Appetite stimulation and weight gain with cyproheptadine (periactin) in tuberculosis patients (double-blind clinical study)


Rahman, K.M.

Medical Journal of Malaysia 29(4): 270-274

1975


It will be seen from the observations that the findings of our trial is in agreement with the above noted investigations that Cyproheptadine is a useful drug in stimulating appetite and weight gain. The patients receiving active drug showed mean weight gain of 10.55 lbs. whereas placebo group gained 4.25 obs. The differents of 6.30 lbs. in 16 weeks of Cyproheptadine therapy and follow-up is highly significant. The drug is particularly found useful for tuberculosis patients receiving PAS and Thiacetazone - the appetite depressant drug. Cyproheptadine is also recommended for patients suffering from other diseases having lack of appetite or poor weight gain. Above studies have established the efficacy of this drug but the specific mode of action is not known, further study is needed to reveal its mode of action.

Appetite
stimulation
and
weight
gain
with
cyproheptadine
(periactin)
in
tuberculosis
patients
(double-blind
clinical
study)
By
Dr.
K.M.
Maqsudur
Rahman,
M.B.B.S.,
D.T.C.D.(U.K.);
M.P.H.
(U.S.A.);
Off
Principal
Medical
Officer
of
Health,
Sabah.
Appetite
stimulation
and
weight
gain
properties
of
Cyproheptadine
were
first
noted
by
Levenstein
et
al.
(1962)
in
asthmatic
children
while
this
was
primarily
administered
as
an
anti
-allergic
drug.
Since
then
many
clinical
trials
have
been
conducted
on
relationship
of
cyproheptadine
with
appetite
stimu-
lation
and
weight
gain.
Cyproheptadine
is
an
anti
-histamine
prepara-
tion
with
anti
-allergic
and
anti-serotonin
properties.
Scrotonin
(5-Hydroxy
tryptaminc)
is
a
normal
con-
stituent
of
grey
matter
of
the
brain,
highest
concen-
tration
being
in
the
hypothelamus,
mid
-brain,
limbic
lobe
and
floor
of
the
fourth
ventricle.
Appetite
centre
is
in
the
hypothelarnus
and
is
said
to
be
under
the
influence
of
serotonin,
which
is
anto-
gonized
by
Cyproheptadine,
thus
releasing
the
appe-
tite
centre
free.
In
pulmonary
tuberculosis,
patients
under-
weight
and
lose
of
appetite
arc
very
important
features.
Anorexia
is
further
aggravated
when
they
arc
treated
with
P.A.S.,
thiacetazone,
and
cthio-
namidc.
In
order
to
improve
the
appetite
and
weight
gain
as
rapidly
as
possible
it
was
thought
that
medical
profession
should
have
a
drug
for
this
disease
with
least
side
-effects.
The
past
studies
by
other
authors
suggest
that
Cyproheptadine
fulfils
the
above
objective.
One
with
this
is
view,
our
study
was
carried
out
on
under
-weight
adult
patients
who
had
chronic
pulmonary
tuberculosis,
at
chest
unit,
Jinnah
Post
-Graduate
Medical
Centre,
Karachi,
Excluded
from
this
study
were
patients
in
whom
steroid,
anabolics
were
contraindicated,
e.g.
impaired
liver
function,
prostatic
carcinoma,
sodium
retention.
Also
excluded
were
pregnant
patients
and
those
who
were
suffering
from
glaucoma
or
gave
a
history
of
urinary
retention.
Material
&
Methods:
Double-blind
control
trial
was
conducted
on
27
patients.
Patients
were
given
drug
according
to
radom
allocation
numbers.
All
patients
were
admitted
in
the
ward
and
kept
for
12
to
16
weeks
excepting
three
patients
who
did
not
complete
their
trials
as
they
left
hospital
against
advice
and
later
did
not
turn
up
in
out
-patient
department
for
follow-up.
Another
patient
was
excluded
who
was
found
to
be
pregnant
4
weeks
after
her
inclusion.
Thus
study
included
23
patients
suffering
from
Pulmonary
tuberculosis.
During
their
indoor
stay
each
patient
got
convalescent
diet
which
consisted
of
about
3000
calories
per
day
on
the
average.
Each
patient
was
given
3
tablets
of
either
active
drug
or
placebo
i.e.
one
tablet
one
hour
before
each
meal
for
12
weeks
and
each
tablet
of
active
drug
contained
4
mgm
of
cyproheptadine.
