Posted by Cam W. on April 17, 2001, at 16:20:13
dj is having trouble with his modem and asked me to post this article which appeared in today's Globe & Mail
- Cam
When one antidepressant isn't enough
Patients who don't respond to one type of drug
are finding new hope with combination therapies
WALLACE IMMENTuesday, April 17, 2001
Gwen remembers her recurring depression as "the most horrible agony you can experience
and still keep breathing."It was with me every moment and followed me in my dreams," says the Toronto executive,
now in her 40s, with the benefit of hindsight.Her episodes of depression would last more than a year, creating loss, pain and
disruption to her life that forced her to quit two earlier careers because she had no
idea that anything could be done."I finally decided I needed help one day when I was standing on a street corner and began
thinking how easy it would be to jump in front of a speeding truck and end it all," said
Gwen, who asked that her real name not be used.But when she did see a doctor, Gwen proved to be one of the 20 to 30 per cent of people
with severe depression who do not respond to drug treatment, a problem that has
frustrated both patients and doctors for decades.Because Gwen's condition improved only slightly when she took Paxil, one of the most
commonly prescribed antidepressants, her doctor switched her to Wellbutrin, another
antidepressant that has a different action in the brain.Only when her doctor prescribed both drugs together did the depression subside.
"It was like a miracle," said Gwen, who has not experienced depression for more than
three years and now readily copes with the stress of a new career.Indeed, combining drugs is a growing trend in treating patients who, at first, appear
resistant to the soothing effects of antidepressant medications.The new approach has been made possible by the simple fact that there are now so many
drugs with different properties on the market, said Dr. Robert Levitan, head of
depression research at the Centre for Addiction and Mental Health in Toronto.A large number of antidepressants affect serotonin, a substance that regulates activity
within a walnut-sized area of the brain that affects mood, pleasure and appetite. Other
drugs moderate levels of two other brain chemicals, norepinephrine and dopamine.The balance of these three substances is sometimes compared to the harmony of three
tenors singing together. If one of the three is off, the effect can be a jarring
disruption in mood.It appears that in some people, more than one type of treatment is needed to create
harmony, but combining medications still must be done in a clinic that specializes in
treating depression because there are no clear guidelines."We can't tell just by examination what person will respond to which combination. A lot
of it is clinical experience to see what affects the patient," said Dr. Levitan, who is
also associate professor of psychiatry at the University of Toronto."The medication situation is a bit of a mess because drugs for depression were developed
in a haphazard manner," explained Dr. Robert G. Cooke, head of the centre's depression
clinic. The first family of antidepressants -- the tricyclics -- were developed almost
by
accident, when doctors in the 1950s found that patients taking a drug for tuberculosis
also had a brightening of mood. Researchers then had to piece together an explanation of
how the drugs work by studying what parts of the brain they affect.Since then, many drugs known as selective serotonin reuptake inhibitors (SSRIs) -- the
family that started with Prozac -- were developed, but researchers are still not entirely
sure why they work, Dr. Cooke said.Aside from complex brain chemistry, there are several clearly identifiable reasons why
some people don't respond to an antidepressant medication. These are things doctors will
consider before combining medications.For instance, some patients may suffer from some other undiagnosed medical problem which
causes the symptoms of depression. Once the medical condition is identified and
successfully treated the depression often goes away.Doctors will test for low thyroid levels, which can resemble depression, or undiagnosed
cancer, which can cause weight loss and lethargy similar to depression.Another large group of non-responders are people who have abused drugs or alcohol for a
long period of time, Dr. Cooke said.In older people, there is evidence that constriction or hardening of the blood vessels
in
the brain, as well as small strokes or early symptoms of Alzheimer's disease can cause
depression.When a patient doesn't seem to respond to a particular antidepressant, the standard
procedure for doctors is to begin by first trying to increase the dosage of the same drug
to see if that reduces the depression.If that fails, the next step is to substitute another medication in the same family of
drugs that might have a slightly different effect."This is a bit like going from oranges to tangerines. The big unanswered question is,
should we go instead to a very different drug?" said Dr. Patrick McGrath, a
psychopharmacologist at Columbia University in New York.While there are now about 30 brands of antidepressant on the market, most of them have
not been tested in combination because drug companies sponsor most of the research and
focus on the effects of their own products, noted Dr. McGrath.To find out how they might work alone and together, a long-term study, costing
$25-million (U.S) is being organized by the U.S. National Institute of Mental Health. A
total of 2,000 patients who do not respond to a single antidepressant will be divided
into groups and use various other medications or psychotherapy along with antidepressant
use, said Dr. McGrath, who is helping to co-ordinate the study.Results of the study, called Star*D, will not be available for at least three years.
However, the findings from earlier small studies suggest that well over half of the
previously treatment-resistant cases improve if medications are combined or are used
along with other therapies, including psychotherapy.The same study will also look at the augmentation of an antidepressant with something
that can boost the drug's effect. Lithium and thyroid hormone are the most commonly used."A lot of times if depression doesn't respond to one drug the patient wants to give up.
