prepared by John M. Friedberg, MD

March 20, 1997

The following articles are selected for their relevance to Neuroleptic Malignant Syndrome and "Lethal Catatonia."

They are organized chronologically, to highlight the differences between "lethal catatonia" of the pre-neuroleptic era and Neuroleptic Malignant Syndrome. NMS is a drug reaction to tranquilizers so terrible that were it to be associated with an antibiotic or arthritis pills or blood pressure medication, such drugs would long since have been abandoned or outlawed.

The fact that after almost 50 years, old-standby drugs like Haldol and new and even more potent relations such as Respiridone, are used more widely than ever is - in my view - entirely due to the myth of mental illness. Labeling someone mentally ill is, to quote Dr. Thomas Szasz, "like hanging a sign around their neck saying ‘garbage.’ " Certainly the label of mental illness leads to playing fast and loose with such persons physical health and human rights.

Case reports of NMS and literature reviews were readily available in both psychiatric and

neurologic journals from 1956, three years after the introduction of the first phenothiazine, Chlorpromazine (Thorazine) by Herman Lehmann. (Lheman HE and Hanrahan GE: AMA Archives of Neurology and Psychiatry: p 227 (vol? Yr.??) Chlorpromazine, a new inhibiting agent for psychomotor excitement and manic states, induced "artificial hibernation" - note that from the outset the phenothiazines inhibited muscle activity. NMS represents an extreme of the intended effect.

As this chronology shows, there was a flurry of reports throughout the decade of the 1970's.

As stated in a The Neuroleptic Malignant Syndrome and Related Conditions (see Lazarus, Caroff and Mann ref No. , below):

"Interest and increased awareness in febrile catatonic states associated with neuroleptic administration was quite evident by the mid 1970's. At this time, NMS had been fairly well reported in France, Japan and England. Several American authors cognizant of the French reports, also began to use the term neuroleptic malignant syndrome to describe similar cases in the United States." (p 5)

The French were the first to observe the artificial hibernation produced by the anti-histamine related group of drugs called phenothiazines and the first to apply this observation for human behavioral control. It is not surprising that the very term Neurologic Malignant Syndrome is a translation of the French term "syndrome malin des neuroleptiques."

Despite the recent obfuscation and conflation (e.g. in the book cited above and the last reference by Max Fink below) of NMS and "Lethal Catatonia of Stauder," the epidemic of NMS which followed the epidemic of neuroleptics in the 1960's was clearly a new and alarming phenomenon.

NMS shares two key signs, muscle rigidity and hyperthermia, with Malignant Hyperthermia, a reaction to anesthetics first noted in the 1920's. Neither fever nor involuntary rigidity are present in catatonia, however construed, except as terminal events in mania.



1. Calmeil - described in Aronson et al: Complications of acute catatonic excitement. A report of two cases. Am J Psychiatry 107:216-220, 1950. According to these authors, Calmeil, a student of Esquirol "described agitated hyperactive patients with auditory hallucinations who precipitously became stuporous and died with hyperthermia as high as 43.3 degrees C."


2. Bell LV: On a form of disease resembling some advanced stages of mania and fever. Am J of Insanity 6:97-127, 1849


3. Kahlbaum, KL: Catatonia. Translated with an Introduction by George Mora, M.D.: John’s Hopkins University Press, 1973. Lib Congress Cat No 72-9960


This is a publication upon which such an eminent authority as Max Fink (see below, 1995) bases his assertion that NMS and Lethal Catatonia are indistinguishable.

Kahlbaum begins by discussing the frustration in finding any anatomical abnormalities in mental illnesses and, although he (and all his professional descendants) maintains a faith in ultimately finding neuropathology, he argues that diagnosis of mental disease does not’t have to be based on physical reality according to the principles of the famous pathologist Virchow’s (for every disease there are cellular changes) and should be based strictly on clinical descriptions.

Kahlbaum describes catatonia as "a condition of atonic melancholy, repetition of words and speeches (verbigeration), stereotyped gestures and habits and negativistic expressions." (p 86)

There is little mention of fever and even the muscle rigidity described by Kahlbaum could only willfully be mistaken for the involuntary rigidity of NMS e.g.

"all the time keeping his (the patient) head slightly above the pillow - tetaniform cramp - his hands folded and his eyes focused on one point (atonicity). The whole night he lay quietly in this manner. The following day he now and then spoke excitedly....and at times very confused in his speech and wishes, signing or shouting loudly...finally he developed a tendency to fixed positions during which lay stiffly extended, without reactions or speech while he pulled at the bedclothes....the patient then lay in his fixed position and gnashed his teeth...." (p 88)

With regard to prognosis, far from being the worst of all mental illnesses:

"....the prognosis of all forms of catatonia is far from hopeless. This is true concerning both the possibility of cure and life expectancy." (p87)

19th Century nationalism enters in:

"We must thus safeguard catatonia from its inclusion in the French concept of degeneration, which unfortunately is already starting to creep into the German literature. This also holds for the disease entity for which I earlier proposed the name hebrephrenia (juvenile insanity)." (p92)

Kahlbaum locates the pathology in cloudy arachnoid membranes (the arachnoid membrane surrounds the brain):

"The arachnoidea is more regularly the site of changes. Only in the youngest case was the cloudiness of this membrane limited to the free leaf between the cerebellum and the medulla oblongata" (p78)

As to cause, Kahlbaum blames masturbation in men and pregnancy in women. In this he shared the bias of his times and was in agreement with his patients such as Paul M:

"the son of a primary school teacher with a hypochondriac and exalted character...He had masturbated since the age of 14." (p35)

But Kahlbaum cautions:

"Among prognostic factors, masturbation is usually regarded as very unfavorable. However, masturbation should not only be regarded as an etiological factor, for it also has symptomatologic importance, i.e. it is the expression of a pathological irritation of the genital organs...."

He recommends that masturbation

"be surgically eliminated (by catheterization) or by means of drugs or a diet. In addition, forbidding the patient to masturbate on moral grounds plus surveillance can be used successfully in the suppression of this harmful factor." (p90)

Risk factors for catatonia include occupation:

"I have observed there is a predominance of teachers, children of teachers and theologians." (p54)

He contrasts this with GPI (General Paresis of the Insane, one form of three forms of tertiary syphilis, the other two being locomotor ataxia or tabes dorsalis and a meningeal form) which favors "merchants and lawyers."(p54).

Catchy words and phrases like catatonia often determine psychiatric thinking for decades. We have Kahlbaum to thank for the picturesque term: "flexibilitas cerea" or "waxy flexibility" which has captured the imagination of five generations of psychiatrists:

"....peculiar manifestations which so often marked the final stage of the disease, consisting of abnormal postures and functional movements of the limbs...(terminating in the final stages in) more or less fully developed cataleptiform waxen flexibility." (p26)

"In part these motor disturbances might be regarded as a mental, and even voluntary symptom comparable to the phenomena which have been discussed earlier under disturbances of the will....A part must be considered to be of cerebrospinal origin such as the condition of waxen flexibility and the crooked positions of the extremities resembling contractures. True paralysis is so rare in catatonia that it cannot be regarded as belonging to the symptom complex of this disease. However, decreased sensibility up to complete anesthesia is common. It is especially mentioned in cases of atonic melancholy that deep needle pricks are borne without any outward signs of pain (I myself have observed such cases.)....After the mental disorder has diminished....some retain the memory of the painful needle pricks...."(p51)

Kahlbaum stakes his claim for the term "verbigeration" (talking too much) which is enjoying something of a comeback and also gets the credit for "flight of ideas" (thinking too fast). He analogizes too much talking with "clonic cramps" and talking too little with "tonic cramps:"

"Loquaciousness and verbigeration could then be compared with clonic cramps and taciturnity with tonic cramps."(p46)


4. Kirby, GH: The catatonic syndrome and its relation to manic-depressive insanity. J. of Nervous and Mental Disease 40:694-704, read before the New York Psychiatrical Society, May 14, 1913.

