amphetamine- the janus of treatment for obesity .pdf

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COMMENTARY ON CLASSICS IN OBESITY

Amphetamine: The Janus

of

Treatment for

Obesity

George

A .

Bray

The paper selected for this Classic in Obesity is the

report by Lesses and Myerson on the use of ampheta-

mines in the treatment of obesity that was published in

the

New England

Journul

of

Medicine in 1938 (20).

This paper stands as a landmark in the field of drug

development for the treatment of obesity. It provides

important lessons in the consequences of use

and

abuse

of agents for treatment of obesity. I have picked the

word Janus for the title because it refers to the two-

faced Roman God (17,30). In the present context, the

two faces are appetite suppression and drug abuse.

In

this commentary,

I

will trace the development

of

drug

treatment for obesity over the past 100 years, since it

was

just 100 years ago that drugs were first used in

treating obesity.

Drug treatment of obesity can be dated to 1893.

The first drug to be used was thyroid extract (25). In the

years before 1890, the clinical condition called myxede-

ma had been clearly identified (13) and related to inade-

quacy of the thyroid gland.

When patients with

myxedema were treated with thyroid extract, they

improved, showing the cause and effect relation of thy-

roid deficiency and myxedema. Patients with myxede-

ma are often overweight. The treatment of overweight

patients with thyroid extract was empirically supported

by the fact that thyroid extract produced weight loss.

These observations prompted Baron (see Putnam [2S])

to use thyroid extract in overweight non-inyxedematous

patients. Tliyroid extract is rich in iodine. It contains

large quantities of thyroxine whicIi was one of the f ist

hormones to be isolated and synthesized (14,16). The

thyroxine in thyroid extract can be converted to tri-

iodothyronine (12), the principle active hormone

by

deiodination in peripheral tissues.

Following the work of Atwater and Rosa 1, also

see Bray commentary [4]) instruments to measure

basal metabolism came into use widely. Thyroid hor-

mones increase basal metabolism and a high or low

From the Department of Medicine, LSU Sclicml of Medicine and Pennington

Biomedical Research Cenler. 6400 Perkins Road. Baton Rouge.

LA. 70808.

Copyridit 019 94

NAASO.

basal metabolism was widely used to diagnose thyroid

disease in the first half of the 20th century (9).

Measurement of basal metabolism in obese patients

(9),

when expressed per unit of surface area, is usually

normal. When expressed per unit of body weight how-

ever, it was often low and led to the concept that obesity

might

be due to low metabolism. This provided a

rationale

for

treatment of obese patients with thyroid

hormone. In contrast to this rationale, total energy

expenditure is increased in obese individuals (26,27).

Thyroid extract, thyroxin, and triiodothyronine

have all been used to treat obesity (6,10,11,21,25).

Since obesity is not due to low basal metabolism

or

low

thyroid hormone levels, treatment with thyroid hor-

mones is not indicated in the absence of hypothy-

roidism, since a major consequence of treatment with

thyroid hormone is to increase metabolic rate and the

catabolism of lean tissue including muscle and bone 6).

The rapid growth of the chemical industry in

Germany, in the 19th and early 20111 centuries, produced

many compounds for dyeing cloth. One of these com-

pounds was dinitrophenol. Factory workers preparing

Uiis chemical were noted to lose weight. This led to

clinical use of dinitrophenol

as

a treatment for obesity,

with unhappy results

5 ) .

Use of dinitrophenol was dis-

continued after the development of skin rash, cataracts,

and neuropathy (29).

Just after dinitrophenol disappeared as a treatment

for obesity in 1938, Lesses and Myerson published their

paper on the use of amphetcamines. Amphetamine was

first synthesized by Edeleano in 1887, but it was not

until

1927 that Alles described its psychopharmacologic

effects (18). Trials of this drug as

a

treatment for nar-

colepsy were initiated in the 1930s and as a pseudo-

serendipitous part of these trials it was observed that

patients lost weight. Following this observation, Lesses

and Myerson

(20)

conducted a clinical trial and demon-

strated that amphetamine (Benzedrine@)was effective

in producing weight loss. This observationhas stimulat-

ed controversy and comment ever since.

The mechanism of amphetamine-induced weight

282 OBESITY RESEARCH Vol. 2 No. 3May 1994


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Commentary on Classics

in

Obesity

loss

is due mainly to reduced food intlake (7, lS) . When

10

human subjects were maintained

on

a constant

caloric intake and treated with amphetamine for 56

days, there was som e weight loss in the first

4

to 8 days

in 7 of the subjects, which they attributed to a slight

increase in energy metabolism

IS).

Other than that,

weigh t remained stable. When dogs were treated with 5

to 10 mg of amphetamine jus t prior t o presentation of

their daily allotment of food, the drug caused complete

abolition for food intake for a period of 10 to 21 days in

som e of these animals. Based on these studies, the

authors felt justified in concluding that amphetamines

significantly reduce food intake as

a

cause for

its

reduc-

tion in body weigh t. Following tlie demonstration that

amphetamines suppressed

the

appetite, it wx i soon real-

ized that the drug produced habituation (18). Appetite

suppression and drug abuse are two sides of the same

compound-dex tr~~amphetainine-itsam s face.

After World War 11, amphetamines became street

drugs which were widely abused and had significant

potential for harm. Amp hetamine was widely used in

the 1950s

by

college students to stay awake while

s tudying for examina t ions . These Be nzed r ine0

inhalers turned into abusive drugs in

the 1960s

and led

to restrictive measures to curtail [his public health prob-

lem.

B er izedr inem

a- eth y 1-phe tiel

h

y 1- :mi lie =

anphetan ine) i s ii compound or the phenethyl-amine

series, resembling ephedrine chemically. This com-

pound and a seri es of others were evaluated by Barger

and Dale

in

1910 2). with the conclusion that a number

of these coinpounds could stiinulate the sympathetic

nervous system hence the tcrm syinpathonimetic

m in e . This work was largely forgotten

unti l

inore than

a decade later, when ephedrine was rediscovered to

produc e sym pathom imetic effects incl tiding dilatation of

the pupils, bronchial c onstriction, vaso -constriction with

hyperten sion, and stitnulation of the heart rate (18).

Because of Uie strong central effects, several stud-

ies in the mid 1930s examined the clinical actions of

these compounds. 111a study of nine cases of nrucolepsy

treated with benz edrine, Priiizinetal and B loomberg

24)

did not report any effects

on

body weight. Similarly,

Myerson (22) in his lirst report with benzedrine for

the

treatment of fatigue in normal and neurotic persons i n

1936 did not note any effect on weight loss. However

Natlianson (23) in a study of 40 patients in 1937 noted

that 10 had a mwkcd loss of appetite with ;I defiiiite

reduction

in

weight. Losses

of

weight varied beiween 7

and 20 Ibs. The loss of weight appe:wed io bc explained

by the lessened appe tite and increased physical activity.

