World Journal of Pharmaceutical Research

Jithesh et al. World Journal of Pharmaceutical Research

SJIF Impact Factor 5.045

Volume 3, Issue 4, 1211-1222. Research Article ISSN 2277 – 7105

AN OPEN CLINICAL TRIAL TO ASSESS THE EFFICACY OF

NIRGUNDYADI GRITHA AS AN ADD-ON THERAPY ALONG WITH
AED IN THE MANAGEMENT OF APASMARA WSR TO PARTIAL
SEIZURE WITH SECONDARY GENERALIZATION

C Ambili1 , M Jithesh*2, S Ram manohar3

1
PG Department Of Manovijnan, VPSV Ayurveda College, Kottakkal,
2
Associate Professor, Dept of Kayachikitsa and Post graduate studies in Manovijnan, V.P.S.V
Ayurveda College, Kottakkal.India
3
Senior consultant neurologist, PVS hospital, Calicut.

ABSTRACT
Article Received on
15 April 2014, Epilepsy is the most common presentation in a neurological setting and
stands next to stroke and dementia in its prevalence. One third of the
Revised on 10 May 2014,
Accepted on 05 June 2014 people with epilepsy seems to be severely affected and continues to
have seizure despite all the available medications. The disease and its

*Author for Correspondence management have high impact on the quality of life of the affected
Dr. Jithesh Madhavan person and also discrimination in education, employment and social
Associate Professor, Dept of acceptance. In Ayurveda, the disease named ‘Apasmara’ has been
Kayachikitsa and Post
explained with its aetiology, symptoms, diagnosis and management. A
graduate studies in
psycho neurological approach has been explained for managing the
Manovijnan, V.P.S.V
Ayurveda College, Kottakkal. condition of Apasmara and it is explained in a medical as well as
India psychological setting. The approach includes a systematic one,
depending on the severity and enormity of the associated doshas. Many
a drugs are also mentioned in this regard, but has not been assessed statistically and the
available data is based on the clinical finding only. Aim: To assess the efficacy of
Nirgundyadi gritha in the management of Apasmara WSR to partial seizure with secondary
generalisation Setting: Kayachikitsa and Manasroga OPD, VPSV Ayurveda College,
Kottakkal, India. Method: An open label uncontrolled clinical trial with sample size 20. Add
on usage of Nirgundyadi gritha was done without withdrawing the ongoing AED and those
with seizure. Assessment was done after one month, 2 months and after 1 month of followup.
Result- It was observed that the selected drug has significant efficacy in the management of

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apasmara wsr to partial seizure with secondary generalisation. The drug Nirgundyadi gritha is
effective in the management of Apasmara and to improve the quality of life of the affected
ones.

KEY WORDS: Apasmara, Epilepsy, Nirgundyadi gritha, AED, EEG.

INTRODUCTION
Many a disorders in the human may not be considered as ultimate, but may lead to much ill
health and mental agony in the due course. Apasmara is one among them, which undoubtedly
makes a man, unhappy and diseased. The individual undergoes a lot of distress, agony and
grief leading to lack of performance at the personal as well as the social level. Hence a divine
contribution was been suspected in the pathogenesis of such diseases in the olden days.

Crude prevalence of epilepsy in India is 5.5/1000.1Prevalence rate is more in urban area and
is higher in the younger age groups. Onset of epilepsy is higher in 1st decades of life. 2 In
more than 50% of the cases, the cause is yet to be known and the thing to be made sure is that
there is no organic cause. The disease and its continuing management can make an impact on
the person’s quality of life, with untoward effects such as depression, anxiety, reduced
vitality and insecurity. The leading nonmedical problem confronting people with epilepsy is
discrimination in education, employment and social acceptance. The mortality rate among
people with epilepsy is two to three times higher and the risk of sudden death is 24 times
greater than that of general population3.

In epilepsy, the normal pattern of neuronal activity becomes disturbed, causing strange
sensations, emotions, and behaviour or sometimes convulsions, muscle spasms, and loss of
consciousness. Anything that disturbs the normal pattern of neuron activity—from illness or
brain damage to abnormal brain development can lead to seizures. A measurement of
electrical activity in the brain with EEG as well as MRI or CT scan is the common diagnostic
test for epilepsy 4.

About 3/4th of those diagnosed with epilepsy can control their seizure with the available
AED’s. However, about 25 to 30 percent will continue to experience seizures even with
which is called intractable epilepsy5. Most seizures do not cause brain damage, but ongoing
uncontrolled seizures may cause damage to the brain. This is the area, where we have to

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study the clinically persuasive Ayurvedic medicines, so as to help them lead a normal life.
This is the real inspiration behind such a study.