Citing Kahlbaum, the author emphasizes that "the prognosis in these cases (is not) particularly bad..." while acknowledging another authority, Aschaffenburg, who "claims that no catatonic completely recovers..." Kirby’s intent is to separate the entity from the gloomy predetermination of Emil Kraeplin’s concept of "Dementia Praecox."(Lerbuche die Psychiatrie 8th ed 1905).

"The most typical catatonic manifestation, the negativistic stupor....whereby the individual practically shuts out the external world."

"Attention has been drawn to the resemblance to....the old reaction seen in animals that in time of danger lie motionless as if feigning death."

Dr. Kirby cites a typical case, a 31 year old woman who came down with catatonia "two days after the death of a 3 month old baby....For 5 years the patient showed in the hospital a very typical catatonic picture. There were mutism, general resistance against passive movement, musuclar tension, fixed postures, hands clenched, head flexed with chin on chest....." She "cleared up" and was discharged 6.25 years after admission.

No fever described, not much of an emergency either.

Another case, an 18 year old "native-born Jewess" became "mute, resistive, gazed vacantly, refused food, paid no attention to pinpricks" as a result of "an attachment she once had for a youth which she repressed because she was a Hebrew and he a Christian" (p699).

This woman exhibited another catchy symptom: "catalepsy:"

"She had several attacks during which she held herself rigid, rolled her eyes upward and forced saliva from the mouth. Following the attacks she would laugh and talk loudly."


5. Kraeplin, E. Dementia praecox and paraphrenia. Edinburgh, 1919. Emil Kraeplin essentially invented schizophrenia and included catatonia as a subdivision. Eugene Bleuler (defined schizophrenia as a "splitting of the psyche" and took the position that catatonia was only schizophrenic in the presence of the four famous "A’s" of schizophrenia:

Affect - flat

Ambivalence - intense

Associations - loose

Autism - self-preoccupation



6. Stauder HK: Die todliche Katatonie. Archiv fur Psychiatr Nervenkrantz 102: 614-634 from the University of Munich

Stauder’s notorious  "todliche Katatonie" is cited by almost every writer on "lethal catatonia," as a landmark. To my knowledge, it has never been published in translation and I have to wonder how many of the authors who rely on it have actually read it.

Stauder describes three cases. The first:

"P.G., 23 years old, a farmer...always healthy and strong, a hard worker...Likes solitude solitude but is otherwise unobtrusive...jumped up suddenly and attacked his relatives with a knife...can barely be contained by four nurses...on day 3 still excessively excited and violent despite a rising temperature to 102. Refuses food...dies on day 4 after admission...Autopsy of the brain without significance..."

Without the psychiatric cant, Stauder, like others before and after, described a neurologically normal individual who gets in trouble for running amok in one way or another, resists his captors and dies from exhaustion. Despite proponents ongoing claims that lethal catatonia is "indistinguishable from NMS" (Max Fink in his latest book, Electroshock: Restoring the Mind, 1999, p 72 - see other cites below) there is no involuntary muscular rigidity, the key finding in NMS.

This difference from Neuroleptic Malignant Syndrome is due to another key difference which seems evident: the words "maniacal excited hebephrenic," - prior to the neuroleptic era - always implied volition on some level. The muscular overactivity was not the involuntary dystonic and spastic muscular overactivity of NMS.


7. Gjessing R: Disturbances of somatic functions in catatonia with a periodic course and their compensation. J Ment Sci 608-621, 1938 (Missing from bound volume at UCSF)


8. Herman, M et al. NY State J Medicine, 42:624, 1942.

Where catatonia is due to organic brain disease there is

"profound disorientation and marked cloudiness of the state of not found in cases of catatonic schizophrenia."


9. Shulack NR: Sudden "exhaustive" death in excited patients. Psychiatr Q 18:3-12, 1944


10. Billig O, Freeman WT: Fatal catatonia. Am J Psychiatry. V100-633-638, 1946

This paper begins:

"There is a certain psychotic syndrome which may prove fatal within a relatively short time.

"Case 2, a 38 yo white woman....became extremely restless, apprehensive and aggressive; on several occasions she attempted suicide by choking and smothering herself; once she tried to jump into the fire. Even several persons could hardly manage her. She refused to eat, her sleep was poor. This lasted six days."

She then lapsed into shock and died.

11. Shulack NR Exhaustion syndrome in excited psychotic patients. Am J Psychiatry 102:466-475, 1946.

"Psychotic patients who maintain a progressive motor and mental excitement are in danger of developing an exhaustion syndrome which may terminate in sudden death...."

Major Shulack defines a 6 part syndrome:

"1)Sustained motor and mental excitement with continual activity for a period usually from two days to two weeks."

2) Rapid thready pulse

3) Rapid loss in body weight

4) profuse clammy perspiration

5) Fall in blood pressure and pulse pressure

6) Hyperpyrexia - this is usually from 100 to 104 F (rectal) if death does not occur...."

Major Shulack refers to his own review of the literature of 1937 where he found a total of "376 cases of exhaustion death." With regard to why a "maniac-depressive" might die after days of not sleeping and pounding walls, he postulated

"constitionally inferior cardio-vascular and autonomic systems, which, in the presence of prolonged exhaustion, are overloaded beyond their viable capacity"

i.e. some people just can’t take it.

He points to the loss of fluids and salt, the buildup of lactic acid, the "small, narrow, thin-walled carotid arteries and cerebral vessels of autopsied schizophrenics" (p469) and then gives contributes 7 cases of his own such as:

"Case 1 - A 19 year old colored male admitted in an extremely hyperactive noise and uncooperative state....on the 23rd day there was general imrprovement in his mental reaction. He became less euphoric and much less hyperactive. He stopped his whistling and dancing and became quiet and tractable."

A combination of "sheeting" ("In addition to chemical sedation, the occasional use of cold wet sheet pack") together with fluid replacement by IV seemed to bring him around.

Muscular rigidity isn’t mentioned.


12. Aronson, MJ and Thompson SV: Complications of acute catatonic excitement. a report of 2 cases. Am J Psychiatry 107:216-220, 1950.

"Acutely excited psychotic patients not uncommonly collapse and die. This experience is extremely disquieting to the physician...."

The authors describe a prodrome followed by a

"...second phase ushered in with intense, wild agitation and violent destructive behavior. The patient then literally demolishes everything in sight, tears furniture into small pieces....This phase lasts a few minutes to several days. Physical examination reveals a rapid pulse, subnormal blood pressure, profuse perspiration....The temperature may be at 100 rectally."


