THE ARMY MEDICAL LIBRARY B'/ THE ASS'N. OF MILITARY SURGEONS

June, 1938] TREATMENT OF SCHIZOPHRENIA : DHUNJIBHOY 321

Original Articles

treatment of schizophrenia by/ INDUCING EPILEPTIFORM SHOCKS' BY THE DRUG CARDIAZOL \f An experimental study of 42 cases

By J. E. DHUNJIBHOY LIEUTENANT-COLONEL, I.M.S.

Medical Superintendent, Ranchi Indian Mental Hospital (Bihar)

andCHlZ0PHRENIA is the psychiatrist's biggest

chiiim?S^ urgent problem, and constitutes a

itiedi6nP investigators in every field of

Path 1 researc"1- Its setiology

is unsettled, its

disnut ^ unknown and

its clinical limits in

than ?' ianc^ yet ^

a more sei'i?lls problem

XJ^it j1 ^ r tuberculosis or carcinoma.

In the

each States of America

statistics show that

divid 7TV S?me thirty to forty thousand

in-

flushfS soon a^ter adolescence

or in the first

to th'? manhood or womanhood

fall victims

thanUS ^reac^ disease. Annually at

least more

inent- ?nf~^uarter of the patients

admitted to

suffer' P^als in Europe

and America are

caScsln^ fr"om this disorder

and the number of

Would ^tted to mental

hospitals in India

the v a^ear to be similar.

It takes its toll of

a^. an aSe when the promise

of life is

and 1 brightest and

strikes at the poor

??rmal\allke- ^ cuts

v^ctims from the

c?nde uman activity and intercourse,

and

Wallg111118 ^em to a life hemmed

in by high

camm prohibitions

which no matter how

sympati ?ed ^y kindness or softened by

or wh t rnake mere existence

a living death

call ' a ^le Present-day psychiatrists

prefer to

of . v?getative existence

'. The importance

(publi llz?Phrenia from the mental hygiene

emphaC ? aealth) viewpoint needs no further

the '

S}S an<^ preventive measures are of

8tages U !Vost importance.

In the early

and t) prognosis is not always poor

dement10 conchtion does not always end in

sible p1U' .Spontaneous remissions are

also pos-

but ' sPecially in the early

stages of the illness

and 0fany these remissions

are temporary

centag C0rnParatively short

duration. The per-

are anc* duration of spontaneous

remissions

down t[erne^y arbitrary. Some authorities put

be bet figure f?r spontaneous

remissions, to

theories 6Gn ^ Per cen^-

^le numerous

are ll08 ?^ten advanced to explain

schizophrenia

only n + c?nfessions of our

ignorance; it is

piricai a ifal ^at

its treatment should be em-

a lar ' As the line of treatment

is empirical,

stances jVar*ety ?f organic and

inorganic sub-

time t +aVC 11 tried by psychiatrists

from

method lme an<^ are s aPPlying these

the rwS- ln order to ameliorate

the condition of

them d fen^S ra^er than stand by and

watch

riorate, and their efforts are sometimes

rewarded by success. Among the various methods of empirical treatment of schizophrenia the following hold pride of place :?

(1) Pyrexial treatment. The production of fever in patients by injections of typhoid vac- cine, sterile milk, pyrifer sulfosin, Dmelcos vaccine, by inoculation of malaria, by diathermy or by any other means.

(2) Glandular products of various kinds, especially testicular, thyroid and ovarian extracts.

(3) Prolonged narcosis by various sedative

drugs such as somnifaine, soneryl, sodium

amvtol, nembutol, luminal, somnos, hypnol, and sodium evipan.

