1.
Meta-analysis of ghrelin alterations in schizophrenia: Effects of olanzapine.
Goetz, RL, Miller, BJ
Schizophrenia research. 2019;:21-26
Abstract
OBJECTIVE Schizophrenia is associated with an increased prevalence of the metabolic syndrome. Patients receiving antipsychotic medications, including olanzapine, are at further risk. Ghrelin is an appetite-stimulating peptide hormone, although whether blood levels are altered by antipsychotic treatment, remains unclear. We performed a systematic review and meta-analysis comparing blood ghrelin levels in patients with schizophrenia before and after treatment with olanzapine. METHOD Two authors independently searched major electronic databases from inception until February 2018 for studies measuring blood ghrelin levels among patients with schizophrenia before and after olanzapine therapy. Random effects meta-analysis calculating standardized mean difference (SMD) and 95% confidence intervals (CI) and meta-regression analyses were performed. RESULTS Six studies met the inclusion criteria. Across these studies, there were 111 patients with schizophrenia (mean age 40, 85% male, baseline BMI 22, and endpoint BMI 23). Olanzapine treatment (mean [standard deviation] duration = 12.3 [7.6] weeks) was associated with a significant decrease in blood ghrelin levels with a medium effect size (SMD = -0.48, 95% CI -0.88 to -0.08, p = 0.018). Age, sex, baseline BMI, geography, olanzapine dose and duration, year of publication, study quality, inpatient status, and antipsychotic washout did not moderate this association. CONCLUSION Our results suggest that in patients with schizophrenia, olanzapine therapy is associated with decreased blood ghrelin levels, a paradoxical phenomenon known to occur in obesity. Future studies should investigate the contribution of dietary factors (e.g., caloric intake) and physical activity to this association, as well as the effects of other antipsychotics on ghrelin levels.
2.
Endocrinopathies and cancer cachexia.
Dev, R, Del Fabbro, E, Dalal, S
Current opinion in supportive and palliative care. 2019;(4):286-291
Abstract
PURPOSE OF REVIEW Cancer cachexia cannot be easily reversed by standard nutritional support and interventions directed at underlying metabolic derangements may be needed to prevent or reverse cachexia and maintain healthy body composition. The following review will highlight the contribution and potential therapeutic interventions for insulin resistance, alterations in ghrelin signaling, and hypogonadism in cancer patients. RECENT FINDINGS In addition to decreased caloric intake, chronic inflammation, and altered metabolism of glucose, proteins and lipids, endocrine abnormalities can propagate weight loss or changes in body composition in cancer patients. SUMMARY Cancer cachexia, loss of muscle mass with or without the loss of fat mass, is a multifactorial syndrome, which is associated with increased morbidity and mortality. Currently, limited therapeutic options for the treatment of weight loss in cancer patients exist, which lead to clinically meaningful improvements in weight gain and performance status. Treatment directed at underlying insulin resistance, low testosterone, and altered ghrelin sensitivity, in the future, may lead to potential therapeutic options for loss of lean body mass and cancer cachexia.
3.
Efficacy of Anamorelin, a Novel Non-Peptide Ghrelin Analogue, in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) and Cachexia-Review and Expert Opinion.
Currow, DC, Maddocks, M, Cella, D, Muscaritoli, M
International journal of molecular sciences. 2018;(11)
Abstract
Cancer cachexia is a multilayered syndrome consisting of the interaction between tumor cells and the host, at times modulated by the pharmacologic treatments used for tumor control. Key cellular and soluble mediators, activated because of this interaction, induce metabolic and nutritional alterations. This results in mass and functional changes systemically, and can lead to increased morbidity and reduced length and quality of life. For most solid malignancies, a cure remains an unrealistic goal, and targeting the key mediators is ineffective because of their heterogeneity/redundancy. The most beneficial approach is to target underlying systemic mechanisms, an approach where the novel non-peptide ghrelin analogue anamorelin has the advantage of stimulating appetite and possibly food intake, as well as promoting anabolism and significant muscle mass gain. In the ROMANA studies, compared with placebo, anamorelin significantly increased lean body mass in non-small cell lung cancer (NSCLC) patients. Body composition analysis suggested that anamorelin is an active anabolic agent in patients with NSCLC, without the side effects of other anabolic drugs. Anamorelin also induced a significant and meaningful improvement of anorexia/cachexia symptoms. The ROMANA trials have provided unprecedented knowledge, highlighting the therapeutic effects of anamorelin as an initial, but significant, step toward directly managing cancer cachexia.