Natural Products in the Clinical Treatment of Mental Illness

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RESEARCH PROFILE

 

Natural Products in the Clinical Treatment

of Mental Illness

 

A Profile of Dr. James Greenblatt, MD

By Joe Leonard

 

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

 

Benjamin, J. et al. 1995. Double-blind, placebo-controlled, crossover

trial of inositol treatment of panic disorder. Am J Psychiatry 52:

1084-1086.

 

Fux, M. et al. 1996. Inositol treatment of obsessive-compulsive

disorder. Am J Psychiatry 153(9): 1219-1221.

 

Levine, J et al. 1997. Controlled trials of inositol in psychiatry.

Eur Neuropsychopharmacol 7(2): 147-155.

 

Mishori, et al. 1999. Combination of inositol and serotonin reuptake

inhibitors in the treatment of depression. Biol Psychiatry 45: 270-273.

 

Palatnik, A. et al. 2001. Double-blind, controlled, crossover trial of

inositol versus fluvoxamine for the treatment of panic disorder. J

Clin Psychopharmacol 21(3): 335-339.