Prolonged narcosis by somnifaine is still in

vogue in England and on the Continent. Advocates of one or more of the above-stated

empirical methods of treatment of schizophrenia will not be found wanting, and no doubt these methods have achieved sporadic success and have caused a certain amelioration of symptoms, yet the results have not been such as to com- mend them universally for the routine treatment of schizophrenia. Moreover all the above methods of empirical treatment of schizophrenia were tried by me from time to time on the

schizophrenics of the Ranchi Indian Mental

Hospital, which is the largest and one of the most modern mental hospitals in India. The results of our successes and failures with these methods of treatment were fully stated in our annual reports of the hospital, and some with encouraging results were published in medical

journals. Recently to the vast armamentarium of the schizophrenic empirical treatment are

added the insulin hypoglycemic therapy by Dr. Manfred Sakel of Vienna and the epilepti- form shock therapy by the drug cardiazol by Dr. Ladislaus V. Meduna of Budapest. It is the writer's aim in this paper to describe in full his own experience of ' convulsive therapy' of

schizophrenia as evolved by Dr. Meduna. Since the introduction of

' insulin therapy ' in

schizophrenia by Dr. Manfred Sakel typical epileptiform attacks are frequently observed in patients undergoing this treatment. Both in Vienna and Munsingen (Switzerland) cases have been observed with such attacks during insulin treatment and it was reported that when an

epileptiform attack appeared it produced a

very favourable effect. Recently a case of status epilepticus during insulin treatment was recorded by Gillies (1937). Incidentally Dr. Hunter Gillies in this article has also men- tioned the work of Dr. Ladislaus V. Meduna. When I was in Budapest in 1935 I was invited by my friend and colleague Dr. Meduna to see his treatment of schizophrenia at the Royal Hungarian State Mental Hospital, Budapest. I was so impressed with all that I saw and more so with the good results obtained by Dr. Meduna by this treatment that I decided to try the treatment in my hospital on my return to India. I will describe in short the

322 THE INDIAN MEDICAL GAZETTE [June, 1938

theory and technique of Dr. Meduna's treat-

ment by cardiazol before I narrate my own

experience with this treatment. The theory.?Dr. Meduna for a long time held

a theory that there might be some biological antagonist to schizophrenia just as Hofrat

Professor Wagner-Jauregg found biological antagonism between malaria and neuro-syphilis. Dr. Meduna with this end in view made an ex-

haustive study of the literature on epilepsy and

schizophrenia and accidently he came across an article written by one of the Continental author- ities on epilepsy wherein the author had stated that epilepsy and schizophrenia are very seldom found in combination in one and the same

person. Dr. Meduna was very much impressed with this new knowledge and he made further studies on this line and was later convinced that

there was some biological antagonism between schizophrenia and epilepsy. For years he

carried out experiments, firstly on animals and later on patients, with various drugs to induce epileptiform fits and found that 25 per cent

camphorated oil solution given intramuscularly produced the best results. He obtained 10

remissions out of the first 26 cases of schizo-

phrenia treated by camphor injections, but later lie found that the tolerance to camphor with patients differed greatly and he was compelled to seek a more stable and reliable medicament for this purpose. Finally, he tried Knoll's cardiazol and the results obtained were highly satisfactory. Cardiazol (penta-methylene-tetra- zol) is generally known to the profession as a

water-soluble synthetic preparation having pharmacological effects similar to camphor, to

which it is distantly related to camphor chemi- cally. The dose given for inducing epileptiform fits is far in excess of the one usually prescribed in clinical practice of this useful drug, yet it has no injurious effect on the normal heart and is not cumulative in its action. I have no inten- tion in this article of entering into any discussion about the theory on which this treatment was evolved by Dr. Meduna, however fantastic it may appear. I am only dealing with the prac- tical side of it, viz, the results obtained by this treatment. Dr. Meduna claims to have obtained 40 to 50 per cent remissions in schizo- phrenics by this treatment.