"proved unsuccessful in the amelioration of excitement during the exhaustion syndrome. In fact the patient’s conditon went rapidly downhill after shock...."

"As regards the second case, a search of the literature fails to reveal any previous reports of death in voluntary apnea."

In other words, Aronson is reporting the world’s first case of a successful suicide by breath holding.

No mention of muscle rigidity.



13. Ayd, F: Fatal Hyperpyrexia during Chlorpromazine Therapy. Journal of Clinical and Experimental Psychopathology, Volume xvii, Number 2, June 1956, p 189-192

A 41 year old man was given increasing doses of Chlorpromazine (Thorazine, the first "major tranquilizer") to 2.5 gms/day. On the 21st day his temperature went to 108, he had several seizures and died.

"Chlorpromazine may cause sudden elevations of temperature accompanied by perspiration and some feelings of prostration."

The syndrome had no name in this first case report.


14. Delay J, Pichot P, Lemperiere T, Glissalde B, Peigne F: Le neuroleptique majeur non phenothiazinique et non reserpinique, l'haloperidol, dans le traitement es psychoses. Societe Medico Psychologique: Ann. Med.-psych., 118th anne, Janvier, Seance du 21 Decembre 1959

This is a study of the new ("non-phenothiazine") neuroleptic haloperidol (Haldol). It summarizes its administration to 63 women ages 19 to 73. These authors find that haldol has a "remarkable efficacy and rapidity."

In the section on "effets neurologiques" they comment:

"The syndrome of hypertonic immobility was observed in almost every case albeit to varying degrees. It appeared progressively during the first week, sometimes within two or three days. The intensity is a function of the dose and the susceptibility of the individual subject."

The immobility may be observed first in the face as a lack of expression. In the majority of cases, a moderate parkinsonian syndrome is produced with trembling, "impatience motrice" (a nice turn of phrase for akathisia) of the legs. It is noted that the first reports on any medical enterprise are often the most honest. Here in 1959, at the very introduction of Haldol, the principal culprit in NMS, the authors clearly describe the effects on the human motor system.

"In cases where rigidity is intense, the effect is total, literally petrifying the patient."

"Thus, in three of the patients, difficulties in chewing and swallowing together with excessive salivation, total insomnia and rapid wasting, obliged us to interrupt treatment. Complete disappearance of these extrapyramidal signs was obtained one to

two weeks after stopping the Haldol." (page 151).

The authors then comment on five instances of "crises excitomtrices" (agitated motoric crises) were observed five times. These occurred in the first two days of treatment in

patients receiving less than ten miligrams per day. The crises had to do with spasms of the face, tongue and throat muscles with trismus, protrusion of the tongue, sucking or pouting movements, facial spasms, either unilateral or bilateral.

"Crises of spasmodic torticollis, rolling movements of the body, forced upgaze, were sometimes evident in addition. In the course of these crises, we have observed 'perturbations neurovegetatives intenses:' racing heart rate, hypersalivation, tearing, hypersweating, sometimes even difficulty breathing with respiratory compromise."

The authors are enthusiastic about Haldol which had been first tried a year prior and in their view was a landmark advance in the "chemotherapy of psychoses." Every single

"side effect" since recorded ad nauseum was observed in these sixty-two women. The initial doses varied from 2 miligrams per day up to 25 miligrams and the only cautionary conclusion recommended by these pioneers was that the dose used should be

"moderate" 3-7 mg per day. Doses today remain in that range.

15. May, RH: Catatonic Like States Following Phenothiazine Therapy. American Journal of Psychiatry 115: 1119-1120, 1959. Prompt report followed in the American literature.

16. Preston, Jane: Central Nervous System Reactions to Small Doses of Tranquilizers - Report of One Death. American Practitoner and Digest of Treatment. April, 1959, pages 627-630. Six cases of fever, muscular rigidity, salivatin, dysphagia are reported and the author warns

"The cases described here should serve as a warning that tranquilizers (Stelazine, Thorazine, Trilafon and one case of Compazine) even in small doses may give rise to serious reactions, which occasionally end in death."



17. Delay J and Deniker P: Methodes Chiotherpiques en Psychiatrie. Masson et Cie Editeurs, Paris, 1961


18. Fish, FJ: Schizophrenia. Baltimore, Williams and Wilins Co. 1962,

"...they (catatonics) beat wildly at everything around them, and they may basng their hands or head on the wall...if electroconvulsive therapy isn’t given death occurs in 1.5 to 14 days" (p 101)


19. Delay J. and Deniker P.: In: Handbook of Clinical Neurology Published by Elsevier 1964 pages 248 to 266. The "handbook" is a misnomer: this multi-volume comprehensive text has long been regarded as the "Old Testament" of neurology and hence, this article by Delay and Deniker has come to be regarded as the landmark paper identifying NMS.

20. Oetle B: Clinical observatins of the side-effects of haloperidol. Acta Psychiatrica Scandinavica 40: 71, 1964


21. Laaskowska D, Urbaniak K, Jus A: The relationship between catatonia-delirious states and schizophrenia in the light of a followup study (Stauder’s lethal catatonia.) Br J Psychiatry 111:254-257, 1965



22. Steadman’s Medical Dictionary, 21st Edition, Williams and Wilkins, Baltimore, 1966.

From the Greek for kata, DOWN, + tonos, + TONE or toned down. Definition 2:

"A type of schizophrenia, showing periods of negativism, excitement, stupor, and stereotype or impulse activity."


23. Zelman, S. and Guillan R.: Heat Stroke in Phenothiazine Treated Patients. A Report of Three Fatalities. American Journal of Psychiatry. 127, 1787-1790, 1970

24. Penn H, Racy J Lapham L et al: Catatonic behavior, viral encephalopathy and death. Arch Gen Psychiatry 27:758-761, 1972

"A case report is presented of a man who seemed to have acute schizophrenia, later developing catatonic features; he became hyperthermic and died after nine days despite electroconvulsive therapy and medical support. Postmortem examination revealed microscopic changes in the central nervous system consistent with viral encephalitis.

In this case the spinal fluid, which showed a lymphocytosis, should have led to the correct diagnosis.

25. Zelman S, Guillan R: Heatstroke in phenothiazine treated patients: a report of three fatalities. Am J Psychiatry 126:1787-1790, 1970


26. Crane, E. (1971), Motor Disorders Induced by Neuroleptics. Archives of General Psychiatry. Volume 24: 179, 1971


27. Behrman, Simon: Mutism Induced by Phenothiazines. Psychiat.(1972), 121,599-604.

Eleven case histories e.g. case 4: 59 year old woman treated with Thorazine becomes progressively mute and dies after 3 years on treatment.

In Dr. Berhrman's summary on page 604, he comments "The central feature was impairment of vocalization. . . and diminution of psychomotor activities eventually leading to akinetic mutism (coma vigil)."

28. Kammerer et. al. : Syndrome Neuroleptique Malin ou Surdosage Neuroleptique. Societe Medico Psychologique Seance du Lundi. 23 Octobre, 1972.

This is a case report of a 39 year old man who developed a full-blown syndrome including elements of Korsakoff's "psychosis."

