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How Physician Obesity Specialists Use Drugs to Treat Obesity
Abstract
Specialist physicians may have prescribing habits that are different from nonspecialist physicians. Little is known about the prescribing habits of physicians specializing in the treatment of obesity. An anonymous survey was given to the physician members of the American Society of Bariatric Physicians (ASBP). There was a 35% response rate (266 physicians) to the questionnaire that was represented nationally. Almost all prescribed medications and all of them recommended phentermine. The average maximal dose of phentermine was above that approved in the package insert, and these physicians disagreed with the National Institutes of Health (NIH) Obesity Treatment Guidelines. Phendimetrazine, metformin, and phentermine plus L-5-hydroxytryptophan (5-HTP) with carbidopa were all used more frequently than either orlistat or sibutramine. The combination of sibutramine and orlistat as well as 5-HTP/carbidopa were prescribed by 14 and 20%, respectively. As 5-HTP-carbidopa was a combination not previously reported for the treatment of obesity, a retrospective chart review was performed in a single obesity practice, which may not be representative. Twenty-two subjects had a 16% weight loss with phentermine over 6 months and an additional 1% weight loss with the addition of 5-HTP/carbidopa for an additional 6 months. One subject who started on 5-HTP/carbidopa alone lost 24.4% of initial body weight over 6 months. This questionnaire revealed that 20% of the obesity specialists responding to the survey used phentermine plus of 5-HTP/carbidopa, an unreported combination. A controlled, randomized, clinical trial to evaluate the safety and efficacy of this combination in treating obesity should be considered.
... inTrODUCTiOn One common treatment of the obesity epidemic involves the use of drugs (Hampp et al., 2013;Valsamakis et al., 2017;Srivastava and Apovian, 2018). One of the most widely prescribed of these drugs for humans in the USA is Phentermine (Phen), which is an appetite suppressant currently approved for the short-term treatment of obesity (Hendricks et al., 2009;Hendricks et al., 2011;Hendricks et al., 2014;Yanovski and Yanovski, 2014). Studies in rodents have also shown that repeated administration of Phen induces body weight loss, decreases food intake, and several psychomotor side effects such as locomotion and stereotypy (Kalyanasundar et al., 2015). ...
... Here, we have extended these studies to 5-HTP. In this regard, Hendricks et al. (2009) reported that obesity specialists widely prescribe Phen plus 5-HTP/CB surpassing other combinations (e.g., caffeine + ephedrine or sibutramine + orlistat) to reduce feeding. Nevertheless, it is not well understood how these three drugs interact with each other to induce greater weight loss. ...
... Here, we have extended these studies to 5-HTP a serotoninergic compound. In this regard, Hendricks et al., 2009 reported that obesity specialists frequently prescribed, in humans, a triple drug combination (Phen, 5-HTP, and CB) for the treatment of obesity. However, there is no preclinical study confirming its efficacy neither its evoked effects in the brain. ...
Obesity has become a serious public health problem. Although diet, surgery, and exercise are the primary treatments for obesity, these activities are often supplemented using appetite suppressants. A previous study reported that obesity specialists frequently prescribed a new drug combination for its treatment that includes phentermine (Phen; dopaminergic appetite suppressant), a serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP; an appetite suppressant that increases the 5-HT concentration), and carbidopa (CB; peripheral blocker of conversion of 5-HTP to 5-HT). Despite its widespread use, there is neither a preclinical study confirming the drug efficacy nor studies of its effects on the brain. To fill this gap, in rats for seven consecutive days, we administered Phen intraperitoneally at different doses either alone or in combination with a fixed dose of 5-HTP/CB. In a different group, we infused drugs via an intraperitoneal catheter while extracellular-recordings were performed in the nucleus accumbens shell (NAcSh), a brain region with dopamine-releasing effects that is involved in the action of appetite suppressants. We found that the triple-drug combination leads to greater weight-loss than each drug alone. Moreover, and as the treatment progresses, the triple drug combination partially reversed psychomotor side-effects induced by Phen. Electrophysiological results revealed that Phen alone evoked a net inhibitory imbalance in NAcSh population activity that correlated with the onset of psychomotor effects. In addition, and unlike the greater weight loss, the addition of 5-HTP/CB did not alter the Phen-evoked inhibitory imbalance in NAcSh responses. Subsequent experiments shed light on the underlying mechanism. That is the majority of NAcSh neurons modulated by 5-HTP/CB were suppressed by Phen. Notably, and despite acting via a different mechanism of action (DA for Phen vs. 5-HT for 5-HTP/CB), both drugs recruited largely overlapping NAcSh neuronal ensembles. These data suggest that the neural correlates of the greater weight loss could be located outside the NAcSh, in other brain circuits. Furthermore, we conclude that Phen + 5-HTP/CB is a potential treatment for overweight and obesity.
... However, in the orthodox approach, the older sympathomimetic drugs, approved before the FDA required long-term trials for obesity medicine approval, are restricted to short-term use, whereas physicians using the pragmatic approach are comfortable using these drugs long term in an off-label manner. 14,15 Adherents to the conventional approach point out that the older drugs are only approved for short-term use, and that no long-term randomized controlled trials (RCTs) have been conducted. Adherents to the pragmatic approach argue that short-term restrictions were added when the older drugs were approved the second time in a political compromise move with no scientific justification. ...
... Surveys of prescribing practices among physicians treating obesity have confirmed that a majority of these physicians continue to prescribe the sympathomimetics off-label in this manner. 14,15 Phentermine is also used off-label in several ways other than long-term. Phentermine is, and has long been, prescribed for patients whose excess adiposity is below the conventional BMI cutoffs. ...
... Whatever the theoretical explanation, doses higher than 37.5 mg/day have been found effective and safe in a number of observational studies. 6,14,15,[19][20][21][22][23] Physicians treating attention deficit use dose-to-effect titration with methamphetamine up to 1 mg/kg/day and methylphenidates up to 2 or 3 mg/kg/day. 24 Attention deficit medicines have considerably greater potentials for abuse than sympathomimetic anorectics. ...
The global pandemic of obesity and overweight now affects between 2.8 and 3.5 billion of the world population and shows no signs of abatement. Treatment for what is now recognized as a chronic disease includes pharmacotherapy, considered an essential component of comprehensive therapy. New drug discovery is robust, but the pace of the US Food and Drug Administration approval for obesity drugs has been glacial, and only a handful of approved drugs are available for treating obesity. In the last 20 years, the US Food and Drug Administration has and 223 endocrinologic drugs, but only 6 for obesity, 2 of which have been taken off market. Currently, there are only 9 drugs approved by the FDA for obesity treatment. US physicians have turned to off-label drug use in their effort to care for increasing numbers of patients with excess adiposity. Phentermine is the most commonly used drug for treating obesity. Although approved only for short-term use, US physicians have used it successfully for long-term since its initial approval in 1959. This drug, used off-label for long-term, has proven to be safe and effective, far safer than the disease it is used to treat. Phentermine and diethylpropion, an equally safe but somewhat less effective drug, are both generic and therefore inexpensive. These drugs have been maligned inappropriately because their two-dimensional structure diagrams resemble amphetamine and also because of unproven presumptions about their potential adverse effects. In the face of an increasing epidemic, worldwide obese and overweight patients deserve effective treatment that prescribing these drugs could provide, if rehabilitated and used more frequently. US physicians will likely continue to use any drug proven useful off-label for this illness until such time as more effective drugs are approved.
... Central-acting agents, such as phentermine, lorcaserin, and the combination of bupropionnaltrexone, suppress appetite by modulating neurotransmitter levels in the brain. Phentermine, a sympathomimetic amine, increases the release of norepinephrine and dopamine, reducing hunger [151]. Lorcaserin, a selective serotonin 2C receptor agonist, enhances satiety signals by activating pro-opiomelanocortin neurons in the hypothalamus [148]. ...
... Phentermine is generally well tolerated, with the most commonly reported side effects being dry mouth, insomnia, and constipation [151]. However, concerns have been raised regarding the potential CV risks associated with phentermine use, particularly in patients with pre-existing heart conditions [155]. ...
