Inositol
Information
There
seems to be a lot of discussion about a way to help reduce the
frequency and intensity of your panic attacks and anxiety simply
be eating foods that are significant sources of Inositol. Use
the google search bar above to look up Inositol after you've read
this article...What I like about Inositol is that there are no
known side effects from eating oranges or nuts unless you've got
a food allergy.
What
Is Inositol?
Inositol
is sometimes considered a part of the Viatmin B complex.
Inositol
is a simple carbohydrate that was originally thought to be essential
to good health, but has since been demonstrated not be a vitamin.
In the body, inositol is metabolized into phosphatidylinositol,
which then acts as a second messenger system to stimulate the
release of calcium from its intracellular storage site in the
endoplasmic reticulum. The sugar has also been implicated in improving
the transmission of neural signals in individuals afflicted with
diabetic nerve damage and numbness. Major
sources of inositol include beans, citrus fruit, cantaloupe, nuts,
rice, veal, pork, wheat
bran,
and wheat
germ. There are no known deficiency symptoms in
humans.
*reference: http://micro.magnet.fsu.edu/vitamins/pages/inositol.html
Technical
Article on Inositol
*source: I used this article here because
I was very concerned that it might be taken down from the website
from which it was found. That website and all credit, belongs
to http://www.mvelectric.com/inositol/panic.html
Received
July 19, 1994; revision received Dec. 9, 1994; accepted Jan. 19,
1995. From Soroka Medical Center, Kupat Holim Sick Fund of the
Hisradrut, Beersheba; the Mental Health Center, Beersheba IMinistrv
of Health; the Division of Psychiatry, Ben Gurion University of
the Negev; and Abarbanel Mental Health Center, Bat Yam Minis-
trv of Health, Israel. Address reprint requests to Dr. Benjamin,
Bldg. 10), Rm. 3D41, NIMH, Laboratory of Clinical Science, 9000
Rockville Pike, Bethesda, MD 20892.
Double-Blind, Placebo-Controlled, Crossover Trial of Inositol
Treatment for Panic Disorder
Jonathan
Benjamin, M.D., Joseph Levine, M.D., M.Sc., Mendel Fux, M.D.,
Alex Aviv, M.D., Daniel Levy, M.D., and R.H. Belmaker, M.D.
OBJECTIVE:
Because they found in an earlier study that inositol, an important
intracellular second-messenger precursor, was effective against
depression in open and double-blind trials, the authors studied
its effectiveness against panic disorder. METHOD:
Twenty-one patients with panic disorder with or without agoraphobia
completed a double-blind, placebo-controlled 4-week, random-assignment
crossover treatment trial of 12 g/day of inositol. RESULTS:
The frequency and severity of panic attacks and the severity of
agoraphobia declined significantly more after inositol than after
placebo administration. Side effects were minimal. CONCLUSIONS:
The authors conclude that inositol's efficacy, the absence of
significant side effects, and the fact that inositol is a natural
component of the human diet make it a potentially attractive therapeutic
for panic disorder. (Am J Psychiatry 1995; 152:1084-1086)
Inositol
is an isomer of glucose and a natural constituent of the normal
human diet (1). Interest in inositol accelerated with the discovery
of the phosphatidyl-inositol cycle. The phosphatidyl-inositol
cycle is a second-messenger system used by some noradrenergic
alpha 1 and serotonin 2 receptors, among others. Kofman and Belmaker
(2) showed that pharmacological doses of inositol have behavioral
effects in animals. Twelve g/day of inositol penetrates the blood-brain
barrier in man (3). Acting on a report that inositol CSF levels
are low in depressed patients (4), we found that inositol in doses
of 6 g/day and 12 g/day is a potential treatment for depression
in both open and double-blind, placebo- controlled trials (5).
Because some antidepressants are also effective against panic
disorder, we decided to conduct a trial of inositol treatment
for panic disorder.
