'Dissolving
Pill' for Sz Medication
Alamo Pharmaceuticals has developed a clozapine pill
that dissolves on the tongue, eliminating the need for
schizophrenia patients to call attention to their
medication. Developers hope that the new delivery method
will help reduce some of the stigma around the disease, and
in turn improve patient compliance.
Fazaclo (brand
name of the pill), is not an entirely new development. There
have been several attempts to find new delivery methods for
schizophrenia medications, among them long-acting injections
and surgically-implanted patches. All of these were created
with a common goal - to improve compliance to medication
treatment.
However, the
main barrier to compliance has always been lack of insight,
a hallmark of many brain diseases (among them
schizophrenia). Although medication delivery methods cannot
help insight, they may still improve compliance for some
patients.
The FDA
officially approved the sale of Fazaclo in February, at it
will be available by 8/23/04. Users of the pill must join a
registry and get regular blood tests, as depletion of white
blood cells is a possible side effect for 1-2% of Fazaclo
users.
To read the
news article, please see "Schizophrenics
may not fear new drug" by Chris Gosier (Daily Record,
8/21/04).
http://www.dailyrecord.com/news/articles/news1-alamo.htm
See more detailed information about Fazaclo, available
from Drugs.com website (http://www.drugs.com/fazaclo.html).
To read about
some other new delivery methods for schizophrenia
medications, please see
Alternatives to Pills in the medications section of the
schizophrenia.com website.
2nd study
links SSRIs, suicidal thoughts
SSRI antidepressants are used mainly to treat clinical
depression and anxiety; however, they are also used by
people with other psychiatric diagnoses (such as
schizophrenia or bipolar disorder) who struggle with serious
depressive episodes.
Selective
serotonin reuptake inhibitors (SSRIs) have been under
scrutiny for months, following an internal review of the FDA
showing that youth who use these antidepressants are more
likely to have suicidal thoughts.
Of the SSRI
antidepressants, which include Paxil, Zoloft, and Celexa,
only Prozac has been officially approved for children under
18.
A recent new
analysis of SSRI drugs confirms the first report. According
to FDA medical reviewer Tarek Hammad, children who use SSRI
antidepressants during clinical studies had almost twice the
risk of attempting or seriously contemplating suicide, as
compared with children taking a placebo pill.
Since the first
warning was released nine months ago from British medical
authorities, the FDA has added a warning to SSRI labels,
cautioning doctors to closely monitor pediatric users.
However, the FDA has not officially disclosed any
information about the newest study, and allegedly will not
discuss the findings until their September meeting.
For the full
report, please see '2nd
FDA Review Confirms Antidepressant Risks: Report' (Aug
10 2004) at HealthCentral News
(http://www.healthcentral.com/).
Suicidal
tendencies may be even higher in bipolar children taking
SSRI antidepressants. See a press release from the Child and
Adolescent Bipolar Foundation: 'Parents
of bipolar children praise FDA warnings on antidepressants,
suicidality.'
(http://www.bpkids.org/frontdesk/pressroom/03-22-04.htm)
New
Schizophrenia Memory Drug in Trials
DATELINE:
CHAPEL HILL, N.C., Aug. 24
Source: Press
Release from DarPharma Pharmaceuticals (see below).
DarPharma
announces that enrollment has begun for a trial of DAR-0100
for the treatment of working memory and cognitive deficits
associated with schizophrenia. This is the first ever
clinical trial of a dopamine D1 receptor full agonist in
treating working memory deficits. The trial is sponsored by
The Stanley Medical Research Institute (SMRI) in which Dr.
E. Fuller Torrey is an active director, and it is the
largest private source of funding for research into
schizophrenia and bipolar disease.
"SMRI is
dedicated to finding ways to improve the quality of life of
people with schizophrenia and bipolar disorder," said Dr.
Michael Knable, Executive Director of SMRI and a member of
DarPharma's Board of Directors. "This is a rare opportunity
to take the exciting science done by Professors Richard
Mailman [University of North Carolina, Chapel Hill] and
David Nichols [Purdue University] and promising, related
science conducted by other investigators throughout the
world and translate it into a clinical study that may open
new horizons for therapy. We at SMRI are very pleased that
we could support this study."