Obesity is a growing public health epidemic worldwide and is implicated in slowing improved life expectancy and increasing cardiovascular (CV) risk; indeed, several obesity-related mechanisms drive structural, functional, humoral, and hemodynamic heart alterations. On the other hand, obesity may indirectly cause CV disease, mediated through different obesity-associated comorbidities. Diet and physical activity are key points in preventing CV disease and reducing CV risk; however, these strategies alone are not always sufficient, so other approaches, such as pharmacological treatments and bariatric surgery, must support them. Moreover, these strategies are associated with improved CV risk factors and effectively reduce the incidence of death and CV events such as myocardial infarction and stroke; consequently, an individualized care plan with a multidisciplinary approach is recommended. More precisely, this review explores several interventions (diet, physical activity, pharmacological and surgical treatments) to address CV risk in obese patients and emphasizes the importance of adherence to treatments.
... Initially ascribed as a central nervous system stimulant which triggers the release of norepinephrine in the hypothalamus [68], recent evidence suggests that phentermine inhibits the reuptake of norepinephrine and dopamine [68]. Subsequently, this suppresses appetite [69] and decreases body weight by reducing food intake and increasing resting energy expenditure [70,71]. Phentermine is a key synthetic drug often illegally added to herbal slimming formulations and nutraceutical supplements [72,73] to boost their efficacy. ...
... Phentermine is a key synthetic drug often illegally added to herbal slimming formulations and nutraceutical supplements [72,73] to boost their efficacy. The use of this anorectic in such formulations has been associated with some adverse cardiovascular effects, such as primary pulmonary hypertension, palpitations, tachycardia, ischemic events [69], and dry mouth. ...
Purpose
This paper examines the scope of anorectics in counterfeit weight-reducing formulations and provides insight into the present state of research in determining such adulterants. Analytical techniques utilised in profiling adulterants found in slimming products, including limitations and mitigation steps of these conventional methods are also discussed. The current legal status of the anorectics and analogues routinely encountered in non-prescription slimming formulations is also explored.
Methods
All reviewed literature was extracted from Scopus, Web of Science, PubMed, and Google Scholar databases using relevant search terms, such as, ‘counterfeit drugs’, ‘weight loss drugs’, ‘weight-reducing drugs’, ‘slimming drugs’, ‘anorectic agents’, and ‘counterfeit anorexics’. Legislation related to anorectics was obtained from the portals of various government and international agencies.
Results
Anorectics frequently profiled in counterfeit slimming formulations are mostly amphetamine derivatives or its analogues. Five routinely reported pharmacological classes of adulterants, namely anxiolytics, diuretics, antidepressants, laxatives, and stimulants, are mainly utilised as coadjuvants in fake weigh-reducing formulations to increase bioavailability or to minimise anticipated side effects. Liquid and gas chromatography coupled with mass spectrometric detectors are predominantly used techniques for anorectic analysis due to the possibility of obtaining detailed information of adulterants. However, interference from the complex sample matrices of these fake products limits the accuracy of these methods and requires robust sample preparation methods for enhanced sensitivity and selectivity. The most common anorectics found in counterfeit slimming medicines are either completely banned or available by prescription only, in many countries.
Conclusions
Slimming formulations doped with anorectic cocktails to boost their weight-reducing efficacy are not uncommon. Liquid chromatography combined with mass spectrometry remains the gold standard for counterfeit drug analysis, and requires improved preconcentration methods for rapid and quantitative identification of specific chemical constituents. Extensive method development and validation, targeted at refining existing techniques while developing new ones, is expected to improve the analytical profiling of counterfeit anorectics significantly.
... This case report describes a case of iatrogenic Takotsubo cardiomyopathy induced by combination sympathomimetic medications. Takotsubo cardiomyopathy was first described in the 1990s [1] , however, drug-induced disease is being increasingly reported [4,6,7] . While the precise aetiology of the condition is still unknown, it has been thought that overstimulation of the sympathetic nervous system causes increased contraction and ballooning of the ventricular myocardium [8] . ...
... In post-menopausal women, the reduced level of estrogen may increase vulnerability to sympathetic overstimulation [5] . Both phentermine and lisdexamfetamine are widely used sympathomimetic medications [6] . While isolated cases of monotherapy or combination stimulants causing TC are described in the literature [7,9,10] , the combination of lisdexamfetamine and phentermine causing TC has not been previously reported in the published literature. ...
Objectives:
This is the first case report of iatrogenic Takotsubo syndrome (TS) due to a combination of lisdexamfetamine and phentermine.
Background:
TS is characterized by transient acute ballooning of the left ventricular wall. Typically, it occurs in extremely stressed post-menopausal women, however a few iatrogenic causes have been described recently.
Results:
A 55-year old woman prescribed lisdexamfetamine and phentermine, presented with acute substernal chest pain. Acute coronary syndrome was excluded. The echocardiogram was diagnostic of TS, and she recovered spontaneously, with supportive care.
Conclusion:
Caution with the use of sympathomimetic medications in post-menopausal women appears warranted.
Learning points:
This is the first case report in the published English literature of medication-induced Takotsubo cardiomyopathy due to combination use of lisdexamfetamine and phentermine.This provides new information about iatrogenic causes of Takotsubo cardiomyopathy.Caution is indicated in the use of such medications, particularly in post-menopausal women, who are at higher risk.
... There is a need for longer-term effective, safe, and affordable pharmacotherapy that can be used as an adjunct to lifestyle change advice. Longer-term use of phentermine in the United States indeed appears to be a pervasive practice (36); 30% of our cohort was made up of individuals with at least one phentermine episode lasting > 12 weeks. ...
... We did not address provider-or health-system-level variables, and it is possible that these factors differed systematically between groups in a way that favored longer-term phentermine users. For example, if physicians willing to prescribe phentermine for longer durations are more likely to be obesity specialists (36), or if this pattern of prescribing is more likely to be associated with participation in a comprehensive weight-management program, such differences could confound the relationship between phentermine use duration and weight loss. ...
Objective
The aim of this work was to study weight loss and risk of cardiovascular disease (CVD) or death associated with longer‐term phentermine use.
Methods
Using electronic health record data, 13,972 adults were identified with a first phentermine fill in 2010 to 2015, creating exposure categories according to a patient’s duration of use (referent: ≤ 3 months). Multivariable linear models were used to compare percent weight loss across categories at 6, 12, and 24 months, and Cox proportional hazards models were used to compare risk of composite CVD or death, up to 3 years after starting phentermine.
Results
The cohort was 84% female and 45% white, with a mean (SD) baseline age 43.5 (10.7) years and BMI of 37.8 (7.2) kg/m². In multivariable models, longer‐term users of phentermine experienced more weight loss; patients using continuously for > 12 months lost 7.4% more than the referent group at 24 months (P < 0.001). The composite CVD or death outcome was rare (0.3%, 41 events), with no significant difference in hazard ratios between groups.
Conclusions
Greater weight loss without increased risk of incident CVD or death was observed in patients using phentermine monotherapy for longer than 3 months. Despite the limitations of the observational design, this study supports the effectiveness and safety of longer‐term phentermine use for low‐risk individuals.
... Depending on the dose (which is typically between 30 and 37.5 mg/d) the placebo-subtracted weight loss attributed to treatment with phentermine (30 mg/d) is in the range of 4-8 kg after 12 weeks of treatment (Kim et al., 2006;Kang et al., 2010;Moldovan et al., 2016). Phentermine is generally well tolerated with little to no abusive potential, even when used chronically for up to 21 years (Hendricks et al., 2009). In a large-scale survey, United States physicians stated that 98% use pharmacological options to treat obesity, and, from those physicians using pharmacotherapies, 97% state to prescribe phentermine, 64% diethylpropion, 60% phendimetrazine, 50% topiramate, 49% sibutramine, and 43% orlistat (Hendricks et al., 2009). ...
