Sanguansak vol. 4 no. 6 page 977-982.pmd
Asian Biomedicine Vol. 4 No. 6 December 2010; 977-982
Brief communication (Original)
Effect of cyproheptadine on weight gain in malnourished
children: a randomized, controlled trial
Sanguansak Rerksuppaphola, Lakkana RerksuppapholbaDepartment of Pediatrics, bDepartment of Preventive Medicine, Faculty of Medicine, SrinakharinwirotUniversity, Nakhorn-Nayok 26120, Thailand
Cyproheptadine has been used therapeutically as an appetite stimulant in various chronic illnesses.
However, no clinical data are available on the therapeutic effect of cyproheptadine in malnourished children
without underlying pathological conditions.Objective:
Investigate the short-term effect of cyproheptadine on weight gain in malnourished children who
appear otherwise normal on physical examination.Methods:
Seventy malnourished children who were otherwise normal on physical examination were recruited to
participate in a randomized, double-blind, placebo-controlled trial. Thirty-seven children were randomized to a
treatment regimen of cyproheptadine (0.1 mg/kg/dose, three times/day for eight weeks), and 33 children were
randomized to receive placebo over a period of eight weeks. Subjects were evaluated at a baseline visit and at four
visits at two-week intervals. Parameters assessed included baseline demographics, anthropometrics (weight,
height, skin-fold thickness, waist and hip circumferences, and fat composition by bioelectric impedance analysis),
adverse events, and pill counts. Data were analyzed by Student’s t-test and Chi-square test; a p- value < 0.05 was
No significant differences were observed in baseline demographic characteristics and anthropometric
parameters between the groups. The cyproheptadine-treated group showed a significantly greater weight gain
over the baseline compared with the control group. The absolute weight gain was significantly higher in the
cyproheptadine-treated group than in the control group at the end of study. No significant difference was observed
in the change in the body fat percentage between the groups. No serious adverse events were reported. Adverse
events included mild sedation, nausea, diarrhea, abdominal pain, and headache. No significant differences in the
frequency of adverse events were observed between the groups.Conclusions:
Cyproheptadine treatment was well tolerated and resulted in significant weight gain in malnourished
children, without increasing the body fat percentage.
Child, cyproheptadine, malnutrition, randomized controlled trial, weight gain
of chronic illnesses such as cystic fibrosis ,
antiserotonergic agent. It has been approved by the
malignancies [3-6], anorexia nervosa , AIDS ,
Thai Food and Drug Administration for the treatment
and renal failure . However, cyproheptadine has
of allergic conditions . A favorable side effect of
not been used clinically in malnourished children who
cyproheptadine is its appetite-stimulating action, which
are otherwise normal. Poor appetite leading to poor
has been exploited therapeutically in the treatment
weight gain is a characteristic finding amongunderweight children without underlying pathologicalconditions.
In this study, we investigated the role of
Sanguansak Rerksuppaphol, MD,
cyproheptadine as an appetite stimulant by using
Faculty of Medicine, Srinakharinwirot University, 62 M7Rangsit-Onkhaluck Rd. Onkhaluck, Nakhorn-Nayok 26120,
weight gain as the end-point and determined its
Thailand . E-mail: firstname.lastname@example.org
efficacy and tolerability in malnourished children.
S. Rerksuppaphol, L. Rerksuppaphol
Materials and methods
and compliance with treatment were monitored at each
The effect of cyproheptadine on weight gain in
visit based on parent reports and pill counts,
malnourished children was studied in a randomized,
double-blind, placebo-controlled trial conducted by the
Weight, skin-fold thickness, MUAC, waist and hip
Pediatric Nutrition Clinic, Srinakharinwirot University
circumferences, and body fat composition were
Hospital, between June and December 2008. Seventy
children (age: 6-15 years), who had recently beendiagnosed as underweight and who appeared normal
on physical examination, were recruited for the study.