Total
duration
of
Ex
-Associate
P.ysician
and
Associate
Professor
(Chest
Diescasis)
Jinnah
Post
Graduate
Medical
Centre,
Karachi
and
Institute
of
the
Dieses
of
Chest
and
Hospital,
Dacca.
270
study
was
16
weeks.
Each
case
was
diagnosed
on
the
basis
of
history,
physical
fi
ndings,
X-ray
chest,
mantou
:
text,
E.S.R.
and
sputum
examination.
All
patients
were
given
routine
anti
-tubercular
treat-
ment
which
consisted
of:-
Inj.
Streptomycin
1
G.
daily
Tabs.
PAS
10
G.
daily
Tab.
1NH
300
mg.
daily
Few
cases
who
gave
history
of
previous
hap-
hazard
chemotherapy
for
a
long
duration
and
were
of
clinically
resistant
type
given
thiacetazone
150
mgm
daily
in
place
of
PAS.
None
of
the
patients
were
confined
to
bed
rather
allowed
to
continue
their
normal
activities
in
the
ward.
At
the
start
of
the
study
patient's
height,
weight,
pulse,
respiration,
temperature,
built
and
nutrition,
were
noted.
Along
-
with
this
following
laboratory
investigations
were
carried
out;
haemoglobin
estimation,
RBC
and
WBC
count,
serum
albumin
estimation,
urine
for
sugar
and
albumen,
stools
for
ova
or
cysts.
In
subsequent
period
weekly
recordings
during
the
fi
rst
month,
forthnightly
during
the
second
and
third
month
and
finally
at
the
end
of
the
fourth
month
were
made.
All
investigations
of
initial
visit
were
repeated
at
above
noted
order.
Along
with
this
any
voluntered
untoward
effects
were
noted
down.
Out
of
23
patients
who
completed
the
trial
11
were
on
active
drug
while
12
are
on
placebo.
Age
and
Sex
Distribution
of
the
patients,
and
drug
allocation
with
sex
distribution
are
shown
in
Table
I
and
II
1.
15
-29
years
2.
30-44
years
3.
45
years/above
Periactin
Placebo
(
Total:
TABLE
I
Age
&
Sex
Distribution
12
patients
Male
5
Female
7
10
patients
Male
9
Female
1
1
patient
Male
1
(50
years)
TABLE
II
Drug
Allocation
with
sex
Distribution
Male
--
8
Male
--
7
Male
--
15
271
Female
3
Female
5
Female
8
=
23)
TABLE
III
Weight
gain
(in
pounds)
on
active
drug
No..
Age
(years)
Sex
Ini-
tial
(lbs.)
4
weeks
(lbs,)
8
12
weeks weeks
(lbs.)
(lbs.)
16
weeks
(lbs.)
Gain(+)
or
loss(—)
at
the
end
of
the
16
weeks
(lbs.)
1.
24
M
102
110
110
111
112
+
10
2.
24
F
75
80
92
96
98
+
25
3.
25
F
80
82 82
86 86
+
6
4.
25
F
69
73
80
84
85
+
16
5.
28
M
110
112
118
118
120
+
10
6.
30
M
76
78
79
78
78
+
2
7.
35
M
88
96
101
106
105
+
17
8.
38
M
75
75
76
76
76
+
1
9.
42
M
74
75
76
78
78
+
4
10.
42
M
97
104
110
110
112
+
15
11.
50
M
105
108
113
115
117
+
12
Total
weight
gain
116
mean
86.45
lbs.
97.00
lbs.
10.55
lbs.
TABLE
IV
Weight
Gain
(in
pounds)
on
Placebo
No.
Age
(years)
Sex
Ini-
tial
(lbs.)
4
weeks
(lbs.)
8
12
weeks
weeks
(lbs.)
(lbs.)
16
weeks
(lbs.)
Gain(+)
or
loss(--)
at
the
end
of
16
weeks
(lbs.)
1.
16
F
67
65
62
65
66
1
2.
19
F
100
102
105
105
104
+
4
3.
20
F
80
80
80
85
85
+
5
4.
22
M
74
79
86
86
86
+
12
5.
24
M
85
86
86
86
86
+
1
6.
25
F
79
76
75
75
76
+
3
7.
25
M
98
101
102
104
105
+
7
8.
30
M
85
89
92
95
95
+
10
9.
34
M
85
88
90
90
89
+
4
10.
40
F
68
70
71
70
71
+
3
11.
40
M
116
120
120
120
120
+
4
12.
43
M
107
110
110
111
112
+
5
Total
weight
gain
51
mean
87
lbs.