... Phentermine is generally well tolerated with little to no abusive potential, even when used chronically for up to 21 years (Hendricks et al., 2009). In a large-scale survey, United States physicians stated that 98% use pharmacological options to treat obesity, and, from those physicians using pharmacotherapies, 97% state to prescribe phentermine, 64% diethylpropion, 60% phendimetrazine, 50% topiramate, 49% sibutramine, and 43% orlistat (Hendricks et al., 2009). ...
With their ever-growing prevalence, obesity and diabetes represent major health threats of our society. Based on estimations by the World Health Organization, approximately 300 million people will be obese in 2035. In 2015 alone there were more than 1.6 million fatalities attributable to hyperglycemia and diabetes. In addition, treatment of these diseases places an enormous burden on our health care system. As a result, the development of pharmacotherapies to tackle this life-threatening pandemic is of utmost importance. Since the beginning of the 19th century, a variety of drugs have been evaluated for their ability to decrease body weight and/or to improve deranged glycemic control. The list of evaluated drugs includes, among many others, sheep-derived thyroid extracts, mitochondrial uncouplers, amphetamines, serotonergics, lipase inhibitors, and a variety of hormones produced and secreted by the gastrointestinal tract or adipose tissue. Unfortunately, when used as a single hormone therapy, most of these drugs are underwhelming in their efficacy or safety, and placebo-subtracted weight loss attributed to such therapy is typically not more than 10%. In 2009, the generation of a single molecule with agonism at the receptors for glucagon and the glucagon-like peptide 1 broke new ground in obesity pharmacology. This molecule combined the beneficial anorectic and glycemic effects of glucagon-like peptide 1 with the thermogenic effect of glucagon into a single molecule with enhanced potency and sustained action. Several other unimolecular dual agonists have subsequently been developed, and, based on their preclinical success, these molecules illuminate the path to a new and more fruitful era in obesity pharmacology. In this review, we focus on the historical pharmacological approaches to treat obesity and glucose intolerance and describe how the knowledge obtained by these studies led to the discovery of unimolecular polypharmacology.
... BMI ranges from 18.5 to 24.9 for most persons, 25 to 29.9 for those who are overweight, 30 to 39.9 for those who are obese, and 40 or more for those who are very obese [4]. As a result, Phentermine, Sibutramine, Orlistat, and treatment were used as keywords in the author's search [5]. ...
Obesity is the main obstacle to human health in the world today, and it is more and more popular in the world.There are many methods to treat obesity in modern society, such as behavioral therapy, surgical treatment and pharmacological therapy.The author aims to give a review of pharmacological therapy for obesity based on existing literature research results and data. This paper mainly introduces the three drugs which are Phentermine, Sibutramine and Orlistat their mechanism.The result shows that these three drugs are applicable to moderate and severe obesity, and they can not be overused. Sibutramine, which can increase the risk of serious cardiovascular and cerebrovasular diseases, has been banned. The remaining two drugs, Phentermine and Orlistat, can be taken normally as long as they are under the guidance of doctors.
... 55 The combination of ephedrine with caffeine has been approved as a therapy for the treatment of obesity in many countries. 56 Bracale et al. provided evidence that 4 weeks of ephedrine/caffeine intake produces significant thermogenic effect not linked to muscle uncoupling protein 3 (UCP3) gene expression. 57 Improved fat loss by the ephedrine/caffeine combination was explained by dual actions: a central appetite suppression and peripheral stimulation of energy expenditure associated with fat oxidation. ...
Ephedrine, a sympathomimetic amine that exhibits several of adrenaline actions, is a plant alkaloid
that is a common ingredient in several cold, asthma and narcolepsy treatment preparations, and in
obesity management, and sport medicine. Its principal action mechanism relies on its direct
adrenergic actions as well as indirect role that involves the release of epinephrine and
norepinephrine, thus increasing the activity of epinephrine and norepinephrine at the postsynaptic
α and β receptors. Nevertheless, its serious side effects including stroke, heart attack, drug abuse
and interactions have never been comprehensively reviewed. We conducted a systematic review
of data on ephedrine including its occurrence in functional foods, pharmacological aspects,
metabolism, pharmaco/toxicokinetics and clinical features. Further, a review of ephedrine natural
structural analogues with regards to their differential adrenergic receptor binding affinities, food
interaction and their impact on the pharmacokinetics and effects relative to ephedrine are presented
for the first time, and in comparison to its action when present in herbs
... Though phentermine fell out of favor in the 1990s due to its association with fenfluramine (and risk of valvular heart disease and pulmonary hypertension), it remains the most commonly prescribed anti-obesity medication today due to its low cost [23]. Yet, no randomized controlled trials or prospective studies have sufficiently determined associated CVD risks and benefits [25][26][27]. This is partially due to the short-term FDA approval for its use. ...
Purpose of Review
To summarize research from the last 5 years on the effects of weight loss treatments, including lifestyle changes, anti-obesity medications, and bariatric procedures on cardiovascular disease (CVD) risk factors and CVD outcomes in adults.
Recent Findings
This narrative review includes and summarizes the contemporary evidence of the effects of these different weight loss approaches individually. A literature search was performed using the key words obesity, weight loss, CVD, cardiometabolic, and risk factors and included key clinical trials from the past 5 years. Obesity management through weight loss is associated with improvements in CVD risk factors, such as improved blood pressure, lipid profiles, and glycemic control, with greater weight loss leading to greater improvements in CVD risk factors. Bariatric surgery is associated with greater weight loss than the other procedures and treatments for obesity, and for this, and possibly for other reasons, it is associated with greater reductions in CVD outcomes and mortality.
Summary
Obesity is an independent risk factor and modulator of other CVD risk factors, and thus, treatment of obesity should be an integral part of management strategies to reduce CVD risk. Future trials and real-world studies of longer duration are needed to inform providers and patients on how to individualize the approach to modifying risks of cardiometabolic disorders through obesity management.
... The conversion of 5-HTP to 5-HT at a peripheral level can be reduced using carbidopa, an inhibitor of the peripheral aromatic amino acid decarboxylase enzyme (Westenberg et al., 1982;Gijsman et al., 2002), which in turn augments the concentration of 5-HT in the central nervous system (Smarius et al., 2008). To date, there are no randomized, placebo-controlled, double-blinded clinical trials studying these combinations, but 5-HTP/carbidopa + phentermine is prescribed by around 20% of Physician Obesity Specialists in the United States (Hendricks et al., 2009). ...
Drug combinations are being studied as potential therapies to increase the efficacy or improve the safety profile of weight loss medications. This study was designed to determine the anorectic interaction and safety profile of 5-hydroxytryptophan (5-HTP)/carbidopa + diethylpropion and 5-HTP/carbidopa + phentermine combinations in rats. The anorectic effect of individual drugs or in combination was evaluated by the sweetened milk test. Isobologram and interaction index were employed to determine the anorectic interaction between 5-HTP/carbidopa and diethylpropion or phentermine. Plasma serotonin (5-HT) was measured by ELISA. Safety of repeated doses of both combinations in rats was evaluated using the tail sphygmomanometer, cardiac ultrasound, hematic biometry and blood chemistry. A single oral 5-HTP, diethylpropion or phentermine dose increased the anorectic effect, in a dose-dependent fashion, in 12 h-fasted rats. A dose of carbidopa at 30 mg/kg reduced the 5-HTP-induced plasmatic serotonin concentration and augmented the 5-HTP-induced anorectic effect. Isobologram and interaction index indicated a potentiation interaction between 5-HTP/30 mg/kg carbidopa + diethylpropion and 5-HTP/30 mg/kg carbidopa + phentermine. Chronic administration of experimental ED40 of 5-HTP/30 mg/kg carbidopa + phentermine, but not 5-HTP/30 mg/kg carbidopa + diethylpropion, increased the mitral valve leaflets area. Moreover, there were no other significant changes in cardiovascular, hematic or blood parameters. Both combinations induced around 20% body weight loss after 3 months of oral administration. Results suggest that 5-HTP/30 mg/kg carbidopa potentiates the anorectic effect of diethylpropion and phentermine with an acceptable safety profile, but further clinical studies are necessary to establish their therapeutic potential in the obesity treatment.