An expert
consensus panel convened by the National Institute of Mental
Health last year selected D1 agonists as the most promising
way to treat working memory deficits in schizophrenia, a
major medical problem with significant social and economic
costs.
"This is the
first clinical study to address the conclusions of the NIMH
experts," said Dr. Prabhavathi Fernandes, President and CEO
of DarPharma.
"Professors
Mailman and Nichols have invested years towards developing
D1 agonists and bringing DarPharma to this point. This trial
of DAR-0100 for treating cognitive deficits is a landmark in
mental health research."
The trial will
enroll patients with schizophrenia who are currently
stabilized on existing medications, and will evaluate the
effect of DAR-0100 on brain activation using a technique
called fMRI, or functional magnetic resonance imaging. The
Medical University of South Carolina is the primary site for
the
trial. Results are expected in the first quarter of 2005.
About
DarPharma, Inc.
Launched in July 2001, DarPharma's primary goal is to bring
to the market dopamine D1 receptor full agonists as
therapeutics for numerous CNS conditions, including the
cognitive deficits and negative symptoms associated with
schizophrenia. Their large intellectual property portfolio
includes multiple drug candidates for dopamine receptors and
other targets. DarPharma's lead compound, DAR-0100, is in a
Phase II study in schizophrenia patients.
For further
information on this 20 person clinical trial, please contact
Dr. Mark George in reference to the "DarPharma schizophrenia
clinical trial". Participants must have been diagnosed with
schizophrenia and be stable on existing medications.
Dr. Mark George
Medical University of South Carolina
843-876-5142
====================
More information on the company that is testing the drug can
be found at:
DarPharma, Inc.
215 Cloister Court
Chapel Hill, NC 27514
Phone: (919) 403-4348
http://www.darpharma.com
Underestimations of Mental Illness in College
The incidence of, and lack of awareness about, mental
illness among college students was revealed in a recent
survey conducted during Bipolar Disorder Awareness Day.
Survey results
(conducted by NAMI) included the following points:
-- One in three
students report having experienced prolonged periods of
depression
-- One in four students report having suicidal thoughts or
feelings
-- One in seven students report engaging in abnormally
reckless behavior
-- One in seven students report difficulty functioning at
school due to mental illness
--50% of students rate their mental health as below average
or poor, as opposed to 25% of parents who report their
student's mental health to be in this range.
According to
Dr. Ken Duckworth, asst. professor at Harvard Medical School
and medical director for NAMI, "[T]he impact of untreated
mental illness on a college student's life can be
devastating. In the majority of circumstances, bipolar
disorder, like diabetes, can be managed and controlled.
However, if left untreated, it can result in negative
outcomes and even premature death. Unless we educate our
students and work to reduce the stigma associated with
seeking help on America's campuses, young people will suffer
needlessly."
Although many
students experience and display warning signs of mental
illness, they go unrecognized by parents, teachers, and
administrators. In response to the survey results, NAMI
strongly encourages parents to speak with their college-age
children about mental illness, and keep in touch throughout
their time at school and young adult years.
"Parents should
talk to their college student about mental illness before
they leave for college and maintain a regular dialogue
throughout the school year," said Mike Fitzpatrick,
executive director of NAMI. "The majority of people with
bipolar disorder, for example, experience an onset of
symptoms before the age of 20, making late adolescence an
essential time for awareness. While parents can't prevent
mental illness, educating themselves and their college age
children can help encourage early diagnosis -- and early
diagnosis can save lives."
Given the
apparent scope of the problem, there is a severe deficit of
available information and awareness among students. Not only
do many students not recieve education about mental health
before beginning college, approximately half say that their
college/university campus does not educate students either.
Due to this lack of education and prevailing stigmas around
mental health services, students continue to suffer in
silence, and misconceptions about mental illness remain
unchallenged. Some common beliefs about mental illness among
parents and students include the following:
-- Thirty-five
percent of parents and 48 percent of students believe
bipolar disorder is at least somewhat attributed to a
character flaw or weak willpower.
-- Fifty-five percent of parents and students somewhat
believe that people with bipolar disorder should not be in
positions of responsibility.
