A clinical study on the management of anxiety neurosis with Sankhaholi

Abstract

Sankhaholi (Evolvulus alsinoides Linn.) has been used to improve brain power, memory and to treat various psychiatric disorders. A single blind, placebo controlled study was conducted to evaluate the efficacy of Sankhaholi in 60 patients of Anxiety neurosis, belonging to 18-50 yrs of age group of both sexes. The severity of anxiety symptoms was assessed by Hamilton's Anxiety Rating Scale (HARS), which was administered at baseline, at every week for 4 weeks, and then at 6th week of treatment (the treatment end point). In Drug group, the mean HARS score before treatment was 22.26, which was trimmed down to 12.21 after 6 weeks treatment. Whereas, in placebo group, pre-treatment mean HARS score was 23.78 and post treatment HARS score were 24.07. Sankhaholi markedly relieved anxiety symptoms without producing any side effects. Statistically the results of Sankhaholi were determined highly significant as compared to the results of placebo.

Full text

Indian Journal of Traditional Knowledge
Vol. 6(4), October 2007, pp. 668-677
A clinical study on the management of anxiety neurosis with Sankhaholi
Yasmeen Shamsi
1
*, Jameel Ahmad
2
& Asim Ali Khan
2
1
Department of Kulliyat, Faculty of Medicine, Jamia Hamdard, New Delhi 110062;
2
Department of Moalijat, Faculty of
Medicine, Jamia Hamdard, New Delhi110062
E-mail: yasmeenshamsi@yahoo.co.in
Received 7 November 2005; revised 22 February 2006
Sankhaholi (Evolvulus alsinoides Linn.) has been used to improve brain power, memory and to treat various psychiatric
disorders. A single blind, placebo controlled study was conducted to evaluate the efficacy of Sankhaholi in 60 patients of
Anxiety neurosis, belonging to 18-50 yrs of age group of both sexes. The severity of anxiety symptoms was assessed by
Hamilton’s Anxiety Rating Scale (HARS), which was administered at baseline, at every week for 4 weeks, and then at 6
th
week of treatment (the treatment end point). In Drug group, the mean HARS score before treatment was 22.26, which was
trimmed down to 12.21 after 6 weeks treatment. Whereas, in placebo group, pre-treatment mean HARS score was 23.78 and
post treatment HARS score were 24.07. Sankhaholi markedly relieved anxiety symptoms without producing any side
effects. Statistically the results of Sankhaholi were determined highly significant as compared to the results of placebo.
Keywords: Anxiety neurosis, Psychiatric disorders, Anxiolytic activity, Sankhaholi, Unani medicine, Nafsiyati amraz
IPC Int. Cl.
8
: A61K36/00, A61P25/00, A61P25/08, A61P25/14, A61P25/18, A61P25/20
Anxiety disorders are most common of all psychiatric
disorders throughout the world
1-3
. The phenomenon of
anxiety is not new; the description of anxiety
disorders in classical literature of Unani medicine is
available, but in separate expressions as Malikholia
(melancholia), Junoon (insanity), Bedari (insomnia)
and Khafqaan (palpitation)
4
. Conventional treatments
for anxiety in Allopathic System of Medicine include
the benzodiazepines, antidepressants and buspirone in
low doses. All these three categories of drugs are
associated with certain disadvantages as well. For
example, benzodiazepines cause sedation, impaired
psychomotor performance and drug dependence.
Antidepressants are somehow associated with
sedation, anticholinergic and/or other adverse effects.
Buspirone and antidepressants may both produce
initial worsening of anxiety symptoms
5
. In Unani
System of Medicine, several drugs have been reported
to have beneficial effects in psychiatric (mental)
disorders. The herbal drug, Sankhaholi (Evolvulus
alsinoides Linn.), as described in Unani literature,
holds Musakkin-e-asab (tranquilizing), Muqawwi-e-
asab (nervine tonic) and Mufarreh (alexiteric)
activities
4,6
. As a brain and cardiac tonic, it has been
effectively used by the Unani physicians to manage
the symptoms of psychiatric ailments such as
Malikholia (melancholia), Junoon (insanity), Bedari
(insomnia) and Khafqaan (palpitation)
4-9
. Keeping in
view the high prevalence rates of anxiety neurosis and
the side effects of the conventional anxiolytic
therapies used in Allopathic System of Medicine, it
was intended to discover safer and effective treatment
of anxiety neurosis.
The word anxiety has been derived from a German
word angst meaning sense of dread and loss, and also
from a Latin word anxietas meaning nervous
restlessness, and from a Greek word meaning to
constrict
10
. The term anxiety is used to describe the
feelings of uncertainty, uneasiness, and apprehension
or tension that a person experiences in response to
internal or external stimuli and can result in physical,
emotional, cognitive and behavioral symptoms
11
.