Davidoff and Reifenstein

i n

1937 (8) oncluded from

their studies with am phetamine that it may be

ol

use

in

reducing weight.

Also

i n

1937, IJlrich (31)

i n

his

report

on the

treatinent of narcolepsy with benzediine

sulfate noted

that

several obese patients lost weight. It

is against this background that the research of Lesses

and Myerson was conducted.

Recognizing the abuse potential of dextro-ampheta-

mine stimulated the pharmaceutical chemists to synthe-

size derivatives of amphetamine to reduce the abuse

potential, while maintaining the appetite suppressing

effects. A variety of these drugs have been tested and

marketed, but with the drug abuse epidemic of the

1 )GOS, all of the deriva tives of amp hetamine s h ave

been tarred with the same brush. As amphetamine fell

from grace, a similar

pall

fell over the entire class of

compounds for be t te r o r for worse , and whether

deserved or not.

To their credit, pharinaceutical chemists developed

coinpounds which reduced

the

risk of habituation, and

actually developed some coinpounds which carry no

risk of habituation , yet retain appe tite suppres sing prop-

erties. One of these provides a particularly importa nt

lesson

in

the semantic pitfalls of tarring all compounds

that look alike structurally with the same mechanism of

action. It is now known, through the work of Leibowitz

and her colleagues (19), that direct hypothalamic injec-

tions of amphetamiiie will significantly reduce food

int2ke. This effect involves

the

release of both norepi-

nephrine and dopamine. I n all likelihood, it is the

response

to

dopamine which is associated with die risk

of habituation. Identifying a model compound that

reduces appet i te

opens

the

way for pharmaceutical

chemists

t o

develop a variety of deriva tives in w hich the

appetite suppressing effects and tlie abuse potential can

be dissociated. Three different groups of compounds

were the result of this synthetic effort.

Th e f i r s t g roup of co inpounds was s imi la r to

amphetamines, but had lower or absent abuse potential,

yet retained the appetite suppressing effects. For this

group of c om pu nd s, the mechanism of action appeared

to be

the

release of norepinephrine from endogenous

srores. A second group of compounds in this group, typ-

ified by mazindol, resulted from

the

observation that a

tricyclic inhibitor of norepinephrine reuptake could

reduce food intake. The third compo und has structural

similarities to amphetamine, but acts by a totally differ-

ent mechanism. This molecule, d , 1-fenfluramine, was

shown to work by releasing serotonin and partially

blocking serotonin reuptake at nerve endings. This dis-

covery opened a whole new area of research into sero-

tonergic agents as drugs for treatment of obesity.

Most of

the

chemical congenors of amphetamine

have noradrenergic effects with little or no dopaminer-

gic effects and m L k e d ly educed risks of habituation.

Fenflurainine, although structurally similar to mpheta-

mine on paper, differs in

21

major way from other deriva-

OBESITY RESEARCH Vol. 2 No. 3 May 1994 283


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Commentary on Classics

in

Obesity

tives of amphetam ine. Whereas treatment of aiiirnals

with most of the derivatives of a np lie tm in e reduced

brain norepinephrine, treatment with fenflurainine did

not. Ra ther , fenfluramirie reduced brain serotonin,

which other amphetamine derivatives did not. It has

become clear in the two decades since fenfluranine was

initially approved for marketing, that

its

mechanism of

action is through a serotonergic receptor system w hich

is important in modulating food intake in man and ani-

mals and that this drug operates by a totally different

mechanism than the noradrenergic agents.

The rigidity of the fedem1 and state regulatory sys-

tems which control

the

approval of drugs in the [Jnited

States led to inclusion of fen flurm ine in the same class

of

scheduled drugs, a s the noradrenergic drugs.

Re-

review of this questionable decision is appropriate, yet

mechanisms for this are, to say the least, cumbersome.

In a four-year study of obese patients, treated with fen-

fluramine and phentermine,

no

abuse was detected (33).

Drugs were shown to be of value to more than half of

the patients who were treated. Yet under the regulatory

restrictions imposed by many s tate licensing boards, use

of these drugs for more than a few weeks to treat

obese patients wilh diabetes or hypertension can lead to

serious medical, legal, and licensing problems for physi-

c ians . I n a free society these r igid restr ict ions

imposed by the legalistic mentality of regulatory agen-

cies appears to be iriappropriate and is certain ly incon-

sistent with good treatm ent of obesity (3).

A key ingredient in the two observations relating to

drug treatm ent of obesity are captured by the word

yseic-

do-serendipi/y. Serendipity refers to finding something

that was unexpected. There are two kinds of serendipity

(28). The first is true serendipily, in which the discovery

has no relationship

to the

usual activity of the individ-

ual. Three such exam ples would be

the

discove ry of the

Rosetta Stone by Napoleons army engineers in Egypt,

the discovery of the Dead Se a Scrolls by boys playing in

caves in Israel, and the discovery

of

the Lascaux Caves

in France by young boys playing in the mountainous

areas of Southern Fnuice. I n each case, the individual

making the discovery had not been trained

in

scientific

disciplines or for discovery.

Th e second sort of serendipity might be better

referred to as pseudo-serendipity, since

i t

~wcurso indi-

viduals who are highly trained

in

their field, but who

make accidenml

but

often m omentous discoveries. The

discovery of TNT by Nobcl and the discovery of x-rays

by Roentgen are two good examples of accidental dis-

coveries by trained minds, but in areas

that related to

their primary search. The observation by Lesses and

Myerson which opened up Uie field of appetite suppres-

satits in the treatment of obesity

m y

e called pseudo-

serendipity

Abraham Myerson (1881-1948) was a neuropsychi-

atrist born i n Yanova, Lithuania. He moved to the

United States in 1892 at age 11. I n Myersons early

years he demonstrated his phenomenal memory and

unusual skills a t speed reading. During his years at Uie

English High School in Boston, he developed a strong

interest

in

biology. After an interval of six years while

he

worked to save money,

he

entered the Columbia

University College of Physicians and Surgeons in New

York, but transferred

to

Tufts Medical School where he

received his M.D. in 1908. His major teaching activities

were at Tufts University where he rose from an a ssistant

professor in 1918 to professor in 1921 and professor

emeritus

in

1940. His m i o r work was in neurology,

which

is

noted by the e p n y m Myersons Sign referring

to

tlie glabellar reflex. H e also developed a procedure

for obtaining carotid artery and intenial jugular vein

samples for study of brain metabolism. Myerso ns

interest in psychiatry was at the physiological level and

he was a strong anti-Fre udian during most of his life. It

was in his role as a neuropsychiatrist that his studies

with amphetamine to relieve narcolepsy were conduct-

ed: He was a talented speake r and a man of great zest

and enthusiasm. He chaired the research committee for

the American Psychiatric Association from 1939 until

1947 and during World War I1 was on the National

R e s e a r c

h

Co un c i1 Re pre sen in g the American

Psych iatric Association (32).