... Thus, NPE induces anorectic effects in the same manner as other phenethylamine derivatives such as diethylpropion, phentermine, bupropion, and cathinone; this is perhaps not surprising because chemically, these substances are all structurally related to amphetamine (Khan et al., 2012). Studies in humans and in rodents revealed that amphetamine congeners produce weight loss and decreased food intake at different levels with the following strength (amphetamine > cathinone > diethylpropion ≥ phentermine > NPE > bupropion) (Zelger and Carlini, 1980;Chen et al., 2001;Cercato et al., 2009;Hendricks et al., 2009;Kalyanasundar et al., 2015Kalyanasundar et al., , 2016Hauner et al., 2017;Lucchetta et al., 2017;Perez et al., 2019). In summary, what they all have in common is that their pharmacological effects on weight loss and food intake require DA signaling (Balcioglu and Wurtman, 1998;Baumann et al., 2000;Chen et al., 2001;Kalyanasundar et al., 2015;Lemieux et al., 2015). ...
... Thus, NPE induces anorectic effects in the same manner as other phenethylamine derivatives such as diethylpropion, phentermine, bupropion, and cathinone; this is perhaps not surprising because chemically, these substances are all structurally related to amphetamine (Khan et al., 2012). Studies in humans and in rodents revealed that amphetamine congeners produce weight loss and decreased food intake at different levels with the following strength (amphetamine > cathinone > diethylpropion ≥ phentermine > NPE > bupropion) (Zelger and Carlini, 1980;Chen et al., 2001;Cercato et al., 2009;Hendricks et al., 2009;Kalyanasundar et al., 2015Kalyanasundar et al., , 2016Hauner et al., 2017;Lucchetta et al., 2017;Perez et al., 2019). In summary, what they all have in common is that their pharmacological effects on weight loss and food intake require DA signaling (Balcioglu and Wurtman, 1998;Baumann et al., 2000;Chen et al., 2001;Kalyanasundar et al., 2015;Lemieux et al., 2015). ...
d-norpseudoephedrine (NPE), also known as cathine, is found naturally in the shrub Catha edulis “Khat.” NPE has been widely used as an appetite suppressant for the treatment of obesity. Although it is known that NPE acts on α1-adrenergic receptors, there is little information about the role of dopamine receptors on NPE’s induced anorectic and weight loss effects. Equally untouched is the question of how NPE modulates neuronal activity in the nucleus accumbens shell (NAcSh), a brain reward center, and a pharmacological target for many appetite suppressants. To do this, in rats, we characterized the pharmacological effects induced by NPE on weight loss, food intake, and locomotion. We also determined the involvement of dopamine D1- and D2-like receptors using systemic and intra-NAcSh antagonists, and finally, we recorded single-unit activity in the NAcSh in freely moving rats. We found that NPE decreased 24-h food intake, induced weight loss, and as side effects increased locomotor activity and wakefulness. Also, intraperitoneal and intra-NAcSh administration of D1 and D2 dopamine antagonists partially reversed NPE’s induced weight loss and food intake suppression. Furthermore, the D1 antagonist, SCH-23390, eliminated NPE-induced locomotion, whereas the D2 antagonist, raclopride, only delayed its onset. We also found that NPE evoked a net activation imbalance in NAcSh that propelled the population activity trajectories into a dynamic pharmacological brain state, which correlated with the onset of NPE-induced wakefulness. Together, our data demonstrate that NPE modulates NAcSh spiking activity and that both dopamine D1 and D2 receptors are necessary for NPE’s induced food intake suppression and weight loss.
... A prior study of bariatric physicians reported that off-label medication use was more common than the long-term FDA-approved anti-obesity medications available at that time. 25 It is clinically lawful for physicians to prescribe a medication off-label once the medication is approved by the FDA, 26 In addition, we identified several factors associated with higher likelihood of guideline concordance. Greater concordance was associated with greater number of obesity-related chronic conditions managed and health system affiliation, which may reflect physicians who have a comprehensive approach to care and access to other resources. ...
Our objective was to determine the clinical services offered by American Board of Obesity Medicine (ABOM) Diplomates and whether guideline concordant services varied by clinical practice attributes. We conducted a cross‐sectional analysis of the 2019 ABOM Diplomate survey (response rate 19.2%). Respondents (n = 494) self‐reported services offered: nutrition, exercise, mental health, minimally invasive bariatric procedures, perioperative bariatric surgical care and FDA‐approved anti‐obesity medications. We graded concordance of services offered with three evidence‐based obesity guidelines, and then conducted bivariate analyses comparing concordance by practice attributes. Most responding ABOM Diplomates offered nutrition (90.1%), exercise (67.8%) and mental health (76.7%). Few offered minimally invasive procedures (24.3%), and most provided perioperative surgical care (63.0%). Most (83.4%) prescribed FDA‐approved medications—typically both short‐ and long‐term agents (70.9%). Few Diplomates had low concordance with the American Heart Association/American College of Cardiology/The Obesity Society (AHA/ACC/TOS) guidelines (24.7%). Those who managed more obesity‐related conditions and endorsed AHA/ACC/TOS guideline use had higher concordance with these recommendations. No differences in guideline concordance existed by population, clinical effort or location. We found similar findings regarding concordance with ) American Association of Clinical Endocrinologists/American College of Endocrinology and Obesity Medicine Association guidelines. In conclusion, most responding ABOM Diplomates offer evidence‐based obesity medicine services. Clinicians may therefore have increased confidence in patient receipt of evidence‐based care when referring to an ABOM Diplomate.
... These include diethylpropion 3 and benzphetamine, 4 both approved in 1960; phendimetrazine, approved in 1976; 5 phentermine, approved in 1980; 6 and phentermine hydrochloride, approved in 2012. 7 Despite the existence of several other classes of drugs to treat obesity, phentermine remains the most often prescribed weight loss drug in the U.S. 8 Although the mechanism of action (MOA) of sympathomimetic drugs is not particularly clear, weight loss from these medications is believed to be due to the increase in the release of biogenic amines (mainly norepinephrine, but also possibly dopamine), from storage sites in nerve terminals. It is possible that these drugs slow catecholamine metabolism by inhibiting the actions of monoamine oxidase. ...
The toolbox of medications available for medical weight management is more robust than ever and includes a wide variety of mechanisms of actions and options for patients.
... A large anonymous survey performed among United Stated physicians provided interesting details about the use of drugs to treat obesity. This report stated that 98% of the physician respondents prescribed amphetamine congeners, and among them, 97% proposed phentermine as first option, followed by diethylpropion (64%) and phendimetrazine (60%) (Hendricks et al., 2009). ...
In the last thirty years, obesity has reached epidemic proportions and is now regarded as a major health issue in contemporary society trending to serious economic and social burdens. The latest projections of the World Health Organization are alarming. By 2030, nearly 60% of the worldwide population could be either obese or overweight, highlighting the needs to find innovative treatments. Currently, bariatric surgery is the most effective way to efficiently lower body mass. Although great improvements in terms of recovery and patient care were made in these surgical procedures, bariatric surgery remains an option for extreme forms of obesity and seems unable to tackle obesity pandemic expansion. Throughout the last century, numerous pharmacological strategies targeting either peripheral or central components of the energy balance regulatory system were designed to reduce body mass, some of them reaching sufficient levels of efficiency and safety. Nevertheless, obesity drug therapy remains quite limited on its effectiveness to actually overcome the obesogenic environment. Thus, innovative unimolecular polypharmacology strategies, able to simultaneously target multiple actors involved in the obesity initiation and expansion, were developed during the last ten years opening a new promising avenue in the pharmacological management of obesity. In this review, we first describe the clinical features of obesity-associated conditions and then focus on the outcomes of currently approved drug therapies for obesity as well as new ones expecting to reach the clinic in the near future.