Anxiety neurosis, also entitled, as generalized anxiety
disorder is a neurotic disorder characterized by
persistent excessive anxiety, which is not caused by
organic brain disease or any other psychiatric
disorder. The symptoms range from mild feelings of
fatigue, apprehension, and tension to more intense
states of restlessness and irritability that may lead to
aggressive acts. In extreme cases, the uncontrollable
emotional discomfort is accompanied by physical
reactions including tremors, sustained muscle tension,
tachycardia, dyspnoea, hypertension, increased
respiration and profuse perspiration. Other physical
_
__________
*Corresponding author

SHAMSI et al.: MANAGEMENT OF ANXIETY NEUROSIS WITH UNANI MEDICINE
669
signs and symptoms include change in the skin
colour, nausea, vomiting, diarrhoea, frequency of
micturition, insomnia, and changes in appetite, all
occurring without any underlying organic cause
12
.
The exact cause of anxiety neurosis is not clearly
understood. However, a number of theories
concerning the etiology of this disorder have been
demonstrated. Mental problems have been recognized
from the earliest time in Unani Medicine. The Greek
Physician, Hippocrates (460-377 BC) was the first
medical man who rejected the idea of demonology
and offered a new theory that mental disorders were
the results of qualitative/quantitative imbalance of
body humors
13
. He stressed the importance of pleasant
surroundings, exercise, proper diet, massage, soothing
baths, music and some other methods such as
bleeding (Fasd), purging (Istefragh) and mechanical
restrains (Amal-e- Kai, Hijamat) in the treatment of
mental diseases. A number of diseases pertaining to
mental illness have been described in Unani classical
literature. However, the symptoms of anxiety
disorders like insomnia, palpitation, phobia,
nightmares, polyuria, depression and apprehension are
seen in the diseases of psychiatric origin mentioned
with the names such as malekholia (Melancholia),
subara, qutrub, mania, sahar, kaaboos and ishq. The
causative factor for all these problems remains same,
i.e. Ghalba-e-Sauda/Safra (abnormal accumulation of
bile), which in due course of time /in chronic course is
transformed into Sauda (Sauda-e-ghair tabayee) due
to the burning of Safra or other humours (Akhlat)
14-17
.
Methodology
The single blind, randomized, parallel designed;
placebo-controlled study was conducted in the Out
Patient Department of Clinical Research Unit of
Majeedia Hospital, Jamia Hamdard, New Delhi. The
test drug Sankhaholi was procured from Khari Baoli
market of Old Delhi. Proper identification of the drug
was made by the Department of Botany, Faculty of
Science, Jamia Hamdard, New Delhi. The millet flour
was used as placebo. The fine powder of Sankhaholi
or placebo was given in the dose of 3 gm daily at
bedtime with 100 ml of water to the respective group
of patients. All patients with symptoms of anxiety
attending the Research OPD, Majeedia Hospital were
screened as per the inclusion and exclusion criteria.
The baseline questionnaire included questions
regarding age, sex, level of education, marital status,
employment, and personal habits. The subjects were
asked questions concerning general, physical and
mental health status, socio-economic status, past
history, medical history and time since symptoms
were first noticed. The subjects were also questioned
about the time since treatment was first sought. They
were asked too, what medications have been
prescribed for their anxiety disorder by a doctor
earlier, either at the anxiety clinic or elsewhere, since
their first visit to the clinic.
After screening patients fulfilling to Diagnostic and
Statistical Manual of Mental Disorders, 4
th
edition
(DSM-IV) criteria for the diagnosis of anxiety
neurosis (generalized anxiety disorder) were
registered in the study
18
. Subjects with other anxiety
disorders (e.g., panic attacks, obsessive compulsive
disorder, post-traumatic or acute stress disorders), or
patients having anxiety with co morbid
somatic/psychiatric disorders (e.g. mixed anxiety and
depression) were excluded. The exclusion was based
on symptoms and assessment questions (Tables 1 &
2). Further selection criteria included an absence of
any cardiac or respiratory disease, hypothyroidism,
and hyperthyroidism, or any other medical or
psychiatric condition that may have prejudiced the
diagnosis or rating of anxiety. No lactating or
pregnant women were registered in the trial. Patients
with significant past or current history of cigarette
smoking, drug or alcohol abuse were also excluded.
Individuals over 50 yrs of age, as well as
postmenopausal women were excluded in order to
gather as much as homogenous groups and also to
exclude postmenopausal anxiety (postmenopausal
syndrome). The exclusion and inclusion criteria were
common to both drug and placebo groups. Eligible
patients were asked to sign an informed written
consent form. All the participants gave their
agreement to participate in the study.
In order to exclude other organic causes of anxiety,
detailed laboratory investigations were carried out,
which comprised chest X-Ray, ECG, blood sugar test
and thyroid function test (Free T
3
, Free T
4
, and TSH).