Acknowledgments

.

Special Lhanks to Judy Roberts, Sandra Graves, and

Stephanie I-iaydel for help in acquiring the Lesses and

Myerson documents.

Refcrciiccs

1 .

Atwatcr

WO,

Rosa

En.

Description of a new respiration

caloruneler and experiments on

the

conservation of ener-

gy i n the hunian body.

U S

Depart~ nent f Agriculture

Office of Experi~neiital tations. 18 99 53 .

2.

nargcr G , Dalc HH. Chen iical structure and sympatho-

iniinetic action

of

aniines.J P/zy.riol. 1910;41:19-59.

3.

Bray GA. Barriers to the treatnient of obesity. Editorial.

Ann

Inicrn

Med.

1991;l

IS:

52-153.

4. Bray

G A .

Conunentary on Atwater Classic. Obes

Res.

1993; 1:223-227.

5. Bray G A . Tlic

OOese

Paiierii. Mrijor

Problerrls in Inter-

nul

Mrr l ic i r ie .

Philade1phia:W.B. Saunders Com pany;

1976:9.

6 Ilray

GA, Mclviii

KEW,

Chopra IJ.

Effect of triiodothy-

roninc on some inetabolic responses of obese patients.

Arrr

J

Cliri Nrctr. 1973;26:715-721.

7. Llrobcck

JR

Larsson

S,

Reycs

E.

A study of the elechi-

cal activity of the hypothalamic feeding mechanism. J

Plyviol.

1956;132:358-364.

284

OBESITY RESEARCH

Vol. 2

No. 3 May 1994


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Commentary on Classics in Obesity

8. Davidaff E, Reifcnstcin E C, Jr. The stimulating action

of benze drine sulfate: a comparative study of the respons-

es of nonnal persons and of depressed patients. JAMA.

9 . DuBois

EF.

BNS(IIrrreru olisrri

in henlrlz

ond

d is rnsq .

Philadelpia: Lea Febiger;

1924.

10. Edwards DAW, Swycr G I M . The co inparative values of

dextroaiiiphctamiiie sulphate, dried thyroid gland and a

p l a c e b o i n t h e t r e a t m e n t o f o b e s i t y . C l i n S c i .

1950;9 2):115-126.

11.

Gelvin EP, McGnvack TH . Dexedrine and weight reduc-

tion. NY S ~ n t e

Med. 1949;49:279-282.

12.

G r o s s J, Pit t -Rivers RV. 3:5:3-Triiodothyronine. .

Isolation from thyroid gland and synthesis. Bioclierrr

J.

1953;53:645-650.

13.

Gul l WW.

On a

creatinoid state supervening

in

adult life

in

women.

Truns Clin Soc Lond. 1873-74;7:180-185.

14.

Harington CR. Chemis t ry

of

thyroxine

I.

Biolrort

J.

15. H a r r i s S C , I v y A C , S c a r l e L M . The inechan ism of

am p h e t ~n i n e - i n d u ced

oss

of weight. A coirelation of the

theory of hunger and app etite.J A M . 1947; 134:1468-1474.

16. Kendall EC. The isolation

i n

crystalline form of the com -

pound containing iodine, which occurs in the thyroid; its

ch e i n i ca l

n

a t u e a nd ph y

s

o

lo

g i c ac i v i t y J A

MA

17. Koestlcr A.

J C I I I I ~ S .

.wrrrrrririg up. New York;Random

House. 1978.

18.

Leake CD. The urrrplierarrrirres. Tlici r ucrions and rtses.

Springfield, IL: Charles C. Thomas; 1958.

19.

Leibowitz

SF,

Rossakis C. Analysis of feeding suppres-

sion produced by perifornical hypothalamic injection of

catecholamines, amphetamines and mazindol.

Erir

J

1937; 108:1770-1776.

1926;20:293-313.

19 15;64:2042-2043.

P ~ u ~ ~ I L978;S3:69-8

1

20. Lesses MF, Myerson A . Human autonomic pharmaco-

logy XVI: enzedrine sulfate as an aid in the treatinent of

obesi ty .NEngi J M e d

1938;218:119-124.

21.

LYOII M, Dunlop DM. Th e treatment of obesity: a coin-

par ison of the ef fe cts of die t and of thyroid extract .

22.

Mgcrson A. Effect of benzedrine sulfate on mood and

fatigue in normal and in neurotic persons.

Arch Nertrof

23.

Natlianson M H. The central action of beta-aminopropyl-

benzene (Benzedrine).

JAMA. 1937;108:528-531.

24. Prinznietal M , Biooniberg W. The use of benzedrine for

the treatment of narcolepsy. J AM A.

1935;105:2051-

2053.

25.

Iiitnani JJ. Cases of myxoedema and acromegalia treat-

ed with benefit by sheeps thyroids: recent observations

respecting the pathology of the cachexias following dis-

ease of the thyroid; clinical relationships of Graves dis-

ease and acromegalia.

AIII

Med Sci. 1893;106:125-148.

26 .

Raviiss in E, Lil l ioja

S,

A n d e r s o n T E , C h r i st i n L ,

Bogartl

us

C. Determinants of

24-hour

energy expendi-

ture in man: methods and results using a respiratory

chamber. Cl in

h e s t . 1986;78:1568-1578.

27. Kaviissiii E, Sivinburn BA. Pathophysiology of obesity.

kince l . 1992;340:404-408.

28 . Roberts RM. Serendipity. Accidental Discoverites in

Science. New York John Wiley Sons, Inc.;

1989.

23.

Sinikins S. Dinitrophenol and desiccated thyroid in the

treatinent of obesity: a coinprehensive clinical and labo-

30. Tenikin

0

Th e double face of Janus. In: The doirble

fhce of Junus nnd other

essuys

in

rlie

liistoiy of niedicine.

Baltimore: Johns Hopkins University Press;1977:3-37.

31. Ulricli H. Narcolepsy and its treatment with benzedrine

sulfate. N Enngl

J

Med

1937;217 18):696-701.

32.

Walter RD. Abraham Myerson.

Dictionmy

of

Arriericnn

Biogrupliy. 1974;24:617-6

18.

33.

Weintra i ib M, S i indare nsan PM,

M a d a n M

e t al.

Long-term weight control (parts 1-7), the National-Heart-

Lung-and-Blood-Institute funded multimoda l interven-

tion

study. Clin

Pliornrucol Tlrer. 1992;s1 5):58 1-646.

QrlorT J Med . 1932;1:331-352.

Pqcl i . 1936;36:816-822.

ratory study.

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1937;108:2110-2193.

OBESITY RESEARCH Vol. 2No. 3

May

994 285


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CLASSICS IN OBESITY

Human Autonomic Pharmacology

XVI.

