Medical Management of Obesity Associated with Mood Disorders
Susan L. McElroy, David B. Allison, George A. Bray in Obesity and Mental Disorders, 2006
Just as antidepressants have varied effects in different mood disorder subtypes, they also have different effects on appetite and body weight. Agents that stimulate appetite or cause weight gain include TCAs (tertiary amines more so than secondary amines), monoamine uptake inhibitors (MAOIs), and the novel antidepressant mirtazipine (32–34,188,189). Agents that are weight neutral or may even suppress appetite or reduce body weight, at least over the short term, include some SSRIs (especially fluoxetine), the novel noradrenergic agent bupropion, and the serotonin–norepinephrine selective reuptake inhibitor (SNRI) venlafaxine (190–200). For SSRIs, controlled data indicate that this weight loss may not be sustained over the long term, but data are mixed as to whether there is weight gain above baseline weight (20,188,189). Paroxetine, though, may be more likely than other SSRIs to be associated with weight gain (188,193,201,202). The precise mechanism(s) of appetite suppression and weight loss of these agents are unknown, but they enhance serotonergic or noradrenergic function without antagonizing serotonin, histamine, and/or dopamine receptors (203–206). [Of note, the antiobesity agent sibutramine is a serotonin–norepinephrine selective reuptake inhibitor similar to venlafaxine (29–31,169).]
Clinical Psychopharmacology of Amphetamine and Related Compounds
John Caldwell, S. Joseph Mulé in Amphetamines and Related Stimulants: Chemical, Biological, Clinical, and Sociological Aspects, 2019
Although others had previously remarked on the suppression of appetite experienced by patients who had taken amphetamine, Davidoff and Reifenstein6 were the first to suggest that the drug’s anorectic activity might be of potential clinical use in the management of obesity. Direct measurement of such an anorectic action in man was not attempted for some 10 years after the drug had been successfully introduced clinically. Harris and colleagues39 demonstrated that amphetamine significantly reduced food intake, but they did not attempt to evaluate its effect on hunger itself. Shortly afterwards, however, Janowitz and Grossman40 reported that 10 mg dextroamphetamine taken orally 1 hr before lunch “abolished all hunger sensations and markedly depressed the desire to eat … in all instances”. Others reported that the maximum anorectic effect occurred some 2 to 3 hr after administration, but, contrary to the findings of Janowitz and Grossman, they noted a wide intersubject variation,41 with only 20% responding markedly. Fifteen years earlier, Bahnsen et al.7 had remarked that a similar proportion of normal subjects experienced an anorectic effect; this was, however, four times as many as those who experienced a similar effect after placebo.
Regulation of Food Intake
Nathalie Bergeron, Patty W. Siri-Tarino, George A. Bray, Ronald M. Krauss in Nutrition and Cardiometabolic Health, 2017
CCK infusion (the C-terminal octapeptide of CCK) decreased food intake in lean individuals [63] suggesting its possible role as an appetite suppressant. The OLETF (Otsuka Long-Evans Tokushima Fatty rat) lacking the CCK1 receptor was demonstrated to be obese and diabetic with defective control of meal sizes, and CCK receptor deficiency was thought to be the reason for obesity in these rodents (along with NPY overexpression) [64]. This suggested that CCK might have a physiological role in meal intake. However, chronic administration of CCK (2 weeks of intraperitoneal infusion) in rodent models was not associated with any changes in body weight or food consumption [65], and trials of CCK agonists in humans have not proceeded beyond phase 2 due to adverse effects. Thus, the therapeutic potential of CCK as an antiobesity agent may be limited.
A critical evaluation of fenfluramine hydrochloride for the treatment of Dravet syndrome
Published in Expert Review of Neurotherapeutics, 2022
An-Sofie Schoonjans, Berten Ceulemans
More recently, in June 2020, the FDA approved fenfluramine for the treatment of seizures in patients with DS. Marketing approval from EMA followed in December 2020. Fenfluramine was identified in the mid-1960s as an anorectic drug and was approved globally for the treatment of obesity in 1973 [27]. It was often used in combination with phentermine (Phen-Fen). However, due to reports of cardiac valvulopathy and pulmonary hypertension, it was withdrawn from the market in 1997, since the possible risk outweighed the benefit in the treatment of obesity [28,29]. A Belgian Royal Decree permitted the continuation of low dose fenfluramine treatment in a trial for DS patients with refractory epilepsy. The investigator-initiated trials showed a remarkable efficacy and safety in this drug-resistant DS, results that have now been replicated in well-designed phase III studies.
Utility of in vitro and in vivo systems for studying the permeability of capsaicin and nonivamide through different intestinal regions
Published in Xenobiotica, 2018
Lian Duan, Huaidong Peng, Guangcan Li, Ruolun Wang, Yanfang Chen
Capsaicin has long been considered a topical analgesic. It has been used to treat chronic neuropathic pain, postherpetic neuralgia, diabetic neuropathy and neuropathic cancer pain (Papoiu & Yosipovitch, 2010). Additionally, it has been demonstrated that capsaicin could inhibit platelet aggregation (Mittelstadt et al., 2012), which may also provide protection against cardiovascular diseases (Bhatt & Topol, 2003). Moreover, oral administration with capsaicin can prevent weight gain in mice by regulating the expression of several anorectic and orexigenic genes and neuropeptides in the hypothalamus which induced by high-fat diet (Janssens et al., 2014). Hot chili is consumed on a daily basis in many populations. As capsaicin has potential beneficial effects on insulin secretion and plasma insulin concentrations (Akiba et al., 2004), fat oxidation (Ludy et al., 2012), antitumorigenic properties (Zhang et al., 2008), it is necessary to understand the permeability of capsaicin through the intestine. Overall, capsaicin has the potential for broad applications.
Serum interleukin 15 in anorexia nervosa: Comparison to normal weight and obese girls
Published in The World Journal of Biological Psychiatry, 2020
Wojciech Roczniak, Agata Mikołajczak-Będkowska, Elżbieta Świętochowska, Zofia Ostrowska, Katarzyna Ziora, Sylwia Balcerowicz, Karolina Górska-Flak, Magdalena Milan, Joanna Oświęcimska
Our research has shown that the average concentration of IL-15 in patients with AN is significantly higher than in control groups, but lower than in obese girls. These results are novel since, in the available literature, there are no such published reports. In the few studies conducted in animals with experimentally induced malignancy, IL-15 administration as well as physical exercise (which is known to increase IL-15 concentration), have been shown to stop the development of cancer cachexia due to the prevention of myocyte apoptosis and loss of muscle mass, inhibition of protein catabolism and fragmentation of DNA, which is accompanied by a reduction in tumour size (Carbó et al. 2000, Figueras et al. 2004, Molanouri Shamsi et al. 2017. Martínez-Hernández et al. (2012) have shown that, in a subgroup of patients with cancer cachexia with fat mass (FM) percentage below 20%, the IL-15 concentration was significantly higher than in the subgroup with FM ≥ 30% (Martínez-Hernández et al. 2012). Based on this observation, we speculate that the increase in IL-15 concentration in AN is an adaptive reaction to chronic starvation, which is thought to prevent loss of muscle mass and increased catabolism of proteins. This hypothesis is also supported by the results of the body composition analysis in anorectic patients using dual-energy X-ray absorptiometry, which has revealed that in those with BMI values >16.5 kg/m2, despite the loss of adipose tissue, the lean body mass and muscle mass were comparable with healthy women (El Ghoch et al. 2017).
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