Am

J Psychiatry

/35:1/,

November

/978

CLINICAL

vious self-injury. He should also be carefully exammed for concrete religious preoccupation, for presence of auditory command hallucinations, and for delusions of reference or of control by outside forces. Careful questioning is then necessary to determine whether the patient trusts his concrete preoccupations, command hallucinations, or delusions. Patients who do not have this trust will often appear anxious and ask for relief from their torment. However, if the delusions and/or hallucinations are trusted, patients may appear outwardly calm. Just as the depressed suicidal patient who shows an elevation of mood and lack of distress may have finally resolved to kill himself, the schizophrenic patient, torn between the forces of God and the devil, may display outward calm, having decided upon the sacrifice of some part of his body for his greater spiritual good. The Bible tells us, Better for part of you to be destroyed than for all of you to be cast into Hell.”

believe

these

outwardly

calm

patients

No solute

one can certainty.

predict self-injurious Based on clinical

ever,

we have

proposed

method this

Anticholinergic

Delirium

BY MARC H. AND HOWARD

HOLLENDER, B. ROBACK,

took

in a Case M.D., PH.D.

ROBERT

ized

behavior experience,

with

to determine

abhow-

which

Since

approach

episodes

at our

of serious

the general hospital,

we

self-injury

adoption have

of

seen

among

no

hospital-

schizophrenics. REFERENCES

1 . Smolev 2. 3. 4.

RS: Use of operant techniques for the modification of self-injurious behavior. Am J Ment Defic 76:295-305, 1971 Blacker KH, Wong N: Four cases of autocastration. Arch Gen Psychiatry 8:169-176, 1963 Kushner AW: Two cases ofauto-castration due to religious delusions. Br J Med Psychol 40:293-298, 1967 Maclean G, Robertson BM: Self-enucleation and psychosis. Arch Gen Psychiatry 33:242-249, 1976

5.

Rosen

6.

young 1972 Tenzer

DH,

Hoffman

psychotic JA,

AM:

Focal

individuals.

Orozco

H:

suicide: Am

J

Traumatic

self-enucleation Psychiatry

glossectomy.

by two 128:123-126, Report

of

a

case. Oral Sung 30:182-184, 1970 7.

8.

for exit literally

Ayd FJ: Guidelines for using short acting intramuscular neuroleptics for rapid tranquilization. International Drug Therapy Newsletter 12:5-12, 1977 Anderson WH, Kuehnle JC, Catanzano DM: Rapid treatment of

acute psychosis. Am J Psychiatry 133:1076-1078, 1976 9. Cutler NR, Anderson DF: A positive response to rapid ment (ltr to ed). Am J Psychiatry 134:329, 1977

ofMunchausen C. JAMIESON,

a method

is encouraging.

system

further

present

saying,

REPORTS

schizophrenic patients present an acute risk for such episodes. When such arisk is established, rapid tranquilization is recommended because it is therapeutic and can prevent self-injury. Our experience with this

the greatest risk of self-mutilation, and we recommend rapid parenteral tranquilization as the treatment of choice. Such patients should be kept under constant observation until the rapid tranquilization brings the psychotic symptoms under control on until sedation supervenes. We consider the risks of rapid tranquilization as described by Ayd and others (7-9) to be mmimal when compared with the risk of self-mutilation. When these patients are no longer psychotic, they usu-

ally regret their self-injurious behavior, ample, “I misinterpreted the Bible and instead of metaphysically” (3).

RESEARCH

Conclusions

‘ ‘

We

AND

treat-

Syndrome M.D.,

EMBRY

A. MCKEE,

M.D.,

Atropine delirium resulting from the use of eye drops has been reported, usually in letters to the cditor, for nearly a century (1). In almost all instances the medication had been used to prepare for a refraction or to treat an eye disease. In only one article was accidental exposure mentioned (2). The case we will report is unique in that an atropine-like substance was self-administered with the intention of producing dilated pu-

pils to simulate a neurologic which was not expected by the nc disorder (delirium).

