A taste alteration-related scale assesses megestrol to improve chemotherapy-induced anorexia.

PURPOSE: We evaluated the efficacy of megestrol in improving chemotherapy-related anorexia by analyzing the related scales of taste alteration. METHODS: We conducted the current study on a group of advanced patients with cancer with two or more chemotherapy cycles. The chemotherapy-induced taste alteration scale (CiTAs) scale helped assess the megestrol effects on basic taste perception, aversive taste changes, unpleasant symptoms, and associated concerns. Furthermore, the Short Nutritional Assessment Questionnaire scale (SNAQ) helped measure the impact of megestrol on malnutrition likelihood in patients experiencing chemotherapy-induced anorexia. The World Health Organization Quality of Life (WHOQOL)-BREF Scale was used to evaluate the quality of life of participants, producing scores related to physical health, psychological well-being, environmental factors, and social relationships. RESULTS: The CiTAs scale assessment indicated that administering megestrol significantly enhanced taste perception among advanced patients with cancer undergoing chemotherapy. Notably, the megestrol group patients showed significantly higher Short Nutritional Assessment Questionnaire (SNAQ) scores than the control group. The megestrol group patients also exhibited higher physiological (PHYS) scores than their control group counterparts. However, this distinction was not statistically significant. The study findings indicate that patients who received megestrol demonstrated significantly higher scores in psychological (PSYCH) and environmental(ENVIR) domains than the control group. Furthermore, megestrol administration was associated with significantly elevated SOCIL and ENVIR levels in patients. CONCLUSION: The proficient efficacy evaluation of megestrol in enhancing appetite, mitigating malnutrition likelihood, and improving the quality of life of chemotherapy-induced anorexic patients can be achieved through taste-related scales.

Propensity score-matching analysis comparing safety outcomes of appetite-stimulating medications in oncology patients.

PURPOSE: Anorexia and weight loss are common complications in the elderly, advanced cancer population. Appetite stimulants are commonly used therapies for oncology patients with weight loss, yet their safety comparison remains unknown. METHODS: This was a two-center, retrospective, study conducted in New York City at Mount Sinai Beth Israel and New York University Langone from January 2016 to July 2019 in adult patients with histologic evidence of malignancy who were taking either megestrol acetate or mirtazapine as an appetite-stimulating medication. Endpoints included safety concerns of mortality, QTc prolongation, venous thromboembolism, fall, somnolence, xerostomia, and hallucinations. Effectiveness of weight gain or maintenance of weight was not assessed. A propensity score-matching analysis was performed using a logistic regression analysis to assess the two comparable groups. RESULTS: The study included 350 patients (69.56 ± 13.31 years) with the most common malignancies being gastrointestinal, breast, and hematologic with metastasis present in over half the patients. Adverse events were commonly seen in the oncology population. After a propensity score-matched analysis, all safety outcomes associated with mirtazapine compared to megestrol acetate were similar; all-cause mortality (7%, n = 7 vs. 12%, n = 12, p = 0.23), QTc prolongation (31%, n = 31 vs. 31%, n = 31, p = 1.00), thromboembolism (11%, n = 11 vs. 11%, n = 11, p = 1.00), somnolence (29%, n = 30 vs. 22%, n = 23, p = 0.34), xerostomia (27%, n = 28 vs. 18%, n = 19, p = 0.24), and hallucinations (17%, n = 18 vs. 8%, n = 8, p = 0.06), respectfully. CONCLUSION: There were no safety differences seen when evaluating both agents.

Megestrol Acetate Induces Declarative Memory Changes and Cortisol Suppression in Healthy Volunteers.

BACKGROUND: The effects of the glucocorticoid and progesterone receptor agonist megestrol on declarative memory, and the ability of phenytoin to block these effects, were assessed. METHODS: Healthy volunteers received each medication combination (placebo and megestrol, phenytoin and megestrol, and placebo and placebo) using a randomized, crossover design. The Rey Auditory Verbal Learning Test assessed declarative memory. RESULTS: Megestrol was associated with a significant reduction in declarative memory (p = 0.0008), which was attenuated by phenytoin, and was associated with significant cortisol suppression compared to placebo (p < 0.001). CONCLUSION: Changes in memory and cortisol suppression were found in healthy volunteers given megestrol.

Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials.

BACKGROUND: Cancer anorexia-cachexia syndrome is associated with increased morbidity and mortality. Anamorelin is an oral ghrelin-receptor agonist with appetite-enhancing and anabolic activity. We assessed the effects of anamorelin on body composition, strength, quality of life, biochemical markers, and safety in patients with cancer anorexia-cachexia. METHODS: Data were pooled, a priori, from two completed phase 2, multicentre, placebo-controlled, double-blind trials in patients with advanced or incurable cancer and weight loss of 5% or more. Patients were stratified by weight loss severity (5-15%, >15%) and randomly allocated (1:1) with a computer-generated randomisation schedule to anamorelin hydrochloride 50 mg or placebo once-daily for 12 weeks. Primary outcome was lean body mass by dual-energy x-ray absorptiometry over the 12 week treatment period in eligible patients who had at least one dose of study drug and post-treatment efficacy assessment. We assessed safety in all patients who received at least one dose of study drug. The trials are registered with ClinicalTrials.gov, numbers NCT00219817 and NCT00267358. FINDINGS: Between June 29, 2005, and Oct 26, 2006, we enrolled 44 patients in the anamorelin group and 38 patients in the placebo group. 74 patients were eligible for the efficacy analyses. Over 12 weeks, lean body mass increased in 38 patients in the anamorelin group by a least-squares mean of 1.89 kg (95% CI 0.84 to 2.95) compared with a decrease of a least-squares mean of -0.20 kg (-1.23 to 0.83) for 36 patients in the placebo group (difference 2.09 kg [0.94-3.25]; p=0.0006). 42 (95%) of 44 patients treated with anamorelin and 33 (87%) of 38 patients treated with placebo had adverse events. The most common grade 3-4 adverse events (treatment-related or not) in the anamorelin group were fatigue, asthenia, atrial fibrillation, and dyspnoea (two [5%] each); in the placebo group, such events were pneumonia (three [8%]) and anaemia, thrombocytopenia, abdominal pain, anxiety, and dyspnoea (two [5%] each). INTERPRETATION: Anamorelin treatment for 12 weeks had a favourable clinical response profile in patients with cancer anorexia-cachexia syndrome. These findings support further investigation in this setting. FUNDING: Helsinn Therapeutics (US), Helsinn Healthcare SA.

Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy.

PURPOSE: The aim of this study was to test the safety, tolerability and efficacy of a novel combination of an anabolic ß2-agonist and an appetite stimulant in patients with cancer cachexia. METHODS: Thirteen patients (M/F 5:8) with advanced malignancy and involuntary weight loss received oral formoterol (80 µg/day) and megestrol acetate (480 mg/day) for up to 8 weeks. Quadriceps size (MRI), quadriceps and hand-grip strength, lower limb extensor power, physical activity and quality of life were measured at baseline and at 8 weeks. Response criteria were specified pre-trial, with a major response defined as an increase in muscle size ≥ 4 % or function ≥ 10 %. RESULTS: Six patients withdrew before 8 weeks, reflecting the frail, comorbid population. In contrast, six out of seven (86 %) patients completing the course achieved a major response for muscle size and/or function. In the six responders, mean quadriceps volume increased significantly (left 0.99 vs. 1.05 L, p=0.012; right 1.02 vs. 1.06 L, p=0.004). There was a trend towards an increase in quadriceps and handgrip strength (p>0.05). The lack of appetite symptom score declined markedly (76.2 vs. 23.8; p=0.005), indicating improvement. Adverse reactions were few, the commonest being tremor (eight reports), peripheral oedema (three), tachycardia (two) and dyspepsia (two). CONCLUSIONS: In this frail cohort with advanced cancer cachexia, an 8-week course of megestrol and formoterol in combination was safe and well tolerated. Muscle mass and/or function were improved to a clinically significant extent in most patients completing the course. This combination regimen warrants further investigation in larger, randomized trials.

Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study.

