SULPHUR TREATMENT IN MENTAL DISEASES

! An experimental study of 100 cases

By J. E. DHUNJIBHOY MAJOR, I.M.S.

Medical Superintendent, Ranchi Indian Menial Hospital The use of sulphur injections in general

paralysis of the insane was originally suggested by Dr. D. F. Tulunji of Paris in 1925, but Dr. Knucl Schroeder of Denmark two years later was the first to put it into practice. Schroeder advocated the use of a 1 per cent,

solution of sulphur in olive oil which lie called ' Sulfosin Leo

' in cases of general paralysis and certain other mental disorders, and published his early results in the Lancet in 1929. Since

then, a considerable number of English, con-

tinental and American observers have recorded

their opinion on this therapy in various medical journals. Several papers have since appeared describing the results of this treatment in the

columns of the Lancet and my first experimental study of 25 cases with this therapy was also

published in the Lancet (1931). The present article now deals with an experimental study of sulphur injections tried at the Ranchi Indian

Mental Hospital over a period of eighteen months on 100 cases suffering from the follow- ing mental diseases :?

(?) Thirty-seven patients of manic-depres- sive psychosis group.

(?) Forty-four patients of schizophrenic (dementia pra?cox) group.

(c) Eight patients of epileptic psychosis group.

(d) Two patients of psychoneuroses group. (e) One patient with disseminated sclerosis. (/) Two patients with chronic epidemic

encephalitis lethargica (with Parkin- sonian syndromes).

Nov., 1932J SULPHUR TREATMENT IN MENTAL DISEASES : DHUNJIBHOY 613

(g) Two patients with paranoia or paranoic! reactions.

(h) Four patients with stupor (1 benign and 3 secondary stupor) group.

The Ranchi Indian Mental Hospital is one

of the most modern and the largest Indian mental hospital in India and ever since its in-

ception in 1925 I have not yet seen a single case of general paralysis admitted for treatment. General paralysis is admittedly a rare disease in India, consequently I had no opportunity to try sulphur injections in this mental disorder like other observers. Out of the 100 cases selected for this therapy there were 60 males and 40 females. Their ages varied from 17 to 52 years and their stay in the hospital from 6 months to 16 years. Some were of recent admission and others had been in the hospital for several years and had shown no improve- ment in their mental condition. In assessing the value of any new therapeutical agent it is essential that the patients selected for treat- ment by this new agent should first be given a fair trial with ordinary treatment. All my cases selected for sulphur therapy had resisted the usual standard routine treatment of the mental hospital, such as rest, diet, tonics, glan- dular therapy, hydrotherapy, occupational therapy and correction of bad habits and

physical defects. Technique and dosage.?Sulfosin Leo as pre-

pared by Schroeder and manufactured for him by Messrs. Lovens Kemiske Fabrik, Copen- hagen, is not obtainable in India so I had to

prepare my own solution. I prepare my solu- tion by rubbing up the required quantity of

sulphur sublimatum with pure olive oil in a

gallipot and heating the suspension in a hot-air oven to a temperature of 90 to 100?C. until all has dissolved. This process of manufacture does not take more than fifteen minutes. After the publication of my first article in the Lancet on this therapy the Crooks Laboratory of London informed me that their preparation called ' Collosal Aqueous

' which is now obtain- able in India gives as good a result as Sulfosin Leo. They also sent me samples of this pre- paration for trial, and on experiment we found no appreciable difference in the results obtained from 1 Collosal Aqueous' and our own freshly prepared solution which costs us next to

nothing. I certainly recommend ' Collosal Aque-

ous ' to those practitioners to whom the cost is

a secondary consideration and time is money, or to those who do not wish to bother about the home-made preparation of sulphur.

Sites for injection.?The technique followed

as regards the actual injection was the same as that originally recommended by Schroeder, viz, to inject the solution supraperiosteally on the lateral side of the femur preferably between the upper and the middle thirds. The next best

sites I prefer are the gluteal regions and the

outer sides of the arms when the thighs are

contraindicated for any diseased condition.

Doses.?I commence the treatment by giving the initial dose of 1 c.cm. and increase the dose

by 1 c.cm. at each injection. A course consists of 12 such injections at the rate of 2 per week. The first injection in the course is 1 c.cm. and the last eventually amounts to 12 c.cm., the

strength of the solution remaining the same

throughout, viz, 1 per cent. The solution should be injected luke-warm and a 3-inch needle is the most convenient size to use. As a rule injections are given at 6 p.m. so that the patients can sleep comfortably at night as the temperature usually rises about 14 to 16 hours after the injection.

