An Early Hope of Psychopharmacology.

Bromide treatment in the turn-of-the-twentieth-century psychiatry.

Howard H Chiang

ABD in History of Science

Princeton University, Princeton, NJ, USA


This article investigates a critical turning point in the history of modern psychopharmacology: the use of bromide as an effective behavioral treatment around the turn of the twentieth century.  The story begins with the British physician Dr. Neil Macleod, who first reported successful cases of curing drug addiction with bromide-induced sleep in 1897.  The bulk of the paper studies the North American reception of Macleod’s bromide therapy, which he first administered in Shanghai, China.  The commendations and criticisms that fueled the reception of Macleod’s bromide sleep were characterized by a central preoccupation with its clinical validity and reliability.  In the midst of these professional tensions from Shanghai to Toronto, curing drug habits through bromide-induced sleep gave doctors an early, if not the earliest, hope of psychopharmacology.

Keywords: Bromide Sleep; Neil Macleod; Psychiatry; Psychopharmacology; Shanghai


Although drug therapy has played an important role throughout the history of modern psychiatry, early drugs such as chloral or apomorphine suppressed symptoms only temporarily.  This article traces the history of psychopharmacology to a pinnacle moment of change: the use of bromide as an effective behavioral treatment around the turn of the twentieth century. 

In 1896, Dr. Neil Macleod, a British physician who practiced medicine in Shanghai, gave one of his female patients a dosage of sodium bromide.  To Macleod’s surprise, the patient’s morphine habit was eliminated after a long bromide-induced sleep.  Between 1897 and 1900, Macleod published three articles in the British Medical Journal (in 1897, 1899, and 1900 respectively) to report up to nine cases of this bromide therapy (1,2,3).  All except for one demonstrated Macleod’s success in removing his patient’s drug habit after inducing a bromide sleep.  “For the first time in the history of psychiatry,” according to historian Edward Shorter, Macleod’s bromide sleep presented itself as “a drug therapy…that seemed to alleviate major psychiatric illness with a physical procedure” (4[p202]).  By as late as the mid-1920s, psychiatrists writing in the official journal of the American Medical Association would continue to claim the novelty of the drug efficacy of bromide.

Even though Macleod published only in British medical journals, news of his findings immediately came to North America through a number of ways.  Not only were his writings republished and abstracted in prestigious medical periodicals, but physicians working in both Canada and the U.S. took an active role in experimenting with the bromide therapy he proposed.  The majority of doctors welcomed his method with great enthusiasm; others were more cautious in considering it as a viable treatment option.  Some claimed that the same therapeutic efficacy could be achieved through different drugs; others argued that what Macleod proposed was not so novel after all.  The debates and praises that fueled the reception of Macleod’s bromide sleep were characterized by a central preoccupation with its clinical validity and reliability.  In the midst of these professional tensions from Shanghai to Toronto, curing drug habits through bromide-induced sleep gave doctors an early, if not the earliest, hope of psychopharmacology.

Macleod’s findings reached North America primarily via British medical reports.  The Canadian Journal of Medicine and Surgery, for instance, reprinted his 1899 article the same year it first caught the attention of British physicians (5).  Macleod’s bromide method also made its way into the pages of the Journal of the American Medical Association and Progressive Medicine in a short frame of time (6).  Both Canadian and American physicians therefore were informed by Macleod’s case studies almost as soon as their British colleagues found out about them. 

Meanwhile, other prominent periodicals, such as the Journal of Nervous and Mental Diseases, simply published brief synopses of his 1899 paper (7).  In that piece, Macleod included six case studies to follow up on the bromide therapy he first proposed in 1897, but two were left out in the synopsis that appeared in JNMD.  Ultimately, what this particular brief synopsis accomplished historically was more than providing American psychiatrists a first glimpse at Macleod’s follow-up study on bromide treatment.  In highlighting one additional case of morphine addiction, a new case of chloral addiction, and two other cases of cocaine and morphine addiction, however briefly, the synopsis conveyed a sense of how the use and treatment effect of bromide injection had expanded.  The morphine habit was no longer the only thing that bromide sleep could cure, but similar procedures could be administered to treat chloral and even cocaine addictions.