PURPOSE: Cachexia in cancer adversely affects patients' perception of symptoms, well-being, and response to therapy, and shortens survival. Anamorelin, an oral mimetic of ghrelin, has been shown to increase body weight and anabolic hormone levels in healthy volunteers and is being investigated to treat cancer cachexia. METHODS: This multicenter, double-blind, placebo-controlled, crossover study evaluated the effects of anamorelin in 16 patients with different cancers and cachexia. Patients were randomly assigned to anamorelin 50 mg/day or placebo for 3 days. A 3- to 7-day washout period followed and then treatments were switched. Assessments included body weight, appetite, food intake, growth hormone (GH) levels, patient-reported symptom assessments (e.g., the Anderson Symptom Assessment Scale [ASAS] and also an inclusion criterion), and safety. RESULTS: Anamorelin significantly increased body weight compared with placebo (0.77 kg vs. -0.33 kg). Food intake increased compared with placebo, but not significantly. GH significantly increased at all time points (0.5-4 h postdose). Insulin-like growth factor-1 (IGF-1) significantly increased by 54.09 ng/mL with anamorelin treatment compared with -3.56 ng/mL for placebo; significant changes in insulin-like growth factor-binding protein 3 (IGFBP-3) were 0.75 µg/mL vs. -0.19 µg/mL, respectively. Patient-reported symptoms, including appetite as measured by ASAS, significantly improved with anamorelin (8.1 vs. 1.0 for placebo). Adverse events (AEs) in four patients were possibly or probably related to anamorelin: hyperglycemia (two patients), nausea (one patient), and dizziness (one patient). Most AEs were mild; no patients withdrew due to AEs. CONCLUSIONS: Anamorelin showed significant metabolic, clinical, and patient-rated effects in cancer cachexia. Further studies are warranted.

Megestrol acetate for treatment of anorexia-cachexia syndrome.

BACKGROUND: This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation. OBJECTIVES: To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies. SEARCH METHODS: We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012. SELECTION CRITERIA: Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology. DATA COLLECTION AND ANALYSIS: Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables. MAIN RESULTS: We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied. AUTHORS' CONCLUSIONS: This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.

Reports of the death of CB1 antagonists have been greatly exaggerated: recent preclinical findings predict improved safety in the treatment of obesity.

CB1 antagonists, including rimonabant (SR 141716A), hold considerable therapeutic potential in the reduction of appetite and lipogenesis and in improving the metabolic profile of obese individuals and those with diabetes. However, rimonabant has not been approved in the USA because of its numerous side-effects, including depression and anxiety. Because of this, it is expected that fewer attempts will be made to introduce CB1 antagonists into the market. However, a 'second generation' of compounds has produced promising results in animal models in terms of these side-effects, and may pave the way toward new development and clinical testing of compounds that lack the side-effects of rimonabant. This new generation includes neutral CB1 antagonists, which likely have less intrinsic activity than clinically tested drugs, and peripherally restricted compounds. The current paper reviews the behavioral profile of rimonabant and related compounds, including a similarity in hypophagic effects with putative neutral antagonists and peripherally restricted antagonists. Emerging evidence of a lack of effects in models of nausea, anxiety, and depression is discussed. It is concluded that, with increasing emphasis on modeling the more troublesome side-effects of CB1 antagonists, safe, efficacious therapeutic targets may emerge. Further rigorous preclinical testing should be carried out.

Clinical studies on the treatment of cancer cachexia with megestrol acetate plus thalidomide.