Py rexia.?The reading of temperatures takes place early in the morning and is then taken

every half hour until the "maximum is reached and then every four hours. The temperature is generally at its height in the majority of cases about 18 to 20 hours from the time of in-

jection and may range from 101 ?F. to 105?F. with or without rigors. It returns to normal in about 14 to 18 hours. In many cases a

secondary smaller rise takes place which comes to normal in 5 to 8 hours. As claimed by Dr. Knud Schroeder I tried to regulate the

pyrexia by dosage but did not succeed like many other observers. In some cases I was able to

register 104?F. by an injection of 3 c.cm., whereas in others 12 c.cm. did not produce the same result. I suppose individual constitution and idiosyncrasy have a say in this matter and each patient should be studied as to his or her individual capacity for responding to this treat- ment. The reaction was greater in females than in males. The maximum temperature recorded in my 100 cases was 105 ?F. and the minimum

100.2?F., the average being 102.1 ?F. A typical temperature chart is attached herewith. Some

patients had nausea and vomiting and a few had rigors. No untoward symptom of a grave nature was ever recorded in my patients during the pyrexial stage except the usual attendant discomfort of pyrexia. The remarkable feature of sulphur injections is the comparatively small disturbance of circulation which is generally associated with such elevations of temperatures. In no case was I able to record a pulse-rate over 120, although the temperature recorded was more than 104?F. Similarly the respira- tion ratio was approximately normal in all cases. No cyanosis and pallor were noted in the patients.

Leucocytosis.?Marked leucocytosis was

noted in all cases. It reached its maximum 22 hours after injection and in a good many cases had returned to normal after 48 hours.

Pain.?The most unfortunate outstanding feature of this therapy I must admit is the pain at the site of injection. Without exception all

my patients complained of pain at the site of

injection. In the majority of cases it subsides after a few hours but in some it persists for some days. Pain is much relieved by hot

614 THE INDIAN MEDICAL GAZETTE [Nov., 1932

compresses or hot water bags. The degree of

pain varies with different patients probably due to individual sensitiveness to this pain. How-

ever, I noticed that in the majority of my cases this pain was unavoidable yet bearable.

Results

The following table shows the results of our experiment on 100 cases :?

Number of

patients

37 44

8

2 1

2

2

4

100

Types of mental disease

Manic-depressive psychosis Schizophrenia (dementia pracox) Epileptic psychosis Psychoneuroses Disseminated sclerosis Chronic epidemic encephalitis lethargica (with Parkinsonian

syndromes). Paranoia and paranoid reactions Stupor (1 benign and 3 secondary stupor)

Total

Improved

16 20

39

Recovered

13

Stationary

15

20

48

I classify my results in the following three

categories :? (1) Improved. (2) Recovered.

(3) Stationary. It will be seen from the above table that out

of 100 cases 39 improved, 13 completely re-

covered and were discharged home as cured, and no improvement of any kind whatever was noticed in 48 cases. Of the 39 improved 18 cases have since relapsed and the remaining 21 have still maintained the improvement. One case of benign stupor, who was fed nasally for over a period of 3^ years and was lying in bed throughout the period as apparently dead to this world and had never spoken a word or

opened his mouth for drink or food, improved marvellously after the first course of sulphur injections inasmuch as he began to talk

although irrelevantly and took his food per mouth. He maintained this improvement for three months and relapsed again and was given

two more courses of injections. He has again improved to the extent that he now takes his food and takes a little interest in his surround-

ings. This patient also ran a temperature between 101 ?F. and 102?F. for three weeks after completion of his first course. We failed to trace any cause for this fever, either bacterio- logically or physically and the patient com-

plained of nothing. A similar case was reported

by Dr. P. C. Collingwood Fenwick (1931); in his case the patient ran a temperature for four weeks after a course of sulphur injections. Similarly the other two secondary stupor cases who were also fed nasally over a period of more than four months have much improved after

the first course of injections and are now able to look after themselves and take an interest in their surroundings. One of them has started work in the garden and the other who is a

literate patient and has not looked at a paper or books for months now spends his time in

reading books and periodicals and takes an

interest in life. The fourth stupor case who

was a female patient showed no improvement after three courses of injections. Moreover six

patients of the improved class have improved to such an extent that they are fit to be dis-

charged home as cured but as they are criminal patients, they have to undergo their probation- ary periods according to the Lunacy Act of

1912, hence we cannot discharge them. By

Name... Konsuz Bin. . .... SO years,. Much /mprovfid.

10 4*

105*

104?