Macleod’s findings were documented almost immediately in the Yale Medical Journal (8) and the Merck’s Archives as well (9).  The entry in Merck’s Archives was called “Bromide Sleep,” a term that Macleod coined in 1900.  Although the term had already appeared once in his 1899 report (2[p898]), and though he had first introduced the concept of “bromidism” in 1897 (1), it was not until 1900 that Macleod actually formulated a systematic definition of “bromide sleep” and thereby described it as a potential treatment of acute mania. 

The Merck’s Archives entry summarized all of Macleod’s nine bromide treatment cases since 1897, and explained the therapy’s general protocol as follows: “For from five to nine days the patient sleeps incessantly and cannot be aroused, cannot walk, stand, sit, speak, or carry on any of the higher cerebral functions.  If left to himself he will not feed or drink; indeed, he cannot even ask for food or drink, being unconscious of these needs, but can be sufficiently nourished with milk during that time….The loudest sound, the strongest light will not disturb him.  During this period the higher nerve centers arrested to an extent that cannot be attained in any other way. Following this sleep is a gradual recovery of the powers of locomotion, speech, thought, etc., the progress being daily visible, lasting about a fortnight—in all about twenty-one to twenty-four days.  This fortnight is also a period of comparative rest, there being a gradual awakening of mental power and a passage from a disordered to an ordered state as regards that function” (9[pp110-11]).  By referring to the status of “the higher nerve centers” during bromide sleep, the entry emphasized a functional component to this treatment.  This physiological style of explaining why the therapy worked thus gave physicians a greater degree of confidence, at least to the extent that went beyond what they could get out of merely observing the patient’s symptoms.

In addition to providing a functional explanation for the somatic mechanism of bromide sleep, the entry in the Merck’s Archives also reassured its therapeutic validity.  It pointed out that in the nine cases in which Macleod induced bromide sleep, “he could discover with benefit to all except one, who owing to a double pneumonia during a pneumonia epidemic died while under the bromide” (9[p111]).  “Apart from this case,” the entry continued, Macleod “observed no interference of respiratory or circulatory function that could cause the slightest alarm.  After recovery no interference with nervous function has occurred” (9[p111]). 

What is striking about this summary is that the pneumonia epidemic became the sole reason for the patient’s death.  But according to Macleod’s initial speculation, “the [patient’s] recent journey from the warm South into our cold weather, the enfeebled health consequent on the habits, and the [overdose of] bromide may have acted as predisposing causes to the acute lung ailment” (2[p897]).  Even Macleod himself thought that some combination of these three criteria was probably responsible for the patient’s death.  By eliminating this complex way of explaining and attributing the case of the patient’s death entirely to a pneumonia epidemic, readers of the Merck’s Archive entry took away from it a rather vague sense of the bromide method’s therapeutic validity.

The author of the entry went a step further by pointing out the various therapeutic potentials of bromide sleep.  Most telling is the suggestion that bromide sleep, when used less dangerously, had the potential of treating all other nervous disorders: “If future experience goes to show that this bromide sleep can be induced without or with little danger, it ought to prove a powerful and effective means of dealing with all maladies of the nervous system in the treatment of which there is need for deep sleep and a profound and prolonged rest of the higher centers” (9[p111],3).  Again, by invoking the functional component of bromide treatment, the entry gave its reader a vague but reasonable correlation between its administration and therapeutic efficacy.

The therapeutic efficacy of bromide sleep did not only come from its validity and potentials, however.  Besides being preoccupied with showing that the treatment was “accurate”—meaning it treated what it was intended to treat—physicians in Britain and North America quickly tested its clinical reliability (or replicability).  Around the turn of the twentieth century, drug addiction was high on the agenda of psychiatrists on both sides of the Atlantic, especially since it was often regarded as the class of behavioral disorders with the most unpromising clinical results.  Following Macleod’s report of his bromide sleep method, many of them supported the consistency of its efficacy by bringing more successful cases of bromide treatment to the public. 