BACKGROUND: The management of cancer-related anorexia/cachexia syndrome (CACS) is a great challenge in clinical practice. To date, practice guidelines for the prevention and treatment of CACS are lacking. The authors conducted a randomized study to confirm the effectiveness and safety of treatment of CACS utilizing megestrol acetate (MA) plus thalidomide. METHODS: One hundred and two candidates with CACS were randomly assigned to two treatment groups (trial group and control group): the trial group received MA (160 mg po, bid) plus thalidomide (50 mg po, bid), while the control group received MA (160 mg po, bid) alone. Treatment duration was 8 weeks. RESULTS: Analysis of the trial group demonstrated a significant increase from baseline in body weight (<0.01), quality of life (p = 0.02), appetite (p = 0.01), and grip strength (p = 0.01), and a significant decrease in fatigue, Glasgow Prognostic Score (p = 0.05), Eastern Cooperative Oncology Group performance status (p = 0.03), IL-6 (p < 0.01), and tumor necrosis factor-α (p = 0.02). In contrast, in the control group, endpoints with a significant improvement from baseline included body weight (p < 0.02) and appetite (p = 0.02). The mean changes in the endpoints from baseline in the trial group were significantly greater compared with the control group: in the primary endpoints, body weight (p = 0.05), fatigue (p < 0.01) and quality of life (p = 0.01), and in the secondary endpoints, grip strength (p = 0.05), Glasgow Prognostic Score (p = 0.02), Eastern Cooperative Oncology Group performance status (p = 0.02), IL-6 (p < 0.01) and tumor necrosis factor-α (p = 0.01). Toxicity was found to be relatively negligible in both groups. CONCLUSION: A combination regimen of MA and thalidomide is more effective than MA alone in the treatment of CACS.

The effect of 6 days of sodium phosphate supplementation on appetite, energy intake, and aerobic capacity in trained men and women.

Ingestion of an acute dose of phosphate has been shown to attenuate energy intake in the subsequent meal. This raises the question of whether the practice of phosphate supplementation over a number of days by athletes to enhance performance also influences energy intake. This study investigated the effect of 6 d of phosphate supplementation on appetite and energy intake, as well as aerobic capacity, in trained individuals. Twenty participants completed two 6-d phases of supplementation with either sodium phosphate (50 mg/kg of fat-free mass per day) or a placebo in a double-blinded, counterbalanced design. On Days 1, 2, and 6 of supplementation, a laboratory meal was provided to assess appetite and ad libitum energy intake. All other food and drink consumed during each supplementation phase were recorded in a food diary. After the 6 d of supplementation, peak aerobic capacity (VO(2peak)) was assessed. There was no difference in energy intake at the laboratory meal after an acute dose (i.e., on Day 1; placebo 2,471 ± 919 kJ, phosphate 2,353 ± 987 kJ; p = .385) or prolonged supplementation with sodium phosphate (p = .581) compared with placebo. Likewise, there was no difference in VO(2peak) with phosphate supplementation (placebo 52.6 ± 5.2 ml · kg(-1) · min(-1), phosphate 53.3 ± 6.1 ml · kg(-1) · min(-1); p = .483). In summary, 6 d of sodium phosphate supplementation does not appear to influence energy intake. Therefore, athletes supplementing with sodium phosphate can do so without hindering their nutritional status. However, given that phosphate supplementation failed to improve aerobic capacity, the ergogenic benefit of this supplement remains questionable.

Decompensated septic shock in the setting of megace-induced severe adrenal suppression in an otherwise healthy pediatric patient: a case report.

A previously healthy 4-year-old boy presented to the emergency department at the Children's Hospital of Alabama with pneumonia caused by Pneumococcus infection and rapid progression to circulatory collapse. He was described as previously healthy except for being a "picky eater" and has been taking Megace (megestrol acetate) as an appetite stimulant for the past 2 years. We believe that the severity of his presentation was due in part to severe adrenal suppression from long-term Megace use. We were able to successfully resuscitate him with the addition of stress dose hydrocortisone, and he went on to have a complete recovery without any permanent disability. Previous literature has reported the adverse effect of Megace in suppressing adrenal function in patients with cancer and acquired immunodeficiency syndrome. This is the first report of this adverse effect in an otherwise healthy child. As the use of Megace becomes more widespread as an appetite stimulant in children, we hope to raise awareness of this important, potentially life-threatening adverse effect among physicians.

Efficacy and Tolerability of Cyproheptadine in Poor Appetite: A Multicenter, Randomized, Double-blind, Placebo-controlled Study.