29. Britt, BA: Recent advances in malignant hyperthermia. Anesth Alg (Cleve) 31:841-849, 1972

30. Ayd PJ Jr: Haloperidol: Fifteen years of clinical experience. Diseases of the Nervous System 33: 465, 1972

31.Allan R and White HD: Side effects of parenteral long acting phenothiazines. Brit Med J 1:221-222, 1972

32. Penn H, Racy J, Lapham L, et al: Catatonic behavior, viral encephalopathy and death. The problem of fatal catatonia. Arch Gen Psychiatry 27:758-761, 1972

"A case report is presented of a man who seemed to have acute schizophrenia, later developing catatonic features; he became hyperthermic and died after nine days despite electroconvulsive therapy and medical support."

The 25 year old in question was given large doses of Thorazine, developed a combination of unrecognized encephalitis combined with unrecognized NMS, and was administered electroshock 6 times in four days, when

"...after the fifth ECT, (CSF) revealed 18 white blood cells..."

He was switched to

"a non-phenothiazine tranquilizer (haloperidol - Haldol) and supportive medical care did not diminish his hyperpyrexia nor change his behavior......His condition continued to deteriorate until the ninth hospital day when he became hypotensive and died."

"Several weeks after his death, we learned that an outbreak of eastern equine encephalitis (EEE) had occurred in southern New Jersey while the patient was in summer camp."

Autopsy confirmed a "lymphocytic meningo-encephalitis.


This 50 year old woman was left permanently paraplegic, incontinent

And rigid 20 years after Neuroleptic Syndrome, unrecognized, was mistaken for

"Lethal Catatonia" and "treated" with ECT.



33. Meltzer HY: Rigidity, Hyperpyrexia and Coma Following Fluphenazine Enanthate. Psychopharamacologia 29:337-346, 1973.

According to Lazarus, Mann and Caroff et al (see below) this paper describes "a 21 year old psychotic college student who became mute, immobile and incontinent 24 hours after she was given a subcutaneous injection of fluphenazine (25 mg). She then developed severe msuscular rigidity, hyperpyrexia (103 F) and increased levels of CPK. She became comatose. The syndrome resolved with supportive treatment."

One of the sources credited as establishing the diagnostic entity of NMS. Both Meltzer and Weinberger (see below) called attention to the importance of not confusing it with Stauder's (1934) "lethal catatonia."

Fluphenazine Enanthate it should be noted is a "depot" drug, meaning that its effects, once administered, will inevitably persist for days and weeks.

34. Oppenheim, G: Mutism and Hyperthermia in a Patient Treated with Neuroleptics. Med. J. Aust., 1973, 2:228-229

This reports a 38 year old man on Haldol, Thorazine and cogentin brought in "almost unconscious" during a heatwave. In this case, the symptoms began 18 months after initiation of neuroleptics.

35. Britt BA: Prevention of malignant hyperthermia. International Symposium on Malignant Hyperthermia. Edited RA Gordon, BA Britt, W Kalow, Springield Ill, Charles C. Thomas, 1973, pp 431-461


36. Westlake RJ, Rastegar A: Hyperpyrexia from drug combinations. JAMA 225:1250, 1973


"To the Editor: An important side effect of phenothiazine-anticholinergic combination is interfence with the body thermoregulatory system resulting in hyperpyrexia and occasionally death in patients exposed to high environmental temperature and humidity."

Reports three cases and comments on the experimental evidence that "chlorpromazine (Thorazine) treated rats have a significant loss in their ability to maintain constant body temperature...." i.e. a disruption of the natural balances called homeostasis, one of the basic precepts of physiology, and well being.

"These cases are being reported to warn internists and psychiatrists...."


37. Cohen, W. and Cohen, N.: Lithium Carbonate and Halopyrodol and Irreversible Brain Damage. JAMA 230: 1283-1287, 1974. This is a report on four patients on both haldol and lithium, a combination which remains quite fashionable and most likely is especially dangerous:

"Symptoms consisted of lethargy, fever, tremulousness, confusion, and extrapyramidal and cerebellar ."

Two patients suffered widespread, devastating, irreversible brain damage. Two others were left with persistent diskinesias.

The significance of this paper is two fold:

a) The emphasis on the encephalopathy or central nervous system effect and

b) The exceptional malignancy of the combination of lithium and Haldol.


38. Simpson, G: CNS Effects of Neuroleptic Agents, Psychiatric Annals 5:11, November


"Neuroleptics and phenothiazines in particular can occasionally affect the temperature center - producing hyperthermia which is TREATED BY DISCONTINUING THE DRUG AND TAKING STEPS TO LOWER THE TEMPERATURE." p 60.

The point of my emphasis is that the basic response to the diagnosis of NMS was established and remains: immediate discontinuation of the offending agent.

39. Harrison GG: Control of malignant hyperthermia syndrome in MHS swine by dantrolene sodium. Br J Anaesth 47:62-65, 1975


40. Greenblatt, et. al: Fatal Hyperthermia Following Haldol Therapy of Sedative Hypnotic Withdrawal. J Clin Psychiatry 39: 673-675, 1976.

A 30 year old Quaalude user was treated for "Delirium Tremens" with Haldol, developed a fever of 103F on the 5th day and died on the 12th hospital day. The authors first statement is: "phenothiazine derivatives are known to produce impairment of thermoregulation. Numerous cases of coma and hyperpyrexia have been attributed to these drugs, some of which have been fatal."

In their discussion they comment that "many afflicted individuals develop intense muscular rigidity." This effect on temperature regulation caused several deaths in prisoners forcibly treated at Vacaville during a heat wave and may account for the many deaths among the elderly (commonly treated with haldol for "sundowner syndrome" -agitation at night.) During last summer's heatwave in Chicago.

41. Shields,W. and Bray, F.: A Danger of Halopiredol Therapy in Children Journal of Pediatrics 88, 301-303 1976.

The case of a 5 year old girl who developped opisthotonous (figure 1) related to Haldol is presented and the authors conclude with regard to Haldol in children: "...we believe that in most cases the risk of incurring a serious neurologic side effect is too great to warrant its use."

42. Powers P, Douglas TS, Waziri R: Hyperpyrexia in catatonic states. Diseases of the Nervous System 37:359-361, 1976

"Three months prior to admission to our facility while still on high doses of Thorazine he became more delusional, developed cogwheel rigidity, marked salivation and an increase in tremulousness."

"Two days prior to transfer he required resuscitation after developing a mechanical obstruction of the larynx by food."

The patient then ran fevers to 40 degrees and was administered 8 electroshocks and a month later was "90% symptom free."

The authors claim to have successfully treated lethal catatonia with ECT. They did not even consider NMS. In my view the patient survived in spite of the treatment, not because of it and yet this paper is cited by Fink (op cit) among others as support for the intentional blurring of the distinction between catatonia and NMS and the administration of ECT in either case.