For example, in 1901, Dr. Arthur Small from Toronto, Canada, reported a case of “alcoholic habit of many years standing in a man forty years of age who at the time of consultation was in a highly nervous and excitable condition and had for many days been suffering from insomnia” (10[p638]).  Small remarked that although he could not induce the kind of “deep sleep” Macleod induced with bromide injection, “nevertheless it gave what might be described as a normal sleep, which [the patient] certainly had not had for many days” (10[p639]).  To conclude his case, Small added: “during the treatment the patient’s temperature was sub-normal, varying between 96.2 and 98o Fahr.” and “so far the alcoholic craving has not returned” (10[p639]).

Before accounts like Small’s began to make their appearance across North America with increasing velocity, other physicians in Europe had already warned against the administration of an unnecessary quantity of bromide to achieve desirable therapeutic results.  In 1900, having treated a young Englishman diagnosed with mania for four days with no signs of improvement, Dr. Philip Ragg decided that in order to keep the patient out of the asylum, he was “determined to try the effect of bromide treatment” in his private practice at Kingston, Jamaica (11[p1309]).  Ragg noted that “in the treatment of this case the drug was not pushed to the extent advocated by Dr. Neil Macleod, as after a twenty-four hours’ cessation I judged further administration unnecessary” (11[pp1309-10]).  Yet, despite his concern about the potential over-dosage of bromide in clinical practice, Ragg still stressed that “[Macleod’s] statement that ‘the full effect of the drug is not manifest for at least twenty-four hours after the last dose’ is well borne out” (11[p1310]).  Publishing this case in the same journal in which Macleod’s papers appeared, Ragg contributed to an increasing awareness among physicians at the time that bromide sleep was probably as effective in treating other nervous diseases as drug habits.

The physician who played the most instrumental role in introducing Macleod’s bromide method to American doctors around the turn of the century was probably Dr. Archibald Church, a Professor of Clinical Neurology at the Chicago Medical College in the Medical Department of Northwestern University (12).  Also a practicing neurologist at the St. Luke’s and Wesley Hospitals, Church was impressed as soon as he read Macleod’s preliminary report on the therapeutic effect of Bromide-induced sleep in 1897.  Church immediately made note of it and abstracted it for the department of Nervous Diseases in the Year Book of Medicine and Surgery (12[p291]).  Church followed Macleod’s subsequent studies very closely, and even before Macleod formally coined the term “bromide sleep” in 1900, Church had already begun experimenting with bromide injection as a method for treating one of his morphine addict patients.

The patient was admitted to St. Luke’s Hospital on 4 December 1899, having consulted with Church and agreed to begin the bromide treatment immediately that evening.  The patient left the hospital by the 23rd of December, after 20 days of inpatient care, weighing 18.5 pounds less than when he was first admitted to the hospital.  Despite the weight loss, according to Church, the patient “said that he felt perfectly well aside from a feeling of weakness” (12[p293]).  Church proceeded to confirm that “The subsequent course of the case has left nothing to be desired.  Sexual power, which had been absent for years, promptly returned, a feeling of strength, buoyancy and mental capacity was immediately established and he went back to his professional work which he has carried on with satisfaction, and promptly picked up the weight that had been lost” (12[p293]).

Whereas other physicians, such as Dr. Small from Toronto or Dr. Ragg from Kingston, reported no fatal results from endorsing Macleod’s method, Church brought to the public a second case in which the patient’s life was actually terminated in the course of bromide treatment.  The patient was a male physician, about 40 years of age, addicted to morphine, whisky, cocaine, and various other stimulants and sedatives.  According to Church, “owing to misunderstanding of directions in this case, however, an extraordinary amount of bromide was given within the first few days, and while as far as the morphine craving and the general condition of the patient was concerned, it gave rise to immediate decided benefit, an old nephritis developed into an acute one and the patient finally died of uremia” (12[p294]).  Despite the fact that the patient had died in the course of treatment, Church felt compelled to emphasize that his death should be attributed to a “misunderstanding of directions” in administering the quantity of bromide.  He also insisted that “the pronounced tremor, restlessness, general apprehensiveness and nervousness subsided altogether during [the] time [of treatment] and [the patient] expressed himself as being better than he had been for a year” (12[p294]).