100*

33*

1?r

sr

.37* Pvlst.* .5*3 ,v ,?58

Name... Konsui Bin. ...30 years.. Much improved-

Nov., 1932j SULPHUR TREATMENT IN MENTAL DISEASES : DHUNJIBHOY 615

improvement I mean that those patients who were dirty, noisy, destructive, attitudinistic, negativistic, some mute and one, who had hitherto led a purely vegetative existence, im- proved in their mental conditions inasmuch as they became quiet, clean in their habits and began to take some little and some more interest in their surroundings and many are now attend- ing the occupational therapy department of the hospital to which place they refused to go before. The following table shows the age, sex, the period of stay in hospital and number of courses given to the 13 recovered cases and is

self-explanatory :?

Table

Mental disease

Dementia proecox Dementia praecox Manic-depressive psychosis Dementia prsecox Manic-depressive psychosis Manic-depressive psychosis Psychoneuroses Dementia pracox Manic-depressive psychosis Psychoneuroses Manic-depressive psychosis Manic-depressive psychosis Paranoid reaction

Sex

Female Female Female Female Male Male Male Male Male Male Male Male Male

Age

25 30 20 18 21 30 27 25 40

33 25 27 36

Stay in the hospital

Years Months

4

6 4

11 11 4

9 1

6 1

6 1

11

Days

16 18 20

17

18 3

3 7

Courses of

injections

1st course. 1st course. 1st course. Two courses. Two courses. 1st course. 1st course. 1st course. 1st course. 1st course. 1st course. 1st course. 1st course.

None of the above discharged patients have yet been readmitted. This shows that they have still maintained the improvement.

Regulation of doses and courses

Doses.?-As stated above the increase of dose by 1 c.cm. at each injection need not be followed as a routine in every case. A temperature of 103?F. and over is considered a satisfactory rise for the treatment. Now supposing a patient responds well to a 2 c.cm. dose, it is not neces-

sary to increase the dose to 3 c.cm. at the next

injection, but to continue the subsequent injec- tions by 2 c.cm. only until it fails to produce the desired temperature, in that case an increase in the dose is necessary. It will be seen from the attached temperature chart that I have increased the doses when a particular dose has failed to bring about the required rise of tem- perature. In this case the patient had 12 in- jections yet the maximum dose never exceeded 9 c.cm.

Courses.?I generally give 12 injections in

the first course of treatment and 8 injections for the second and third courses respectively. Courses are given after a lapse of four weeks after the end of each course. Courses are only repeated if the improvement is not satisfactory. In a few cases as an experimental measure we gave more than three courses but the patients derived no further benefit. We then came to

the conclusion that if a patient does not derive any benefit by three courses of sulphur therapy he or she is not likely to be benefited by fur- ther treatment and we followed this method as a standard routine. In our series of 100 cases,

25 patients had one course. 18 patients had two courses. 47 patients had three courses. 10 patients had more than three courses. Out of the 39 improved cases,

10 had one course.

9 had two courses.

20 had three courses.

Out of 13 recovered patients, 11 had one course. 2 had two courses.

It will be evident from the above figures that the improvement was very satisfactory and

lasting in those cases who improved by the first course. Recovery was also greater and relapses were smaller in number. In the second and third courses 29 improved, 16 relapsed and 2 recovered. It will be seen from the above results that there exists no hard and fast rule as to the doses and number of courses in sulphur therapy, but that each patient has to be judged on his or her individual capacity for respond- ing to this treatment.

Discussion.?It has been a common experi- ence of all psychiatrists that intercurrent febrile illness in the insane sometimes causes

amelioration of the mental symptoms and occa- sionally a spontaneous cure occurs. In my

experience of psychiatry work in India and

Europe I have seen several cases recovering spontaneously or definitely improved after a

severe attack of any infection such as pneu- monia, typhoid, influenza, smallpox, measles, etc. How this is effected still remains a

mystery in the domain of psychiatry although many have ventured to explain this phenomenon in various ways. Some state that the brain cells thus exposed to hyperpyrexia may be

exercising some specific influence, whereas others

616 THE INDIAN MEDICAL GAZETTE [Nov., 1932

state that the fever produces phagocytes and antibodies are stimulated and they attack some hidden source of chronic bacterial toxemia. On the other hand some suggest that by the fever metabolism is stimulated and in its turn it in-

creases oxidation and hastens elimination of

toxic waste products from the brain cortex and body generally. Based upon the frequent reports of psychoses being healed through the intercurrent infections, many investigators have tried various toxic and infectious agents to

bring about a cure in mentally-afflicted persons. The substances commonly used have been Koch's tuberculin, all vaccines particularly T. A. B. and B. coli, turpentine, milk, blood and blood sera, malaria, sulphur, etc. The induc- tion of fever by inoculation with a view to

amelioration of psychosis has recently come

into prominence owing to the treatment of

general paralysis with malaria. In 1917 Pro- fessor Wagner Jauragg of Vienna inoculated 9 cases of general paralysis with tertian malaria, 6 of whom were highly benefited and returned to their homes and resumed their daily work. Of the many reputed pyrexial agents, I have

experimented with the following with indifferent results, except sulphur :?