Technique and dosage as evolved by Dr. Meduna.?Dr. Meduna starts the treatment by using a 10 per cent solution of cardiazol, com- mencing with an injection of 5 c.cm. and increasing each injection by one c.cm. until the fit is produced. Should 5 c.cm. induce a fit the dose for that particular patient is not increased. One may use a solution of greater strength but in any case Dr. Meduna suggests commencing with 0.5 gramme of cardiazol and if necessary increasing each successive dose by 0.1 gm. The intravenous route is always preferred but if this is not possible on account of the depth of the veins the injections may be given intra- muscularly the dose then being increased from

0.3 gm. to 0.5 gm. above the intravenous do?e; No definite plan can be laid down as to h?

g many injections are necessary for each case ^ they vary considerably in different patie1^' Some schizophrenics have shown full remissi^ with 3 or 4 injections and others have not ^ proved at all after 20 to 30 injections. ]A ever, Dr. Meduna suggests that no case sh?u ,

be given up as hopeless for this treat?^, without giving the patient the benefit of at le^ 20 such injections, or, to be more accurate,. ^ such convulsive shocks. Dr. Meduna has trie^ this treatment on a large number of cases ^ has obtained 40 to 50 per cent remissions

1

out any untoward results. i

Contra-indications for treatment.?The ment is contra-indicated in acute bodily or chronic disease affecting the heart, bl??

vessels, lungs and kidneys.

Our experience with cardiazol therapy ,

For the purpose of this experiment I selece , 42 typical cases of schizophrenia. CardiaZcQ was not obtainable in India in powder fori11

*

I wrote to Messrs. A. 'G. Knoll for a free sUP?e(j of this powder and the firm readily respo11^ to my request and sent me a sufficient qua11 for the experiment. The majority of j

selected were chronic schizophrenics who ,g not responded to any of the known treatmen for this disease.

J

Preparation of patients for cardiazol treats ^ A routine examination of heart, urine

blood pressure of each patient was made a ,][ previous to the one fixed for injection. ^ patients are given a cup of hot milk at

ab? ,

7 a.m. and are then taken to a special ^ e opened for the purpose, where the beds

?

screened from each other. The injections^11 j-)* ? vii tiO CAi 1 CI V %J Ci . Ill? 1111 i 'jm

posted with a tampon in his hand bel1 ^

the head of the patient's bed. One attends*1 ^ placed on either side of the patient's bed

i ^iwiwu v^ij. D1UC Ul fiiv^ pcfcuiv^ixv kj

? ,

prevent him from falling out or being inJul es

during the fit. The fourth attendant prep11 f the patient's arm and holds it to be ready ^ the intravenous injection by the doctor. ^ second doctor stands at the foot of the bed a watch to time the injection and the fit ? ^ to make clinical observations. In order to

unhampered movements of the extremities d

j.

ing the fit no clothes are allowed except ,

pyjamas which are also undone at the ^oJ1 The cardiazol is then injected, due attefl ^

being paid to the speed at which the solu enters the vein. .

.

c* A typical fit.?Immediately after the

tion and sometimes before the needle is ^ ,

drawn the patient's eyelids begin to quive^ie a sign found in the majority of patients-'"^ face becomes anaemic, the body stiffens and y patient makes a few futile attempts to get a from the bed by irregular movements of

^ hands and feet. He then loses conscious

JuNE, 1938] TREATMENT OF SCHIZOPHRENIA : DHUNJIBHOY 323

and a typical tonic stage sets in.

The posture

lsj with clenched hands, wrists and el ow a

slightly flexed, arms held to the sides,

the legs

extended, also the back, and the face

becomes

cyanosed. The patient at this stage never

fails

0 open his mouth and he keeps

it convenien y

?pen for a few seconds and this is the

time 1

attendant inserts an improvised tampon to prc-

^ent the patient from biting his

tongue. ie

tampon is made 6 inches long and i men

tfek. In the few seconds that follow

the clonic

.age starts and the convulsions take the form

ot

lrregular jerks and spasms. During this phase

*** patients pass urine and some ejaculate

Vth. ?r without erection. At the end

o

e onic stage the patient goes into a deep .coina

sleep which lasts from 5 to 20

minute..

he Patient then regains consciousness;

he nrst

^PPears to be confused and dazed

and it is

Jitter to let him sleep and not to

disturb him

^th questions. I always encourage the patients

J0 ?]eep for a few hours and no

one is allowed

? leave the bed for at least 5 to

6 hours after

t ?}? A* far as possible no food or drink

be allowed for a few hours after the

flections as they are often rejected by tne

^ given earlier. Our routine

is to giv

Sections at 9 a.m. and to serve food

at about

t .p-m- Formerly the injections were given

aHCe a week but now they are given every

'ternate day.