PURPOSE: Cyproheptadine, an antihistamine and antiserotonergic agent, is an appetite stimulant that is efficacious in promoting weight gain in children and adults with poor appetite. Despite numerous studies showing that cyproheptadine achieved positive outcomes, studies documenting its effectiveness on appetite are limited. This study evaluated the efficacy and tolerability of cyproheptadine in adults with poor appetite in South Korea. METHODS: Patients aged 19 to 64 years with poor appetite were randomly assigned to receive either cyproheptadine or placebo for 8 weeks. The primary end point was the difference between the groups in change in appetite, as measured by the Korean version of the Edmonton Symptom Assessment System from the beginning to the end of the study period. The secondary end points included effects on weight, anthropometrics, body composition, Simplified Nutritional Appetite Questionnaire-measured appetite, and toxicities. A total of 375 patients were randomly assigned to the two groups (189 cyproheptadine, 186 placebo). FINDINGS: The cyproheptadine group experienced a mean (SD) change in appetite score of -2.42 (0.12) compared with -2.03 (0.13) in the placebo arm, representing a statistically significant appetite gain in the cyproheptadine group (difference, +0.38 [0.18]; 95% CI, -0.73 to -0.04; P = 0.0307). Patients in the cyproheptadine group experienced significant increases in weight and body mass index. The most common adverse event was somnolence, as predicted. Cyproheptadine was well tolerated, with one serious adverse event (colitis) which was classified as a moderate adverse effect unlikely to be related to the study drug. IMPLICATIONS: We present the largest randomized, double-blind, placebo-controlled clinical trial of cyproheptadine versus placebo in healthy adults with poor appetite using the lowest effective dosage of cyproheptadine. Cyproheptadine is a safe treatment option in patients with poor appetite. Our findings provide important information for the use of cyproheptadine to ameliorate poor appetite in adults. Further randomized studies focused on the effect of cyproheptadine in older populations are needed.

Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia.

PURPOSE: A phase III, randomized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass (LBM), resting energy expenditure (REE), and fatigue-and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines. PATIENTS AND METHODS: Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were randomly assigned to one of five treatment arms: arm 1, medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4, thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment duration was 4 months. RESULTS: Analysis of variance showed a significant difference between treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms. CONCLUSION: The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents.

[Treatment of uraemic anorexia with megestrol acetate]. / Tratamiento de la anorexia urémica con acetato de megestrol.

BACKGROUND: Anorexia is a common disorder in patients treated with regular haemodialysis and is a contributing factor to malnutrition. The aim of this study was to evaluate the effectiveness of megestrol acetate, an appetite stimulant used in cancer patients, as a treatment for anorexia in dialysis patients. MATERIAL AND METHOD: In 2009, 16 patients in our haemodialysis unit, three with diabetes mellitus, were treated with megestrol (160 mg/day single dose) for anorexia defined according to a Likert scale of appetite. The schedule and dialysis dose were not changed during the study. RESULTS: In the third month of treatment there was, in the overall group, an increase in dry weight (60.8 vs 58.9 kg, P<.01), in albumin concentration (4.02 vs 3.8 g/dl, P<.05), in creatinine concentration (9.73 vs 8.26 mg/dl, P<.01), and protein catabolic rate (1.24 vs. 0.97 g/kg/day, P<.0001). Non-significant variations in the concentration of haemoglobin, erythropoietin dose, and lipid concentrations were found. One patient with diabetes mellitus had to increase the dose of insulin and two other patients suffered mild hyperglycaemia. Megestrol acetate did not suppress the secretion of pituitary sex hormones, but in 3 of 10 patients studied was found inhibition of ACTH secretion. The response was not homogeneous: one patient did not respond and reduced his dry weight, in 5 the weight gain was minimal (less than 1 kg) and in the remaining ten the response was good, with an increase in dry weight ranging between 1.5 and 5.5 kg. CONCLUSIONS: Megestrol acetate can improve appetite and nutritional parameters in patients treated with periodic haemodialysis who report anorexia. Megestrol acetate may induce hyperglycaemia and inhibit the secretion of ACTH in some patients. These side effects should be assessed when administering this treatment.

Randomised placebo-controlled cross-over study examining the role of anamorelin in mesothelioma (The ANTHEM study): rationale and protocol.