... Como se mencionó anteriormente, la fentermina es el fármaco anorexigénico que se prescribe con más frecuencia, aunque está aprobado para su uso a corto plazo. 72 el topiramato es un agonista GABAérgico que está indicado como anticonvulsivante para el tratamiento de la epilepsia y para la prevención de la migraña a una dosis de 100 mg/día. Aunque no está aprobado su uso como monoterapia para suprimir el apetito, la eficacia del topiramato para disminuir y generar saciedad se atribuye a que actúa a través de neuronas GABAérgicas, antagoniza parcialmente los receptores AMPA/kainato y bloquea los receptores de calcio y sodio dependientes de voltaje. ...
La obesidad no es un estilo de vida elegido, sino una enfermedad causada por una predisposición biológica y la exposición constante a un ambiente "obesogénico." Para abatir la pandemia actual de obesidad es vital encontrar las causas biológicas que predisponen a ciertas personas a ser obesas. Además del problema que representa la obesidad en sí misma, esta contribuye al desarrollo de una cornucopia de desórdenes crónicos tales como la hipercolesterolemia, enfermedades cardiovasculares, diabetes tipo 2 y algunos tipos de cáncer, entre los que se destacan el cáncer de colon y el de esófago. Por todo ello, la obesidad representa una gran carga económica para el país y amenaza con llevar a la bancarrota a los sistemas de salud pública.
... Combinações de medicações de uso off-label são frequentemente utilizadas. Na Inglaterra, 65% dos médicos especialistas em obesidade afirmavam prescrever estas combinações (27) . Apesar de, infelizmente, poucos estudos avaliarem a sua segurança e eficácia a longo prazo, os ensaios clínicos com maior probabilidade de sucesso são aqueles realizados com combinações de medicamentos, que a taxa de sucesso no estudo em 10 vezes (28) . ...
RESUMO
A obesidade é uma doença crônica progressiva e recidivante, e alcança proporções de epidemia global. É uma causa prevenível e tratável de aumento de mortalidade precoce, entretanto, na maior parte dos casos, alcança apenas sucesso temporário. O emagrecimento em pessoas obesas provoca aumento persistente dos hormônios orexígenos e redução dos sacietógenos, o que leva a um contínuo aumento da fome e redução do gasto de energia corporal. No ambiente obesogênico atual, este desequilíbrio metabólico provoca recidiva da obesidade. O foco do tratamento da obesidade deve estar na manutenção do peso reduzido, com a escolha de dietas com maior teor de proteínas, exercício intenso frequente e uso de associações de medicamentos que se contraponham à adaptação metabólica que se manifesta com o emagrecimento.
... Fenfluramine, which works primarily through serotonin receptors and to a less extent norepinephrine, will be discussed further below. Despite phentermine's past association with fenfluramine, phentermine is now the most commonly prescribed medication for the treatment of obesity in adults (41)(42)(43). Even with the high frequency in which phentermine is prescribed, no randomized control trials or prospective trials sensitive enough to determine the CV risks and benefits of this medication have been conducted. ...
Obesity is a complex disease influenced by many neurohormonal pathways which regulate body weight toward homeostasis. Presently, the disease of obesity effects over a billion individuals worldwide with scalable treatment options in dire need. Pharmacologic interventions for obesity have been developed to help promote weight loss in individuals with obesity. This area is rapidly developing and will only exponentially increase to serve the demand for persons with obesity seeking biologically orientated solutions to treat their disease. Therefore, understanding the cardiovascular risks and benefits of these weight loss medications is of particularly importance due to obesities strong association with cardiovascular (CV) disease risk. Moreover, past experiences with pharmacotherapy agents with weight loss properties have demonstrated an association with adverse CV outcomes, leading to market removal, in most cases and concerns over using similar medications. To better understand the CV risks and benefits pharmacotherapy agents used for weight loss, this review will discuss medications which are FDA-approved for weight loss, as well as medications commonly used off-label for this indication. The goal is to provide an overview of the risks and benefits many of these medications can offer to help guide clinical decision making and patient education.
... It is currently prescribed for short-term appetite suppression (,3 months). Compared with placebo, it significantly reduces body weight in obese individuals and is currently the most widely prescribed antiobesity therapy, in part due to its relatively low cost (31)(32)(33). Although reports suggest phentermine can increase blood pressure, numerous studies demonstrate that when used for weight loss, phentermine does not adversely influence the cardiovascular system. ...
Liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, and phentermine, a psychostimulant structurally related to amphetamine, are drugs approved for the treatment of obesity and hyperphagia. There is significant interest in combination use of liraglutide and phentermine for weight loss; however, both drugs have been reported to induce systemic hemodynamic changes, and as such the therapeutic window for this drug combination needs to be determined. To understand their impact on metabolic and cardiovascular physiology, we tested the effects of these drugs alone and in combination for 21 days in lean and obese male mice. The combination of liraglutide and phentermine, at 100 mg/kg/day and 10 mg/kg/day, respectively, produced the largest reduction in body weight in both lean and diet-induced obese (DIO) mice, when compared with both vehicle and monotherapy-treated mice. In lean mice, combination treatment at the aforementioned doses significantly increased heart rate and reduced blood pressure, whereas in DIO mice, combination therapy induced a transient increase in heart rate and decreased blood pressure. These studies demonstrate that in obese mice, the combination of liraglutide and phentermine may reduce body weight but only induce modest improvements in cardiovascular functions. Conversely, in lean mice, the additional weight loss from combination therapy does not improve cardiovascular parameters.
... Phentermine, a sympathomimetic (norepinephrine reuptake inhibitor), was approved by the FDA in 1959 for individuals >16 years of age for "short term use" and is currently the most widely prescribed medication for the treatment of obesity in adults (8). Although there are no randomized, controlled studies of this medication in adolescents that are more than 1-month in duration, a retrospective chart review of adolescents with severe obesity treated in a pediatric weight management clinic reported the six-month outcomes of phentermine plus LSMT on BMI. ...
There is a gap in treatment modalities for pediatric patients with obesity for whom lifestyle modification therapy, on the one hand, may be insufficient to meaningfully reduce BMI, and bariatric surgery, which on the other hand, may not be indicated, available or desired. Although pharmacotherapy may help fill this treatment void, there is a paucity of FDA-approved medications indicated for pediatric obesity and further, most are single agents with only modest mean treatment effects. In contrast, combination pharmacotherapy, such as phentermine/topiramate, appears to offer greater weight loss efficacy in adults and may prove to be superior to monotherapy for pediatric patients as well. This case report describes the clinical management of severe obesity in a 10 year old girl with lifestyle modification therapy and subsequent addition of first topiramate and later phentermine. Using the case as a platform, the current state of pharmacotherapy for pediatric obesity will be described thereby highlighting the limited efficacy of single agents. Additionally, the biological rationale for combination pharmacotherapy, including potential mechanisms which may account for the poor response to single agents, will be discussed.
... Phentermine potently releases norepinephrine, but is effective on the release of dopamine and serotonin, too, to a lesser extent [157]. The drug is a "weak substrate of the serotonin transporter and has minimal effects on plasma serotonin in vivo" [158][159][160]. "Although increased catecholamine release may be thought to increase the odds for adverse cardiovascular effects, norepinephrine released in the brain may act to decrease sympathetic activity, through a "clonidine-like" effect" [161][162][163]. ...
... Тем не менее, монотерапия гипертензии очень часто неэффективна, поэтому в настоящее время почти повсеместно используются комбинации препаратов. Эта стратегия начала использоваться и в лечении ожирения, в частности она уже нашла свое выражение в утверждении комбинаций фентермин/ топирамат и бупропион/налтрексон [17]. ...
(Закінчення, початок в No 4/2016 р.) В огляді описана еволюція фармакотерапії ожиріння – починаючи від застосування рослинних засобів, тиреоїдних гормонів і симпатоміметиків, і закінчуючи серотонінергічними препаратами, інгібіторами ліпази, аналогами пептидів і комбінованими засобами. Описано препарати, затверджені в даний час для тривалого лікування ожиріння, такі як орлістат, лоркасерін, ліраглутид, і комбінаціі фентермін/топірамат і налтрексон/бупропіон. Зроблено висновок, що найбільш перспективними препаратами для лікування ожиріння в майбутньому будуть комбінації препаратів з різними механізмами дії.
