- New Drug Treatments
by Robert Mason Ph.D.
a recent extensive European survey, 17% of the adult population claimed they had
suffered from depression in the last 6-months. But there may be good news for
these millions of people, because over the last couple of years there has been a
explosion of new anti-depressive drugs. The most interesting aspect to this
"new generation" has been its approach.
and almost uniquely, patients were given a selective-serotonin
reuptake inhibitor (SSRI) such as Prozac®, Paxil®, or Zoloft®. The thinking was
that depression occurred because brain serotonin levels were low.
Therefore, by raising serotonin levels, depression could be alleviated. SSRI's do
represent a significant improvement for the majority of people suffering depression
and they are a major advance over the use of
slow-acting tricyclic drugs. But to attribute low serotonin levels for all
forms of depression is far too simplistic. Other factors need to be
considered, including the possibility of a "lack of brain energy,"
which may be the result of an imbalance of oxygen, blood, or glucose
levels. Also to be considered is the imbalance of brain neurotransmitters other than serotonin. The individual's
interpretation of these varied brain imbalances may cause many patients to claim
that they feel depressed.
Several different kinds of drugs, some
of which were originally designed for a completely different purpose, have been
found to produce an anti-depressant effect.
is especially true of stimulants which often make the patient feel more alert
but often also produce an improvement in feelings of "well-being."
The relatively recent edition of the eugeroic drugs, adrafinil and
modafinil; with their unique action of selectively enhancing the activity of
the neurotransmitter noradrenaline were designed
specifically as stimulants, but they lead not only to a stimulatory action but also the improvement of well-being for most patients.
serotonin plays a vital role In mood, noradrenaline is essential to drive and
motivation. Chronically depressed individuals typically have
dysfunctional and atypical noradrenergic systems, particularly with regard to
alpha-2 and beta-adrenoceptors.
Edronax®), is a recent anti-depressant development from the
pharmaceutical company Pharmacia & UpJohn. Edronax®
is a selective noradrenaline reuptake inhibitor (NARD and it has shown itself to
be effective in both the short term (4-8 weeks) and long-term (up to 12-months)
for the treatment of depression. Apart
from regulating energy, drive, and motivation, the noradrenaline neurotransmitter
is also involved in regulating the sleep-wake cycle, food intake, endocrine
function, and peripheral sympathetic function.
Dr. Borson from Pharmacia & UpJohn stated "it is possible that
movement, initiation speed and the stamina of individuals is conditioned in part
by noradrenergic mechanisms."
Reboxetine- Clinical Trials
long-term open label study was conducted with 139 people whose mean age was 74.
Two thirds of the participants were women. It was discovered that those patients
who improved within a 6-week period maintained their gains over the year. Nearly
88% of the patients improved their depression and reboxetine was well tolerated.
In fact improvements were noted to be better in severe depressive cases than
those that could normally be achieved with SSRI's.
further extensive study by Pharmacia & UpJohn with 549 patients showed that
reboxetine was as effective as Prozac® within an 8-week period.
Patients in the double-blind placebo controlled study taking reboxetine
had a 19 point drop in depression scores compared to a 17point drop for
Prozac®. Side effects with reboxetine were noted as dry-mouth,
Insomnia and constipation. The
study was conducted at the Hospital Clinic in Barcelona, Spain by Dr. Juan
Massana who who stated; "these studies provide important information on the
role that (noradrenaline) plays in depression and a possible treatment option
for the many patients around the world who suffer from depression."
have been numerous other studies with up to 2000 patients taking part in
double-blind placebo-controlled conditions. They all Indicate that reboxetine is
an effective anti-depressant with few and usually minor side effects.
Reboxetine has proven to be effective In short term use and equivalent if
not better than the standard SSRI drug interventions.
Dosages, Contraindications and Side Effects
The most noted side effects
of reboxetine use have been dry mouth, insomnia, constipation, increased
sweating, tachycardia and vertigo. Although it has proven to be than the
SSRI’s, its use in patients with severe heart conditions is .not advised.
Furthermore, reboxetine should only be given under close supervision to patients
with a history of seizure disorders. As with nearly all anti-depressants,
switches from mania to hypomania have occurred.