Apasmara
In the Ayurvedic literature, epilepsy is described as ‘Apasmara’ which means loss of smrithi
ie. Consciousness, which seems as a temporary one.6 The term ‘Apa’ means ‘parivarjana’ ie.
loss and Dalhana gives its meaning as gamana7. The term Smara means smarana, ie. smriti.
Smriti is defined as bhootartha vijnaana8; ability to remember the past experiences. The term
tama: pravesha has been used by Dalhana, which leads to jnaana abhaava or lack of
awareness during the episode of Apasmara.

The Caraka Samhita contains abundant references regarding all the aspects of epilepsy
including symptomatology, etiology, diagnosis and management. The samhitas also described
the factors like diet, life style, injuries; psychological factors etc. leading to its causation.
Detailed description of the pre-ictal and ictal phases are also available. The components
which gets altered is smrithi (recollection), budhi (awareness) and satwa (mental strength) 9.

Ayurveda has given equal importance to psychological factors just like as to the somatic
factors. Even though, the disease is included among the Kayachikitsa or general medical
conditions; it is explained along with the psychiatric disorders. This explains the dual as well
as the most practical approach of Ayurveda, in the management of Apasmara, which is now
very well appreciated by the modern medical world.

There is also a limitation in the diagnostic aspect, due to the transitory loss of consciousness
of the subject during a seizure. The drug selected for the study was Nirgundyaadi ghrita
which is widely used in Apasmaara cikitsa. It contains many drugs like nirgundi which have
antiepileptic effect. It also contains rasayana drugs like Lasuna, Citraka, Vaca, Yashti,
Aswagandha etc which acts as a booster to the functioning of nerves, which seems to have
altered in Apasmara.

Caraka has classified cikitsa into three types ie. Daiva Vyapaasraya, Yukti Vyapaasraya and
Satvaavajaya.10All these three are used as a combination accordingly to effectively manage
the conditions like Apasmara. The management protocol differs during and in between the
seizure in the case of a disease like Apasmara, which are having vegas or is episodic. The
Cikitsa of Apasmaara can be sodhana or samana, depending on the severity of affection of the

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doshas as well as the bala of the patient. The protocol includes snehana, sodhana, vasthi,
Nasya, Anjana, Dhoopana and Lepa, as per the condition 11.

Siva aaraadhana, Sree panchaakshari mantra seva, and wearing ratna are explained in the
treatment of Apasmaara as a part of the daivya vyapasraya aspect.12 Satvavachaya aims at
improving the mental strength or satvabala of the individuals, by adopting the different
methods of psychotherapy 13. The improvement in satwabala is very much helpful in avoiding
the relapse in conditions like apasmara.

Clinical study
Aim And Objective
 To study the types of epilepsy in detail from the Ayurvedic point of view
 To evaluate the efficacy of Nirgundyadi gritha as an add on therapy along with AED in
management of Apasmara WSR to partial seizure with secondary generalisation

Research Question
Does Nirgundyadi ghrita, has any significant add on effect along with AED in the
management of Apasmara WSR to partial seizure with secondary generalisation at a dose of
30 ml, administered for 2 months, at 9 PM, in those in the age group of 16 – 50 years,
attending the OPD of VPSV Ayurveda college Kottakkal?

Materials
1. Concerned Modern and Ayurvedic literature
2. Participants 20 in number
3. Nirgundyadi gritha
4. Patient Consent Form
5. Case Record Form
Clinical Study
Study Design
Open label Uncontrolled Clinical Trial.
Settings
 Kayachikitsa OPD & IPD - VPSV Ayurveda College Hospital, Kottakkal
 OPD of Govt. Ayurveda research institute for mental diseases, Kottakkal
Duration of Treatment:
 2 month’s intervention and 1 month follow up

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Intervention
Nirgundyadi gritha 30 ml was administered at 9PM for 60 days with anupana of sufficient
quantity of warm water.
Sample size: 20
Ethical committee clearance: Synopsis submitted and approved by The Research
Committee and Institutional Ethics Committee on 11. 04. 2011 (Approval No: IEC/ CL/ 002/
11 dated 18.04.2011).
Informed consent: obtained from all the included subjects.