Collective and individual peculiarities in our

cases

in The tonic and clonic

stages differed m

31Vldual cases. Some had a good tonic stage

nd others clonic. We found that those patients

tnoii and prolonged clonic

stages even

ally derived much benefit by the treatment,

eni'i^ ,?ifteen patients invariably showed

post-

hnii ? excitement which lasted for a fe*

slen+S a^ter each injection, but in the nig

i

P Well without any hypnotics. Four patients after

the fit always used o

a fo ^eir necks, thighs, groins and arms

foi

^ minutes only.

conv^ r^Wo patients always used to spit a ter

tiiS^i8 out of the fit and this mannerism

con-

ed for a few minutes.

cri' u^Ve Patients always gave an

epilep ic

before the onset of the tonic stage.

for o j.^Wo Patients always smacked their lips

if it w minutes after coming out of the fit,

as

the ^ac* s?nie taste left in the

mouth y

bv and their gestures proved

that it was

*

f7N? means pleasant. hilJJ Ten Patients always remained in an

an?us condition after the fit for about

half

of v, iV*", They sang songs and showed

fee mgs

aLt^eing almost like the first stage of

coho1 intoxication.

his I ??e katatonic patient who had

murdered

r?ther and never admitted it before the

court or to anybody else suddenly one day after the fit made a frank confession of his crime and described in detail the scene of murder which when verified with the police report was found to be correct. On the other hand we tried to get a confession out of another patient who was also charged with murder and would not admit it, but we failed in this case.

(9) A katatonic with marked flexibilitas cera and mutism on the day of the fifth injection implored us not to give him the treatment and said that he would act and behave like a

normal person in every way. I gave him a

chance and he behaved very like a normal

person for two days but relapsed on the third and the treatment was continued in his case

and after a full course he showed a great im- provement in his katatonic condition.

(10) Three patients during the course of in-

jections twice showed conditions like larval

epilepsy or epileptic equivalents, i.e., their fits after a full dose of cardiazol (1 gm. in 10 per cent solution) were replaced by a condition of excitement almost amounting to furor which lasted for 15 to 30 minutes. On coming round the patients had no memory of their excitement and they showed complete amnesia of events, a point of great medico-legal importance.

(11) Some patients as soon as the drug was injected started coughing a little as if the drug had irritated their throats and they invariably went into fits. The cough is now regarded by us as an unfailing sign for the production of fits.

Dangers and complications.?I am glad to be able to state here that not a single case showed any dangerous symptom and I agree with the

findings of Dr. Meduna that the treatment is

perfectly free from any danger in selected cases. Four patients during fits had dislocations of shoulders which were soon put right when they were in the amnesic state and with proper care the trouble never recurred, although we sub-

sequently induced many fits in the same

patients. It is said that any hypnotic, especially mor-

phia, hyoscine, paraldehyde and sodium evipan, will counteract any dangerous symptoms produced by cardiazol. In our emergency tray these drugs were always kept ready for imme- diate use but we never had any occasion to use them.

Comments

We found in our series of cases that those

patients in whom severe fits were induced by the initial dose of 0.5 gm. of cardiazol for the first 8 to 10 injections showed better improve- ment than those in whose case the initial dose had to be increased in the first 4 or 5 injections to 1 gm.

(2) Rapidity of injections also plays a great; part in the induction of fits. We experimented

324 THE INDIAN MEDICAL GAZETTE [June, 1938

with large doses of stronger solution and injec- ted the dose very slowly and no fits were pro- duced but in the same patients the next day we gave 0.5 gm. dose at a speed of 1 c.cm. per quarter second and produced beautiful fits.

Our usual rate of injection is 5 seconds.

(3) The treatment is very simple and can be undertaken by any physician with a little know- ledge of the technique.

