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 Background: 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
considered significant.
Results: 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.
Keywords: Child, cyproheptadine, malnutrition, randomized controlled trial, weight gain
of chronic illnesses such as cystic fibrosis [2], antiserotonergic agent. It has been approved by the malignancies [3-6], anorexia nervosa [7], AIDS [8], Thai Food and Drug Administration for the treatment and renal failure [9]. However, cyproheptadine has of allergic conditions [1]. 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 Correspondence to: 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: [email protected] 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 Statistical analysis
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 [10]. 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. control 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
December 2010
Table 1. Comparison of baseline parameters. Data are represented in mean (SD).
Cyproheptadine
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.
Table 2. Anthropometric parameters on follow-up visits. Data are represented in mean (SD).
Cyproheptadine
TSF=triceps skin fold, BSF=biceps skin fold, SSSF=sub-scapular skin fold, SISF=supra-iliac skin fold,MUAC=mid-upper arm circumference.
Adverse events
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 Treatment compliance
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
Discussion
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 [11]. 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 [25].
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 [11]. 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 [11]. 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 [26] 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 [11]. 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 [11].
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
December 2010
Acknowledgments
therapy. J Pediatr. 1987; 110:140-3.
We thank Mr. Adisorn Saengzue and Mrs.
13. Couluris M, Mayer JL, Freyer DR, Sandler E, Xu P, Kulvadee Robloo for their assistance in the study. The Krischer JP. The effect of cyproheptadine present study was supported by grants from Faculty hydrochloride (periactin) and megestrol acetate of Medicine, Srinakharinwirot University. We have (megace) on weight in children with cancer/treatment- related cachexia. J Pediatr Hematol Oncol. 2008; 30:791-7.
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