Benzedrine Sulfate as

an

Aid

in

the Treatment of

Obesity

Mark

E

Lesses*, Absuhum Myesson f

Boston

When energy int,lke

in

the form of food is greater

than energy output, the excess potential energy is stored

as body fat. If imbalance between food intake a i d ener-

gy output occurs, a change

i n

weight must cake place;

whether it is to be a gain or a loss depends on the direc-

tion of the imbalanc e. From this point of view,

the

cause of obesity may be a defect of the appetite-regulat-

ing mechanism, rather than an alteration of metabolism.

The perfect appetite mechanism will adjust itself to all

changes of energy output, or metabolism, by a corre-

spond ing change in e nergy, or food int,ake, and

thus

the

body will maintain its usual weight. De fect of the

appetite mechanism w ill create imbalance in

the

energy

outpu t-intake relation, and a chang e in weight will

result.

The factors which govern the appetite may

he

divided into the following groups:

I )

physical status,

particularly with reference to the endocrine glands;

2)

social habits; and

3)

psychologic influences. The effect

of physical status on the appetite may be considered

under the two aspects of disturbances due to acute or

chronic organic disease, and disturbances due to meta-

bolic abnormality as mediated through

the

endocrine

glands. With regard to Uie forme r, little comment is

needed, as the appetite disturbance of

the

sick is a mat-

ter of comm on knowledge. With regard to metabolic

abnormalities, the bulimia of hyperthyroidism and the

anorexia of Addisons disease may be mentioned as

contras ting pictures.

A

more subtle disturbance of

metabolism, mediated especially through the pituitary

gland, has been invoked by many writers from von

Norder onward, and has given rise to the concept of

exogenous versus end ogenous obesity 1).

In this connection, the work of Newburgh and his

associates

(2)

shows that energy exchange is in no way

different in a proved ca se of pituitary disease (Cushings

Syndrome) from w hat it

is

in normal persons. The

loss

in weight caused by any given reducing diet may be

predic ted for any per iod wi th grea t exac tness .

Furthermore, in patients suffering from rnyxedema,

where the depression in energy metabolism is greater

than it is in any other disease, striking obesity is the

exception.

All visceral functions, including the appetites, are

strongly modified by social habits. The app etite for

food and eating have become almost

as

much social as

they have physiologic and psychologic. People eat

without particular desire under the influence of social

feeling,

as

at parties and banquets. They are also forced

to defer eating when the desire for food is very great,

because of social conventions as to the serving of meals.

In

addiiion, the social and economic environment makes

food and drink easily accessible to many without physi-

cal exertion (3,4).

The

relation

of

physiologic, pathologic, and socio-

logic phenomena to the causation and maintenance of

obesity having been pointed out, there remains for d is-

cussion the effect on the appetite of num erous psycho-

logic influences. In previous papers (3,4,5), one of us

A.M.) has described a syndrome as part of the neurosis

known as anhedonia. This symptom complex consists

in a diminution, even to the point of disappearance or

antagon ism, of satisfactions norm ally obtained from life

activities, and in a los s or distortion of the appe tites and

desires. The appetites involved are hunger, thirst and

sex, desire for rest and recuperation, and desire for

social relations, work and entertainm ent.

When satisfaction becomes impaired and there is no

corresponding diminution

in

appetite, as is the case in

lhe

seek-

ing for Stimulation in Order

to

Secure the longed-fo r sat-

isfaction. Th e mood hecomes unpleasant, and the

eXpreSSio11 of it may t&e Inany form s. On e of such

From

the Division

of

Psychiatric Research. Boston Stare Hospital. Boston. aided

by grants brom the Cornmcmwealrl~ f Massachusettes and the Rockefeller

Foundation. *Research associates. Boston State

H t q i l a l .

tDirectcr

of

research.

Boston Slate Hospital.

Lesses

MF

Myerson A. Human Aulononiic Pllarmacolopy XVI. Benzedrine

Sulfate as an Aid in

the Treatiiwnt of

Obesity.

N ErigIJMerI

i 9 3 ~ : 2 i 8 : 1 1 ~ - 1 2 4 .

Mass achus ettes Medic al Society. R eprioted with permission from [lie

NCIV

Englarrdlouninl o/Mcdicinc.

1440Main SI..Wallham, MA 011.54-164Y.

stages Of anlledollia*here is a

expressions, ~ o ~ ~ ~ n o ~ ~ l ~

een

in sedentary

persons,

is

286 OBESITY

RESEARCH

Vol. 2 No.

3

May 1994


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Classics in Obesity

frequent

eating.

People wlio are resiless because their

lives

are

unsatisfied may be seen nibbling candy, nuts,

crackers o r

the

like.

The

ingeslion

of

food becomes ia

a

certain measure

an escapc.

Food

is

easily obtained, and

eating is often merely a somelliing-to-do wliicli

lias

become a prine need.

The etiology

of

obesity

and

treatinelit of the obese

person therefore appear

to

involve

a careful

considcra-

tion of

the

anliedonic syndrome, since in many such

patients there is an associated neurosis of varying

degree. A similar concept h a s been elaborated by

Newburgh and

his

;usoci;itcs 61, wlio have pointed out

that obesity is in the main outcome of a perverted Iiahit

and

that

tliere is dulling of the acuity

o f the

sensa-

tions.. .weak will a i d

a

plcznurc-.seekingout1tx)kupon life.

To attack tlie syndrome of mliedonic obesity

through

the

psychologic inechanisrns involvctl. i n

; i n

effort to cut down

11ie

uiipliysiologic desire for food,

seems more rational h i i Uie usual therapeutic

efforts,

which

are

largely aimed at increasing the inctabolisin

t

liroug ti drug ad in i n s t r;i t ion-for cxa inple

li y

roid

extract

or

dinitrophcnol-

o r

exercise,

or

decreiisilig

tlie

food

intilke

by

S ~ ~ C I I ~ J O ~ J S

ieting.

Tlic

latter Inelhods are

successful, but d o nothing

to

cliiniii;i~e

lic

c;iuse,

tliat is.

the anhedonia. Ib is neurotic relalion is shown by tlie

easy fatigability

of the obese,

which

is,

we belicvc, due

not

so

inuch to

Ihe

excessive weight that must

be

c;irricd

as to the neurotic factors which have

prcxluccd

;uid are

sustaining the obese st;i e. This

is

wcll attes~etl y the

fact that

in

many of the

cases

to be

described the

fatigue

was not

that

seen

afier

physical

effort,

unusual

o r

cus-

tomary,

as in

norinal pcrsons.

but WiiS the

ch;ir:icleristic

morning tiredness,

occurring

even withoul the cxpcn-

diture of energy. which is see11 i n the neurotic

~ii it l

the

physically sick.