... As such, data on the clinical effectiveness of phentermine would provide valuable information guiding decision-making about the need for subsequent clinical trials evaluating this agent, especially because phentermine is sometimes prescribed "off-label" for the treatment of adolescent obesity. 4 Therefore, we conducted a retrospective chart review of pediatric weight management clinic patients who were treated with phentermine in addition to standard of care (SOC) lifestyle modification therapy versus those receiving SOC only. We further examined changes in heart rate and blood pressure that occurred over time. ...
Phentermine is the most widely prescribed obesity medication in adults, yet studies of its use in the pediatric population are limited. We conducted a retrospective chart review of adolescents with obesity treated in a pediatric weight management clinic to examine the weight loss effectiveness of phentermine added to standard of care lifestyle modification therapy (SOC) versus SOC alone. All patients receiving phentermine plus SOC (n=25) were matched with a comparison group receiving only SOC (n=274). Differences at 1, 3, and 6 months were evaluated using generalized estimated equations adjusting for age, sex, and baseline body mass index (BMI) and robust variance standard error estimates for confidence intervals and P-values. Phentermine use was associated with a greater percent change in BMI at 1 month (-1.6% [95% CI (-2.6%, -0.6%); P=0.001), 3 months (-2.9% [95% CI (-4.5%, -1.4%); P<0.001]) and 6 months (-4.1% [95% CI (-7.1%, -1.0%); P=0.009]) compared to SOC alone, with no differences in systolic or diastolic blood pressure between groups. Heart rate was higher at all time-points in the phentermine plus SOC compared to SOC only group. These data suggest that short-term use of phentermine added to SOC may enhance weight loss in adolescents with obesity in the clinical setting.International Journal of Obesity accepted article preview online, 24 October 2016. doi:10.1038/ijo.2016.185.
... Given the high prevalence rates of obesity and its harmful effects on health, it is crucial to explore treatment options for this disease. Pharmacotherapy and the use of meal replacements (in conjunction with a lifestyle intervention) have consistently demonstrated the ability to treat obesity (3)(4)(5)(6)(7). ...
Objective:
To examine the effects of phentermine combined with a meal replacement program on weight loss and food cravings and to investigate the relationship between food cravings and weight loss.
Methods:
In a 12-week randomized, double-blind, placebo-controlled clinical trial, 77 adults with obesity received either phentermine or placebo. All participants were provided Medifast(®) meal replacements, were instructed to follow the Take Shape for Life(®) Optimal Weight 5&1 Plan for weight loss, and received lifestyle coaching in the Habits of Health program. The Food Craving Inventory and the General Food Cravings State and Trait Questionnaires were used to measure food cravings.
Results:
The phentermine group lost 12.1% of baseline body weight compared with 8.8% in the placebo group. Cravings for all food groups decreased in both groups; however, there was a greater reduction in cravings for fats and sweets in the phentermine group compared with the placebo group. Percent weight loss correlated significantly with reduced total food cravings (r = 0.332, P = 0.009), cravings for sweets (r = 0.412, P < 0.000), and state food cravings (r = 0.320, P = 0.007).
Conclusions:
Both phentermine combined with a meal replacement program and meal replacements alone significantly reduced body weight and food cravings; however, the addition of phentermine enhanced these effects.
... The fact that phentermine, which was FDA approved in 1959 for short-term use and with little clinical trial data, remains the most frequently prescribed antiobesity pharmacotherapy, by a large margin, is likely due to its low cost and its familiarity among patients and prescribers. Phentermine's high proportion of continuing prescriptions to new prescriptions indicates that it is often being prescribed off-label, i.e., for longer than 3 months (15,40). Ironically, the very low continuing prescription to new prescription ratio of new antiobesity pharmacotherapies, which are approved for longterm use, indicate that they are being used for the short term. ...
Objective:
To characterize the adoption of antiobesity pharmacotherapies, as compared with that of the newest antidiabetes pharmacotherapy, subtype 2 sodium-glucose transport protein inhibitors (SGLT2s), among prescribers in the United States.
Methods:
A retrospective analysis of 2012 to 2015 data extracted from the IMS Health National Prescription Audit™ and Xponent™ assessed adoption rates of antiobesity pharmacotherapies and SGLT2s.
Results:
The number of dispensed antidiabetes prescriptions was 15 times the number of dispensed antiobesity prescriptions. The antiobesity market share was: 74.0% phentermine, 18.6% new antiobesity pharmacotherapies. The mean increase in prescriptions/month were: 25,259 for SGLT2s, 5,154 for new antiobesity pharmacotherapies, and 2,718 for phentermine. Medical specialties prescribing the majority of the analysis medications were Family Medicine/General Practice and Internal Medicine. Endocrinology had the highest prevalence of prescribers of any subspecialty.
Conclusions:
The adoption rate of SGLT2s was nearly exponential, while the adoption rate of new antiobesity pharmacotherapies was linear. Considering the relative prevalence of obesity to diabetes and that obesity is a major cause of diabetes, these results are paradoxical and suggest systematic barriers against the prescribing of antiobesity pharmacotherapies. The under-prescribing of antiobesity pharmacotherapies is widely acknowledged, but this is the first prescription data of these new medications to demonstrate its extent in the United States.
... Boys aged <17 years are more likely to be treated with stimulants than girls the same age, whereas females aged ≥17 years are slightly more likely than males in that age group to be so treated (17). The excess prescribing among adult women might reflect the fact that stimulants also are prescribed for weight control (21). ...
Problem/condition:
Drug overdose is the leading cause of injury death in the United States. The death rate from drug overdose in the United States more than doubled during 1999-2013, from 6.0 per 100,000 population in 1999 to 13.8 in 2013. The increase in drug overdoses is attributable primarily to the misuse and abuse of prescription drugs, especially opioid analgesics, sedatives/tranquilizers, and stimulants. Such drugs are prescribed widely in the United States, with substantial variation by state. Certain patients obtain drugs for nonmedical use or resale by obtaining overlapping prescriptions from multiple prescribers. The risk for overdose is directly associated with the use of multiple prescribers and daily dosages of >100 morphine milligram equivalents (MMEs) per day.
Period covered:
2013.
Description of system:
The Prescription Behavior Surveillance System (PBSS) is a public health surveillance system that allows public health authorities to characterize and quantify the use and misuse of prescribed controlled substances. PBSS began collecting data in 2012 and is funded by CDC and the Food and Drug Administration. PBSS uses standard metrics to measure prescribing rates per 1,000 state residents by demographic variables, drug type, daily dose, and source of payment. Data from the system can be used to calculate rates of misuse by certain behavioral measures such as use of multiple prescribers and pharmacies within specified time periods. This report is based on 2013 de-identified data (most recent available) that represent approximately one fourth of the U.S.
Population:
Data were submitted quarterly by prescription drug monitoring programs (PDMPs) in eight states (California, Delaware, Florida, Idaho, Louisiana, Maine, Ohio, and West Virginia) that routinely collect data on every prescription for a controlled substance to help law enforcement and health care providers identify misuse or abuse of such drugs.
Results:
In all eight states, opioid analgesics were prescribed approximately twice as often as stimulants or benzodiazepines. Prescribing rates by drug class varied widely by state: twofold for opioids, fourfold for stimulants, almost twofold for benzodiazepines, and eightfold for carisoprodol, a muscle relaxant. Rates for opioids and benzodiazepines were substantially higher for females than for males in all states. In most states, opioid prescribing rates peaked in either the 45-54 years or the 55-64 years age group. Benzodiazepine prescribing rates increased with age. Louisiana ranked first in opioid prescribing, and Delaware and Maine had relatively high rates of use of long-acting (LA) or extended-release (ER) opioids. Delaware and Maine ranked highest in both mean daily opioid dosage and in the percentage of opioid prescriptions written for >100 MMEs per day. The top 1% of prescribers wrote one in four opioid prescriptions in Delaware, compared with one in eight in Maine. For the five states whose PDMPs collected the method of payment, the percentage of controlled substance prescriptions paid for in cash varied almost threefold, and the percentage paid by Medicaid varied sixfold. In West Virginia, for 1 of every 5 days of treatment with an opioid, the patient also was taking a benzodiazepine. Multiple-provider episode rates were highest in Ohio and lowest in Louisiana.