(4) It is true that the induction of epilepti- form fits in patients is not a very pleasant sight for onlookers but to the patients themselves it makes no difference as they become unconscious at the very onset of the fit and even on recovery they do not remember anything. In fact, they have complete amnesia of events. Patients

generally learn about the fits from other patients or the attendant staff, or at times after recovery from a fit they sometimes try to peep through the screen when other patients are being given the same treatment in their ward, although every effort is made to prevent the patients from getting the information.

This point was further elucidated by giving injections to one of the staff who volunteered to undergo this treatment in the cause of science. He also informed us that he had no

knowledge of what happened from the time the needle was introduced into his vein until he recovered his senses. He further said that he suffered no pain or felt no shocks and did not remember anything (complete amnesia of events).

(5) On the days when n,o cardiazol is given, patients are allowed to attend the occupational therapy classes and to take part in all daily activities of the hospital life.

Results of our experiment and conclusions Out of 42 cases selected for the experimeI^

there were 31 males and 11 females. The 1? ^

lowing table shows the number and types schizophrenics selected and their sex :?

Table I

Number of oases

15

17

Types of schizophrenics

Katatonic

Hebephrenic

Dementia para- noides.

Simple dementia

Male

11

13

6

1

Female

4

4

2

1

Tot*1

15

17

Table II shows the results of our experimen on 42 cases :?

Table II

Number of cases

15

17

Types of schizophrenics

Katatonic

Hebephrenic

Dementia para- noides.

Simple dementia

Full remis- sions

Improved Station81?

^ Table III gives more information of the ,

cases who got full remissions and were s^e sequently discharged as quite recovered by board of visitors of the hospital :?

Serial number

1

2

3

4 5 6

7

8

9 10 11 12 13

Types of schizophrenics

Katatonic

Hebephrenic

Dementia paranoides

Katatonic Do. Do.

Do.

Hebephrenic

Katatonic Hebephrenic Katatonic Hebephrenic

Do.

Sex

M.

M.

M.

M. M. M.

M.

M.

M. M. M. F. F.

Table III

Period of stay in the hospital before the commence-

ment of the treatment

Y. M.

5

11

3 2 5 3 11

D.

10

15 18 8

19 0

Number of injections given and amount

Total

20

11

13

20 11 10

7

6

5 11 30 12 11

0.5r.

7

11

8

7 8 4

1

4

5 8 27 12 3

0.6 g. to

0.8 g.

1.0 g.

13

5

11

2

6

Remarks

C IIV Discharged as

recovered. . , jjis

He has now rejoined office as a clerk, jjy

Discharged as

recovered. Do. Do.

. , jjis

He has now rejoine service on the ra?

He is now working salesman. ruiiy

Discharged as

recovered. Do. Do. Do. Do. Do.

June, 1938] TREATMENT OF SCHIZOPHRENIA ; DHUNJIBHOY 325

Table III shows that schizophrenics are curable in their early stages and the earlier the treatment is applied the better are the results, rhe majority of the cases who improved under treatment were early cases as shown in column 4 of table III. All the discharged patients have still maintained the improvement. Case 11 was wrought on a stretcher as an acute case ot Catatonia. On admission he could neither walk ??r talk, he refused to take his food and was *ed

nasally for a few days. After the third Injection of cardiazol he began to talk and took lls, food and after the tenth injection he became quite normal and began to walk. He was given ^ full course of 30 injections?27 or 0.5 gin. and ?r 1 gm> He improved very much in his Cental and physical health and was discharged lls fully recovered by the board of visitors. In

opinion this was a great success for cardiazo the case on admission appeared to be qui e n.?peless. Of the 15 improved cases 5 have *lnce relapsed after maintaining the improve- ment for a varying period from 2 to 5 months, ue remaining 10 cases have still maintained le improvement and are now working satis-

factorily in the hospital. By improvement, ^e.an those cases who before the treatment were i^sy, attitudinistic, negativistic, showing flexi- Ujtas cera and a few of them were partly 1Xlng a vegetative existence, improved alter ardiazol injections inasmuch as they began to ;fke an interest in their surroundings and in uemselves and are now attending the occupa-

therapy departments in the hospital, to which place they refused to go and work before, ourteen cases showed no improvement at a spite of the full course of 20 to 30 injections rp.Ven to them and they remained stationary. le

results of the experiment can be called en- gaging and the results in percentages were as follows

full remissions ? ? 31 per cent Improved ? ? 36 ,, ?