Hence, the general lesson Church had hoped other physicians would learn from his second case study must be evaluated on a level beyond the simple notion that bromide sleep could be as dangerous as it was effective.  Indeed, Church was not the first to raise awareness about the danger of bromide sleep in a reputable medical journal.  As mentioned above, Dr. Ragg from Kingston expressed similar concerns about bromide over-dosage.  And as early as 1899, in explaining the death of the only patient who had died from his bromide treatment, Macleod himself clearly indicated that it was probably because “more bromide was given than necessary” (2[p897]). 

But although he was well aware of the danger of excessive bromide injection, Macleod maintained that “any physician with the aid of vigilant nurses can deal with the case in any hospital or private house, no special institution is needed” (2[p897]).  Here is where Church departed most drastically from Macleod’s perspective.  In Church’s words, “Macleod stated in his early communications that the use of the bromide in the manner he had outlined was practically without danger” (12[p291]), but his own intention in publishing the second case in which the patient actually died in the course of bromide therapy was precisely to demonstrate “very positively that the bromide treatment of morphine addiction is not without danger” (12[p294]).

There were three main conclusions Church drew from his two case studies.  First, he confirmed Macleod’s observation that “the drug [bromide] should only be given in the day time” (12[p295]).  This added another layer of validity and reliability to Macleod’s initial clinical observations.  Second, Church urged other physicians to remember that “the bromide acts in a cumulative manner” (12[p295]).  This was the first time in medical history that the effect of bromide on patients was so explicitly spelled out.  Finally, despite its danger, Church still regarded bromide sleep as an incomparable therapeutic approach.  According to Church, “as compared with the difficulties of the ordinary methods that are pursued in correcting addiction to morphine, [bromide treatment] seems to me to be of very definite value in well selected cases, and in such cases I should not hesitate, under appropriate conditions to employ it” (12[p295]).  By “appropriate conditions” Church meant “hospital equipment, trained nurses and a competent resident physician,” a caveat Macleod did not fully acknowledge (12[p295]).

Church’s report provoked a wide spectrum of opinions on this new cure of drug habits from physicians across North America.  On the one end of the spectrum, some doctors considered bromide sleep probably the best therapy available for treating drug addictions.  Dr. Richard Dewey from Wauwatosa, Wisconsin said that he had been “very much interested in the paper of Dr. Church, for the reason that any method of treatment which furnishes a prospect of relief or of cure of these most unpromising cases of drug habit should be accepted by [the medical profession]” (12[p296]).  “So far as we can judge at the present time in reference to the results,” Dewey asserted, “they are as good as can be expected from any treatment” (12[p296]).  Dr. J. N. Black from Clayton went so far as to suggest that the method Church derived from Macleod stood as “one of the grandest things in the whole vocabulary of medicine” (12[p296]).

Other doctors were less optimistic and expressed a more moderate position on the matter.  Dr. J. W. Pettit from Ottawa, for instance, began his comments by stating that “The practical value of [Church’s] paper turns upon the permanency of the cure.”  “It is the experience of physicians,” Pettit proceeded with his concern, “that by various methods we can succeed in withdrawing the opium, but the common experience of the profession is like that of my own, that there is no permanency of cure, as a rule.  I would like to ask the author of the paper as to the permanency of the cure, and what he regards as the time limit, if he has fixed it?” (12[p296]).  Central to Pettit’s concern about the bromide treatment option advocated by Macleod and Church is the question of how the “permanency” of a cure could be determined. 

Following Pettit, Dr. O. J. Roskoten from Peoria offered the harshest criticism, insisting on adhering to a bioscientific basis when evaluating the cure: “If this treatment can be applied for two or three months at intervals until the faulty metabolism of the cells has been gradually corrected, each generation of cells approaching more nearly the normal action than the one preceding it, then we can speak of a radical cure, but not before” (12[p297]).

To Dr. E. J. Brown from Decatur, however, the question posed by Pettit seemed moot.  For Brown, “any remedy or treatment that will relieve an unfortunate person from the drug habit for a month or six weeks is a permanent cure, so far as the remedy is concerned” (12[p296]).  In this regard, most of the cases presented by both Macleod and Church had certainly met this criterion.  Lest other doctors were unsure about what to think of the treatment itself if the drug habit does come back after four to six weeks, Brown added that “If the patient persists in going back to his habit, I do not believe there is any remedy that will cure him, nor can we hope to have a remedy taken that will forever relieve a man from relapsing into the drug habit” (12[p296]).