The severity of anxiety symptoms was assessed by
Hamilton’s Anxiety Rating Scale (HARS), which was
administered at baseline, at every week for 4 weeks,
and then at 6
th
week of treatment (the treatment end
point). The Hamilton’s Anxiety Rating Scale (HARS)
is an observer rated scale used to measure the severity
of anxiety symptoms in clinical studies. It consists of
14 items rated on 5 points scale {0= not present,
1=mild, 2= moderate, 3= severe, 4= very severe

INDIAN J TRADITIONAL KNOWLEDGE, VOL 6, No. 4, OCTOBER 2007
670
(grossly disabling)}
19
.
Many items correspond to
grouping of symptoms (e.g. gastrointestinal
symptoms, cardiovascular symptoms). A score of 18
is indicative of clinically significant anxiety. In each
group, differences between pre-treatment and post-
treatment mean HARS scores for each patient
(difference between pairs of observations) were
analysed by using the non parametric Wilcoxon
Signed Rank test. The mean difference of pre-
treatment and post- treatment scores of HARS for all
items, was compared between Drug and Placebo
groups by using the independent sample Student’s‘t’
test with modified degree of freedom. Paired‘t’ test
was used to test difference between pre-treatment
and post-treatment scores of HARS different items.
Mean scores of HARS for all items at baseline and at
end point were also compared by applying the paired
‘t’ test.
Results
Total 60 patients belonging to 18-50 yrs of age and
both sexes, diagnosed as cases of anxiety neurosis
(generalized anxiety disorder) as per DSM-IV
diagnostic criteria were registered. Out of 60 subjects,
43 were included in the drug group and 17 in the
placebo group. Three cases of placebo group dropped
the study at 2
nd
week of treatment due to the lack of
benefit; while14 cases completed the study till end
point (6 weeks). One case of drug group did not turn
up after the first visit, whereas 42 cases accomplished
the study satisfactorily for 6 weeks. On analysis of
Mizaj (temperament) recorded as per the classical
parameters (Ajnas-e-ashra), the patients belonged
either to Safravi Mizaj (bilious temperament) or
Saudavi Mizaj (melancholic temperament) (Table
3)
20
. On exploring different symptoms of anxiety on
HARS, most frequently found symptoms were
palpitation, restlessness, fatigability, frequency of
micturition, difficulty in concentration, feeling of
weakness, and hot or cold flushes (Table 4).
Sankhaholi treatment produced significant reduction
in all symptoms of anxiety neurosis. The differences
between pre-treatment and post-treatment, total
HARS scores of all patients in the drug group
(differences between paired observations) were
computed by applying Wilcoxon signed rank test. The
value of Z was calculated as 5.50 for positive
differences and –5.50 for negative differences. The
value 5.50 is greater than 2.20 (the table value of Z)
and –5.50 is greater than –2.20 (table value of Z).
Hence, it is a statistically significant result (p<. 02)
(Table 5). Wilcoxon signed rank test was also applied
on differences between baseline HARS scores and
post-treatment HARS scores of placebo group
patients. The calculated value of Z was recorded as
1.22, which is less than 1.65 (table value of Z) and -
1.22, which is less than -1.65 (table value of Z).
Therefore, this is a statistically insignificant result (p
>.10) (Table 6). By applying paired ‘t’ test
independently for each group, pre-treatment and post
treatment mean scores of each individual item on
HARS were also compared. The difference was found
significant in case of drug group and insignificant in
case of placebo group (Tables 7 & 8) (Figs. 1 & 2).
Paired ‘t’ test was also used to assess the difference
Table 1⎯Assessment questions to exclude other anxiety
disorders
Symptoms related to panic disorder:
Have you experienced severe distress in which your heart was
racing, you had difficulty in breathing, and you thought you
might be having a heart attack? (Yes / No)
Symptoms of obsessive thoughts or Compulsive behaviors,
related to OCD:
Do you find yourself constantly having recurrent thoughts that
are difficult to control or stop? (Yes / No)
Symptoms related to phobic disorder:
Do you have severe fears of persons, places, or things that
prevent you from doing things you want? (Yes / No)
Symptoms related to post-traumatic stress disorder:
Have you experienced a severe tragedy in your life that comes
back to you in dreams or flashbacks? (Yes / No)
OCD=Obsessive Compulsive Disorder
Table 2⎯Assessment questions to exclude depressive disorders
Do you notice feelings of worthlessness, guilt, doom, or ideas of
self-harm? (Yes / No)
Do you have anorexia with weight loss? (Yes / No)
Do you suffer from very early morning awakening? (Yes/ No)
Table 3⎯Mizaj (temperament) of patients (N=56)
Mizaj (Temperament)
Variance
Damwi
(Sanguin)
Balghami
(Phlegmatic)
Safravi
(Bilious)
Saudavi
(Melancholic)
No of patients
in drug group
0 0 22 20
No of patients
in Placebo
group
0 0 9 5
Total No. of
patients in
0 0 31 25

SHAMSI et al.: MANAGEMENT OF ANXIETY NEUROSIS WITH UNANI MEDICINE
671
between pretreatment and post treatment mean scores
of HARS for total items. Significant difference in case
of drug group and insignificant difference in case of
placebo group was computed (Table 9; Figs. 3 & 4).