Stationary ? ? 33 >>

All the recovered cases were given four ? Ejections after recovery as recommended

tn ? ,' Meduna. In all our cases we were able nf lnc^uce the first fit at an initial dose of 0.5 gm.

cardiazol and in most cases this initial dose J! , later and we had to increase the dose in i- uations up to 1 gm. One gramme of car- lazol never failed to induce fits in all our

w le^s hence our initial dose for every patien as 0-5 gm. and maximum dose 1 gm.

e diagnostic aid of cardiazol in suspected cases of epilepsy

-^r. Schonmehl (1936) gives an interesting ccount of cardiazol as an aid to diagnosis in ^pected cases of epilepsy and other allied

?uditions. Durine his experiments on stuporous cK?nditions in epilepsy he found that fits could Je Educed in epileptics by very small doses of

cardiazol (0.5 to 3 c.cm.). We also experi- mented with our epileptic patients with small doses of cardiazol which failed to induce fits in our schizophrenic patients but induced severe

fits in epileptic patients. Doses given by us

were from 1.5 c.cm. to 3 c.cm. Dr. Meduna states that to produce epileptic fits in a normal healthy individual the dose required would be approximately 10 c.cm. only. In schizophrenic cases we could not induce fits below the mini- mum dose of 0.5 gm. It therefore proves that the small doses of cardiazol can produce con- vulsive fits in epileptics only. One of the

patients of Dr. Schonmehl had been successful in convincing the authorities when applying for a motor driving licence that he was not a

sufferer from epilepsy. He was brought to

Dr. Schonmehl who injected a small dose of cardiazol and induced severe fits in him and thus confirmed the diagnosis. We had a patient in the female section who was a suspected case of epilepsy; no medical officer had seen her in a fit because she had occasional fits only during the night and by the time a medical officer was called the patient had recovered from the fit, as she was suffering from a mild type of epi- lepsy. We therefore decided to use cardiazol in this case and injected 2.5 c.cm. of cardiazol; the patient went into a fit at once. We could not carry out further experiment by cardiazol in this direction as we had no other suspected cases of epilepsy.

Summary (1) The problem of schizophrenia is very

briefly described with its empirical treatment. (2) Forty-two cases of schizophrenia were

treated with cardiazol after the method of Dr. Meduna; the technique fully described.

(3) The results of the experiment were en-

couraging. (4) Cardiazol treatment appears to be per-

fectly safe in selected cases and is well worth a trial in all cases of schizophrenia, and more so

in the katatonic and hebephrenic varieties.

(5) It is free from any dangerous complica- tions and does not require such constant medical and nursing attention as in the case of insulin therapy. I would certainly give this treatment preference over insulin therapy. Acknowledgments.?We are indebted to

Messrs. A. G. Knoll for the free supply of car- diazol powder for our experiment.

I should like to acknowledge my appreciation of the valuable help I have received from the medical and nursing staff of the hospital.

I am also indebted to my friend and col- league, Dr. Gyarfas Kalman of Budapest, for the translation of Dr. Meduna's paper.

References

Dhunjibhoy, J. E. (1938). Lancet, Vol. I, p. 370.

Gillies, H. (1937). Brit. Med. Joum., Vol. I, p. 1254.

(Continued at foot oj next page)

(Continued from previous page)

von Meduna, L. (1935). Psychiat.-neurol. Woch., Vol. XXXVII, p. 317. Schonmehl (1936). Miinchener med. Woch., Vol.

LXXXIII, p. 721. Wilson, I. G. H. (1936). A Study of Hypoglycemic

Shock Treatment in Schizophrenia. His Majesty's Stationery Office, London.