43. Gelenberg, Alan: The Catatonic Syndrome. The Lancet, June 19, 1976 p 1339-1341. The authors first review the etymology catatonia concluding essentially that no-one knows what it is or can agree on a definition:

"Clinical reports on catatonia have suffered from lack of a precise definition of this syndrome."(p1340)

" would seem reasonabnle to insist that most of the signs typical of catatonia be present. Thes should include motor signs (posturing, catalepsy, rigidity), psychosoial withdrawl (mutism, staring, negativism) or exitement (impulsiveness, combativeness, nudism) and bizarre repetitious behavior (grimaching, stereotypies, mannerisms, echolalia, command automatism and echopraxia.) (p1340)


In all the many and varied definitions over the years, prior to the era of neuroleptics, the definitions and descriptions never emphasized fever, sweating, tachycardia and the extreme muscular rigidity, involuntary muscular rigidity, seen with NMS.

Gelenberg concludes:

"Of the many cuses of the catatonic syndrome, some are potentially life-threatening. Early detection is possible only if physicians maintain an awareness of the many possible causes of catatonia and do not automatically diagnose schizophrenia and refer the patient to a pyschiatrist. Antipsychotic medication or ECT in an organic case may produce a temporary improvement, a worsening, or simply confuse the clinical picture delaying definitive diagnosis and appropriate treatment."

It would appear that Gelenberg was not aware of NMS but he does include the comment that

"Schizophrenics are at a higher risk for catatonia induced by antipsychotic drugs..." (p1341)

As a means of separating catatonia due to organic brain disease from psychogenic catatonia this paper (and other) recommends an "amytal (truth serum) interview."

"psychogenic cases beoome more talkativein characteristic ways and organic cases become more confused or obtunded."

44. Heffron JJA, Isaacs H: Malignant hyperthermia syndrome - evidence for denervation changes in skeletal muscle. Klin Wochenschr 54:865-867, 1976

45. Wilson LG: Viral encephalopathy mimicking functional psychosis. Am J Psychiatry 133:165-170, 1976

"Encephalitis, particularly herpes simplex encephalitis frequently presents as a disorder with puzzling psychiatric symptom..."

This paper presents three young individuals all mis-diagnosed and "treated" for Schizophrenia - catatonic type, who actually had viral encephalitis, probably herpetic in each case.

"Case 1...was a 30 year old divorced mother who...said she was ‘living in a dream’"

"She was begun on 400 mg Thorazine per day. After several days of increasing medication she began to display intermittent mutism, staring, exaggerated poses and immobile postures...Medication was further increased after the appearance of waxy flexibility, and ECT was considered because she refused to eat."

"While in the intensive care unit the patient was given 5 electroconvulsive treatments over a two day period, with brief improvement after each treatment. ECT was discontinued because of EKG changes and the development of gram negative sepsis."

Cerebrospinal fluid, a rise from acute to convalescent Herpes titres, abnormal EEG and vital sign abnormalities finally gave away the diagnosis. Two years later case 1 had mild ogoing impairment.

"Case 2...was an adopted 17 year old High School girl...She had been hospitalized for 7 days because of the acute onset of bizarre behavior and subsequent lethargy and mutism. The referring psychiatrist believed that catatonic schizophrenia was the diagnosis but sought neurological consultation before consideration of ECT."

She had been treated with Haldol 7 mg and Cogentin .5 mg

"...she became dysarthric and later became mute....An EEG showed very severe generalized disturbance of brain function...."

"...After several weeks....Gradually she began speaking recognizably, but repeated words or phrases in an echolalic fashion....Follow-up EEG at 6 months showed continuing abnormalities in the temporal regions..."

The third patient was also sent for ECT but ruined the plan when he began having spontaneous convulsions:

"Case 3 was a 20 year old unmarried male who lived with his parents...described as having aspaced out appearance with some possible seizure activity.....A diagnosis of catatonic schizophrenia was made and treatment was begun with Chlopromazine (Thorazine), haloperidol (Haldol) and benztropine Mesylate (Cogentin)."

"In spite of large doses of haloperidol up to 80 mg per day, the patient’s behavior deteriorated. He became delusional and claimed he was dead. He began to show posturing and would hold his extremities in unusual fixed positions for long periods of time..."

After the spontaneous convulsion a spinal fluid showed lymphocytes and an EEG was abnormal and a diagnosis of Herpes Encephalitis was made.

The authors summarize:

"One patient received ECT after intensive neurologic investigation was inconclusive. The two others were referred to the university hospital for ECT for their presumed catatonia..."



46. Henschel EO, Locher WG: The Wausau story - malignant hyperthermia in Wisconsin. Malignant Hyperthermia: Current Concepts. Edited by EO Henscehl, New York, Appleton-Century Crofts, pp 3-7, 1977

47. Rigestein et. al.: Sudden Catatonic Stupor with Disastrous Outcome JAMA 238; pages 618-620 1977.

"Catatonia was first described by Kahlbaum in 1874 as ‘that condition in which the patient sits quietly or completely mute and motionless, immovable with a staring coutneance, the eyes fixed on a distant point apparently completely without volition without any reaction to sensory impressions, sometimes with a full fledged waxy flexibility as in catalepsy."

"Opinion has differened on whether fever accompanies uncomplicated catatonic stupor..."

He reports to cases: case two involves a "22 year old college student.....dropped out...became deluded..." treated with Haldol 5 mg TID, became mute, immobile, febrile, treated with ECT:

"Immediately after the sixth ECT, the EKG, heart rate slowed to 56 beats per minute.....within one minute ventricular fibrillation occurred. Vigorous resuscitative efforts including intracardia epinephrine were initiated....but the patient remains comatose after 7 months..."

Patient one had also been on neuroleptics (Thorazine) when she developped what was, in retrospect, unrecognized Neuroleptic Malignant Syndrome. It is noteworthy that in the case of the 22 year old college student, 6 shock treatments aggravated NMS complicated by staphylococcl pneumonia, venous thrombosis and pulmonary embolism.

Died after ECT used to treat cataonia actually induced by chlorpomazine (Thorazine).

48. Toru M, et. al.: Neuroleptic Malignant Syndrome-like State Following a

Withdrawal of Antiparkinsonian Drugs. Journal of Nervous and Mental Diseases Volume 169, pages 324-327, 1977

After reporting the case of a 63 year old woman in which anti-Parkinsonian (dopaminergic) drugs were abruptly withdrawn producing an NMS like syndrome, the authors "suggest that dopaminergic hypoactivity in the brain" may exist in NMS, a condition produced by chronic dopamine blockade.

EEG slowing is documented.

49. Weinberger D and Kelly M: Catatonia and Malignant Syndrome: A Possible

Complication of Neuroleptic Administration: Report of a Case Involving Haloperidol. Journal of nervous and Mental Disease Vol 165 No 4, 1977.

A 20 year old foreign exchange student was admitted to Harvard's Peter Bent Brigham Hospital with a diagnosis of "catatonic schizphrenia." After a total of 25mg over 24 hours of IM HALDOL "...he stoodmotionless on one leg with his other leg extended and his eyes staring fixedly. he was immobile with generalized muscular hypertonicity and typical flexibilitas cerea (a "pathognomonic" sign of catatonic schizophrenia) His doctors interpreted this change as either a worsening of his psychiatric condition or a severe extrapyramidal reaction..." He survived.

50. Gellenberg and Mandel: Catatonic Reactions to High Potency Neuroleptic Drugs. Archives of General Psychiatry, 34, 947-950, 1977.