(1) Malaria.

(2) Turpentine (fixation abscess). (3) T. A. B. vaccine.

(4) Milk.

(5) Sulphur. Recently in Europe and America the produc-

tion of fever in general paralysis and other

psychoses without the introduction of foreign infections is in vogue. This is done by induc- ing aseptic fever in patients by the super-

power diathermy apparatus. The average treat-

ment requires from 6 to 8 hours and must be done under the constant supervision of a trained person who is familiar with its application. A

trained operator can manage two cases simul-

taneously. The technique itself is very simple. The electrodes are placed on the chest, abdomen and on the back so that high frequency elec- trical energy passes through the body, which offers resistance to this electrical current and the body temperature rises. The essence of the treatment is to keep the patient above 103.5?F. for at least 6 hours. Two treatments are given per week and a course consists of such 8 to 15 treatments. The apparatus ensures complete management and control of temperature as to the limits of its height, duration and extent. In 1930 I had personally seen the diathermy apparatus working satisfactorily in many large mental hospitals of Europe and America. These machines are now obtainable in India but they appear to be very expensive. The 1

mechanism of cure by sulphur has been recently explained by R. P. Mackay of Chicago (1931) who after having experimented with sulphur on animals and human beings tentatively came to the conclusion that the fever is due to the :

liberation of protein from muscle tissues which

have been damaged by injection of the sulphur or by irritant hydrogen sulphide. He further

states that the reaction is more biological than chemical. Mackay concludes that '

Sulphur can accomplish what fever produced by any other method can accomplish and that by virtue of the long duration of the fever produced sulphur should bring results more rapidly and surely than any other method'. Recently a

book has been published by Professor K. Bonhoeffer (1931), the eminent neurologist of

Berlin, with Dr. P. Josemann. In this book the results obtained with malaria and other fever-

producing agents are fully discussed. From

1922 to 1929, 2,000 cases of general paralysis were treated in Berlin by malaria therapy and the authors claim 23 per cent, of cures and 40

per cent, with definite improvement in their

cases. Dr. Kellmann in his contribution

acknowledges the remarkable success of malaria therapy by the authors, but points out that malaria therapy cannot be pronounced quite harmless and safe as it kills a certain propor- tion of patients. Dr. Kellmann considers sul-

phur injections safer and remarks that even if

this method is found to be inferior to malaria

injection in potency it will nevertheless find a

field of usefulness in the treatment of the debi- litated for whom more drastic therapy is too

dangerous. Conclusions

1. There can be no doubt that injections of sulphur in olive oil invariably produce a degree of pyrexia. The temperatures obtained range from 100.2?F. to 105?F., the average being 102.1 ?F., and the temperatures cannot be regu- lated by doses.

2. Pain at the site of injection in every case was unavoidable but certainly bearable. *3. Sulphur injections should be given un-

hesitatingly, because unlike malaria therapy they are perfectly safe and can be given to

young and old alike. The injections are well worth a trial by any medical practitioner.

4. Earlier cases respond better to treatment than the old chronic cases and the earlier the treatment is instituted the greater is the chance of recovery.

o. I am of opinion that sulphur merits a

trial in all early cases of psychoneurosis and psychosis and seems definitely useful in chronic psychotics who have hitherto failed to respond to other methods of treatment. It also appears to be very useful in cases of benign and secon- dary stupors. ,

6. Dr. Knud Schroeder of Denmark has

undoubtedly shown to the profession the use

of sulphur as an unfailing agent for the arti- ficial induction of pyrexia and its distinct thera- peutic possibilities.

I would like to express my acknowledgment of the valuable help given to me by the medi- cal and nursing staff of this hospital, as the

experiment had undoubtedly thrown an extra (Continued at. foot of opposite page)

(Continued from previous page) burden on their shoulders over and above the daily heavy duties of their office.

\ ....

References

BonhoefTer, K., and Josemann, P. (1931). Ergcbnissc Reiztherapie bei Progressiver Paralyse, p. 154. Berlin:

S. Karger. Dhunjibhoy, J. E. (1931). Lancet, Vol. II, p. 1407. Fenwick, P. C. C. (1931). Lancet, Vol. I, p. 241.

Mackay, R. P. (1931). Arch. Neurol, and Psychiatry, Vol. XXVI, p. 102.

Schroeder, K. (1929). Lancet, Vol. II, p. 1081.

Tulunji, D. F. (1925). Lancet, Vol. II, p. 408.