Drug and placebo groups were compared with each
other by using unpaired student ‘t’ test. The value of
‘t’ was calculated as 9.08, which is much higher than
the table value of ‘t’ (3.55) at 54 degree of freedom (p
<. 001) (Table 10).
Fig. 1⎯Pretreatment of individual item of HARS
Fig. 2⎯Post treatment of individual item of HARS
Fig. 3⎯Pretreatment of total items of HARS
Fig. 4⎯Post treatment of total items of HARS
Discussion
The aim of the present study was to find out an
effective and safe treatment (as Sankhaholi) of
anxiety neurosis and to ascertain the anxiolytic effect
of Sankhaholi (Evolvulus alsinoides Linn.). In the
single blind, placebo controlled trial, the effects of
Sankhaholi as well as placebo were monitored on all
four degrees of anxiety. Although, the number of
patients having severe degree of anxiety was small.
Sankhaholi treatment produced significant relief in all
the symptoms of anxiety neurosis irrespective of
duration of illness and severity of anxiety within 2-6
weeks period. In placebo group, reduction in anxiety
scores was also observed at 2
nd
or 3
rd
week of
treatment but in the later period of placebo treatment
no further improvement was noticed, rather an
increase in the anxiety scores was observed. The relief
in anxiety with Sankhaholi treatment was found
sustained and progressive; the relief at the early phase
of placebo treatment was appealing; however, such
placebo response rates (40-50%) are well known with
anxiety disorders
21-23
. The test drug Sankhaholi was
well tolerated, no significant adverse effect was
reported during and after treatment. After 6 weeks of
treatment abrupt withdrawal was not associated with
any withdrawal symptoms. The drug induced normal
sound sleep in the patients without any hangover.
None of the patients reported somnolence, withdrawal
fatigue or worsening of the symptoms. Thus,
Sankhaholi appeared to have several of the
advantages but none of the disadvantages of
conventional anxiolytic drugs such as
benzodiazepines, tricyclic antidepressants, and
buspirone. The study therefore confirmed that
Sankhaholi is a safe and effective drug for the
treatment of anxiety neurosis. As preliminary
pharmacology of Sankhaholi (Evolvulus alsinoides
Linn.) discovered that its alkaloid, evolvine decreased
the heart rate and force of contraction in small doses
and caused cardiac arrest in large doses in a pithed
frog
8
. Sankhaholi has some effects on noradrenergic
neurotransmission, and it alleviates anxiety by
modulating noradrenergic neurotransmitter system, as
the role of noradrenergic malfunctioning has been
linked to the etiology of anxiety neurosis
24-27
. Further

INDIAN J TRADITIONAL KNOWLEDGE, VOL 6, No. 4, OCTOBER 2007
672
Table 4⎯Frequency of different anxiety symptoms on Hamilton Anxiety Rating Scale
Drug group Placebo group
Symptoms
Frequency % Frequency %
Irritability 18 42.86 6 42.85
Worries 8 19.05 4 28.57
Easy fatigability 12 28.57 5 35.71
Feeling of tension 7 16.66 3 21.43
Startle response 2 4.76 0 0
Restlessness 16 38.09 6 42.85
Fear 7 16.66 5 35.71
Difficulty in falling asleep 9 21.43 6 42.85
Broken sleep 5 11.90 2 14.28
Fatigue on waking 10 23.80 2 14.28
Dreams / night mares 2 4.76 0 0
Difficulty in concentration 12 28.57 3 21.43
Poor memory 6 14.28 2 14.28
Loss of interest 4 9.52 2 14.28
Lack of pleasure in hobbies 5 11.90 2 14.28
Depression 1 2.38 0 0
Hot or cold flushes 10 23.09 4 28.57
Blurring of vision 2 4.76 1 7.14
Feeling of weakness 12 28.57 4 28.57
Picking sensation 2 4.76 0 0
Jerks 10 23.80 6 42.85
Unsteady voice 4 9.52 2 14.28
Increased muscular tone 13 30.95 3 21.43
Palpitation 30 71.43 9 64.28
Pain in chest 2 4.76 1 7.14
Throbbing of vessels 1 2.38 0
0
Fainting 0 0 0 0
Feeling of missing beats 0 0 0 0