But Brown had something else to offer as well.  He claimed that he had “effected a permanent cure” in an earlier case of morphine habit by administering an entirely different drug—phosphate of codeine.  “The patient has regained health,” according to Brown, “and is well today” (12[p296]).  The administering of a drug that was not bromide in order to cure drug habit struck a strong resonance with another physician, Dr. J. F. Percy from Galesburg.  Percy reported a seemingly successful case of treating morphine addiction with a drug called strychnia (12[p296]).  Therefore, Macleod’s “accidental” discovery of the effectiveness of bromide in treating morphine habits and other nervous conditions emerged in a context when physicians around the world, from Shanghai to Galesburg, eagerly experimented various ways of treating drug behavior.

Indeed, in the same year Macleod coined “bromide sleep” and Church publicized Macleod’s finding in the Illinois Medical Journal, Dr. W. B. Fletcher from Indianapolis said that he had “for years used [the same] drug in cases of morphia mania and alcoholic mania brought on by suddenly quitting either, by one, two, and even three ounces of bromides given in from twenty-four to thirty-six hours” (13[p13]).  Fletcher even performed the treatment in two successful cases of traumatic tetanus, and “[had] no doubt it would do as well in hydrophobia” (13[p13]).  Therefore, at a time when drug addiction was a shared therapeutic concern among physicians, regardless of where they were located, Macleod’s bromide therapy reached the European and North American medical profession so quickly because it already existed as a treatment option for some of the doctors there.

Given that this article has focused on the reception of Macleod’s bromide treatment method, it is worth emphasizing the location where Macleod first administered it: Shanghai.  Because the familiar story about the global development of modern medicine often casts Western biomedicine as a tool of cultural expansion, penetration, and even imperialism that displaced “indigenous” treatment techniques, the case of bromide use around the turn of the twentieth century offers a rare window on an alternative historical trajectory.  This example of an early hope of psychopharmacology reminds us that the development of Western medicine often depended upon, as much as it shaped, the therapeutic happenings outside the core regions of its seemingly most matured form.


Howard H. Chiang is the Founding Editor of Critical Studies in History.  Under the co-supervision of Benjamin Elman and Angela Creager, he is currently completing his doctoral dissertation provisionally titled “Passion and the Flesh: A History of Sex-Alteration in Modern China.”  His recent and forthcoming publications can be found in the Journal of the History of the Behavioral Sciences, Journal of the History of Biology, Critical Studies in History, East Asian Science, Technology and Society, and Studies in History and Philosophy of Biological and Biomedical Sciences.  He can be reached at: hchiang@princeton.edu.


References.

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2. Macleod N. Cure of morphine, chloral, and cocaine habits by sodium bromide. BMJ. 1899; 1(1998):896-898.

3. Macleod N. The bromide sleep: a new departure in the treatment of acute mania. BMJ. 1900; 1(2038):134-136.

4. Shorter E. A history of psychiatry: From the era of asylum to the age of Prozac. New York: J. Wiley & Sons; 1997.

5. Macleod N. Cure of morphine, chloral, and cocaine habits by sodium bromide. Can J Med & Surg. 1899; 6:183-190.

6. Bromides. Prog Med. 1901; 4:337-341.

7. Patrick. Cure of morphine, chloral and cocaine habits by sodium bromide. J Nerv & Ment Dis. 1899; 26(1): 585.

8. The treatment of the opium habit by the bromide method. Yale Med J. 1900; 7(2):71.

9. Bromide sleep. Merck’s Arch. 1900; 2(3):110-111.

10. Small AA. The bromide sleep. Can Lancet. 1901; 34(12):637-639.

11. Ragg PM. The bromide sleep in a case of mania. BMJ. 1900; 2(2079):1309-1310.

12. Church A. The treatment of the opium habit by the bromide. Illinois Med J. 1900; 50-2(7):291-297.

13. Fletcher WB. Cure of morphine and alcohol habit by bromides. Indiana Med J. 1900; 19(1):12-13.

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