91.25
lbs.
4.25
lbs.
272
Results:
These
patients
with
active
drug
showed
a
mean
increase
of
weight
of
10.55
lbs
(Table
III).
While
those
on
placebo
showed
a
mean
increase
of
weight
of
4.25
lbs
(Table
IV)
after
12
weeks
of
treatment
and
follow-up
of
upto
16
weeks.
This
difference
is
significant.
It
is
interesting
to
note
that
the
mean
initial
weight
was
almost
equal
in
both
the
groups
i.e.
86.45
in
active
group
and
87
lbs.
in
placebo
group.
The
mean
dinal
weight
after
16
weeks
of
medication
shows
a
significant
difference
i.e.
97
lbs.
in
active
drug
group
and
91.25
lbs.
in
placebo
group.
This
means
that
the
active
drug
clearly
comes
out
to
be
superior
for
stimulating
appetite
and
producing
weight
gain
in
tuberculosis
patients.
Side
Effects:
The
main
side
effect
noted
was
slight
drow-
siness
in
seven
active
cases
of
whom
5
had
this
com-
plaint
almost
throughout
the
treatment
period.
On
the
other
hand
4
placebo
cases
had
slight
drow-
siness
initially
for
1-2
weeks.
An
interesting
feature
noted
was
that
of
unexplained
slight
restlessness
initially
for
1-2
weeks
in
2
active
and
placebo
cases.
Laboratory
results:
No
deviation
in
laboratory
reports
noted
either
in
active
cases
or
in
placebo
cases.
However,
response
to
chemotherapy
was
noted
by
diminished
E.S.R.
X-ray,
shadows
and
sputum
results.
Corntnents
and
discussion
All
the
23
cases
who
completed
the
trial
come
from
very
poor
socio-economic
community
and
all
of
them
had
chronic
pulmonary
tuberculosis
for
a
long
time
and'
received
standard
anti
-tubercular
chemotherapy
outside.
The
same
chemotherapy
was
continued,
for
16
cases
and
the
rest,
i.e.
seven
cases
likely
to
be
resistant
to
one
or
more
of
standard
chemotherapy
were
given
thiacetazone
in
place
of
PAS.
Hospitalization
of
these
patients
was
necessary
for
infectious
status
of
their
disease,
severe
clinical
manifastations
and
complications
like
haemoptysis.
All
the
patients
were
either
young,
adult
or
early
middle-aged.
Children
were
excluded
for
the
reason
that
in
a
clinical
trial
like
this
growth
and
develop-
mental
factors
may
influence
the
result
if
observation
is
continued
for
a
long
time.
It
has
been
observed
that
admitted
patients
with
effective
specific
chemotherapy,
gain
weight
very
rapidly
due
to
response
to
the
treatment
and
high
calorie
diet.
Those
patient
with
non-
effective
chemotherapy
i.e.
treatment
failure
cases
also
show
weight
gain
but
slowly
due
to
good
diet.
Adequate
rest
also
contribute
in
weight
gain
which
these
patients
rarely
get
when
treated
on
domiciliary
basis.
Lack
of
appetite
is
one
of
the
commonest
clinical
feature
of
active
pulmonary
tuberculosis.
When
these
patients
are
treated
with
PAS
or
thiacetazone
(which
is
invariably
given
with
INH
and
or
Streptomycin)
their
appetite,
is
further
depressed.
Gastric
intolerance
like
nausea,
lack
of
appetite,
gastralgia,
fullness
of
stomach,
vomiting
and
diarrohea
are
most
important
side
effects
of
PAS
and
thiacetazone,
and
lack
of
appetite
is
the
commonest
of
all.
It
is,
therefore,
desirable
to
find
a
drug
which
not
only
counteract
the
effect
of
the
disease
itself
but
also
prevents
the
depressing
effect
of
PAS
and
thiacetazone
medicaments.
Thus
the
drug
will
enhance
the
appetite
to
a
degree
with
when
they
will
eat
more
thereby
gain
weight
speedily
so
that
tubercular
patients
can
return;
to
their
job
quickly.
With
this
in
view,
the
clinical
trial
of
Cyphoheptadine
was
conducted.
The
Cyproheptadine
has
been
studied
by
many
authors
for
its
appetite
stimulating
and
growth
promoting
properties.
It
was
used
in
patients
of
different
ages,
suffering
from
chronic
diseases.
It
was
also
studied
in
otherwise
normal
person
with
poor
appetite
and
underweight.