Pressure or constriction in chest 12 28.57 4 28.57
Chocking feeling 6 14.28 2 14.28
Dyspnoea 5 11.90 2 14.28
Difficulty in swallowing 0 0 0 0
Abdominal pain 6 14.28 2 14.28
Burning sensation in abdomen 4 9.52 2 14.28
Abdominal fullness 3 7.14 0 0
Nausea / vomiting 6 14.28 4 28.57
Loose motions / constipation 4 9.52 3 21.43
Frequency of micturition 12 28.57 8 57.14
Menstrual irregularities 3 7.14 1 7.14
Premature ejaculation 4 9.52 3 21.43
Loss of libido 0 0 0 0
Impotence 0 0 0 0
Dry mouth 5 11.90 3 21.43
Flushing / pallor 2 4.76 1 7.14
Tendency to sweat 6 14.28 2 14.28
Giddiness 6 14.28 2 14.28
Tension headache 8 19.05 4 28.57
Tremors of hands 9 21.43 6 42.85
Dilated pupils / exophthalamos 0 0 0 0
Strained face / furrowed brows 10 23.80 5 35.71
Swallowing 2 4.76 2 14.28

SHAMSI et al.: MANAGEMENT OF ANXIETY NEUROSIS WITH UNANI MEDICINE
673
Table 5⎯Wilcoxon signed rank test for the results of Sankhaholi
Participants HARS Score
before treatment
HARS Score after
treatment
Difference Sign of
difference
Actual rank Place of
rank
Rank
given
1 24 11 +13 + 11 31 +31.5
2 33 15 +18 + 15 41 +41
3 22 11 +11 + 9 18 +22
4 21 14 +7 + 5 6 +6.5
5 25 17 +8 + 6 8 +9
6 18 10 +8 + 6 9 +9
7 18 6 +12 + 10 27 +28.5
8 19 10 +9 + 7 11 +12.5
9 18 8 +10 + 8 15 +16
10 18 8 +10 + 8 16 +16
11 18 7 +11 + 9 19 +22
12 19 10 +9 + 7 12 +12.5
13 22 8 +14 + 12 33 +34.5
14 22 11 +11 + 9 20 +22
15 29 14 +15 + 13 37 +38
16 23 8 +15 + 13 38 +38
17 19 7 +12 + 10 28 +28.5
18 19 19 0 0 - - -
19 20 6 +14 + 12 34 +34.5
20 21 9 +12 + 10 29 +28.5
21 21 7 +14 + 12 35 +34.5
22 24 25 -1 - 1 1 -2
23 21 10 +11 + 9 21 +22
24 23 10 +13 + 11 32 +31.5
25 21 10 +11 + 9 22 +22
26 21 22 -1 - 1 2 -2
27 23 6 +17 + 14 40 +22
28 20 11 +9 + 7 13 +12.5
29 23 12 +11 + 9 23 +22
30 23 9 +14 + 12 36 +34.5
31 22 16 +6 + 4 4 +4.5
32 20 13 +7 + 5 7 +6.5
33 24 25 -1 - 1 3 -2
34 19 8 +11 + 9 24 +22
35 21 15 +6 + 4 5 +4.5
36 26 18 +8 + 6 10 +9
37 23 12 +11 + 9 25 +22
38 29 19 +10 + 8 17 +16
39 27 15 +12 + 10 30 +28.5
40 24 15 +9 + 7 14 +12.5
41 22 11 +11 + 9 26 +22
42 30 15 +15 + 13 39 +38
Calculations
Sum of ranks given to positive differences 855
Sum of ranks given to negative differences 6
Total number of observations 42
Number of untied observations 41
Number of tied observations 1
Mean of the rank sums {0.25 n × (n+1)} 0.25 × 41 (42) =430.5
Variance of the rank sums {n (n+1) (2n+1) / 24} 5955
Standard deviation 77.17
Z statistics for positive differences (Z) (855-430.5) /77.17= 5.50
Z statistics for negative differences (Z) (6-430.5) /77.17= -5.50
5.50 numerically exceeds 2.20 (Table value of Z) and -5.50 exceeds -2.2 which is a statistically significant result (p<. 02).

INDIAN J TRADITIONAL KNOWLEDGE, VOL 6, No. 4, OCTOBER 2007
674
Table 6⎯Wilcoxon Signed Rank Test for the Results of Placebo
Participants HARS score
before treatment
HARS score
after treatment
Difference Sign of
difference
Actual
rank
Place of
rank
Rank given
1 24 25 -1 - 1 1 -6.5
2 24 22 +2 + 2 13 +13.5
3 20 21 -1 - 1 2 -6.5
4 22 23 -1 - 1 3 -6.5
5 19 18 +1 + 1 4 +6.5
6 25 26 -1 - 1 5 -6.5
7 28 29 -1 - 1 6 -6.5
8 20 21 -1 - 1 7 -6.5
9 23 24 -1 - 1 8 -6.5
10 31 30 +1 + 1 9 +6.5
11 27 28 -1 - 1 10 -6.5
12 26 28 -2 - 2 14 -13.5
13 19 18 +1 + 1 11 +6.5
14 25 26 -1 - 1 12 -6.5
Calculations
Sum of ranks given to positive differences 33
Sum of ranks given to negative differences 72
Number of observations 14
Mean of the rank sums {0.25 n × (n+1)} 0.25 × 14 (15) =52.5
Variance of the rank sums {n (n+1) (2n+1)/24} 253.75
Standard deviation 15.93
Z statistics for positive differences (Z) (33-52.5) /15.93= -1.22
Z statistics for negative differences (Z) (72-52.5) /15.93= 1.22
-1.22 is less than -1.65and 1.22 is less than 1.65 therefore; it is a statistically insignificant result (p>.10).