I b t i s , the

cxccss

food

ingestion

1

Ilic

anliedonic obese

person

larely occurs i n

the

morning,

when desire

and

mood are especially low,

but

coincs

later in

[lie

day and

i n the

evening.

Benezedrine sulliite plieiilisopropylnIninc)

is

a n

advantageous drug will1 which to att:ick

the

problem.

Its action is primarily that of a syrnparhctic stirnulaiil:

clicmically speaking, i t is

;iii

atlrenergicdrug. lhus. on

the

eye

and

the

vascti1;ir system

is

lias

he

classic

effects

of sympatlicric stimihlion: i t relaxes tlic sprisin o f the

gatroiiirestional lmct (8), ;uid

leiids to

dccrcasc the gas-

lric

juice

while increasing its acidity (9). Its

cflccts

on

tlie mood, on

the

sensation

o f

cncigy ;ind ils output,

;ind

on

tlie

gastrointcstioal

trac[

offercd

t l ic desired

psy-

chopliysiologic action. Given

i n

small

doses,

below

(lie

point where i t produces mwketl changes in the visceral

activities, henezedrine sulfate prevents slecpiiicss :ind

drowsiness; this

is

the basis Ibr its use in narcolepsy

10).

The

dissipation of

the feeling o f

f;iliguc and [lie

beneficial inllucnce

on

sI;itc

o f

iniiitl effected by this

drug in both nonnal and neurotic persons have been

established by recent

reports

(1

1,12,13).

Because of

these psychologic effects the urge to eat as a means of

tilling out an empty existence

is

lessened.

The direct effect of benzedrine sulfate on the

appetite for food is

of

primary inportance in the

group

of

cases

to

be

discussed. That it seems to cause a

loss

in

weight has already been noted by Nathanson

12).

Evidenceof its availability to reduce the appetite will be

adduced

below.

A group of 17

unselected

and consecutive private

patients, with a priinary complaint

o f

obesity, were

placed

after

initial

study

on a

measured, unweighed diet

of about 1400 calories, with an approximate composi-

tion

of protein 69 gin

and

iron

0.014

gm. No further

instructionsas to Uie diet were given after tlie first visit.

N o patient was urged to follow

the

diet,

or

to do other-

wise t1i;iii obey his narural desire. All patients were

observed at intervals

1

from seven to fourteen days,

ant1 at

each visit the weight,

blood

pressure and pulse

ralc were observed. All reported syinptoms were noted,

and

leading qucslions which might obscure die subjec-

tive

effect of

~Iie rug were avoided. Prolonged obser-

vation by Mycrson

and

his associates

14)

indicated that

in

iniiii the elevation of

the

blood pressure was Ihe most

toxic cllcct of haizedrine. This hypertensive effect was

rarely associated with iiii increase in the pulse rate. The

dosage

1

hcnzedririe utilized never caused blood-pres-

sure elevation,

even

i n pnlicnrs with hypertension.

Subjectively, the inore important criteria of benzedrine

toxicity were ncrvousiiess,

a

jittery sensation and

noc-

luroal

insoinnia.

Icre

again,

aueful

regulation of the

dos;igc prevented these rcaclions.

Bcnzctlriiie sulfate is distributed

in 10

mg. tablets,

which

are

scored

s o

that they may be broken into

quar-

ters. each representing

2 3

ing. The most satisfactory

plan

of treatment was to give three doses daily-a large

dose i n the inoriiing iminediarely on waking o r rising,

a

moderate dose

at

noon, and small o r moderate dose in

tlie kite ;ifleimoon. As I rule, we started with 7 3 mg on

arising,

S

m g t iioon, and 2 3 mg at S p.m. This dosage

was gradually increased from week to week as Uie need

;irose, but

tlie dosage

was

slopped

well

sliort

of the point

at which nervousness or noctunial insomnia was pro-

duced. Ordinarily, :in increase

o f

5 mg weekly caused

no uiiroward symptoms. The largest dose given any

palicnt was 30 ing. daily, divided into three

unequal

doses (12.5

mg.

o ~ i

rising,

10

mg. at

noon and 7.5

mg.

at S pin.)

This dosage sclietlule accomplished two desirable

rcsulrs: tlie

largest

dose was given in

Uie

morning, when

the

lieling

of

energy was at its lowest, and

the

smallest

was givcii in the afternoon, wlien tlie energy

output

was

increasing ml tlie rime for sleep was approaching.

I n

OBESITY RESEARCH

Vol. 2 No.

3May

994 287


7/11

Classics

in Obesity

occasioiial cases, w here the appetite for excess ingestion

of

food

during Uie evening was unconll-ollablc,

the

pl:m

of giving a large dose in

the

morning, a small

dose

at

noon, and a moderate or large dose at

S

p.m. wx. wicd

with some success, particularly if insomnia did not h l

low. All patients were supplied with only enough

tablets to

last

unt i l

tlie

next visit,

i n

order

to

prevent

dange rous self-rnedicatioo.

No

patient was given a pre-

scription for

tlie

drug

or

W;LS told

its

name.

Tolerance to tlie drug ,

so

far

;is its

effect on the

appetite was concerned, did

i i o t

seem

to

develop, for

substitution of placebo tablets or oinission of the

drug

always caused a retiini of in crexm l appetite, even alier

months

of

adminisuatioii.

Out of

the

group of

17

cases, the complete histories

of 8 are given below. Table 1 gives llie factual data for

Uie entire group. Although we liere strcss

the

utiliziilion

Table 1.

The Effect

ofh cwxdr ine

S i d f i i t c ~

i s t in

A i d

in

the

lreeolrizenl

o

Obesity.

Case

No.

1

2

3

4

5

6

7

8

9

10

1 1

12

13

14

15

16

17

Sex

F

F

F

F

F

F

M

F

F

F

F

F

F

F

F

F

F

Iuitial Period Iotal Avcragc Maximum

Weight ol

Weight

Wcckly Daily

Lb.

17

1

210

194

216

I45

217

316

189

150

23 1

157

176

135

145

151

207

179

~ t i s c r - L& Weight

vation

Loss

17 29 1.7

15 17 1 . 1

23 26

1 1

6 1/2 I I 1/2 1.7

10

I 1

1 1

6 7 3/4 1.3

12 1/2

54 4.3

20

112

32 I .5

19 27 I

.4

25 48 1.9

10

18

1.8

10 0

0

12 13

1 1

14 9 0 .6

10 1/2 20 1/4 1.9

10

I 0 o

I 0

1/2

13 1/2 1.3

[ h e

f

Bciizcclriiic

l1I.g.

22.5

27.5

22.5

25.0

13.0

22.5

30.0

20.0

22.5

27.5

20.0

22.5

22.5

30.0

17.5

27.51

5 .o

of benzedrine in

cases of

obesity which arc wsoci;itctl

with varying degrees of aii1ietloni;i aotl neurosis, tlie

drug was found to be of a s much heiiclit in cases of obc-

sity wirliout any obvious neurotic backg round, such :is i i

case associated wilh narcolepsy and several

cases

wirli

endocrine stigmas.