One
of
the
frequently
quoted
observations
of
Lavanstein
et
al's
double-blind
trial
of
28
patients
conducted
in
Pediatric
Clinic
of
Johri
Hopkin
School
of
Medicine
showed
the
effect
of
Cyproheptadinc
on
weight
gain
and
liniar
growth
children
suffering
from
bronchial
asthma.
In
this
study
the
comparison
was
made
with
chlorpheniramine
for
about
6
months
and
a
significant
weight
gain
wiht
marked
improve-
ment
in
appetite
was
reported
in
patients
receiving
Cyproheptadine.
Another
investigation
was
carried
out
by
Chakr-
barty
et
al
to
sec
the
effect
of
Cyproheptadine
on
the
electrical
activity
of
the
hypothalmic
feeding
centre
and
medial
`Satisty
Centre'
in
cats.
Increase
hungar
behaviour,
increased
food
intake
and
weight
gain
was
reported
in
all
cats
and
occassional
pa-
roxysm
of
drowsiness
was
also
recorded
in
addition.
Noble
in
his
study
of
12
healthy
underweight
adult
out
-patients
for
56
days
observed
the
mean
273
weight
in
PERIACTIN
group
was
significantly
higher
statistically
than
corresponding
placebo
group.
Chowdhury
et
al
reported
the
benefit
of
PERIACTIN
for
promoting
weight
gain
in
double-
blind
trial
of
20
under
-weight
subjects
who
were
otherwise
normal.
Seven
out
of
ten
cases
active
drug
gained
weight
and
only
two
placebo.
The
study
period
in
this
series
was
rather
short
as
the
subjects
were
given
medicament
and
placebo
for
4
weeks
only.
However,
they
are
closely
observed
for
6-8
weeks
after
stoppage
of
therapy.
Shah
has
reported
another
clinical
double-
blind
trial
on
56
underweight
tubercular
patients
and
his
findings
of
weight
gain
and
improved
appetite
are
in
agreement
with
our
result.
It
will
be
seen
from
the
observations
that
the
findings
of
our
trial
is
in
agreement
with
the
above
noted
investigations
that
Cyproheptadine
is
a
useful
drug
in
stimulating
appetite
and
weight
gain.
The
patients
receiving
active
drug
showed
mean
weight
gain
of
10.55
lbs.
whereas
placebo
group
gained
4.25
obs.
The
differents
of
6.30
lbs.
in
16
weeks
of
Cyproheptadine
therapy
and
follow-up
is
highly
significant.
The
drug
is
particularly
found
useful
for
tuberculosis
patients
receiving
PAS
and
Thiace-
tazone-the
appetite
depressant
drug.
Cyprohep-
tadine
is
also
recommended
for
patients
suffering
from
other
diseases
having
lack
of
appetite
or
poor
weight
gain.
Above
studies
have
established
the
efficacy
of
this
drug
but
the
specific
mode
of
action
is
not
known,
further
study
is
needed
to
reveal
its
mode
of
action.
The
author
is
grateful
to
Messrs.
Sharp
&
Dohme
Ltd.
for
the
supply
of
drugs
and
research
grant
for
trial.
The
paper
was
presented
in
the
Sabah
Medical
Association
Clinical
meeting
in
Duch-
esma
of
Kent
Hospital,
Sandakan
in
August,
1974.
REFERENCES
1
Cakrabarty,
A.S.
et
al.
'Effect
of
Cyprohep-
tadine
on
the
Electrical
Activity
of
the
Hypo-
thalmic
Feeding
Centre.'
Brain
Research,
6:561-9
1967.
2.
Chowdhury,
A.Q.M.B.,
Jehangir,
`Cyprohep-
tadine-Vitamin
&
Weight
Gain'.
PJMR,
20-
22,
1970.
3.
Lavenstain,
A.F.
Decency,
E.P.,
Lasagua,
L.
and
Van
Metre,
T.E.
"Effect
of
Cyprohep-
tadine
on
Asthamatic
Children".
JAMA,
780:
912-16,
1962.
4.
Nobel,
R.E.
'Effect
of
Cyproheptadine
on
Appetite
&
Weight
Gain
in
Adults'.
JAMA,
209:205-55,
1969.
5.
Shah,
N.M.
'A
double-blind
study
of
Appetite
Stimulation
&
Weight
Gain
with
Cyprohep-
tadine
as
adjunct
to
Specific
Therapy
in
Pulmonary
Tuberculosis'.
Current
Medical
Practice,
12:861-4,
1970.
274