Health Focus
RESEARCH PROFILE
Natural Products in the Clinical Treatment
of Mental Illness
A Profile of Dr. James Greenblatt, MD
Inositol
Inositol is a naturally occurring isomer of glucose
and a key intermediate molecule of second messenger signal transduction
pathways used by serotonergic, cholinergic, and noradrenergic neurons.
Inositol is believed to play an important role in the intracellular
phosphatidyl inositol second messenger system to which several key
serotonin receptor subtypes are linked. As such, compounds containing
inositol may represent novel therapeutic agents in treating some
psychiatric disorders.
Dr. James Greenblatt of McLean Hospital, a Harvard
Medical School teaching hospital, is currently using inositol supplementation
as part of the treatment of patients with mental illnesses, particularly
depression, panic disorder, and obsessive-compulsive disorder (OCD).
A considerable body of research is accumulating that
inositol plays an important role in treating these mental illnesses.
Inositol is likely involved in signal transduction pathways involving
serotonin, a neurotransmitter that becomes out of balance in several
of these illnesses. Inositol’s efficacy in the absence of side
effects makes it an attractive addition to treatment plans for specific
mood disorders.
Depressive patients show decreased levels of inositol
in their cerebrospinal fluid (Levine et al., 1997) and inositol
has a similar therapeutic profile to pharmaceutical selective serotonin
reuptake inhibitors (SSRIs) often used to treat depression (Mishori
et al., 1999).
Serotonin plays a definitive role in OCD as well and
Fux et al. (1996) brought about significant improvement in OCD patients
by administration of 18 grams/day of inositol in a random, double-blind,
placebo-controlled study (p=0.04 relative to control).
Treatment with 12 grams of inositol per day (vs. placebo)
has also been shown to significantly reduce the severity and frequency
of panic attacks in patients with panic disorder (Benjamin et al.,
1995) in a double-blind, placebo-controlled, crossover experiment.
The average number of panic attacks per week fell from 10 to 3.5
in patients receiving inositol.
Recently, Palatnik et al. (2001) completed a double-blind,
controlled, crossover trial of inositol vs. fluvoxamine (Luvox®,
Faverin®) in the treatment of panic disorder that reinforces
previous research that inositol is effective in treating this serious
illness. Fluvoxamine is an effective drug for treating panic disorder
in the short term, though its side effects of nausea and tiredness
often cause patients to stop taking it.
In this study, 20 patients taking inositol (up to
18 grams/day) showed improvements on the Hamilton Rating Scale for
Anxiety, agoraphobia scores, and the Clinical Global Impressions
scale, that were comparable with fluvoxamine. In the first month
of treatment, inositol reduced the number of panic attacks per week
by 4 compared with a reduction of 2.4 per week with fluvoxamine,
a significantly improved outcome (p=0.049). Side effects were considerably
less with inositol than with fluvoxamine. This is the first comparison
of inositol with an established drug for treatment of panic disorder
and suggests inositol may be just as effective as some drugs in
the treatment of this disorder, with fewer side effects.
The side effects of inositol are minimal. It is speculated
that inositol’s regulation of serotonin may enhance sleep and
help patients with insomnia, though there are not currently any
valid clinical studies to back this up.
The action of inositol in treating psychological disorders
is largely theoretical. Inositol is known to act as a second messenger
for a number of neurotransmitters in the brain. Antidepressant medications,
such as SSRIs, increase the amount of neurotransmitter in neuronal
synapses within 24 hours by blocking the receptors that sequester
them. However, Greenblatt points out that the psychological effects
of this inhibition can take 2-4 weeks to manifest, suggesting that
second messengers in the biochemical pathways of neurotransmission,
such as inositol, are likely to be involved.
Inositol is not considered an essential dietary nutrient,
because it is made in the body and is shuttled around to various
tissues as needed. Overconsumption of sugar, however, may disrupt
the inositol shuttle system and associated second messenger pathways,
essentially leading to deficiency.
Often, the patients that Greenblatt treats are not
able to make positive dietary changes, but he has shown that supranutritional
doses of inositol are effective in treating illnesses even when
the diet is lacking in some way. He has also used inositol in conjunction
with SSRIs, particularly where high doses of SSRIs cause sleep disturbances.
Inositol can be taken with the medication to alleviate these disturbances.
Greenblatt has used inositol effectively in treating
obsessive-compulsive disorder in both children and adults. He has
been able to use inositol to treat children with OCD without requiring
any other medical intervention. In adults he has used it alone to
treat sleep disturbances.
In most clinical research trials, 10-18 grams of inositol
are used in treatment. Greenblatt reports that he rarely uses more
than 10 grams and in children he successfully uses much lower amounts,
approaching physiological doses (2 grams or less per day).
Greenblatt is excited about current research on inositol
for treating mental illnesses in children because it seems it sometimes
can be used alone without the need for pharmaceutical drugs. He
is anxious to get the word out to other psychiatrists who are reluctant
to use a new and purely nutritional product without the research
to back it up. The body of published literature on inositol in treating
mental illness is significant, but it still has not been incorporated
into mainstream clinical thinking because of the difficulty in getting
past the heavy drug company influence in mental health. A major
academic question Greenblatt asks is, why?
“There is scientific literature in peer reviewed
psychiatric journals demonstrating that inositol appears to work
as effectively as SSRIs (Prozac, Zoloft, and Paxil),” Greenblatt
said. “Studies show consistent improvement in symptoms, significantly
better than placebo.”
Because inositol is a natural substance that is safe
and effective, without significant side effects, Greenblatt believes
it may be particularly effective for use in the treatment of geriatric
and pediatric populations before addressing their illnesses with
pharmaceutical medications.