METHOD
The subjects for the study were 25 patients who had a DSM-III-R
diagnosis of panic disorder or panic disorder with agoraphobia.
They were screened with a routine psychiatric and medical evaluation.
Exclusion criteria were other psychiatric disorders, physical
disorders, and pregnancy. All patients gave written informed consent
to their participation in the study, and the design was approved
by the insti- tutional review boards of the centers where the
study was conducted. Patients who were taking medications withdrew
from them at least 1 week before beginning a formal washout period;
only two patients actually withdrew from medications this close
to the study. Patients were prepared to curtail conventional treatments
for panic disorder in the hope of finding a new treatment without
troubling side effects. The only medication allowed apart from
inositol and placebo was 1 mg of oral lorazepam as needed for
anxiety.
Placebo was mannitol (N=10) or glucose (N=11) (21 patients completed
the study). The treatments were supplied in identical appearing
white powders with similar tastes and solubilities. Patients took
6 g of medication dissolved in juice twice a day. All patients
began with a 1-week 'run-in" period during which they received
open placebo (N=IO) or no medication (N=11). Thereafter each pa-
tient was randomly assigned to double-blind placebo or inositol
for 4 weeks; each patient then crossed over to the alternate substance
for another 4 weeks.
Patients completed daily panic diaries (6) in which they recorded
the occurrence of panic attacks, the number of symptoms (from
a DSM-III-R list) in each attack, and the subjective severity
of each attack. They also recorded their daily use, if any, of
lorazepam. Inves- tigators reviewed the diaries at each weekly
assessment and com- pleted the Marks-Matthews Phobia Scale (7),
the Hamilton Anxiety Rating Scale (8), and the Hamilton Depression
Rating Scale (9).
A panic score was calculated by taking the mean rating of severity
of attacks (range=O-lO; O=nonexistent, 10=worst ever) and the
num- ber of symptoms per attack and multiplying this mean by the
number of attacks per week.
Baseline
measures were the results at the end of the run-in week. Since
the run-in phase of the trial was brief, and there was no washout
phase between the placebo and the inositol phases, we used the
means for the end of the third and fourth weeks of the two treatments
to compare placebo and inositol results.
RESULTS
Of the 25 patients enrolled in the study, 21 completed it. Two
withdrew before beginning treatment. One patient completed 4 weeks
of inositol and 1 week of placebo and then withdrew without a
clear explanation; he improved while taking inositol. Another
patient com- pleted the initial 3 weeks of placebo but dropped
out because of hypomania before the crossover to inositol.
Nine
of the patients were men and 12 were women. Their mean age was
35.8 years (SD=7). Five patients had panic disorder and 16 had
panic disorder with agoraphobia. The mean duration of illness
was 3.9 years (SD=3). Response to previous treatments did not
affect response in this study (data not shown). Ten patients were
randomly assigned to placebo first, and 11 were assigned to inositol
first.
Patients improved more on every outcome measure while receiving
inositol than they did while receiving placebo. The difference
in number of panic attacks, panic scores, and phobia scores was
significant (tables 1 and 2);
the
difference in Hamilton anxiety and depression scores was not (not
shown). When we conducted an analysis of covariance (ANCOVA) with
baseline data as the covariate on the data from weeks 3 and 4
of the first month alone, as if this were a parallel groups study,
we found that the phobia scores did not differ in the first month.
This ANCOVA found that the number of panic attacks was significantly
lower during inositol treatment, however: the mean number of panic
attacks was 10.1 (SD=1O) during placebo administration and 2.4
(SD=1) during inositol treatment (F=5.7, df=l, 18, p=0.03). The
ANCOVA aIso found that panic scores tended to be lower in the
first month: the mean panic score was 41.7 (SD=41) during placebo
administration and 9.4 (SD=9) during inositol treatment (F=3.5,
df=l, 18, p=0.08).