The results were presented as mean, standard
A body weight of less than 90% of the predicted body
deviation (SD), and percent values. Pearson chi-square
weight for a given age and gender was defined as
was used to compare proportions between the two
underweight for purposes of this study. Children with
groups. Student’s t-test was used to compare the two
chronic illnesses, congenital abnormalities, or allergy
groups at the baseline visit and at each follow-up visit
to antihistaminic agents were excluded from the study.
thereafter. The paired t-test was used within each
The study protocol was approved by the Ethics
group to compare various parameters at each visit with
Committee of Faculty of Medicine, Srinakharinwirot
the values at the baseline visit. A p-value <0.05 was
University. Written informed consent was obtained
considered statistically significant. All analyses were
from the parents or legal guardians of all study
carried out using the SPSS 11.0 software package.
using a computer program: 37 children received
Seventy underweight children (mean age: 11.3
cyproheptadine (0.1 mg/kg/dose, three times/day)
years) completed the study. The study group comprised
and 33 children received a placebo over a period of
61.4% boys. The average baseline weight, height,
eight weeks. Demographic profiles and baseline
BMI, and body fat composition of the cyproheptadine-
anthropometric data, including weight, height, skin-fold
treated group (25.5 kg, 132.2 cm, 14.8 kg/m2, and 9.6%,
thickness, mid-upper arm circumference (MUAC),
respectively) were similar to those of the control
waist and hip circumferences, and fat composition
group (25.3 kg, 129.5 cm, 14.8 kg/m2, and 9.6%,
(measured by bioelectric impedance analysis), were
respectively). The baseline demographic and
obtained. Measurements of weight, height, and
anthropometric data of the children in both groups are
MUAC were done in accordance with the WHO
shown in Table 1
. The mean body weights of the
Expert Committee guidelines . Weight was
cyproheptadine-treated group and the control group
measured to the nearest 100 g, and height, to the
were 25.8 and 25.7 kg at two weeks, 26.0 and 25.4 kg
nearest millimeter. Body mass index (BMI) was
at four weeks, 25.9 and 25.9 kg at six weeks, and
calculated as weight/(height)2 [kg/m2]. MUAC
26.8 and 25.9 kg at eight weeks, respectively.
was measured midway between the tip of the left
Significant weight gain occurred in both groups as early
shoulder blade and the tip of the elbow, with a normal
as week 2 of treatment (p <0.05) compared with the
non-stretch tape to the nearest 0.1 cm. Waist and hip
baseline body weight. Children in the cyproheptadine-
circumferences were measured in the upright position
treated group showed a greater increase in weight
at the narrowest girth in the waist area and at the
over the baseline weight at every follow-up visit than
level of the greatest posterior protuberance of the
the children in the control group (Table 1
buttocks, respectively. Triceps skin fold (TSF), biceps
The change in body fat from the baseline visit until
skin fold (BSF), sub-scapular skin fold (SSSF), and
the end of the study did not significantly differ between
supra-iliac skin fold (SISF) were measured on the left
the two groups (cyproheptadine 1.01% vs.
side, using a Lange skin-fold caliper. The children
0.31%; p = 0.54). The change in skin fold thickness,
returned for four follow-up visits at two-week
and hip and waist circumferences from the baseline
intervals and were weighed by a registered nurse
visit until the end of the study also did not significantly
at each visit on the same scales. Adverse events
differ between the two groups (Table 2
Vol. 4 No. 6
Cyproheptadine therapy in malnourished children
Comparison of baseline parameters. Data are represented in mean (SD).
BMI=body mass index, TSF=triceps skin fold, BSF=biceps skin fold, SSSF=sub-scapular skin fold,SISF=supra-iliac skin fold, MUAC=mid-upper arm circumference.
Anthropometric parameters on follow-up visits. Data are represented in mean (SD).
TSF=triceps skin fold, BSF=biceps skin fold, SSSF=sub-scapular skin fold, SISF=supra-iliac skin fold,MUAC=mid-upper arm circumference.
differences were present between the two groups for
No severe adverse events resulted in treatment
withdrawal in either of the groups. The adverse eventsrecorded in the cyproheptadine-treated group were
mild sedation (24.3%), nausea (5.4%), abdominal pain
Treatment compliance was calculated as the
(5.4%), diarrhea (5.4%), and headache (2.7%),
percentage of total intake doses from the total eligible
whereas in the control group, mild sedation (12.1%),
dose and was high in both groups (82.3% in the
nausea (3.0%), abdominal pain (6.1%), and headache
cyproheptadine-treated group and 81.8% in the control
(3.0%) were reported. No statistically significant
S. Rerksuppaphol, L. Rerksuppaphol
fat percentage or other anthropometric indices
The present results show that cyproheptadine at
indicating fat mass. This was an indirect indication
a daily dose of 0.3 mg/kg resulted in weight gain
that cyproheptadine treatment resulted in weight gain
among underweight children who were otherwise
without changing the body fat composition. Height
normal on physical examination. This effect was
velocity was not measured in this study because of
sustained from the second week of treatment through
the relatively short follow-up period.