Diagnostic criteria

ICD 10 criteria for partial seizure with secondary generalization [14].
Patient selection
 Those satisfying the inclusion and exclusion criteria
Inclusion criteria
 Age group 15 – 60 years
 Those with an established diagnosis of epilepsy
 At least 1 seizure within a month in spite of ideal AED
 Continuing appropriate AED at least 6 months prior to treatment
 No sex, age, religion and financial discrimination
 Those willing to give a written consent
Exclusion Criteria
 Pseudo seizures
 Recent history of alcoholism and drug abuse
 Pregnancy and lactating mothers
 Chronicity greater than 10 years
 Other organic brain disorders
 A known hepatic, renal, cardiac or endocrine disease
Assessment Criteria
 Based on the four parameters15
 Severity of attack, Frequency of attack, Duration of attack, Post ictal features
The assessments were done before treatment, at the end of 1st month, at the end of 2nd
month and after the follow up of one month.

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Analysis
The outcome was measured and the data was statistically analyzed by paired t test16.

Drug Study
Nirgundyadi gritha is a classical preparation extensively used by practitioners all over Kerala.
The drug reference is in the Yogagrandha, a compilation from several books edited by PS
varier published by Arya Vaidya Sala Kottakkal 17. The same combination is available in use
in the gritha as well as the gutika form. The gritha is used by traditional vaidyas for
application on the body parts, to relieve the attacks. Nirgundyaadi Ghrita is a combination of
36 medicines. It is indicated in Garavisha, Kukshyaamaya, Apasmaara, Bhootonmaada,
Sirasoola and in all the Baalarogas. The lipophilic action of ghee facilitates transportation to a
target organ and final delivery inside the cell since the cell membrane also contains lipid, also
is the case of blood brain barrier. That is the logic behind the mention of maximum ghee
preparations in psychiatric conditions.

The drug nirgundyadi gritha was prepared from a GMP certified company, as per the
requirement of the study.

Observation and Analysis

A) Demographic data
35% patients in the study were of 21-25 years age group. Many studies from the developing
countries point to the highest prevalence of epilepsy in the 2nd and 3rd decades of life 18
.
Maximum of 55% participants had age of onset between 11-20 years, 10% participants had
age of onset between 1-10 years, 15% patients had age of onset between 21-30 years, the
prevalence in the age of onset decreases, with the increasing age 19.

In the study 70% participants were male and 30% participants were female. Prevalence rate
of epilepsy in male is more compared to female as per modern texts like Cecil Medicine and
other studies20. Out of the 20 participants in the study, 70% participants were Muslim and
30% participants were Hindus as the study was conducted in a muslim dominated area. Out
of 20 participants, 70% were unmarried and 30% participants were married. According to the
study conducted by Agarwal P et.al subjects with epilepsy had lower marriage prevalence
rate, delayed marriage, withheld marriage and higher divorce rate compared to general
population21

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Maximum ie. 60% of the patients have only primary class education. A study conducted by
Singh et.al states that the educational problems are commoner in children with epilepsy.
Maximum (45%) patients of this study were from lower middle class, 35% were
economically poor and 20% were from upper middle class. The studies shows that prevalence
of epilepsy is higher in people with low socio economic status.22

B) Data related to clinical picture

65% of the patients in the study were taking mixed food and 35% of the patients were
vegetarians. 30% of the participants in the study were anxious about the disease, 25% of
participants had depressed mood, 25% were having euthymic mood and 20% of the
participants were with other mood like anger. In the present study, 60% patients were with
kapha vaata prakrti, 25% patients were of kapha pitta prakrti and 15% patients were with
vaata pitta prakrti. 90% participants in the study were not addicted to cigarette, alcohol or any
other addiction forming substances. Maximum of 50% of the participants reported sleep
deprivation as the precipitating factor in epilepsy. Tension, irregular food intake etc were also
reported as the precipitating factors. Studies show that, sleep deprivation is the main
precipitating factor in epilepsy23.

40% of the participants in the present study had frequency of attack of 1-2 times per month,
30% participants had frequency of attack between 2-5 times per month and 30% participants
had frequency >5 times per month. 60% of the patients were with duration of the attack of 1-
5 minutes, 40% were with duration less than 1 minute. Post ictal features were present but
relieved with in 1 hour of attack in 50% cases. 90% patients in the study reported loss of
consciousness with falling and mild convulsions.

C) Observations on the effect of therapy

Assessment was done at the end of first month, second month and after the follow up of one
month. Laboratory investigations were done before and after study. EEG was also included as
the investigative tool24. The data obtained were assessed using self gradation scale. Severity,
frequency, duration of attack and post ictal features was assessed.