-- More than 70 percent of parents and students would be
uncomfortable to some extent if a close friend or family
member was dating or marrying a person with bipolar
disorder.
-- Nearly one in four parents and students do not agree that
untreated bipolar disorder can lead to suicide, but other
studies show as many as 50 percent of people with untreated
bipolar disorder attempt suicide at least once.
-- More than one in four parents and students do not
understand that untreated bipolar disorder can lead to
contact with the criminal justice system, yet sources show
that people with untreated mental illnesses spend twice as
much time in jail.
All of us -
campuses, parents, and students - must take an open stand
mental health and illness, destigmatizing this vital issue
and staving off preventable tragedies within our future
generation.
To read the
full article, please see
"Mental Illness Prolific Among College Students" (Aug 25
2004). http://biz.yahoo.com/prnews/040825/lnw009_1.html
Listen online
to the following radio programs concerning college-age
students and mental health:
1)
Mental Health and Illness in Teenagers (BBC radio).
2)
College students and Mental Health (Voice in the Family
public radio).
Gov
officials take on mental health issues, reduce stigma
Among the many factors that affect widely varying suicide
rates of U.S. states, a major one is adequate access to
mental health services. However, the stigma around utilizing
available services is a major problem, which also
contributes to rising suicide rates. "Most people with
mental disorders fear a negative or patronizing response,
even from health-care providers" says Dr. Michael Craig
Miller, author of a recent Boston Globe editorial on suicide
rates in U.S. states. "The more severe their distress, the
greater the dread of reaching out."
President Bush, as well as several prominant Republicans in
government, have publicly advocated the importance of mental
health care for all. As he introduced the New Freedom
Commission on Mental Health, Bush said, "Stigma leads to
isolation and discourages people from seeking treatment they
need. Political leaders, health care professionals, and all
Americans must understand and send this message: Mental
disability is not a scandal; it is an illness." Previously,
he alledgedly believed that mental illness could be solved
through hard work and prayer (this is based on uncited
quotations).
This change of
heart from our national leader is welcome and needed, as
many local and national surveys still report that a majority
of United States citizens consider mental illness the result
of immorality or sin, rather than a biological disorder. It
just goes to show that anyone can reconsider old dogmas, and
public advocacy by people with personal experience is a key
factor in changing minds and hearts.
Other
government officials have been staunch advocates for mental
health care services. Senator Pete Domenici of New Mexico
has authored lots of recent mental health legislation, and
Bush created the Mental Health Commission at his request.
The US Air
Force has also dramatically decreased suicide rates within
their forces, by initiating programs to raise suicide
awareness and make treatment available. Top officials were
primary advocates, which reduced the natural stigma around
seeking help from mental health services.
In his
editorial, Dr. Michael Craig Miller praises the efforts of
these public figures, and urges all politicians and
concerned citizens to do the same. "They could save
thousands of lives by following the lead of Bush, Domenici,
and the Air Force and by supporting the National Strategy
for Suicide Prevention. As leaders in their home
communities, they can help their constituents to understand
that mental illness is a medical problem, not a moral one."
See the Boston
Globe editorial by Michael Craig Miller, "A
Suicide Map of the U.S." (Aug 22, 2004).
http://www.boston.com
See a fact sheet about suicide statistics in the U.S.
(pdf file) - incidence among populations, factors that
affect suicide rates, etc. From
http://www.suicidology.org
For resources,
information, and advice about suicide, and what to do if you
or someone you love is considering suicide, see
Preventing Suicide on the schizophrenia.com homepage.
Cannabis-like brain molecule higher in Sz patients
A team of international researchers conducted a study to
measure a cannabis-like brain molecule (called anandamide)
in the cerebrospinal fluid of people with schizophrenia,
people at risk for psychosis, and healthy controls. Their
results showed that those at-risk had levels six times as
high as control subjects, and those diagnosed with
schizophrenia had levels eight times as high.
Cannabis is
strongly linked with the onset of psychotic symptoms, and up
to 60% of people with schizophrenia use the drug.