"Eight patients developed a syndrome marked by features of catatonia....while receiving high-potency neuroleptic drugs."

The authors suspect the dopamine blockading effects of phenothiazines but state

"While it's mechanisms are obscure, it is clear that a syndrome characterized by stiffness, rigidity, withdrawal, regression, and other catatonic and parkinsonian features can occur in patients treated with high potency anti-psychotic drugs...The drug induced nature of this syndrome should be recognized so that the patients are not subjected to increasing dosage of psychotropic medication . . . we recommend that when a clinician observes catatonic signs developing in a patient receving neuroleptic medication, he first consider the posibility of a drug induced catatonic syndrome before assuming a schizophrenic process."

The Archives of General Psychiatry comes free to all psychiatrists who are members of the AMA. It is among the most widely read journal in psychiatry. This warning regarding NMS was essentially broadcast loud and clear to the psychiatric community with this 1977 article.

51. Itoh H, Ohsauka, N, Ogita K et al: Malignant neuroleptic syndrome - It’s present status in Japan and clinical problems. Folia Psychiat Neurol Jpn, 31:565-576, 1977. This paper is evidence of the worldwide occurrence and recognition of NMS. The authors cite a mortality rate of "20-33%."


52. Scialli, J. and Thonton, W: Toxic Reactions from a Halopiredol Overdose in Two Children - Thermal and Cardiac Manifestations. JAMA January 2, 1978 Volume 239 No.1 pages 48-49.

53. Greenblatt PJ, Gross PL, Harris J et al: Fatal hyperthermia following haloperidol therapy of sedative hypnotic withdrawal. J Clin Psych 39, 57-59, 1978

54. Van der Kolk BA, Shader RI, Greenblatt DJ: Autonomic effects of psychotropic drugs in Lipton MA, DiMascio, A Killam KF (eds): Psychopharmacology: a generation of progress. New York, Raven Press, 1978

55. Isaacs H: Myopathy and malignant hyperthermia. Second International Symposium on Malignant Hyperthermia. Edited by JA Aldrete, BA Britt, New York Grune and Stratton, 1978, pp 89-102

56. Wingard DW, Gatz EE: Some observations on stress susceptible patients, in Second International Symposium on Malignant Hyperthermia. Edited by Aldrete JA, Britt BA. New York, Grune and Stratton, 1978, pp 363-372


57. Bronstein ST, Ryan DE, Soloman CC et al: Dantrolen sodium in the management of patients at risk from malignant hyperthermia. J Oral Surg 37:719-724, 1979

58. Geller,B. and Greydanuus, D: Halopyridol Induced Comatose State with

Hyperthermia and Rigidity in Adolescents: Two case reports with a

literature review. J Clin Psychiatry 40:102-103, 1979.

"Two adolescents developed severe extrapyrimadal reactions due to haloperidol....this is a rarely reported result of utilizing this medication in children and youth and caution is urged in its use. Prolonged reactions have occurred."

59. Bernstein, R: Malignant Neuroleptic Syndrome, An Atypical Case.

Psychosomatics December 1979 Volume 20, No. 12 pages 840-846. A 36 year old woman on Thorazine and Trilafon developed parkinsonian symptoms on her 8th day of psychiatric hospitalization.

"During this period (day 11 to 13) the patient went from a state of passive hopelessness with fear of impending death to a highly agitated manic state."

The significance of this paper is that on 3 separate challenges intentional resumption of medication) the patient developed recurrences.

The persistent vulnerability of victims of NMS was established in 1979 and yet as of 1997, some psychiatric authorities condone resumption of the causative drug even while acknowledging 30% recurrence rates.

60. Gunhaus N. et. al.: NMS Due to Depot Fluphenazine. Journal of Clinical Psychiatry 40:99-100, 1979. These authors give credit to Delay and Deniker (1964) for term "Nuroleptic Malignant Syndrome"

This paper reports on a fifteen year old female and a twelve year old male both of whom developed fevers to 104F and all the other symptoms of NMS. Both had been

getting Haldol.

In a discussion of the literature prior to 1979, the authors state:

" 'Syndrome malin'is a term used to describe hyprthermia, hyprtension, disphoesis, regidity and various levels of coma occurring during the course of halopyridol therapy. . . .It has also been referred to as the hypothalamic syndrome and the neuroleptic malignant syndrome. . . . Treatment consists of early recognition, immediate cessation of the drug, supportive care as needed, and a trial of medications."

This widely read journal establishes the standard of knowledge of NMS as of 1979. Its' references range from 1963 to 1976. They credit three french authors with identifying a "fatal malignant syndrome" in 1971.




61. Franks R et al: ECT use for a patient with malignant hyperthermia. Am J Psychiatry 139:1065-66, 1982

"The authors used dantrolene as a prophylactic during ECT in a depressed patient susceptible to malignant hyperthermia. Succinylcholine and MAO inhibiting anti-depressants can precipitate malignant hyperthermia and were thus avoided."

"Our experiernce suggests that such a patient (prone to malignant hyperthermia), if depressed, may be given ECT safely through prophylactic use of dantrolene and avoidance of succinylcholine."


62. Jessee S and Anderson G: ECT in the neuroleptic malignant syndrome: case report. J Clin Psychiatry 44:186-188, 1983.

Uring that "ECT should be considered in cases of NMS in which there is life-threatening fever the authors recount two cases.

1) "A 30 year old man....Within the first 24 hours of hospitalization received 20 mg of haloperidol and 30 mg of trifluoperazine." The next morning his temperature was 39.5 C, Haldol was continued, he became infected, finally haoldol was discontinued and ECT begun and the patient recovered.

2) Case 2, a 31 year old woman had been on trifluoperazine, developed hypertension to 180/100, fever, extreme agitation alternating with stupor and "her only response during an amobarbital sodium interview was an expletive uttered when she was physically prodded. Rapid tranqulization with haloperidol, 60 mg over 6 hours, produced no clinical change. At this point, all neuroleptic were discontinued, IV’s begun and then ECT.

"Informed consent for ECT was obtained from a close relative. Within 3 hours of the first treatment the patient’s temperature dropped to 38 C and significant fever did not recur."

These two cases are hailed as triumphs of ECT - lucky for everyone is what I would call them. The authors reiterate that neuroleptics cause dopamine receptor blockade and that includes not only motor systems but the hypothalamus, master gland regulator of the brain. They emphasize helpfully that "fever is a cardinal feature of NMS and sets this syndrome apart from other adverse reactions to neuroleptics Besides the effect on the thalmus, the fever results from increased generation of heat by intense muscular rigidity combined with a paralysis of sweating (anticholinergic effect) of the Cogentin or Artane or other drug always given for the "side effects" of neuroleptics, and of course, succinylcholine.



62. Fink, M: Meduna and the origins of convulsive therapy. Am J Psych 141:1034-1041, 1984

Max Fink, quarterbacking the offense for ECT, leads off this elegy to the founding father of shock with a poignant biblical cite:

"A prophet is not without honour, save in his own country, and in his own house." - Matt., 13:57

"Fifty years ago Ladislas Meduna induced repeated seizures with intramuscular injections of camphor in a catatonic patient. The patient recovered, and a new therapeutic era in psychiatry began."