the end of study. Children in the cyproheptadine-
The mechanisms underlying cyproheptadine-
treated group exhibited significantly higher weight gain
mediated weight gain are not well understood. Two
than that exhibited by the children in the control group,
hypotheses have been postulated to explain this
with no significant differences in body fat indices
phenomenon. The first hypothesis is based on the
effect of cyproheptadine on the hypothalamic
The clinical significance of cyproheptadine
“feeding” center via its antihistamine and antiserotonin
administration to malnourished children has not been
action[17-19]. Cyproheptadine was reported to
extensively studied . Studies have documented the
stimulate appetite and caloric intake in animal [17, 20,
role of cyproheptadine therapy in promoting weight
21] and human subjects [22-24]. The unreliability of
gain in children with chronic pathological conditions
recording food intake in children made it difficult to
[2, 12, 13]. However, not much is known about the
directly measure this appetite-stimulating effect .
efficacy of cyproheptadine in malnourished children
However, most subjects reported an increased appetite
without underlying pathological conditions. Our results
at the end of the study when compared with the
agree with the study by Mahachoklertwattana et al.
beginning of the study. The second hypothesis is based
. They reported that cyproheptadine therapy
on the effect of cyproheptadine on the growth hormone
resulted in an absolute weight gain of 0.66 kg in
and insulin-like growth factor (GH-IGF) system.
underweight children aged 2-10 years (n = 11) within
Cyproheptadine therapy has been reported to
two months, and the weight gain velocity effected by
increase the serum levels of insulin-like growth factor-
cyproheptadine therapy in undernourished children
I (IGF-I) in addition to enhancing growth velocity in
declines proportionately with time of treatment. In our
underweight children . IGF-1, a GH-mediated
study, we obtained a relatively early therapeutic
growth factor, is now recognized as a potent mitogenic
response, starting in the second week of treatment.
agent  and is one of the best indicators of growth
We used a higher dose of cyproheptadine (0.3 mg/kg
hormone levels [27, 28]. Even though most
daily) than that (0.1 mg/kg daily) used in a previous
of our subjects reported an increased appetite,
study . Our findings suggest that the greater
an investigation of the exact mechanism of
weight gain in our study is due to the dose-dependent
cyproheptadine action is beyond the scope of this
effect of cyproheptadine on weight gain.
Body composition is roughly divided into two
Compliance with cyproheptadine therapy in
compartments, body fat and fat-free mass. Although
our study was 82%, and the therapy was generally
studies have investigated the overall weight gain
well tolerated. All adverse events reported on
achieved by cyproheptadine therapy, no information
cyproheptadine therapy were consistent with the
is available on post-treatment body composition.
labeling on the package insert. Moreover, the drug
Disproportionate weight gain in fat and fat-free mass
related adverse events were mild and did not lead to
could result in altered body composition and adiposity.
discontinuation of the drug. The most commonly
Skin-folds, bioelectrical impedance analysis, and
reported adverse event was mild sedation, a finding
anthropometric studies are reliable and widely used
that is consistent with that of an earlier study .
in field and clinical settings to assess body composition
In conclusion, we achieved significant weight gain
[14,15]. Comparing baseline anthropometric indices
without increase in body fat percentage among
to indicate body fat mass of the malnourished children
malnourished children on an 8-week regimen of
in our study, we found that these indices were lower
cyproheptadine. Cyproheptadine was well tolerated.
than reference standards of Asian children [15,16].
It is a good candidate for routine management of
At the end of the study, we observed a significantly
childhood malnutrition after larger sample sizes have
higher weight gain in the treatment group than in the
control group, without significant difference in body
Vol. 4 No. 6
Cyproheptadine therapy in malnourished children
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