Table 7⎯Effects of Sankhaholi on different symptoms of anxiety on Hamilton Anxiety Rating Scale
Mean scores Symptoms
Before
treatment
After1
week
treatment
After 2
weeks
treatment
After 3
weeks
treatment
After 4
weeks
treatment
After 6
weeks
treatment
Mean
difference
after 6
weeks
SD ± SE ±
t p
Anxious mood (n=26) 2.92 2.88 2.23 2.11 1.73 1.57 1.35 084 0.16 8.43 <. 001
Tension (n=37) 3.24 3.16 2.23 2.40 1.97 1.78 1.46 0.80 0.13 11.23 <. 001
Fear (n=7) 2.28 2.00 1.57 1.43 1.57 1.28 1.00 1.00 0.77 2.70 <. 05
Insomnia (n=26) 2.88 2.73 2.07 2.19 1.46 1.50 1.38 0.98 0.19 7.26 <. 001
Intellectual/ Cognitive
(n=19)
2.73 2.68 2.00 2.05 1.94 1.73 1.00 0.94 0.22 4.54 <. 001
Depression (n=10) 2.25 2.10 2.10 1.80 1.70 1.50 0.75 0.98 0.31 2.41 <. 005
Somatic (sensory) (n=26) 3.08 2.83 2.45 2.33 2.15 1.92 1.16 1.12 0.22 5.27 <. 001
Somatic (muscular)
(N=27)
3.03 2.83 2.20 2.30 1.80 1.60 1.43 0.77 0.15 9.50 <. 001
Cardiovascular (n=33) 3.06 2.81 2.39 2.45 1.90 1.66 1.40 1.00 0.17 8.23 <. 001
Respiratory (n=23) 2.82 2.60 2.21 2.08 1.69 1.47 1.35 0.83 0.17 7.94 <. 001
Gastrointestinal (n=23) 2.87 2.65 2.22 2.00 1.61 1.39 1.48 0.81 0.18 8.22 <. 001
Genitourinary (n= 19) 2.44 2.44 2.27 1.94 1.94 1.44 1.00 0.91 0.20 5.00 <. 001
Autonomic (n=27) 2.74 2.48 2.03 2.03 1.66 1.26 1.48 0.97 0.19 7.78 <. 001
Behavioral (n=21) 2.63 2.45 1.95 1.90 1.45 1.45 1.18 1.09 0.24 4.91 <. 001
n= Number of patients; SD= Standard deviation; SE= Standard error

SHAMSI et al.: MANAGEMENT OF ANXIETY NEUROSIS WITH UNANI MEDICINE
675
Table 8⎯Effects of Placebo on different symptoms of anxiety on Hamilton Anxiety Rating Scale
Mean scores ymptoms
Before
treatment
After1
week
treatment
After 2
weeks
treatment
After 3
weeks
treatment
After 4
weeks
treatment
After 6
weeks
treatment
Mean
difference
after 6
weeks
SD ± SE ±
t p S
Anxious
mood (n=26) 2.50 2.10 2.10 2.30 2.30 2.40 0.10 0.57 0.18 0.55 >.10
ension (n=37) 2.93 2.21 2.00 2.78 2.71 2.90 0.30 0.68 0.18 1.66 >.10
(n=7) 2.00 1.80 2.40 2.60 2.20 2.20 0.20 0.45 0.20 1.00 >.10
nsomnia (n=26) 2.40 1.50 2.10 2.20 2.50 2.50 0.10 0.74 0.23 0.43 >.10
n=19)
2.20 2.00 2.00 2.20 2.20 2.00 0.20 0.84 0.37 0.54 >.10
ession (n=10) 2.00 2.00 2.00 1.75 2.50 2.50 -0.50 0.58 0.29 1.72 >.10
matic (sensory) (n=26) 2.33 1.66 2.22 2.22 2.33 2.22 0.11 0.78 0.26 0.11 >.10
matic (muscular)
n=27)
2.72 2.09 2.36 2.54 2.36 2.33 0.39 1.03 0.31 1.25 >.10
diovascular (n=33) 2.40 2.20 2.10 2.40 2.50 2.30 0.10 0.81 0.25 0.40 >.10
atory (n=23) 2.37 2.00 2.50 2.37 2.00 2.25 0.12 0.64 0.22 0.54 >.10
ointestinal (n=23) 2.45 2.09 2.63 2.72 2.45 2.72 -0.27 0.65 0.19 1.42 >.10
inary (n= 19) 2.66 1.83 2.58 2.00 2.41 2.33 0.33 1.07 0.31 1.06 >.10
mic (n=27) 2.66 1.95 2.33 2.33 2.83 2.83 -0.16 0.72 0.21 0.76 >.10
al (n=21) 2.23 2.00 2.00 2.46 2.00 2.38 -0.15 0.80 0.22 0.68 >.10
atients; SD= Standard deviation; SE= Standard error
T
Fear
I
Intellectual/ Cognitive
(
Depr
So
So
(
Car
Respir
Gastr
Genitour
Autono
Behavior
n= Number of p
Table 9⎯Paired‘t’ test
Mean HARS
score before
treatment
Mean
HARS
score after
1 week
Mean HARS
score after
2 weeks
Mean HARS
score after
3 weeks
Mean
HARS
score
after 4 weeks
Mean
HARS
score
after 6 weeks
Mean
difference
after 6 weeks
SD ± SE ±
t p
22.26 21.00 17.07 16.74 13.76 12.21 10.05 4.48 0.69 14.56 <. 001
lacebo
23.78 19.14 22.21 23.14 23.14 24.07 -0.28 1.16 0.31 0.90 >.10
Variable
Drug group
(n=42)
P
group (n=14)
Table 10⎯Unpaired ‘t’ test
∑ X
Variable n
∑
X
2
(∑ X)
2
/n
∑ (X-X X) = ∑ X
2
-
(
∑ X)
2
/n