Interpretation:
This report presents rates of population-based prescribing and behavioral measures of drug misuse in the general population that have not been available previously for comparison among demographic groups and states. The higher prescribing rates for opioids among women compared with men are consistent with a higher self-reported prevalence of certain common types of pain, such as lower back pain among women. The trend in opioid prescribing rates with age is consistent with an increase in the prevalence of chronic pain with age, but the increasing prescribing rates of benzodiazepines with age is not consistent with the fact that anxiety is most common among persons aged 30-44 years. The variation among states in the type of opioid or benzodiazepine of choice is unexplained. Most opioid prescribing occurs among a small minority of prescribers. Most of the prescriptions by top-decile prescribers probably are written by general, family medicine, internal medicine, and midlevel practitioners. The source of payment varied by state, for reasons that are unclear. Persons who are prescribed opioids also are commonly prescribed benzodiazepine sedatives despite the risk for additive depressant effects.
Public health actions:
States can use their prescription drug monitoring programs to generate population-based measures for the prescribing of controlled substances and for behaviors that suggest their misuse. Comparing data with other states and tracking changes in these measures over time can be useful in measuring the effect of policies designed to reduce prescription drug misuse.
... As a matter of fact, depression is frequent in chronic diseases of organic or functional origin [58,59]. Antidepressant drugs are used for the treatment of obesity [60] and for functional digestive diseases [61], but our patients had no active depression defined by DSM IV criteria at the time of the medical examination. ...
Obesity is considered as a risk factor for many functional gastrointestinal disorders. The aim of the study was to evaluate if functional digestive disorders are associated with specific body mass index groups and gender.
A total of 1074 patients (50.3 ± 16.5 years, 67 % females) filled out a standard Rome III questionnaire (79 % acceptance rate). The patients were assigned to five groups according to their body mass index: underweight (6 %), normal (49 %), overweight (28 %), obese (12 %), and morbidly obese (5 %). Data analysis was performed using multinomial logistic regression; subjects with the normal weight were the reference group.
Patients presented specific demographic and clinical characteristics according to the weight groups. Underweight patients were younger (p < 0.001), and presented a female predominance (p = 0.006), dysphagia (p = 0.013) and soiling (p = 0.021). Overweight patients were older (p = 0.001), and reported more frequently globus (p = 0.001), regurgitation (p = 0.004), postprandial distress syndrome (p = 0.009). Obese patients reported more frequently regurgitation (p < 0.001). Morbid obese patients reported dyspepsia (p = 0.046). In patients, the odds of regurgitation increased with body mass index from underweight to obesity, but not when compared to morbid obesity. The probability of globus and regurgitation increased with body mass index and presented a steeper increase in females.
In patients with functional gastrointestinal disorders, globus and regurgitation are associated with body mass index, mainly in female patients.
... One possible explanation is that the patients had obesity when they were first prescribed antiobesity drugs, and these drugs helped them to lose weight effectively. They may have been continuing on the drugs under physician monitoring in order to maintain weight loss (30). Alternatively, in spite of the 1998 Guidelines, physicians may have been open to prescribing antiobesity medications to overweight individuals, those with BMI in the range 25-30, in order to help prevent additional weight gain. ...
To describe the antiobesity drug-prescribing patterns of US physicians over the past decade.
Data for adult patients were obtained from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. Obesity was identified using ICD-9 codes, BMI values, and a chronic-obesity-condition variable. For patients with obesity, a logistic-regression model was estimated to determine the odds of receiving pharmacotherapy.
Of the 987 million visits by patients with obesity from 2005 to 2010, 2.0% mentioned an antiobesity drug. Additionally, there were 6.5 million visits by patients without obesity but with an antiobesity drug mention. Visits made by females (OR = 2.89; 95% CI: 2.08-4.03), by white patients (OR = 1.55; 95% CI: 1.08-2.24), by younger adults (OR = 1.71; 95% CI: 1.34-2.20), and in the South (OR = 3.39; 95% CI: 1.49-7.72) were more likely to involve an antiobesity drug prescription.
Only 1 in 50 patients with obesity received a prescription for an antiobesity medication. Moreover, in contrast to what the 1998 Guidelines suggested, physicians tended to prescribe antiobesity medications to self-paying, young, white females, many of whom lived in the South, and not all of whom had obesity.
© 2015 The Obesity Society.
... Moreover, we must also take in mind that our patients had a relatively low BMI (22.5 kg/m2), possibly due to the fact that around 85% of our patients were IDUs. HIV infection and chronic drug abuse both compromise nutritional status of patients despite major advances in the HIV treatment [44], allowing that HIV-positive IDUs had lower BMI. ...
Background
Peroxisome proliferator-activated receptor gamma-2 gene (PPARγ2) rs1801282 (Pro12Ala) polymorphism has been associated with lower risk of metabolic disturbance and atherosclerosis. The aim of this study was to analyze the association between the Pro12Ala polymorphism and cardiometabolic risk factors in human immunodeficiency virus (HIV)/Hepatitis C virus (HCV)-coinfected patients.
Methods
We carried out a cross-sectional study on 257 HIV/HCV coinfected patients. PPARγ2 polymorphism was genotyped by GoldenGate® assay. The main outcome measures were: i) serum lipids (cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), LDL-C/HDL-C, and atherogenic index (AI)); ii) homeostatic model assessment (HOMA-IR) values; iii) serum adipokines (leptin, adiponectin, resistin, plasminogen activator inhibitor-1(PAI-1), hepatic growth factor (HGF), and nerve growth factor (NGF)). Generalized Linear Models (GLM) with gamma distribution (log-link) were used to investigate the association between PPARγ2 polymorphism and continuous outcome variables. This test gives the differences between groups and the arithmetic mean ratio (AMR) in continuous outcome variables between groups.
Results
The rs1801282 CG/GG genotype was associated with low values of cholesterol (adjusted arithmetic mean ratio (aAMR) = 0.87 (95% of confidence interval (95% CI) = 0.79; 0.96); p = 0.004) and LDL-C (aAMR = 0.79 (95% CI = 0.68; 0.93); p = 0.004). Furthermore, rs1801282 CG/GG was associated with low values of HOMA-IR (aAMR = 0.69 (95% CI = 0.49; 0.98); p = 0.038) among patients with significant liver fibrosis (F ≥ 2). Moreover, rs1801282 CG/GG was also associated with low serum values of hepatic growth factor (HGF) (aAMR = 0.61 (95% CI = 0.39; 0.94); p = 0.028), and nerve growth factor (NGF) (aAMR = 0.47 (95% CI = 0.26; 0.84); p = 0.010). The serum levels of leptin, adiponectin, resistin, and PAI-1 did not show significant differences.
Conclusions
The presence of PPARγ2 rs1801282 G allele (Ala variant) was associated with a protective cardiometabolic risk profile versus CC genotype in HIV/HCV-coinfected patients. Thus, PPARγ2 rs1801282 polymorphism may play a significant role in the development of metabolic disorders in HIV/HCV coinfected patients, and might have an influence on the cardiovascular risk.
As obesity prevalence increases, more and more drugs that assist with weight loss have been developed. Numerous weight loss drugs had been approved, but many have also been withdrawn based on their lack of efficacy as well as safety concerns. Initial approaches in developing weight loss drugs was by increasing physiological energy expenditure and suppressing the appetite. Subsequently, as more physiological mechanisms for weight gain has been unearthed, drugs targeting newly discovered receptors and/or enzymes have been introduced with improved safety profiles and fewer psychological adverse events. Additionally, drugs targeting hunger or satiety signaling have been actively studied, and have shown increased adoption by physicians. Studies have also evaluated drugs that target metabolic tissues—such as adipose tissue or muscle—to promote weight loss, however to-date nothing has carried on into clinical practice. Starting with a brief history of early obesity treatments, this review evaluates current weight loss pharmaceutical options based on their duration of therapy status.