Eleven patients used lorazepam for anxiety. Lorazepam use did
not differ between the placebo and inositol phases (mean=3.8 mg/week,
SD=6, during placebo administration and mean=3.0 mg/week, SD=5,
during inositol treatment) (t= 1.6, df=20, p=0.12, paired t test).
Lorazepam use did not interact with inositol's effects on panic
attacks. The patients who were taking lorazepam had less response
to inositol for phobia than did those who were not taking lorazepam
(F=8.9, df=l, 14, p= 0.01, for phobia scores by treatment by lorazepam
use).
Two
patients complained of sleepiness while taking inositol. One patient
complained of stomachache while taking placebo.
DISCUSSION
The
effect of inositol appears to be clinically meaningful: the number
of attacks per week fell from about 10 to about six while patients
were taking placebo, and to about three and a half while they
were taking inositol. Ten of the 21 patients were classified as
"true" inositol responders and three were placebo responders
(analysis available on request from Dr. Benjamin).
We
have previously shown that inositol has antidepressant efficacy
(5). Many antidepressants are also antipanic agents. Most biochemical
theories of anxiety and depression implicate the same protagonists--
namely, noradrenergic and serotonergic pathways. Important subtypes
of these receptors use the phosphatidyl-inositol cycle as their
intracellular second messenger (10).
The
absence of substantial side effects and the fact that inositol
is a natural component of the human diet make it a potentially
attractive therapeutic. Inositol has been given to patients with
diabetes in a dose of 20 g/day without ill effects (11). Future
attempts to replicate or augment the effect reported here should
consider using the higher dose. The second-messenger strategy,
as opposed to the transmitter-receptor strategy, is a novel one
for psychopharmacology and deserves further investigation.
REFERENCES
1.
Reynolds JEF: Martindale: The Extra Pharmacopoeia, 30th ed. London,
Pharmaceutical Press, 2993
2.
Kofman O, Belmaker RH: Biochemical, behavioral and clinical studies
of the role of inositol in lithium treatment and depression. Biol
Psychiatry 1993; 34:839-852
3.
Levine J, Rapaport A, Lev L, Bersudsky Y, Kofman O, Belmaker RH,
Shapiro J, Agam G: Inositol treatment raises CSF inositol levels.
Brain Res 1993; 627:168-170
4.
Barkai A, Dunner DL, Gross HA, Mayo P, Fieve RR: Reduced myo-inositol
levels in cerebrospinal fluid from patients with af- fective disorder.
Biol Psychiatry 1978; 13:65-72
5.
Levine J, Barak Y, Gonzalves M, Szor H, Elizur A, Kofman O, Belmaker
RH: Double-blind controlled trial of inositol treatment of depression.
Am J Psychiatry 1995; 152:792-794
6.
Ballenger JC, Burrows GD, Dupont RL Ir, Lesser LLI, Noyes R, Pecknold
JC, Rifkin A, Swrnson RP: Alprazolam in panic disor- der and agoraphobia:
efficacy in short-term treatment. Arch Gen Psychiatry 1988; 45:413422
7.
Marks IM, Matthews AM: Brief standard self-rating for phobic patients.
Behav Res Ther 1979; 17:263-267
8.
Hamilton M: The assessment of anxiety states by rating. Br j Med
Psychol 1959; 32:50-55
9.
Hamilton M: Development of a rating scale for primary depres-
sive illness. Br J Soc Clin Psychol 1967; 6:278-296
10.
Snider RH, Fisher SK, Agranoff BW: Inositide-linked second messengers
in the central nervous system, in Psychopharmacoi- ogy: The Third
Generation of Progress. Edited by Meltzer HY. New York, Raven
Press, 1987, p 320
11.
Arendrup K, Gregersen G, Hawley J, Hawthorne IN: High-dose dietary
myo-inositol supplementation does not alter the ischemia phenomenon
in human diabetics. Acta Neurol Scand 1989; 80: 99-102