It is important to find something that works early on so the patient keeps at it," Dr.
McGrath said.Even so, the growth of effective options is encouraging more and more patients to seek
treatment, said Dr. Stan Kutcher, head of the department of psychiatry at Dalhousie
University in Halifax.Dr. Kutcher was an adviser to a study by IMS Health that found the number of patients in
Canada who sought treatment for depression went up by as much as 10 per cent in the past
year and a total of 36 per cent over the past five years.This is because awareness of treatments has been raised by media coverage and
drug-company advertising, according to the study by IMS, which advises the pharmaceutical
industry on trends.Still, Dr. Kutcher estimated that as many as three million people in Canada have had at
least one long-lasting episode of depression, but two thirds of them suffer in silence.This is not just having a bad hair day -- to be considered medically depressed you have
to have experienced symptoms for four weeks or more.In most cases, people who seek help have been depressed for more than six continuous
months. In addition, an estimated one per cent of Canadians suffer bipolar shifts between
mania and depression.Many of these depressions are intermittent. An important question that must be given more
research is whether some patients can go off their medication once their depression
lifts, Dr. Cooke said."Our experience with the drugs used since the 1950s is that people don't develop a
tolerance to them. We haven't discovered any terrible ticking time bomb of side effects,"
Dr. Cooke said."If people are taking them and they have effect, it is probably a good idea to continue
to take them."What pills are right for you?
Bromides and opiates: In the early half of the last century, manic-depressed patients
were given opiates or bromides to calm their agitation, but they ended up feeling
sedated.
Mood elevators and stablizers: After the Second World War, mood elevators were available.
They caused intoxicating side effects and were often abused. The natural salt lithium was
found to stabilize mood, but when used alone at doses that relieve depression it can
cause intestinal problems and tremors.
Tricyclics: The 1950s brought the first specific antidepressants, a class of drugs called
tricyclics, including Tofranil and Norpramin. These produce side effects such as dry
mouth or constipation and sometimes extreme drowsiness.
MAOIs: Monoamine oxidase inhibitors were developed to treat both depression and anxiety
and include Manerix and Nardil. They can react with other drugs or foods to affect blood
pressure.
SSRIs: In the late 1980s, a new class of antidepressants earned the nickname "designer
drugs" because they act on specific mood-regulating areas in the brain. Prozac was the
first of many selective serotonin reuptake inhibitors (SSRIs) that elevate levels of
serotonin without affecting other chemical levels in the brain. Other SSRIs include
Celexa, Luvox, Paxil and Zoloft. Prozac has been dogged by the controversy that it may
cause suicide in some people. The drug's maker, Eli Lilly and Co., says there is no good
evidence to support such claims.
SNRIs: Variations on the designer drugs are selective norepinephrine reuptake inhibitors
(SNRIs), such as Effexor, which increases both norepinephrine and serotonin, and
Wellbutrin, which affects brain dopamine but not serotonin. Wellbutrin is marketed on the
basis that it does not reduce sexual desire -- a problem that affects some patients on
SSRIs.
In the works: New drugs being tested in clinical trials include what are known as
substance P blockers, which inhibit release of a hormone in the brain linked to
depression. Other research is looking at corticotropin releasing hormone blockers, which
reduce anxiety and stress in mice.Beyond the medicine cabinet
Aside from antidepressant medications, researchers are exploring other ways to beat the
blues:Herbs: European trials of the herb St. John's Wort have demonstrated some success
alleviating depression, but little is known about effective dosages or side effects. The
U.S. National Institute of Health is now running a long-term test of sustained-release
pills containing the herb.For information, see the Web site http://hypericum.rti.org.
Hormones: Hormone levels also have an effect on the efficacy of antidepressants and
require more study. Women have a higher incidence of depression and research is looking
at the role of estrogen.Small studies have also found thyroid supplements and the natural steroid DHEA
(dehydroepiandosterone) can help improve the response to antidepressants in some
patients.
ECT: For depressions that resist all other treatment, electroconvulsive therapy (ECT)
remains the standard. It has received a lot of bad press in North America in the past,
though long-term studies show that it does not cause damage to the brain. In its modern
form, only a mild shock is used, causing the patient to shiver momentarily. A series of
treatments are sometimes needed before it provides relief. The antidepressant effect of
ECT tends to fade over time and treatment may have to be repeated.But a recent study suggests that the chance of relapse is reduced when ECT is used in
combination with antidepressant and antipsychotic medications.
Implants: Health Canada has just approved a new option of an implantable device that
stimulates the vagus nerve in the neck. Results of a year-long trial by the device's
maker, Cyberonics, Inc., found that about half of patients in a test group reported at
least 50-per-cent improvement in their depression symptoms.About 18 per cent of people who did not respond to drugs responded to them after a year's
use of the implant.
-- Wallace Immen
poster:Cam W.
thread:60209
URL: http://www.dr-bob.org/babble/20010417/msgs/60209.html