CASE b P O I C l 3

Cuse 1

(obesity and psychoneurosis). A houscwifc

of 24 complained of bcing overweight and

of

abnorin;il

fatigability. She

had

gained 25 Ib. since Uic birth 1

her

baby

7

months before. For over a year she had noted

increased fatigue, particularly on wakening in the morn-

ing.

The

past history was otherwise negative.

The

height wx. 62 in. and the weight 160 Ib. SO b.

overweight). The re was no deviation from norinal

except for tlie generalized obesity. The blood pressure

was

11O/G4.

Tlie

urine was free of albumin,

sugar

and

abnorm alities of tlie sediment.

lhe patient was

placed

on the

standard

low-calorie

diet. She did not return again until 11 months later,

wlien

she

weighted 171 lb. She slated that she felt tired

and sleepy a l l llie time, had become very nervous and

had

frequent

crying spells. Examination at

the

time

revealed

no

change from

Uie

previous

one.

The

blood

In view of tlie fact thnt the patient was suffering

l i om psyclioiieurosis, she was given both stiinulating

and sedative therapy.. She was

p1:iced

on benzedrine

sulfate,

5

mg.

on

arising.

5

ing.

at

noon

and

2.5

mg at

5

pin. ,

;ind

Arnyral (isomyletliyl barbiruric acid),

IS

mg

at ~ i o o n , uppcr a i d bedtime.

In

addition, she wits given

[lie

stantlard low-caloric diet. Duiing

Lhe

course of the

I I C X I

mootli slie wits seen at weekly intervals a n d

showed ii weight

loss 0 1

16 lb. Her nervousness gradu-

ally

dccrcascd,

her crying

spells

disappeared, and slie

stopped rnuncliing bclween m eals.

She

had no difficulty

i n

gctting I satisfactory nights sleep. She stated, I am

not

hungry any

more.

For

the

first time in

her

life,

however,

slie

hccame slighcly constipated . During this

period

the

hltx)rl pressure

and

pulse rate remained

unal-

tcrctl.

At

the close of the

1st month

of llierapy the patient

was given

:i 2

weeks supply of the tablets aid told to

return

;it

tliat time.

Ihis

slie was unable

to

do, s o that

slic was

not

seen again u n t i l 6 weeks

later. A t

this visit

she statcd that following the omission of the benzedrine

tablets

she

had had

a

marked increase

in

appetite:

I

kept nibbling all day. When I take Uie tablets [of ben-

zcdrinc] I 1i;ivc to force myself to

eat.

Whereas

slie

had

lost

16lb. i n her 1 s t inoiitli of Ireatmelit, during the

suhscquciil

6

wccks

she

lost only 5

Ib.

During the period

01 benzcdrinc dicrapy. slic liniilly attained a dosage of

10

ing

o n

rising,

7.5

mg

;it

noon,

and

S

mg

;it

p.m.

The t;iblcts of isoainylethyl harbit uric acid were oinirted

wlica rlic nervous symptoms disappeared. Following

thc resumption of beiizetlriiic Uieixpy Ihe loss in weight

continued, ant1 i n

tlie

lioal 6 weeks

she

lost 8

Ih.

During

2 of tlicse weeks

she

again missed an appointment

a i d

was williout henzctlrine for

2

weeks. Upon cessation of

the

bciizcdrine her appetite hecane tremendous, and

she iitc s o inucli

that

there was ii temporary gain in

wcighi. At her last visit slic stated Lhat slie felt perfectly

well, and physical examination disclosed no abnorinali-

ty.

Slic

lost

29 Ih.

dr1ring the 17 wceks of observation.

pressure was

110/60

288 OBESITY

RESEARCH

Vol.

2No. 3

May

1994


8/11

Classics in Obesity

Cme 2 (obesity with psyclioneurosis). A housewife

of 32 complained 1 being overweight and o f weakness,

easy fatigability antl

tiredness.

She had always been

overweight, but since her 1n;irri;igc 8 years prcviously

her weight had increased froin 165 to 212 Ib. without

apparent cause. Her appetite

had

always been very

good, and she ate a great deal between meals. She h;id

had weakness ai d easy fatigability

for

the

past

year. Six

and a half years previously, following

the

birth

of

her

first child, she had had a nervou s brcakdown. During

that period she lost 3.5

Ib., so

that her weight dropped to

140 Ib. Since

then

her weight had increased to its pre-

sent figure. The cause

of

Ihe breakdown was not known

to her. She said that at that time, I could not cat ...

could not look at food

had

t e r r ib le and crazy

Lhoughts; nothing interested me. ..I did not c u e for any-

thing

... had

frequeiit itleas

of

liilling. She wiis i l l for

about a year with this condition, and t hcn gradu;tlly

improved. She had always slept well but awoke every

inoniing with a tired feeling

and

without

a

norrn;il sen-

sat ion of restfulness. Durin g

the

day her fat igue

occurred without

relation to

exertion. The rest of

the

history was irrelevant.

The height was 61 in. and the weight 210th 87

Ib.

overweight). The

patient

show ed centripet;il obesity,

the fat being chietly over Uic buttocks, thighs, ;ibdomen

and upper arms. The hands ;ind feet were smill and i n

proportion

to

the height . The blood

pressure

was

120/80. The rest of

the

examination was normal. The

hemoglobin was

6

per cent (Sahli) with 4,100,000 red

blood cells

p e r

cu. min.

The blood

smear showed inod-

erate hypochrorn ia of the red cells, but no abnornxlilies

of the white cells. A sug;w-tolerance test, following the

ingestion of 100 gin.

of

dexlrosc in 20 percent solution,

showed no glycosuria up to 2 hours. The blood sugar at

tlie end of the second hour wiis 72 mg. per cent Folin-

We method).

This patient was placed on

the

standard low-calorie

diet a i d

W;L

given benzedrine

sulfate,

7.5 mg. on rising,

5 mg. at noon and 5 mg. at 5 p.m. This was gradually

increased to 10mg on rising, 10 mg. at noon and 7.5 mg

a t 5 p.m. The patient was observed at weekly inlervals

for

15

weeks, during which time she

lost

17

Ib. IIcr

fatigue disappeared,

although

her sense of well-being

was not pLarticularly mproved. There was a significant

decrease in

Ihe

appetite. The blood pressure rcin:incd

within nonnal

liiniLq. This

patient is still under observation.

Cuse 3 (obesity with psychoneurosis).

A

housewife

of 38 complained of being overweight and

of

nervous-

ness . She had been overweight mos t o f her lite.