INTRODUCTION: Cachexia is common in malignant mesothelioma (MM); half of patients have malnutrition and low skeletal muscle mass. Malnourished patients have worse quality of life (QoL). Weight loss is strongly associated with poor survival. Anamorelin is an oral ghrelin receptor agonist that improves appetite, body weight and QoL in advanced cancer. The aim of this study is to examine the efficacy of anamorelin in improving appendicular skeletal muscle mass (ASM) and patient-reported outcomes in patients with MM with cachexia. METHODS AND ANALYSIS: A single-centre, phase II, randomised, placebo-controlled cross-over pilot study with 28-day treatment periods and 3-day washout. Forty patients will be randomised. Primary outcome is change in ASM relative to height measured by dual energy X-ray absorptiometry at end of period 1. Secondary outcomes include cancer-specific and cachexia-related QoL, objective physical activity, dietary intake and adverse events. Eligible patients will have confirmed MM, Eastern Cooperative Oncology Group 0-2, expected survival >3 months and cachexia (defined as >5% weight loss in 6 months or body mass index <20 kg/m2 with weight loss >2%). ETHICS AND DISSEMINATION: Ethical approval has been granted. Results will be reported in peer-reviewed publications. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (U1111-1240-6828).

Ghrelin increases hunger and food intake in patients with restricting-type anorexia nervosa: a pilot study.

Ghrelin increases hunger sensation and food intake in various patients with appetite loss. Anorexia nervosa (AN) begins with psychological stress-induced anorexia and some patients cannot increase their food intake partly because of malnutrition-induced gastrointestinal dysfunction. The effects of ghrelin on appetite, food intake and nutritional parameters in anorexia nervosa (AN) patients were examined. Five female restricting- type AN patients (age: 14-35 y; body mass index: 10.2-14.6 kg/m(2)) had persistently complained of gastrointestinal symptoms and failed to increase body weight. They were hospitalized for 26 days (6 days' pretreatment, 14 days' ghrelin-treatment, and 6 days' post-treatment) and received an intravenous infusion of 3 microg/kg ghrelin twice a day. Ghrelin infusion improved epigastric discomfort or constipation in 4 patients, whose hunger scores evaluated by visual analogue scale questionnaires also increased significantly after ghrelin infusion. Daily energy intake during ghrelin infusion increased by 12-36 % compared with the pre-treatment period. Serum levels of total protein and triglyceride as nutritional parameters significantly increased after ghrelin treatment. There were no serious adverse effects including psychological symptoms. We found that ghrelin decreases gastrointestinal symptoms and increases hunger sensation and daily energy intake without serious adverse events in AN patients. Although the present study had major limitations of the lack of a randomized, placebo-controlled group, non-blindness of the investigators and the small number of patients recruited, it would contribute to further investigations for therapeutic potential of ghrelin in AN patients.

Usage of megestrol acetate in the treatment of anorexia-cachexia syndrome in the elderly.

UNLABELLED: The aim of this review is to assess the efficacy and safety of megestrol acetate (MA) in geriatric cachexia. The paper presented here reviews a previously published study of MA use in 69 patients in a randomized double blind placebo-controlled trial. This paper will also address the underlying pathogenesis of cachexia (specifically, the role of cytokines) along with the use of MA, its mechanism of action and its side effects. OBJECTIVE: To compare the effects of MA oral suspension (O.S.), 800 mg/day, versus placebo on weight in geriatric nursing home patients with weight loss or low body weight. DESIGN: Twelve weeks, randomized, double-blind, placebo-controlled trial with a 13-week follow-up period. PATIENTS: Northport VAMC Nursing home patients with weight loss of * 5% of usual body weight over the past 3 months, or body weight 20% below their ideal body weight. INTERVENTIONS: Patients were randomly assigned to receive placebo or MA 800 mg/d for 12 weeks and were then followed for 13 weeks off treatment and mortality 4 years post treatment. MEASUREMENTS: Primary outcome- weight and appetite change. Secondary outcome-sense of well being, enjoyment of life, change in depression scale, laboratory nutrition parameters, energy intake counts, body composition, and adverse events. RESULTS: At 12 weeks there were no significant differences in weight gain between treatment groups, while MA-treated patients reported significantly greater improvement in appetite, enjoyment of life, and well being. At week 25 (3 months after treatment), 61.9% of MA-treated patients had gained * 1.82 kg (4 lbs) compared to 21.7% of placebo patients. There was no difference in survival between MA and placebo groups. Considering possible confounders, higher initial IL-6, initial TNFR-p75 levels, and final neutrophil percentage were associated with elevated mortality, whereas higher initial pre-albumin, initial albumin, final pre-albumin, final albumin and final weight gain were associated with decreased death.