Greenblatt has been interested in nutritional medicine
since the early 1980s in medical school. He completed traditional
training in adult psychiatry and child psychiatry and believes medications
play an important role in mental health. However, he does not believe
this role should be primary to effective nutritional and dietary
approaches to treating illness.
One of Greenblatt’s main goals is to educate
mental health professionals in the use of nutrition and dietary
supplements as alternatives to pharmaceuticals. Since the mid 1980s,
he has treated thousands of children with both therapy and medication,
but during the past 10 years he has become primarily interested
in helping people find alternative therapies for treating psychiatric
disorders.
| “Patients are looking
for alternatives,” he said. “They are going to alternative
practitioners and coming home with a list of perhaps 30 synthetic
supplements to take for depression. There is little scientific
research to support the use of many of these supplements, and
more importantly, they are not getting better.” |
Greenblatt did an internship with allergist Marshal
Mandel in the 1970s. His introduction to using alternative medicine
in mental illness was observing the behavioral responses of people
to food allergies. “I saw tapes of very sick patients, be it
ADHD, schizophrenia, or depression, before and after eliminating
certain foods that they were allergic to,” Greenblatt said.
“The differences were dramatic!”
The future of inositol in mental health
In spite of the evidence that inositol is effective
in treating mental illness, the medical community is slow to adopt
its use. In order to get the word out, Greenblatt wants to examine
inositol in a host of pediatric disorders that are responsive to
SSRIs: depression, panic disorder, and OCD. He intends to repeat
previous successful adult studies on children. Inositol in pediatric
OCD will be the first study he plans to conduct. It may take a year
or more to complete and two years before appearing in a peer-reviewed
journal.
“It is important to wait for scientific research,”
he said. “But it is also OK to begin to utilize nutritional
interventions that are not harmful and appear to be therapeutic.
Inositol is often a third line treatment for OCD. Medications are
used first, and it doesn’t make a lot of sense that inositol
is not used first, particularly in children and geriatric populations
[on whom drugs may have the most adverse effects].
“What does it take for the medical community
to accept inositol when the research has been done? I don’t
know of any other nutrient in the psychiatric literature that has
undergone the kind of scientific study that inositol has.
| Many medications that we use
in children are not approved for use in children. Most have
only been studied in adults, with not a single study on children.
Yet, we use them every day in children. We have no idea how
they affect brain development or if they even work when we use
them in children. Yet professionals are reluctant to use a safe
herbal or nutritional supplement just because they say, ‘There
is no research on it.’ |
“Up until a few years ago, all the antidepressants
and neuroleptics (antipsychotics) had never been studied in children,”
he said. “Now a few studies are coming out like the use of
Luvox for OCD in children. These studies are funded by the drug
companies. They are very short and they do show some benefit, but
we just don’t know what their effects are over time. In addition,
whenever you treat these disorders, particularly OCD, you always
get a subset, sometimes 30% or 40%, that does not respond to medication.
That is a whole other segment of the population that could benefit
from nutritional intervention.”
Greenblatt recommends emphasizing nutrition with whole
foods and whole food concentrates with higher-dose supplementation
in certain cases.
“The difficult concept is that what we want to
recommend to our patients is to stop eating sugar, junk food, and
white flour, which is going to help a large majority of our child
patients,” Greenblatt said. “When you look at even the
adult mentally ill patients, they are just living on junk food.
To address these lifestyle issues is clearly the first goal. But,
if they are not able to change their diet right away, are there
other alternatives that we can use? Clearly the food we are feeding
our children as a culture is destroying brain cells and having an
adverse effect on growth and development. The kids who are biologically
vulnerable to mental illnesses are going to develop them at much
earlier ages and I think in much more severe forms.”
OPC
Dr. Greenblatt is also interested in the use of oligoproanthocyanidins
(OPCs) in the treatment of mental disorders, particularly for Attention
Deficit Hyperactivity Disorder (ADHD). OPCs have been used for many
years in Europe for vascular complaints such as hemorrhoids and
varicose veins. Greenblatt has seen improvements in the electroencephalograms
(EEGs) of patients with ADHD and improved handwriting, attention,
and behavior in children with ADHD, an effect also observed with
stimulant drugs used to treat ADHD.
“We have found that people respond to OPC whether
or not they have a diagnosis of ADHD,” Greenblatt said. “They
are generally more focused and more attentive. Depressed patients
show an improvement of mood and energy level. PMS is a common complaint
for which we have used OPC with good success.”
In treating ADHD with OPC, Greenblatt sees about a
60% success rate in adults and slightly less than that in children.
“It is not that every patient gets better,” Greenblatt
said. “But for a non-medical intervention it has been quite
successful.”
As a consequence of administering OPC to treat psychiatric
illnesses, Greenblatt is also hearing qualitative reports from patients
of very rapid improvements in joint pain that are noticeable within
a couple weeks of starting OPC. “Older patients will often
report that the joint pain they have had for 20 years is better,”
Greenblatt said. “Then they will suggest it to their relatives.
Joint pain has really been probably the most dramatic improvement
I have seen with the OPC.”
The effect on joint pain may be because OPC prevents
the breakdown of collagen, a structural molecule in joints and blood
vessels. This may also explain why OPC is reported to improve varicose
veins.
Diet is a major component of Greenblatt’s supplement
protocol. Adults and children who can make positive dietary changes
have a much higher likelihood of success. “OPC sometimes can
work without significant dietary interventions and lifestyle changes,
but clearly it works better with those changes.”
OPC is found in pine bark, grape seed, Ginkgo biloba,
and other plant sources and a question arises as to what is the
best source of OPC to use therapeutically. Clinically, Greenblatt
has observed that some people respond to one source of OPC better
than another, but in general patients do better taking a mixed source
of OPC, such as OPC Synergy™ (Standard Process Inc.).
References
|