Combined variance
SD
2
SD
± SE ±
T
54
p
ug group 42 422 10.29 5058 4240.09 817.91
oup 14 -6 -0.43 20 -2.57 22.57
15.56 3.94 1.18 9.08 <. 001
atients; SD= Standard deviation; SE= Standard error
Dr
Placebo gr
n= Number of p

INDIAN J TRADITIONAL KNOWLEDGE, VOL 6, No. 4, OCTOBER 2007
676
investigations are required to identify the mechanism
of action of Sankhaholi in relation to noradrenergic
neurotransmitter system.
Most of the modern drugs used as anxiolytics have
tranquilizing and sedative properties. These drugs
relieve anxiety by facilitating GABA transmission,
which in turn causes neuronal inhibition in CNS. In
Unani literature, the drug Sankhaholi has also been
described to possess tranquilizing (Mussakin-e-asab)
and sedative properties
4,8
. As mentioned in the
classical literature of Unani medicine, that various
Nafsiyati Amraz (Psychiatric diseases) like
Malikholia, Subara, Mania, Qutrub, Kaboos, etc. (in
which the symptoms of anxiety neurosis are seen) are
caused by the abnormal and excessive accumulation
of Safra (bile) or Ghair Tabayee Sauda (abnormal
black bile). According to the fundamental concepts of
Unani medicine, formation of Ghair Tabayee Sauda
(abnormal black bile) in the body takes place when
any of the four humours is burnt due to excessive
body heat. The above mentioned Nafsiyati Amraz are
initially caused by excessive and abnormal
accumulation of Safra, which in due course of time is
transformed into Ghair Tabayee Sauda by its own
heat/body heat
14, 15
. The drug, Sankhaholi has been
reported to be effective in the disorders caused by
excessive bile (biliousness)
6
. Out of total participants,
31 patients were of Safravi Mizaj (bilious
temperament) and 25 were of Saudavi Mizaj
(melancholic temperament) (Tables 5 &10; Figs.
5&10). Consequently, the drug Sankhaholi seems to
be effective in the treatment of anxiety neurosis by
antagonizing the properties of excessive and abnormal
Safra or Ghair Tabayee Sauda-e-Safravi (The Sauda
which is produced as a result of burning of Safra).
Conclusion
The results of Sankhaholi obtained in this clinical
trial are remarkably encouraging. Sankhaholi
treatment produced marked relief in all the anxiety
symptoms irrespective of duration and severity of
anxiety. Although, some reduction in the anxiety
scores was also noticed initially with placebo
treatment, but the drug Sankhaholi showed the
marked anxiolytic superiority over the placebo at
week 2 or week 3, and a statistically significant
anxiolytic superiority at week 6. The test drug
Sankhaholi was well-tolerated, no significant side /
toxic effect was observed during or after treatment.
After completion of treatment abrupt withdrawal did
not appear to be associated with any withdrawal
symptoms or worsening of the symptoms or
breakthrough anxiety. It is concluded that Sankhaholi
holds potent anxiolytic activity and it is a safe and
valuable drug for the treatment of anxiety neurosis.
However, to make out the exact mechanism of action
of this drug in anxiety neurosis, extensive research
work is required. It is believed that in future the study
will provide a better understanding about anxiety
neurosis and the role of certain other Unani drugs in
this common psychiatric disorder.
References
1. Kessler RC, McGongale KA, Zhao S, Nelson CB, Hughes
M, Eshleman, Wittchen HU & Kendler KS, Lifetime and
12-month prevalence of DSM-III psychiatric disorders in the
United States, Arch Gen Psychiat, 51(1994) 8-19.