The authors

develop brief organic brain reactions after installation of atropine in the eye. In the Comprehensive Textbook ofPsychiatry’ Linn (5, p. 807) stated, Atropine

Mention sulting

in psychiatric

from

eye

texts

cine,

Vanderbilt

lender is Professor dent, Dr. McKee son

University,

Nashville,

of Psychiatry, Tenn.

School

37232,

where

of McdiDr.

Hol-

and ©

re-

‘

‘

‘

,

(Psychology).

1-1407$0.40

delirium

is seldom

‘

and Chairman, Dr. Jamieson is Co-Chief Resiis Assistant Professor, and Dr. Roback is Profes-

0002-953X/78/OOl

of atropine

more than a passing comment. Levin (3) stated in the American Handbook of Psychiatry ‘Poisoning can occur even from small doses [of atropmnc], such as those used to dilate the pupils. Chapman (4) noted, ‘Children occasionally ,

drops

‘ ‘

are with the Department

disorder. The result, patient, was a psychiat-

1978

its derivatives

American

Psychiatric

‘ ‘

may

cause

Association

characteristic

Lilliputian 1407

CLINICAL

AND

RESEARCH

Am

REPORTS

hallucinations in drug-sensitive adults receiving relatively small quantities in the form of eyedrops In the same textbook, Peterson (5, p. 1 1 14) noted, “Solutions of these agents [piperidine derivatives] arc also widely used in ophthalmology. These solutions may be swallowed in the tears by way of the nasolacrimal duct and produce anticholinergic intoxication.” In our search of periodicals, we found cases of atropine delirium resulting from eye drops cited in general medical, ophthalmologic, and pediatric journals, but not in psychiatric publications. Although psychiatrists are sometimes called on to treat this disorder, they seem less well acquainted with it than some other specialists. Kounis (6) commented, Atropine contributes more frequently than is appreciated, and in smaller doses than is believed, to the atropine eyedrop delirium. Hopkins and Robyns-Jones (7) stated, “We are told by ophthalmologists that delirious states associated with atropine administration are not uncommon. It has been suggested that mild mental disturbances following eye surgery ‘attributed to emotional stress of the post-operative regimen may be due in part to atropine intoxication’ (8). In recent years various atropine-like postsynaptic blockers have been substituted for atropine sulfate in the practice of ophthalmology. In addition, as in the case we will report, other anticholinergic medications may be used systemically, producing an additive effect. It seems appropriate, therefore, to speak of an anticholinergic delirium rather than an atropinc dclirium. .

.

.

.

.

/35:1/,

November

1978

Ms. A, previously diagnosed as having Munchausen syndrome, had had numerous hospital admissions in Nashville and elsewhere. She had at various times consulted many specialists-ophthalmologists,

rosurgeons,

internists

endocrinologists,

orthopedic

,

neurologists,

neu-

surgeons,

and psy-

.

‘ ‘

‘

J Psychiatry

.

.

.

‘

.

.

chiatrists-for

her

“illnesses.”

Soon after this admission to the psychiatric unit Ms. A had a seizure, presumably psychogenic. She was informed that in view of extensive tional studies were ing

this

hospital

Two

bottles

mydriatic,

neurologic planned. No

studies in the other seizures

past, no addioccurred dur-

stay.

of tropicamide

were

found

(Mydriacyl),

in Ms.

A’s

hospital

a short-acting room.

She

was

told that dilated pupils which did not respond to pilocarpine could only be due to eye drops and that she must be responsible

for

the

pathological

finding.

Initially,

eye drops, but she soon broke into tears that she had. Following discontinuation her pupils gradually returned to normal, tions

persisted

for

she

denied

using

and acknowledged of the medication but the hallucina-

2 weeks.

.