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Table 1 Effect of the therapy on symptoms

Mean % of
Symptom BT AT SD t p
diff relief
Severity of attack 2.05 1.55 0.5 24.4
0.8272 2.703 <0.02
Frequency of
1.9 1.35 0.55 28.94 1.1356 2.166 < 0.05
attack
Duration of attack 1.6 1.05 0.55 34.37 0.686 3.584 <0.01
Post ictal feature 1.30 1.0 0.30 23.07 0.5712 2.349 < 0.05
(BT – before treatment; AF – after treatment; SD – standard deviation)

Table 2 Overall effect of the therapy

BT AT Mean diff % of relief SD t p
6.85 5.00 1.85 27 1.785 4.635 <0.01

Severity of attack
Nirgundyaadi Ghrita is effective in reducing the severity of attack of the disease. The change
occurred in the severity of attack after the first month of the treatment was statistically
significant (p <0.05) with 17% relief. After the second month, the percentage of relief was
24.4% which was statistically significant (p < 0.02). Severity of attack after the follow up
was same as that of after treatment. The percentage of relief was 24.4% and also statistically
significant (p < 0.02).

Frequency of attack
In frequency of attack, the percentage of relief was 26.31% after the first month of the
treatment which was statistically significant (p <0.001). Frequency of attack after second
month was also statistically significant (p <0.001) with a percentage of relief of 31.58%.
After follow up, the percentage of relief on frequency of attack was 28.94%. The result was
statistically significant (p <0.05).

Duration of attack
Duration of attack was reduced after first month of treatment by 15.63% relief which was
statistically insignificant (p >0.05) But after second month of treatment patients got 37.5%
which was statistically significant (p<0.001). Effect on duration of attack after follow up was
34.37% with a p value <0.01 which was statistically significant.

Post ictal features

Change in post ictal feature after first month of treatment was 19.23% which was not
statistically insignificant (p >0.05). After second month of treatment the percentage of relief

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was 26.9% which was statistically significant (p <0.01). After follow up period, the
percentage of relief was 23.07% which was statistically significant (p <0.05).

Overall effect of the drug

The drug is effective in reducing the severity, frequency, duration and post ictal features of
the disease and the effect is maintained during the follow up period also. The overall effect
was 19.7% after first month (p <0.01), after second month the effect was 29.92% (p<0.001).
The effect after follow up was 27% (p<0.001).

DISCUSSION
Eventhough medical world claims of the advancements in the management of Apasmara,
many a drugs are not working as expected. The present AED medication has so many draw
25
backs like adverse reaction, drug interaction and teratogenecity . Cognitive impairment to
an extent, is also seen in some patients, with epilepsy. This points to the need for the search
and development, of newer drugs in this regard.

The Ayurvedic preparations work astonishingly in this area and can do a spectacular job.
Ghrita has a main role in the management of diseases with prominent psychological
component, like Apasmaara. Puraana ghrita is indicated in Apasmaara due to its property in
bringing all the doshas to normalcy 26.

Nirgundyaadi ghrita is a combination of 36 drugs. Many of the ingredients in this medicine

have established anti convulsive activity. Also they are good anti oxidants. According to
recent researches increased level of free radicals are seen during the seizure in an individual
27
. These free radicals can damage the neurons leading to cognitive impairment.

The drug Nirgundyaadi ghrita is ushna in veerya and katu in vipaaka. Due to the sookshma
guna of these, the drug is able to remove the aavarana of srotus. The drugs in the formulation
have Deepana and paacana properties, which control the formation of ama in the initial stage,
which is very important in preventing the manifestation of the disease. Due to the deepana,
paacana and srotosodhaka property, there is an increase in agni of the patient which helps to
trim down the remaining doshas after the vegaavastha. Thus there will be a decrease in the
post ictal feature of the disease. Nirgund’yaadi Ghrita also contain drugs like Triphala, Vaca,
Yashtimadhu, Lasuna, Citraka etc which are well known for its rasaayana property28.

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Rasayanas have a crucial role to play in the management of diseases like apasmara, where
there is involvement of all the three doshas and also the satwa or the mind 29.

CONCLUSION
For many people with epilepsy, the risk of seizures restricts their independence and also
recreational activities 30. AED’s are not answering the problem in a reasonable manner. Some
of the drugs tried here like Nirgundyadi gritha, is to be studied scientifically to evaluate the
efficacy in such condition. The drug has given statistically significant results in reducing the
partial seizure, with secondary generalization. Thus the vast Ayurvedic literature is able to
provide effective contribution in improving the quality of life of those, affected with
conditions like Apasmara.

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