Childhood virilization and adrenal suppression after ingestion of methandienone and cyproheptadine.

We report a combination of precocious pseudopuberty and adrenal insufficiency in a 4 year-old boy who had received an off-label 'appetite stimulant' syrup and excessive virilization in a 2 year-old girl who had received the same medication. Both patients presented with excessive virilization for a period of approximately 1-2 years. The syrup contains cyproheptadine and methandienone, a derivative of testosterone. Both cyproheptadine and methandienone were responsible for severe adrenal suppression in the boy. Methandienone undoubtedly caused precocious virilization in both children. Cessation of the syrup led to partial regression of virilization in both children and normalization of adrenal reserve function in the boy.

Megestrol acetate-associated adrenal insufficiency.

BACKGROUND: Megestrol acetate (MA) is commonly used to promote weight gain in malnourished elderly patients. Although adrenal insufficiency has been reported as an adverse effect of MA, this association is not well recognized in clinical practice. CASE SUMMARY: An 80-year-old woman with worsening dyspnea was transferred to our university-affiliated community medical center from an inpatient psychiatric facility, where she was being treated for major depressive disorder with psychotic features. She had undergone a general decline in physical function accompanied by some weight loss and anorexia consistent with failure to thrive and, 1 month earlier, had been started on MA 400 mg/d to stimulate her appetite and improve her nutrition. During hospitalization at our center, the patient's dyspnea worsened and she was transferred to the intensive care unit, where she was intubated. While in the intensive care unit, the patient developed hypotension. Infectious, cardiac, and neurologic causes of hypotension having been ruled out, a cosyntropin stimulation test was performed to rule out adrenal insufficiency. Cortisol levels before, 30 minutes after, and 60 minutes after administration of cosyntropin were 1.6, 7.1, and 9.8 microg/dL, respectively, indicating a suboptimal response. The adrenocorticotropic hormone level was 8 pg/mL (normal, 10-60 pg/mL). Based on these findings suggesting adrenal insufficiency, MA was discontinued and steroid replacement was initiated. The patient's blood pressure normalized and she improved slowly. She was weaned from the ventilator several weeks later and was discharged to a skilled nursing facility. At 2-month follow-up, the patient's strength and respiratory function were improved, and the results of a repeat cosyntropin stimulation test were normal (cortisol response before, 30 minutes after, and 60 minutes after cosyntropin administration: 15.4, 22.6, and 25.2 microg/dL, respectively). The Naranjo score for this case was 7, indicating a probable correlation between MA use and adrenal insufficiency. CONCLUSIONS: This case of adrenal insufficiency in an elderly woman was probably related to MA use. Clinicians should be alert to the possibility of this adverse effect when considering use of MA therapy.

Clinical Inquiry: Is megestrol acetate safe and effective for malnourished nursing home residents?

No. Megestrol acetate (MA) is neither safe nor effective for stimulating appetite in malnourished nursing home residents. It increases the risk of deep vein thrombosis (strength of recommendation [SOR]: C, 2 retrospective chart reviews), but isn't associated with other new or worsening events or disorders (SOR: B, single randomized controlled trial [RCT]). Over a 25-week period, MA wasn't associated with increased mortality (SOR: B, single RCT). After 44 months, however, MA-treated patients showed decreased median survival (SOR: B, single case-control study). Consistent, meaningful weight gain was not observed with MA treatment (SOR: B, single case-control study, single RCT, 2 retrospective chart reviews, single prospective case-series).