Seventeen yem previously, at the time of her marriage,

she had weighed

140

Ib.,

and

since then

had

gt~idually

gained in weight. One year previously

she

had under-

gone ;I tonsillectoiny, antl

had

gained 15 Ib. shortly

tlicreaftcr.

Her

appetite had always been excellent, but

she

was not accustonied

to

eating between meals. She

stated tha t she had always done

her

own cooking and

did d o ii good deal of tasting. Recently she had become

accustoined

to sleeping

10 or 11 hours at night. She had

been nervous and easily irritable since

her

husband had

been t1i;ignosed :LS having heart trouble. Her farher had

died of Brights disease at

the

age of

52,

and one brother

had diabetes

and

heart uouble. The rest of the history

was negative.

The height was

64 n.

and tlie weight 194

Ib.

(62 Ib.

ovcrweight). Except for generalized obesity, the physi-

cal

examination W;LS negative. The blood pressure was

126/80. Th e urine was free of albumin, sugar and

abnormalities

of

the sediment. The hemoglobin was

78

per cent Sahli). The basal metabolic rare in

a

satisfacto-

ry test was-15 percent (May o standards ).

The patient was placed on

the

standard low-calorie

diet ant1 given benzed rine sulfate, 2.5mg. on rising, 2.5

ing. in mitl-morning and

2.5

mg. at noon. The dosage

was gradually increased unt i l she was taking 10 mg. on

rising,

7.5

mg. at

noon

and 5 mg. at 5

p.m.

This patient

was

seen at

weekly intervals for

;I

period of 23 weeks

and in that time

lost

26 Ib. The craving for food was

IOSI:he nervousness and irritability becane markedly

decreased. She slept well, was free of all unpleasant

sub.jective symptoms and i n fact

had

;I sense of well-

being. Benzedrine was omitted and placebo tablets

were given

for

2 weeks during Uie period of observa-

tion; during

that

time,

she

spontaneously slated,

she

had

had a return o f her nervousness and craving for food.

During this period there was a

gain

in weight of 2 Ib.

rrse 7 (obesity with narcolepsy). A 34-year-old

salesinan coinplained

of

being overwe ight and of sleep i-

ness. I-Iis

birth weight was

16

Ib. and he had been con-

tinuously overweight since birth.

At

the age of 16 he

weighed 140 Ib.; at the age of 19, 200 Ib.

His

weight

gradually increased unti l at tlie age of 29

he

weighed

over 300 Ib. The weight had been stationary for the last

4 years.

His

appetite had always been very good, and he

ate continuously

throughout

the

day.

In

addition

to

sleeping

9

or 10 hours at night,

lie

found himself contin-

ually

falling

of f to sleep throughout the day whenever

the opportunity presented itself. In

the

past history there

was nothing of importance except that he had had gon-

orrhea

18 years

before,

which had apparently never

clewed up,

as

since then he had noted a slight penile

discharge intermittently. He had

also had

nocturia dur-

ing the I ; L~ I

7

or 8 years, but apparently no daytime fre-

quency o r polyuria. There was no iinpairme nt of sexual

desire

or

potency.

The height W;L

69 in.

and

tlie weight 316 Ib. (158

OBESITY RESEARCH Vol. 2 No. 3May 1994

289


9/11

Classics

in

Obesity

Ib. overw eight). Th e blood

piwm~re

was 104/80. The

patient was very obese, will] llie excess adiposity con-

centrated about tlie abdomen. There were a few

red stri-

ae over the lower abdomen. The fundi showed clear and

well-outlined nerve heads, normal arteries and slightly

engorge d veins. Th e mouth, throat, neck, heart, and

lungs were normal. Th e genitalia were norma l.

All

reflexes were normal. Th e urine had iio albumin

or

sugar, but the sediment showed 10white

blood

cells per

high-power field, and

the

stained urinary sediment

showed m any extracellular cocci. The prostatic sme;LT

showed inany

pus

cells and cocci.

The

b~w1 etabolic

rate was +8 and

+10

percent (Mayo slantlards) in two

fairly satisfactory determinations. The blood I - l in ton

test was negative. Blood sugars t


10/11

Classics in

Obesity

During a 2-week period the patient was given placebo

tablets and gained 4 lb.

She

noted a return of sleepy

spel ls arid m,arked increase in appetite.

Case Y (obesity following subtotal diyroidectomy).

A houseworker of 3 8 complained of being overweight.

Two years before her first visit she had had a subtotal

thyroidectomy for hyperthyroidism , from which

she

had

completely recovered. In

the

2 years following tlie

operation she had gained 35 lb., mostly

in

Ihe lirst year.

The rest of the history was irrelevant.

The height was 61 in. and the weight was 150 Ib.

(27 lb. overweight). There was generalized obesity.

The eyes were prominent but showed

no

lid lag. The

skin over the elbows and over

the

posterior surlaces of

the upper arms was somewhat dry and rough. The hair

was slightly course.

The

neck showed a well-healed

diyroidectomy scar, with a small arnouiit

of

tliyroid tis-

sue

palpable in boll1 lobes. There was slight puffiness

under the eyelids. Th e urine was free

o f

albumin, sugar

and abnorm alities of [hesediment.

The

hemoglobin was

7

8

percent

S

ah

1 ); he

red b

1ood

-

ce I

co

u n

was

4,650,000; the smear was normal; (lie basal metabolic

rate was -3 percent (Mayo standards )

i n

a satisfactory

test; the blood pressure was 110/80.

There was an apparent disturbance in tlie appetite-

regulating mechanism,

;IS

videnced by a constant crav-

ing for food. There was no clear-cut clinical evidence

of myx edema, and tlie basal metabolic rate bo re out

this

negative impression. She was therefore

pl;icetl

on

llie

standard low-cdorie diet a id was given benzedrine sul-

fate,

5

mg.

on

rising,

5

mg. at noon and 2.5 mg. at

5

p.m. Her highest blood-pressu re reading durin g the

course of treatment was 126/84. Th e pulse rate was

always within normal limits. She was seen at biweekly

intervals during the next

19

weeks, during which time

she lost 27 lb. There were no untoward symptoins

throughout

tlie

course of observation. Her sleep was not

interfered with and she found

it

very easy to follow tlie

diet. Her appetite was gotxl, but she lost the craving for

food. She was discharged after 19 weeks of treatment

because

she

had attained her normal weight.

The

f ina l

phy sicd ex amination showed

no

abnonnalities.

Cuse

10 (obesity). A housewife of 45 coinplained

of being overweight and of easy fatigability. She h;rd

been overweigh t all her life. Twenty year previously, at

the

time of her marriage, slie weighed 170 Ib. Her

appetite had always been unusually good

She

hati diet-

ed many times but without any success, and

in lact

widi-

in

the

preceding mon ths had gained

S

Ib. Tlie rest of

the

past marital and family histories was irrelevant.