Comment

‘ ‘

‘

‘

Case

Report

Ms. A, a 28-year-old licensed practical nurse, came to the emergency room of Vanderbilt University Hospital late one evening stating that she began to experience frightening visual and auditory hallucinations a half an hour after taking two tablets ofa proprietary medication (Sominex). The visual hallucinations were of bugs, dogs, long black snakes coming out of faucets, and laughing faces in cups of coffee, and the auditory hallucinations were of voices telling her how horrible

her

life

situation

was.

She

seemed

to be disoriented

to time, place, and person. (Subsequently, it was learned that, in addition to the Sominex, she had taken chlorpromazinc, 200 mg, and amitriptyline, 150 mg.) When seen in the emergency room, Ms. A was wearing a neck brace and a cast on her left forearm. She claimed to have broken her left radius and sprained her neck in a car accident. (During subsequent interviews, she reported first that her ulna was fractured, then that the radius and ulna were fractured, and still later that the fracture included the radius,

ulna,

and

metacarpals.)

X rays

ofthe

left forearm

re-

vealed no evidence offractures, and the police had no record of a car accident in which she had been involved. On physical examination Ms. A’s pulse was rapid (116 beats per minute), and her pupils were markedly dilated and fixed. The pupils did not constrict in response to the application of 1% pilocarpine eye drops. Based on the clinical findings, the internist and neurosurgeon who examined her concluded that Ms. A was delirious. She was then referred to a psychiatrist who admitted her to the psychiatry unit. 1408

It is well known that atropine eye drops can produce delirium but less well known that delirium can appear with few or no significant peripheral signs of intoxication (7). In Ms. A’s case the only physical signs were rapid pulse and dilated pupils. The old description of atropine intoxication-hot as a hare, red as a beet, dry as a bone, blind as a bat, and mad as a wet hen-applied only in part to her. Cases of delirium have been ascribed to inherent susceptibility to the drug’ or to idiosyncratic susceptibility.” In other instances the large amount of the medication absorbed (one drop ofthe 1% solution contains 0.75 mg ofatropine) probably reached a toxic 1evel. Atnopine eye drops are carried to the nasal mucosa and intestinal tract mixed with tears via the nasolacrimal ducts. How much eye medication Ms. A used is not known, but it is known that she did not exert pressure on the inner canthus of the eyes to prevent fluid from passing through the nasolacrimal ducts. Although mention is made of special susceptibility to atropine delirium in the very young and the aged, many reported cases arc in middle-aged patients. The age range is from early childhood to 82 years, and no age is spared. The clinical picture may resemble delirium tremens because of visual hallucinations of insects and animals, as in Ms. A’s case. Restlessness, fearfulness, agitation, confusion, and fever arc commonly reported. Much less often there may be paranoid delusions and some resemblance to schizophrenia. In most instances, discontinuation of the eye drops has resulted in the relief or disappearance of all symptoms ofatropinc intoxication in 6 to 48 hours. In only a few instances have the symptoms subsided in less than 6 hours or persisted for more than 48 hours. The diagnosis ofatropine delirium has been confirmed by injection of small doses of atropine to reproduce the disorder (8, 9). To differentiate pupillary change produced by eye ‘ ‘

‘

‘ ‘

Am

J Psychiatry

/35:/I,

November

1978

CLINICAL

drops from neurologic disease, pilocarpine, a parasympathomimetic agent, is safe and reliable. It causes constriction of the iris sphincter unless atropine or another postsynaptic blocker, such as tropicamide, the substance involved in this case, has been used. Physostigminc salicylate (Antilirium) was not used, but it is effective in treating anticholinergic intoxication when administered intramuscularly (1 mg repeated in 15-20 minutes if necessary). In Ms. A’s case, the anticholinergic effects of chlorpromazine amitriptyline scopolamine (Sominex) (10), and tropicamide were probably additive. Although her disorientation cleared rapidly, Ms. A maintained that hen hallucinations persisted during her 2-week hospitalization. However, it is difficult to know whether this was actually the case. Given the previous diagnosis of Munchausen syndrome and her unusual willingness to assume the psychiatric patient role as well as the medical-surgical patient role, it is not unlikely that she was attempting to prolong her hospitalization. ,

,

Neuroleptic-Induced BY

Supersensitivity

GUY CHOUINARD, M.D., LAWRENCE ANNABLE,

AND

AND

RESEARCH

REPORTS

REFERENCES’

1. Tyson 2. 3.

Wi: Toxic

effects

try,

vol 2. Edited p 1226 4.

ofatropine

Chapman

by Arieti

AH:

Textbook

JB Lippincott Co, 1967 5. Freedman AM, Kaplan Textbook Co, 1975

of Psychiatry,

8.