2. Sartorius N, Ustun TB, Lecrubier U & Wittchen HU,
Depression co-morbid with anxiety; Result from the WHO
study on psychological disorders in primary health care, Br J
Psychiat, 168 (1996) 38-43.
3. Clark DM, Anxiety states, panic and generalized anxiety, In:
Cognitive Behaviuor Therapy for Psychiatric Problems; A
Practical Guide, by Keith Hawton, (Oxford University Press,
Oxford), 1994, 52-96.
4. Ghani MN, Khazainul Advia, Vol 2, (Sheikh Mohd Bashir
and Sons, Lahore), 1926, 863-864.
5. Andrade C, Psychopharmacology, In: Handbook of
Psychiatry, by Bhugra D, (Oxford University Press, New
Delhi), 2000, 422.
6. Kritikar KR & Basu BD, Indian Medicinal Plants, 2
nd
edn,
Vol III, (International Book Distributors, Dehradun), 1987,
1738-1739.
7. Kabiruiddin M, Makhzan-ul-Mufradat, (SM Bashir and Sons,
Lahore), 1976, 359-360.
8. Kapoor LD, Handbook of Ayurvedic Medicinal Plants, (CRC
Press, Inc BocaRoton, Florida), 1990, 184.
9. Dey AC, Indian Medicinal Plants Used in Ayurvedic
Preparations, (Bishen Singh Mahendra Pal Singh,
Dehradun), 1994, 65.
10. Venkoba Rao A & Kuruvilla K, Anxiety disorders, In:
Psychiatry, (Churchill Livingstone, New Delhi), 1998, 96-
103.
11. Mary Ann Boyd & Marry Ann Nihart, Psychiatry Nursing-
Contemporary Practice, (Lippincott, Philadelphia, New
York), 1998, 476-477.
12. Uhde TW & Nemiah JC, Anxiety disorders, In:
Comprehensive Textbook of Psychiatry, 5
th
edn, Vol 1, by
Kaplan HL & Sadock BJ, (William & Wilkins, Baltimore),
1989, 136-139.
13. Kendell RE, The distinction between mental and physical
illness, Br J Psychiat, 178 (2001) 490-493.
14. Jurjani AH, Zakhira Khawarazam Shahi, Vol II, part VI,
Urdu Translation by Hakim Hadi Husain Khan, (Munshi
Naval Kishore, Lucknow), 1930, 24-29.
15. Kabiruddin M, Tarjuma Sharah-e-Asbab, 9th edn, Vol 1,
(Hikmat Book Depot, Hyderabad), 1916, 97-111.
16. Khan Mohd Azam, Aksir-e-Azam, Urdu Translation by
Hakim Kabiruddin M, (Tibbi Company, Rawalpindi,
Lahore), 1940, 214-268.

SHAMSI et al.: MANAGEMENT OF ANXIETY NEUROSIS WITH UNANI MEDICINE
677
17. Tabari ABR, Firdausul Hikmat Fi-Tibb, Urdu Translation by
Nadvi RA, (Sheikh Mohd Bashir & Sons, Urdu Bazar,
Lahore), 1981, 91-97.
18. American Psychiatric Association, Diagnostic and Statistical
Manual of Mental Disorders, 4
th
edn, (American Psychiatric
Association, Washington DC), 1994.
19. Hamilton M, The assessment of anxiety states by rating, Br J
Med Psychol, 32 (1959) 50-55.
20. Ahmad I, Mizaj (temperament), In: Kulliyat-e-Asri, (New
Public Place, Delhi), 1987, 34-83.
21. Fossey MD & Lydiard RB, Placebo response in patients with
anxiety disorders, In: Handbook of Anxiety, Vol IV, by
Noyes R, Roth M & Burrows GD, (Elsevier, Amsterdam),
1990, 27-56.
22. Schweizer E, Patterson W, Rickels K & Rosenthal M,
Double blind placebo-controlled study of a once-a-day,
sustained-release preparation of alprazolam for the treatment
of panic disorder, Am J Psychiat, 150 (1993) 1210-1215.
23. Londborg RD, Wolkow R, Smith WT, DuBolf E, England D,
Ferguson J, Rosenthal M & Welse C, Sertraline in the
treatment of panic disorder; a multi-site, double-blind,
placebo-controlled, fixed-dose investigation, Br J Psychiat,
173 (1998) 54-60.
24. Mathew RJ, Hob T & Kralik P, Anxiety and platelet MAO
levels after relaxation training, Am J Psychol, 138 (1981)
371-371.
25. Johnson MR & Lydiard RB, The neurobiology of anxiety
disorders, Psychiat Clinics North America, 18 (4) (1995)
681-725.
26. Noyes R Jr & Hoehn-Saric R, The Anxiety Disorders,
(Cambridge University Press), 1998, 162.
27. Viyas JN & Tyagi Dinesh, Anxiety disorders, In: Textbook of
Psychiatry, 2
nd
edn (Jaypee Brothers Medical Publishers,
New Delhi), 1999, 262.