oils, an alternative is flax seeds and flax
seed oil.
I am opposed to animal research and have learned it is very often
duplicative, misleading (aspirin kills cats etc), expensive and unnecessary as
many more alternatives exist now than did in the past. For more info contact
Physician's Committee for Responsible Medicine at:
http://www.pcrm.org
MCMAN'S WEB
Check out more than 190 articles on all aspects of depression and bipolar, plus
a bookstore, readers' forum, message boards, and other features at: http://www.mcmanweb.com
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