S. New of

Br Med J 2:921,

York,

Br Med

of Psychia-

Basic

Books,

HI,

Sadock

BJ (eds):

Comprehensive

ed.

Baltimore,

drops

delirium

J 2:1390-1392,

Williams

D. JONES,

M.D.,

bibliography

& Wilkins

(ltr to ed). associated

Can

with

following

Med

atropine

atropine

eye-

1958 toxicity

from

eyedrops

5, Leff R: Toxic psychosis from sleeping scopolamine. N Engl J Med 277:638-639,

complete

1959,

2nd

E, Siddiqui N: Atropine ed). N Engl J Med 282:689, 1970

‘A more thors.

ed).

Philadelphia,

9. German

10. Bernstein containing

1889 to

Psychiatry.

Hopkins F, Robyns-Jones J: Psychosis administration. Br Med J 1:663, 1937 Baker JP, Fancy JD: Toxic psychosis

drops.

(ltr

Clinical

6. Kounis NG: Atropine eye Assoc J I10:759, 1974 7.

drops.

Weinstock FJ: Dilated fixed pupils from atropine JAMA 229:267-268, 1974 Levin M: Toxic psychoses, in American Handbook

is available

on request

(ltr

to

medicines 1967

from

the au-

Psychosis

M.SC. (PHARMACOL), DIP. STAT.

BARRY

Dopamine receptor binding sites have been reported to increase in the neostniatum after chronic treatment with neuroleptics, which could account for the dopamine hypersensitivity that induces tardive dyskinesia (1). We propose that similar changes may occur in the mesolimbic region in response to the chronic dopamine blockade of these drugs. Three kinds of clinical evidence are compatible with this hypothesis: 1) central nervous system (CNS) drug tolerance; 2) psychosis following neuroleptic withdrawal, which is correlated with signs of dopamine supersensitivity and which we would therefore term “supensensitivity psychosis” ; and 3) psychosis associated with a sudden decrease in prolactin levels following neuroleptic withdrawal.

with fluphenazine decanoate given every 4 weeks in the maintenance treatment of 48 schizophrenic outpatients (2). Before entering the trial, patients had received fluphenazine enanthate routinely for periods of I to 42 months (median= 14). All patients underwent a further 1-month period of stabilization

with

fluphenazine

enanthate.

The

bimonthly

dosages

of the fluphenazine enanthate-treated patients on entering the trial ranged from 2.5 to 125 mg (median=25 mg, mean= 39.3 mg) and after 7 months of treatment ranged from 2.5 to 325 mg (median= 50 mg, mean=69. I mg). Thus, substantial increases in dosage were required to maintain the mean therapeutic effect at the same level. In animal studies, prolonged exposure to neurolcptics leads to increased dosage requirements to block the behavioral effects of apomorphine (3,4).

Psychosis associated with signs of dopamine supersensitivity In a 6-week double-blind trial of tryptophan-benserazide we studied the relationship between tardive dyskinesia and psychotic relapse in 32 patients with process schizophrenia (5). Half of the subjects received tryptophanbenserazide instead of their regular neuroleptic medication and half received chlorpromazine. In the tryptophan group, the severity oftardive dyskinesia (assessed on a 9-point dinical impression scale of the Extrapyramidal Symptom Rating Scale [2]) tended to be greater in the 8 patients who deteriorated than in the 6 patients who did not (means±sD= 5.4±1.4 and 3.8±1.7, respectively, t=1.85, p