After describing Meduna’s theory that epilepsy might cure schizophrenia by inducing protective scars (based on 6 human "ablation" operations in Berlin, 1932), Fink then quotes the great man himself:

"And with faint hope and trembling desire, the inexpressible feeling arose in me that perhaps I could use this anatagonism (epilepsy vs schizophrenia), if not for curative purposes, at least to arrest or modify the course of schizoprhenia." (p1035)

Meduna then tries out strychnine, thebaine, nikethamide,. caffeine, absinthe and camphor, settles on the last and in 1934 finds a low profile Hungarian State mental hospital

"To carry out human experiments and treatments....He did so because he feared discharge from the university and ostracism from his peers for the heresy of seeking a treatment for a hereditary disease. Meduna found a patient, a man in a catatonic stupor of 4 years duration, who seemed suitable for the initial clinical trials."

Obviously this patient did not have lethal manic catatonia to have survived four years. After getting the man up and moving

"Meduna induced seizures in 26 patients, first with camphor and then with pentylenetetrazo (Metrazol). He achieved recovery in 10, good results in three and no change in 13."

Fink then recapitulates Manfred Sakel’s great contribution of hypoglycemic coma with and without convulsions ("wet" and "dry") and despite a success rate of 50% lauds both men, honoring their competing and contradictory claims by dividing the credit:

"Both Sakel and Meduna were ambitious....and both were imbued with the optimism that followed on the success of fever therapy..."

Fink than cites himself twice to mis-state that

"Comparative studies of ECT with sham patients with depressive disorders found ECT clearly the more effective intervention."

Not all ECT - multiple shocks at one time and techniques such as Glissando had, by 1979, been "tested, found wanting, and discarded." (p1039) To support this, Fink cites himself again, in this case his 1979 Raven Press book: Convulsive Therapy.

Fink concludes:

"And, on this 50th anniversary, we should honor ladislas Meduna for his achievement and for his fortitude in facing the rejections of his associates."


63. Lazarus A: Treatment of neuroleptic malignant syndrome with electroconvulsive therapy. A single case study. J Nerv Ment Dis 174:47-49, 1986b

"A case of NMS unresponsive (after two weeks) to supportive medical therapy was successfully treated by electroconvulsive therapy."

"The rationale for using ECT in NMS apparently is based on its effectiveness in lysing catatonic reactions and on its ability to increase synthesis of catecholamines, including dopamine, in the brain." (For the catecholamine theory the author cites Max Fink’s 1979 Convulsive Therapy: Tehory and practice, New York, Raven Press, pp 143-153).

In this case report the patient’s defervesced just as the ECT was beginning. In my view, the fallacy of "post hoc ergo propter hoc" applies. 90% of NMS patients will recover in a month if left alone.

64. Yacoub OF, Morrow DH: Malignant hyperthermia and ECT. Am J Psych 143:1027-1029, 1986

"...malignant hyperthermia reamins one of the most dangerous and challenging

complications of aneasthesia."

"...knowledge of such susceptibility to malignant hyperthermia before ECT is given could be lifesaving. Pretreatment with dantrolene and avoidance of succinylcholine could be the answer."

Because anesthesia usually preceded by Anectine (succinylcholine) is given repeatedly to electroshock recipients, and because so many cases of NMS were being mistaken for catatonia and given ECT, anesthesiologists and others were interested in prognosticators which might avert fatal, irreversible and actionable outcomes.

This brief paper essentially equates malignant hyperthermia with NMS, points out Haldol as a major precipitant, warns against using Anectine and is one of the favorite papers of those now advocating ECT for NMS.

65. Hughes JR: ECT during and after the neuroleptic malignant syndrome: a case report. J Clin Psychiatry 47:42-43, 1986

66. Weiden P, Harrigan M: A clinical guide for diagnosing and managing patients with drug induced dysphagia. Hosp Community Psychiatry 37:396-398, 1986



67. Friedman J and Wagner R: Symptoms of NMS. Am J psychiatr 144:8, August 1987 in a letter commenting on one of the spate of articles appearing around this time confounding and conflating NMS and catatonia:

"....we hope that fever will be restored to its role as a cardinal feature." (p 1105)

68. Kalinowsky, Lothar: Lethal catatonia and neuroleptic malignant syndrome. Am J Psychiat 144:8, August 1987. This grand old man of ECT - the leading importer of ECT direct from the laboratory of Cerletti and Bini in Rome, 1938 - Kalinowsky, weighs into the epistolary debate in the same issue plumping for the term "pernicious catatonia" rather than "lethal catatonia" because 2 or 3 quick ECT’s in the first 24 hours will prevent any lethal outcomes.

He further opines, based on absolutely nothing other than his own hoary authority:

"It is striking that most of the patients with neuroleptic malignant syndrome who fail to respond to dantrolene are treated successfully with ECT." (p 1106)


69. Horn E, Lach B et al: Hypothalamic pathology in the neuroleptic malignant syndrome. Am J Psychiatry 1988; 145:617-620

This unique paper suggests an explanation for the organic brain syndrome associated with NMS.

A 48 year old woman is given two courses of ECT followed by three weeks of escalating doses of imipramine and phenelzine and perphanzine.

At this point she "was found to be drowsy when seen on morning rounds," spikes a fever to 41.1 degrees Centigrade by noon; has hypertension and tachycardia to 140/minute, tachypnea to 32/minute, exhibits "tremors of the hands and lips, rigidity of the arms and wrists, and clenched jaw" and dies 24 hours later.

The post mortem shows rather unique changes:

"Microscopic examination of multiple sections of the hypothalamus revealed conspicuous bilateral foci of pyknosis and disintegration of neurons and sponginess of the neuropil in the anterior hypothalmus (figures 1 and 2).

After commenting that this finding would be unusual in stroke or anoxia, the authors suggest they have discovered cause of the autonomic dysregulation that accompanies NMS:

"In view of the experimental evidence indicating the role of the anterior hypothalmic temperature regulation, the presence of early necrosis in this area in our patient may indicate the relevance of this lesion to the development of neuroleptic malignant syndrome."

The authors then comment:

"In our patient the possibility of a somewhat unique etiopathic situation also might have existed in which the role of both the tricyclic antidepressant and the MAOI, along with the neuroleptic, might have rfacilitated the development of the neuroleptic malignant syndrome.

Not to mention the 13 electroshocks (ECT’s) the patient had received just before the drug experiment. The current path and density is greatest between the electrodes, precisely the location of the hypothalamus.

The authors conclude their paper modestly:

"When depression of thermal regulation in the hypothalamus is superimposed on an already physically exhausted and compromised individual, the likelihood of hyperthermia becomes more probable."