The height W X 65 in. and the weight 231 Ib. 95 lb.

overweight). There was generalized distribution of the

excess lht except for Uie breasts, which were

normal

in

size.

The

blood pressure was 152/78. The heart was

not

enlarged, but a barely audible systolic murmur was

heard over the apex. Th e rest

of

the exam ination was

normal. Th e urine was free of albumin, sugar, and

ahnonnalities of sediment.

Tlie patient was placed on

the

standard low -calorie

diet and was given benzedrine,

5

mg.

on

rising, 2.5 rng.

in mid-morning and 2.5 m g. at noon. T his dosage was

gradually increased and the time of administration was

rearranged, so that eventually slie was taking 12.5 mg.

on

rising, 1 0 mg. at noon and

5

rng. at

5

p.m. She was

seen at intervals of 10 days over a period of 25

weeks,

and during that time lost 48 Ib. Tlie initial blood pres-

sure, which was somew hat elevated, showed

a

normal

reading on subsequent visits, and on several occasions

went ;IS ow as 104/70. During the period

of

observa-

tion she noted a decreased appetite and an increased

feeling of energ y. Iliere were no oth er su bje cti ve

changes.

She

found

it

easy to follow the diet.

For

sev-

eral weeks the rate of

loss

in weight was

so

marked that

the

diet had to tx increased.

A t

no time was there inter-

ference with tlie ability to fall asleep or stay asleep.

During one 10-day interval blank placebo tablets were

substituted for tlie benzedrine sulfate. Th e patient

@ied

weight i n that period and noted a m,uked return

of appetite and ex treme hunger.

Crrse

12

(obesity-failure of benzedrine to aid in

reducing weight). This patient. a student of 20, had been

under intermittent observation for a period of 3 years.

She liad undergone a previous course of reducing with

diet and thyroid extract quite satisfactorily, attaining a

linal weight of 135 Ib., 2 1/2 years before die present

period of study.

In

the interim she liad gradually gained

weight to a maximuin of 177 lb. This gain occurred

while slie was working as a cook.

The height was 63 in. and the weight 176 Ib. (48

Ib. overweight). Exm inalion showed centripemi obesi-

ty, the excess adiposity being largely confined to the

middle third of the body, ~ u i dmost marked over the but-

tocks and upper thighs. The breasts were small and

pubescent. The hair distribution was normal. The rest

of the examination was normal. The basal metabolic

riitc in

two

determinations

was +O

percent (Mayo stan-

dards). The blood pressure was

04/60.

The patient was placed on uie standard low-calorie

diet

and

was given benzedrine sullhte, 7.5 mg. on rising,

S mg. at noon and 2.5 mg at

5

p.m. The dosage was

gradually increased

to

10 mg.

on

rising, 7.5 mg. at noon

and 5 mg. a t 5 p.m. Over a period of 10 weeks Uiere

was no change in weight. Numerous unpleasant symp-

toms w ere cornplained of-inability to breathe deeply,

marked nervousness, constipation, dry cough, increased

OBESITY R ESEARCH

Vol.

2 No.

3

May 1994 291


11/11

Classics in

Obesity

irritability with difficulty in falling asleep and marked

fatigue. Further study of the emotional background dis-

closed that

just

before coming under observation the

patient had gone through an unliappy love affair, which

had left her quite depressed. She stated that during her

periods of greatest depression she ate large amounts of

food in an effort to compensate for her disturbed emo-

tional state. The benzedrine in this instance had of

course failed to restore the feeling of well-being and of

increased energy, which is often essential to its action in

reducing the appetite. Appropriate psycliotherapy in

this patient eventually restored some degree of emotion-

al calm, and the administration of benzedrine during this

phase effected moderate loss in weight without unpleas-

ant symptoms.

Benzedrine sulfate is an import,ant aid in the treat-

ment of obesity of any type;

on

the one

hand

i t

decreas-

es the appetite, and

on

the other

so

increases the sense

of well-being and of energy that physical activity is

spontaneously increased. Its proper place in the treat-

ment

of

obesity is

a

an adjuvant.

In

associated with a

properly selected low-calorie diet, it helps the patient to

follow the diet with greater ease by abolishing the neu-

rotic and ill-timed craving for foods which plays

so

important a role in the genesis and maintenance of obe-

sity. Our experience, however, shows that benzedrine

will not so readily effect weight reduction when

i t

does

not lift the patients mood and increase the sense of

well-being.

I n

the more profound neuroses where eleva-

tion of mood is not in any permanent way affected by

the drug and where the appetite is already absent, ben-

zedrine sulfate is not indicated. Its use in tlie neurotic

obese, therefore, is largely limited to tliose cases associ-

ated with what we have here termed a mild aihedonic

state.

SUMMARY

ND

CONCLUSIONS

1. Obesity is often due to a defect in the mood which

upsets the appetite-regulatingmechanism. I n such cases

increased eating, which does not represent true hunger,

takes place in order to offset aid compensate for the dis-

turbed mood.

2. The commonest cause of this disturbance in

appetite is the anhedonia associated with psychoneuro-

sis.

3.

Benzedrine sulfate, by improving tlie anhetlonic

state, acts

as

xi aid in obese neurotic persons.

4 Benzedrine sulfate has a direct effect in depressing

the appetite and in increasing physical activity, and is

therefore useful in any type of obesity

5.

In a group of obese patients suffering

from

associat-

ed psychoneuroses, endocrine disease arid narcolepsy,

292 OBESITY RESEARCH Vol. 2 No. May 1 9 9 4

benzedrine sulfate has been used as an adjuvant to

weight. reduction without development of any toxic

signs or symptoms, during periods ranging from six to

twenty-five weeks.

At the time of going to press benzedrine sulfate has

been used in the treatment of 40 obese patients over

periods of from three to nine months. The above con-

clusions are substantiated with regard to benefit and

lack of toxicity

in

the indicated dosage.

371

1.

2.

3.

4.

5.

6.

7.

Commonwealth Avenue

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Means JH.

Obesity. In: Cecils Texf-Book

of

Medicine.

3 r d ed . Ph i l ad e l p h i a an d L o n d o n : W.B. S a u n d e r s

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Frcyberg

RH, Newburgli

L H . Obesity and energy

exchange in a verified case of pituitary hasophilism. Arch

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Myersori

A. The social conditioning of

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Engl Mcd. 1934;211: 189.

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Psychology. New York: Prentice-Hall

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Mycrson A,

Tliaii W. Human autonomic pharmacology;

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Arch

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Myersoii A ,

Ritvo

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hlyerson A,

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Danieshek

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10. Irinzmetal

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Bloonibcrg W . The use of benzedrine for

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11.

Myerson

A.

Effect of henzedrine sulfate on mood and

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The central action of beta-aninopropyl-

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JAMA.

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1937;108:1770.

14. Myerson A, Loman J, Dcnicslick W . Physiologic effects

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