Researchers initially hypothesized that an overload of the
chemical from the brain's natural cannibinoid system was
contributing to schizophrenia symptoms in patients. However,
results also showed that patients with more severe
schizophrenia symptoms actually had relatively lower levels
of anandamide than those with less severe symptoms. The team
then suggested that the natural cannabis-like substance is
released by the brain in response to psychotic symptoms,
actually helping to control them, rather than being the
direct cause of them. For those with more severe psychosis,
the brain might be unable to produce enough anandamide to
adequately reduce symptoms.
The research
suggests that the anandamide system in the brain could be a
potential target for new anti-psychotic drugs; however, the
situation is more complicated. It has been proven that using
cannabis actually worsens psychosis rather than improving it
- clearly, there is not a direct correlation between
absolute levels of cannabis-like molecule in the brain and
the control of psychotic symptoms. It is possible that
frequent use of cannabis (which binds to anandamide
receptors) makes the brain less sensitive to its own natural
molecular products. Related research has also shown that
among schizophrenia patients, anandamide levels are lowest
among those who frequently use cannabis.
For the full
article, please see
"Brain may produce its own antipsychotic drug" in
NewScientist (www.newscientist.com), Aug 25 2004.
To read more
about the connection between schizophrenia and marijuana
use, see the following newsblog stories at
schizophrenia.com:
1)
Street Drugs and Schizophrenia (Newsblog entry, Aug 20
2004).
2)
Stronger Evidence for Pot-Psychosis Link (Newsblog
entry, July 14 2004).
3)
Cannabis Linked Again to Schizophrenia (Newsblog entry,
April 21 2004).
Drug
Cocktails hit Psychiatry
The Wall Street Journal reported on Aug. 10th that:
"Psychiatrists
are increasingly turning to creations of multi-drug
'cocktails' to treat wide range of mental disorders from
schizophrenia to depression, and patients who don't respond
to single medication".
No big news
here to anyone in the psychiatry field or on the consumer
side. At the NAMI California conference last weekend
(Burlingame, CA) a doctor responding to people in the "Ask
the Doctor" session - suggested that while its generally
preferable (from the perspective of avoiding side effects,
and minimizing the potential for drug/drug interactions) to
minimize the number of medications a person is taking - this
desire is increasingly being overruled by the desire to
improve the quality of life for people or at least make
people functional at some basic level and the polypharmacy
approach (of multiple drugs) is proving effective in many
people.
Cell's Energy System (Mitochondria) May Play Role in
Schizophrenia
Scientists at
the Babraham Institute have made significant advances in
understanding schizophrenia. Schizophrenia is a mental
illness which has been estimated to affect over 1% of the
population and costs the NHS over £2.5 billion per year.
Babraham scientists have pinpointed a breakdown in
mitochondria – the power stations of the cell – as a key
factor.
The discovery,
described in an article published in Molecular Psychiatry,
was made by a team of scientists working in Dr Sabine Bahn’s
research group at the Babraham Institute, Cambridge. The
large-scale, multi-disciplinary approach has identified
differences in the _expression of genes related to energy
production between schizophrenia patients and unaffected
people.
The team
studied tissue from over 100 brains and screened over 22,000
genes. Dr Bahn comments: “This study is the most extensive
study of its kind so far, and we believe its multi-tier,
complementary approach has provided surprising and
convincing data. We hope that our findings will lead to
advances in treatment, diagnosis and hopefully prevention of
schizophrenia and related illnesses.”
Further
information
The Babraham
Institute, located just south of Cambridge, UK, is an
educational charity focussed on delivering science of the
highest quality that will add significantly to knowledge and
find applications in the biomedical, biotechnological and
pharmaceutical sectors. The work described was funded by the
Stanley Medical Research Institute in Bethesda USA, and was
carried out in conjunction with scientists at the University
of Cambridge, the Human Genome Mapping Project – Resource
Centre (Cambridge), as well as collaborators from the
Stanley Laboratory for Brain Research (Bethesda, USA) and
John’s Hopkins University (Baltimore, USA).
Another Gene tied to Causing Schiz, Identified
In India, schizophrenia researchers have announced that they
have identified another gene that they believe may be
implicated in causing schizophrenia.