70. Abrams. R: Electconvulsive Therapy. Oxford University Press, 1988 p76-77

The "neuroleptic malignant syndrome" (NMS) is characterized by the develpment of fever, rigidity and stupor in a patient receiving neuroleptic drugs. The rationale for treating NMS with ECT is obscure, but may derive from the resemblance of NMS to "febrile" or "lethal" catatonia, a rare and reportedly higholy ECT-responsive syndrome (Lostra et al 1983). Although there are numerous instances of the successful use of ECT to alleviate NMS (Powers et al 1976; Jesse and Anderson 1983; Greenberg and Gujavarty, 1985; Liskow, 1985, Lazarus 1986; Abbot and Loisou 1986; Addonizio and Susman, 1986; Mann et al, 1986) two reports indicate an increased cardiac risk with such a procedure. Regestein et al (1977 SEE REFERENCE ABOVE) reported a 22 year old man diagnosed as having catatonic stupor, who clearly met criteria for haloperidol-induced NMS (Abbot and Loisou, 1986) complicated by thrombophlebitis, atrial tachycardia, pneumonitis and massive pulmonary embolish that required inferior vena cava clipping. Immediately after his sixth ECT he developed ventricular fibrillation and lapsed into a coma with decrebrate posturing in which he remained at the time the report was written 7 months later. This malignant outcome was doubtless aggravated (if not caused) by five days of parenteral (injected) administration of chlorpromazine just prior to the course of ECT in an unsuccessful attempt to treat the "catatonia." Hughes (1986) reported a 33 year old woman with NMS who developped cardiac arrest during a session of multiple bilateral ECT, from which she was successfully resuscitated. Interestingly, neither of these two patients experienced significant relief of their NMS from ECT."


71. Horn E, Lach B, Lapierre Y et al: Hypothalamic pathology in the neuroleptic malignant syndrome. Am J Psych 145:617-620, 1988

72. Lazarus A, Mann S and Caroff S: The Neuroleptic Syndrome and Related Conditions. American Pyshciatric Press Inc., 1400 K Street, N.W. Washington, DC 20005

This book summarizes many of the known facts about the condition including the dramatic presentation, the reported incidence (ranging from .02% to 3.23%), the mortality if unrecognized (from 0 to 50% in various series) and the fact that "haloperidol (Haldol) has been associated with nearly half of all reported cases." (p9)


"Patients with classic signs of NMS present in ‘hypothalamic’ crisis or adrenergic crisis..."(p 15)

"Body temperature has exceeded 40 degrees Centigrade in about 40 percent of cases and temperatures in excess of 42 degrees Centigrade have been reported."(p17)

"CPK elevations may occur in up to 95% of NMS cases, reaching as high as 2000 times normal...."

"....perhaps related to the rate of loading, intramuscular and intravenous routes of administration seem to potentiate the development of NMS."

"At this time (mid 1970’s) NMS had been fairly well reported in France, Japan and England.....Caroff (1980 - one of the authors of this book) published a frequently cited review of NMS in English in 1980. He examined more than 60 cases described in the world literature at that time...."

"Discontinuation of neuroleptics is significantly correclated with recovery from NMS (Addonizio et al 1987) in 65 recently reported cases involving oral neuroleptics (and not treated with dantrolene or dopaminergic agonists), the mean SD recovery time after drug discontinuation was 9.6 plus/minus 9.1 days; 23 percent recovered in 48 hours, 63 percent by 1 week, 82 percent by 2 weeks and 97 percent by the end of a month." (p41)


Unfortunately, the authors muddy the all-too-clear waters:

"...the difficulty in distinguishing it (NMS) from Stauder’s (1934) ‘lethal catatonia,’ an identical condition..."(p5)


73. Fricchione G et al: ECT and cyclophosphamide in combination for severe neurospychiatric lupus with catatonia. Am J of Medicine, 88: 442-443, April, 1990.

After two course of shocks and 90 days a 25 year old woman with very severe Lupus Erythematosus

"became progressively more verbal, euthymic, and cooperative with eventual resolution of her cataonia and delirium."

74. Fleischacker WW et al: The neuroleptic malignant syndrome and its differentiation from lethal catatonia. Acta Psychiatr Scand 1990: 81: 3-5, 1990.

This really should read the DE-differentiation of catatonia and NMS.

The authors warn "young clinicians" not to forget the eminently treatable (with ECT) lethal catatonia before jumping to a fashionable diagnosis of NMS. Asserting that fever and rigidity are features of catatonia the authors cite four German language references, all from the 1930’s and 1940’s, including Stauder (op cit) and Arnold whose own words, in their considerate translation, belie the alleged similarity:

"...the picture of such a raving person (the catatonic) with his totally senseless and irresponsible vigor is doubtless one of the most impressive conditions in psychiatry. It lasts for about 8 days..."

after which the catatonic drops dead from exhaustion. There may be pre-terminal fever.

This isn’t NMS.



75. White, DAC: Catatonia and the neuroleptic malignant syndrome - a single entity? Br J Psych, 161: 558-560, 1992.

Here is one of the recent exercises in obfuscation:

"It is suggested that it is misleading to view these conditions (catatonia and NMS) as separate diagnostic entities and that NMS is probably more correctly incorporated into catatonic disorders."

"Muscular rigidity is a common and early feature of NMS whereas muscular rigidity in so-called lethal catatonia of the pre-neuroleptic era appeared in the terminal stage ofthe syndrome. It is suggested that muscular rigidity, probably extra pyramidal in nature, may be the only feature differentiating the so-called neuroleptic malignant syndrome from catatonia....we therefore believe that the clinical entitiy recognized as the NMS is ot a separate disorder...."



76. Fink, Max: Catatonia. Prepared for Behavioral Neurology, edited by M. Trimble and J. Cummings, Butterworth/Heinemann, Oxford, UK. Due spring 1996.

This article employs a combination of misleading citations and twisted logic to conclude that NMS and catatonia are one and the same and both should be treated with ECT. As usual, Dr. Fink takes the lead in stretching envelope of indications for shock, where no one has dared go before:

"There are no features that distinguish NMS from catatonia, particularly pernicious catatonia, and many authors argue that these syndromes have a similar pathogenesis." (p5)

"If NMS is viewed as a type of catatonia, then witholding neuroleptics remains essential, sedative drugs are prescribed, and if these fail electroconvulsive therapy remains a definitive treatment."(p6)

"....since catatonia is a risk factor for the development of NMS...."(p13)

"For patients with pernicious catatonia, the efficacy of ECT is life-saving..." (p15)

"Efficacy is not limited to adults; the report by Cizaldo and Wheaton (1995) describes the successful treatment ofan 8.5 year old catatonic girl with ECT."(p15)


As of 1997 an explosion in the popularity of ECT was underway. This was documented in the Fort Worth Start Telegram front page story for Tuesday, March 18, 1997 by Lou Chapman, the number of recipients of ECT in Texas institutions age 65 was 2-3 times greater than the number of recipients age 64. This is not because "mental illness" suddenly strikes at age 65. It’s because Medicare coverage usually begins at that age.

The elderly are being harvested for ECT.

The rationale for its use is based on "literature" such as I’ve cited above.

Obviously, there’s literature and then there’s literature. The psychiatric literature sows confusion intentionally.

The basic problem is the myth of mental illness, the attempt to divide in three: real illness, no illness, mental illness. I learned from an art teacher once that the human eye can divide quite precisely in two but has a hard time dividing in thirds and I suggest that the same applies to diagnosing in psychiatry especially, and to a lesser extent, medicine generally.

TDbefor.jpg (10432 bytes)

TDafter.jpg (9593 bytes)

Before Respirdal


NMS isn't the only adverse effect of neuroleptics.

coming soon



Comments? Mail to:
John M. Friedberg, M.D.
copyright 1995-98