Thus patients who suffer with chronic depression and suicidal tendencies
require close supervision. At high dosages urinary difficulties have also been
noted in a few rare cases. As such
the manufacturer recommends that persons with an enlarged prostate or glaucoma
(increased pressure in the eyes) avoid use.
anti-fungal Ketoconazole has been shown to increase the concentration of
reboxetine. Reboxetine should not
be taken with tricyclic antidepressants, MAO inhibitors, SSRI’s, and lithium
because potential reactions have not yet been studied in clinical trials. No
tests have been conducted in pregnancy; therefore pregnant and lactating women
should avoid reboxetine. Persons
suffering from severe liver or kidney disorders should also avoid reboxetine, (these cautions
apply to all of the drugs mentioned in this article).
maker also suggests the avoidance of certain types of antibiotics including
erythromycin, fluvoxamine and anti-fungals such as fluconazole, flecainide and
cyclosporin. The manufacturer’s
drug insert also suggests avoidance of ergot derivative drugs (such as Hydergine,
bromocriptine, and nicergoline).
dosages have been 4mg to 8mg per day, up to 12mg (20mg per day were used for a
few weeks in some trials). There
is probably little need to exceed 8mg per day as most side effects begin to appear at dosages in excess of 8mg per
The Acetylcholine Factor
levels decline as we age and acetylcholine
is the neurotransmitter most affected in Alzheimer's disease.
Just as in Parkinson's disease where there is reduced dopamine, it is only when
acetylcholine levels reach a severely low state that
Alzheimer's is actually diagnosed. In the United Kingdom, an estimated 20% of
people over the age of 65 are diagnosed with some degree of Alzheimer's.
This figure climbs to an alarming 50% for people over the age of 80.
Yet while $23,000 is spent on AIDS research each year per AIDS patient,
less than $700 is spent per cancer patient, and only $15 is spent on research
per Alzheimer's patient. So
far, specific Alzheimer's drugs have not been particularly effective and many
have had quite toxic side effects (usually upon the liver).
While natural products like DMAE, Lecithin, and Choline have been taken
in to raise Acetylcholine levels in Alzheimer's patients, they have
not been very effective even when taken with Acetyl L-Carnitine, (which has
shown to be beneficial). To use an
analogy if one waits until the engine is smoking before changing the oil,
there's little benefit to be gained from the oil change. The diagnosis of Alzheimer's already
that major neuronal damage has taken place and the best that can be hoped
for is a slowing down of the disease progression. Age related memory decline
needs to be recognized and treated before it becomes a senile dementia, if we
are to live long and productive lives.
of the most recent and most promising new drug
therapies for Alzheimer's have focused on the enzyme acetylcholinesterase (AChE).
This enzyme breaks down the neurotransmitter Acetylcholine and therefore its
inhibition helps improve Acetylcholine availability, (these kinds of ACh5
inhibitors are abbreviated AchEl). A
number of new AChB's have been developed in the last couple of years including
Novartis' Exelon® (rivastigmine tartrate) and Bayer's metrifonate. But the most
interesting of them all, I believe, is Janssen's Nivalin® (galantamine), also
called ReminyI® in some countries.
has shown to have two methods of action, which make it special among the
current range of
1). It delays the deactivation of the enzyme acetylcholinesterase thus
improving Acetylcholine levels.
2). It also stimulates nicotinic receptors,
which may release even more Acetylcholine.
It is nicotinic stimulation that
represents the new area for AIzheimer's research and it is hoped that this will
result in fewer amyloid plaques which have come to characterize Alzheimer's.
They are microscopic, spherical structures containing deposits of beta-amyloid
peptide, dead and dying neurons and evidence of inflammation. Data from
galantamine trials indicate that improvements have been shown in cognitive and
global scales commonly used to assess the progress of people with Alzheimer's. Thus
galantamine improved functional ability, memory, and learning ability. While
galantamine is specifically approved as an AIzheimer's drug, it also appears to
produce a mild anti-depressant effect.
the Clinical Trials
has been approved in Austria and Sweden for Alzheimer's disease and it is currently undergoing stage II and stage III clinical trials
in several other countries. In a pivotal US
study with 636 Alzheimer's patients, the galantamine group recorded an
improvement of 1.7 points while the control group performance declined by 2
Contraindications and Side Effects
date galantamine has not shown any impact upon liver
function in human trials. This is a significant point because most Alzheimer's treatments
negatively affect the
liver. One aspect of galantamine's
relative safety may be the fact that
it is an extract of the Galanthus Nivalis plant, a type of snow drop
in the daffodil family. To date
most side effects have been limited to increased respiratory function,
dizziness, lowering of heart rate, increased sweat and saliva production, loss
of appetite, nausea, sleep disturbance and headache. In an overdose case, a
lowering of blood pressure and heart rate was seen.
is contraindicated in myocardial infarction, bronchial asthma, epilepsy, low
blood pressure, diabetes, ulcers, gangrene, and Parkinsonism. The standard
dosage has been 5mg twice daily but dosages as high as 6 tablets (5mg each) daily
have been used. continued