The report
noted that:
"The gene was
identified in three members of a family and its mutation was
observed in all the individuals affected by the mental
disorder," Professor Samir K Brahamachari, Director,
Institute of Genomics and Integrative Biology, and a member
of the team of scientists that made the discovery, said.
The scientists
found that the three patients had a mutation in gene
'Synaptogyrin 1', he said, adding that the gene is located
on Chromosome 22 in a region that is implicated in
development of schizophrenia by several studies.
The gene has a
potential for predictive diagnosis and it is expected to
give a better understanding of schizophrenia vis-à-vis the
"cure", Brahamachari said.
A US patent has
been granted for the method of detection of the mutation, he
said, adding that the National Institute of Mental Health
and Neurosciences also participated in the study.
Brahamachari,
however, said this is not the only gene responsible for the
disorder. "We are looking at many more genes."
The study paper
has been published in
Biological Psychiatry journal.
Glutamate Affects SZ Traits
Researchers at the National Institute of Mental Health
released findings that link one small section of one gene -
which codes for the neurotransmitter glutamate - with many
schizophrenic traits. The gene GRM3 normally regulates the
amount of glutamate neurotransmitter that is released into
nerve synapses during cell-to-cell communication. Scientists
hypothesize that an abnormally functioning GRM3 releases an
improper amount of glutamate in the brain, affecting
cognition and raising the risk for schizophrenia.
"Because of the
small effects of individual genes in complex genetic
disorders like schizophrenia, it is difficult to make
significant associations with any one particular marker.
However, this study brings us closer to unlocking the
genetic clues that increase the risk for schizophrenia,"
said NIMH Director Thomas R. Insel, M.D.
Previous
research has already identified many candidate genes that
likely contribute to the onset of schizophrenia, and some of
these also affect the glutamate system.
Glutamate is a
neurotransmitter that plays a role in brain cell
communication - chemical signaling between nerve cells.
This recent
study focuses on one section of the GRM3 gene - a sequence
of code that may differe by just one base pair (the
"letters" of the genetic code) in patients affected by
schizophrenia. According to the data, people with
schizophrenia are more likely to have a gene variant with
the base "A" (adenine) in this crucial spot, rather than a
sequence with the letter "G" (guanine). Study results also
showed that people inheriting this "A" variant have lower
levels of glutamate in their brains, and scored less well on
cognitive tests than those with the "G" variant.
Having this
GRM3 variant does not cause schizophrenia - rather,
scientists hypothesize that people with a G in this sequence
have a higher level of cognitive protection, and are less
likely to develop schizophrenia symptoms in response to
other, undetermined events. Paradoxically, the gene sequence
including the higher risk "A" base is more common among
humans. The reason for this is currently unknown.
For the full
article, see
"Schizophrenia Gene Variant Linked to Risk Traits" (Aug
11 2004) in NIH News (http://www.nih.gov/news/).
For more
research linking glutamate function to schizophrenia
symptoms, see the following:
1)
Glutamate paths surface in schizophrenia (Sept 8, 2001)
- Science News article.
2) June 20
schizophrenia.com NewsBlog entry -
Glutamate levels elevated in teens at-risk for
schizophrenia.
Measuring Schizotypy Personality through Questionnaires
The Psychometric Detection of Schizotypy: Do Putative
Schizotypy Indicators Identify the Same Latent Class?
Horan, WP;
Blanchard, JJ; Gangestad, SW; Kwapil, TR.
Journal of Abnormal Psychology. 2004 Aug Vol 113(3) 339-357
There is a lot
of research being done to identify personalities of
individuals prone to the development of schizophrenia, so
that early intervention is possible. One type of personality
that is involved with a risk for schizophrenia is called
schizotypy. People with this type of personality have
features known as anhedonia (difficulty experiencing
pleasure), cognitive slippage, ambivalence (uncertainty) and
interpersonal aversiveness (preference to be alone). One
theory is that individuals with some schizophrenia genes
(schizotaxia) will have a necessary but not sufficient
condition for the development of schizophrenia. In other
words, they are members of a latent class (or taxon) within
the general population who carry the genes but do not
express schizophrenia fully. Instead they may show
schizotypal personality traits. Some of the questionnaires
that measure schizotypy include the Perceptual Aberration
Scale (PAS), Magical Ideation Scale (MIS) and the Revised
Social Anhedonia Scale (RSAS).
This study
argues that it is unclear whether all 3 of these
questionnaires are able to identify a common group of
individuals who constitute the same (presumably genetically
determined) latent group. So, the researchers used
statistics to look at the independent and joint latent
structures of the RSAS, MIS, and PAS in students from public
universities. They wanted to see if the positive and
negative traits in these questionnaires are able to identify
a common group in the general population. They found that
these 3 questionnaires, that were thought to tap the same
latent class that was assumed to be schizotypy, actually do
not share this property. They suggest that this might
explain why there have been differences in studies that have
used these questionnaires since they actually measure
different causal processes within the clinical syndrome of
schizophrenia or psychosis proneness more generally. Further
research is needed to look at the characteristics and
outcomes of individuals who actually have the taxa that is
measured by both the RSAS and the PAS and/or MIS, so that we
can understand what their roels are in schizophrenia. The
authors argue that it doesn’t make sense to use these
questionnaires to idenify a common latent class of people.
This research
was supported by Grant MH-51240 from the National Institute
of Mental Health.
Click here to find this article on PubMed
Patient and family attitudes toward schizophrenia
treatment
Irani F, Dankert M, Siegel SJ.
Current
Psychiatry Reports. 2004 Aug;6(4):283-8.
While each
person has their own unique experiences and beliefs, this
review focused on highlighting the current research on
attitudes towards illness, medications, non-pharmacological
treatment and psychiatric research.
This review
highlighted the importance of considering both patient and
family member attitudes for the treatment of schizophrenia.
It discussed the involvement of family members in caring for
affected loved ones, despite their subjective burden.
Furthermore, it described studies showing that individuals
with schizophrenia can sometimes have contradictory ideas
(eg endorsing the need for continuous use of medication, yet
reporting that they do not need psychiatric medication once
they feel better and that they would not get sick if they
stopped taking psychiatric medicine). In contrast, family
members consistently report overwhelming support for the
need for their loved one to take psychiatric medicine, even
if they may be relatively hesitant to take medicine for
their own physical ailments. The review further suggests
that family members are also more aware of the risks
associated with discontinuing treatment than individuals
with schizophrenia. Furthermore, the review found that even
when individuals with schizophrenia accept that they have a
psychiatric illness, they are less likely to report symptoms
and diagnoses consistent with their doctors. Such
discrepancies between doctors and patients highlight the
need for more open discussions about attitudes so that
treatment plans can be most effective. This is particularly
relevant when assessing side effect profiles of various
medications. In terms of non-pharmacological treatments, the
review suggests that therapy interventions with highly
individualized and heterogeneous concepts of illness,
etiology and a positive view regarding prognosis are most
effective.
Attitudes
towards depot, extended release medications and implantable
medicine are also reviewed. Most studies convey a positive
opinion of depot medication, although in one Australian
study depots were seen as being unhelpful. Patients taking
extended release formulation of psychiatric medications such
as weekly fluoxetine have been reported to consider
once-weekly dosing more convenient than daily dosing.
Long-term delivery will be extended with the introduction of
surgically implantable medicine that can provide
uninterrupted access to psychiatric medication for up to one
year. Results of a survey suggest that patients are almost
equally split between favorably and not favorably
considering such implantable medications.
With the advent
of new treatments, the attitudes of patients, family members
and health providers towards biomedical research can provide
valuable direction for future interventions. This review
found that patients, family and psychiatrists strongly
support research participation due to increased hope and
benefits to others that research participation provides. The
data further suggested that patients may not be against
clinical trials in principal, but maybe less likely to
participate in placebo-controlled clinical trials.
Furthermore, individuals with schizophrenia and family
members offer strengths in assessing not only ethically
important design elements of research in psychiatry, but
also provide crucial information to guide the treatment of
schizophrenia.
This work was
supported in part by Stanley Medical Research Institute. The
surveys and more information are available at
http://stanley.med.upenn.edu/Surveys.html, or
email: scetp (at sign) bbl.med.upenn.edu
Click here to find this article on PubMed