Obesity is often incorrectly viewed as a self‐inflicted consequence of personal lifestyle choices, and as a result, people commonly delay or avoid seeking medical advice or treatment. Before considering pharmacotherapy, initial management strategies should focus on diet, exercise, and behavioral support. Rather than to replace this first line management, the role of anti‐obesity drugs is as an adjunct to lifestyle and behavioral modification when these methods alone do not achieve clinically meaningful weight loss and/or to help maintain weight loss. The potential use of glucagon‐like peptide 1 analogs in the management of obesity is discussed in the future therapies section of this chapter. Currently, a number of medications and therapeutic targets are being considered in the management of obesity. Some of these are currently licensed for the management of conditions other than obesity but have incidentally been shown to have a positive impact on weight loss.
Obesity is a chronic, relapsing, stigmatized disease process that is increasing in prevalence, affecting both adults and children. It is the result of a small positive energy imbalance from too much food or too little activity. These underlying causes are influenced by many environmental factors. The food we eat is more than “calories,” and focusing on calories alone may not be as productive as focusing on patterns of eating and the role of sugar and fat in the diet. Obesity increases the risk of many diseases and shortens life span, and weight loss provides benefits in reducing health risks and improving the quality of life. Management of obesity must redress the energy imbalance using one of several strategies, including diet, lifestyle modification, exercise, medications, and, potentially, bariatric surgery. Five drugs are approved by the FDA for long-term treatment of obesity, and they can effectively improve health-related risks. Bariatric surgery has become a major treatment strategy and can reduce long-term health risks from obesity.
In the last thirty years, obesity has reached epidemic proportions and is now regarded as a major health issue in contemporary society trending to serious economic and social burdens. The latest projections of the World Health Organization are alarming. By 2030, nearly 60% of the worldwide population could be either obese or overweight, highlighting the needs to find innovative treatments. Currently, bariatric surgery is the most effective way to efficiently lower body mass. Although great improvements in terms of recovery and patient care were made in these surgical procedures, bariatric surgery remains an option for extreme forms of obesity and seems unable to tackle obesity pandemic expansion. Throughout the last century, numerous pharmacological strategies targeting either peripheral or central components of the energy balance regulatory system were designed to reduce body mass, some of them reaching sufficient levels of efficiency and safety. Nevertheless, obesity drug therapy remains quite limited on its effectiveness to actually overcome the obesogenic environment. Thus, innovative unimolecular polypharmacology strategies, able to simultaneously target multiple actors involved in the obesity initiation and expansion, were developed during the last ten years opening a new promising avenue in the pharmacological management of obesity. In this review, we first describe the clinical features of obesity-associated conditions and then focus on the outcomes of currently approved drug therapies for obesity as well as new ones expecting to reach the clinic in the near future.
Using pharmacotherapy for weight management is consistent with treating obesity as a chronic and life-threatening disease that requires a multifactorial and long-term approach, encompassing behavioral intervention, dietary change, and appropriate medical treatment. Bariatric surgery is a very effective intervention for achieving weight loss and ameliorating obesity-related comorbidities, but is associated with risks and higher costs relative to nonsurgical interventions, and thus, it is not feasible or desirable for several individuals with obesity. Therefore, pharmacotherapy, with an efficacy level that falls between that of lifestyle and surgical interventions, can thus bridge the gap that exists. Current guidelines recommend that individuals who fail to respond to lifestyle interventions after 6 months of treatment and have a BMI of ≥30 kg/m² or a BMI of ≥27 kg/m² with an obesity-related comorbidity may be considered for weight loss medication treatment. The US Federal Drug Administration (US FDA) has approved several new medications for the treatment of obesity in the past 5 years. The objective of this chapter is to provide a profile of the effectiveness of currently anti-obesity medications and their side effects. The reviewed anti-obesity medications reported in this chapter include medicines approved for short-term use of weight management, drugs for chronic weight management, the off-label use medications for weight control, and future anti-obesity pharmacotherapeutics.
Objective:
Mexico has the second largest prevalence of obesity among adults worldwide, a condition especially affecting the low-income population. There is a pressing need to improve therapeutic options for weight loss. Phentermine is an old and low-cost agent given as an adjuvant therapy for obesity for a 12-week period, at an initial dose of 15 mg or 30 mg. However, there are no precise guidelines on the suitability of both the starting dose and the continuation of treatment for 6 months. The aim of this study was to evaluate the 3- and 6-month efficacy and safety of phentermine in obese Mexican patients to elucidate the aforementioned.
Materials and methods:
In this prospective, multi-center, open-label study, 932 obese adults received 15 mg or 30 mg phentermine once daily for 6 months.
Results:
30 mg phentermine was more effective than 15 mg phentermine in improving anthropometric variables in the 3-month follow-up, but not after completing the 6-month treatment period. Nearly 40% of 3-month non-responders reached a body weight reduction of at least 5% at 6 months. Conversely, ~ 65% and 25% of 3-month responders maintained or improved, respectively, their body weight reduction with long-term phentermine. Potential tolerance as weight regain was ~ 10% from 3 to 6 months. None of the doses increased cardiovascular risk, although mild-to-moderate adverse events were more frequent with 30 mg phentermine.
Conclusion:
30 mg phentermine was more effective than 15 mg phentermine after 3 months, but not at 6 months of treatment. An important number of subjects could benefit following the therapy from 3 to 6 months.
La obesidad ha ido aumentando considerablemente en las últimas décadas y es causante de producir 180 problemas distintos, además de que intervienen aproximadamente todos los sistemas incluyendo el cerebro. Generando que las personas les cueste bajar de peso y aún más conservar su peso adecuado, puntualizaron los expertos durante la presentación.
Entre las primeras enfermedades que se ve afectada una persona con sobrepeso se encuentra las enfermedades metabólicas como la diabetes mellitus tipo II, enfermedades cardiovasculares, las dislipidemias o el cáncer; contribuyendo a la generación de discapacidad y mortalidad temprana como consecuencias.Además se le anexan las afectaciones biosicosociales a la persona que lo padece, sin dejar de mencionar la generación de baja autoestima y la discriminación.
Por lo tanto pretenden que con este libro los médicos puedan generar más medidas preventivas para que no se llegue a aplicar un tratamiento, considerando que es una enfermedad de difícil manejo y representa un reto para la salud mundial. Teniendo en consideración que en estos tiempos el sobrepeso no respeta edad o sexo, por eso es necesario modificar los programas de estudio de los diferentes profesionales de la salud en cuestión de tratamiento, prevención y sus comorbilidades.
Purpose:
Phentermine is the most prescribed antiobesity drug in America, with 2.43 million prescriptions written in 2011. Case reports suggest there are anesthetic risks, such as refractory hypotension, involved with its perioperative use. Despite these risks and the frequency of phentermine use among plastic surgery patients, there are no published guidelines for the perioperative management of phentermine use in the plastic surgery literature. To address this patient safety issue, we performed a systematic review and provide management recommendations.
Methods:
A systematic review of the pharmacology of phentermine and the anesthetic risks involved with its perioperative use was undertaken using the search engines PubMed/MEDLINE, EMBASE, and Scopus.
Results:
A total of 251 citations were reviewed, yielding 4 articles that discussed perioperative phentermine use and complications with anesthesia. One was a review article, 2 were case reports, and 1 was a letter. Complications included hypotension, hypertension, hypoglycemia, hyperthermia, bradycardia, cardiac depression, and acute pulmonary edema.
Conclusions:
The relationship between phentermine and anesthesia, if any, is unclear. Hypotension on induction of general anesthesia is the most reported complication of perioperative phentermine use. Specifically, phentermine-induced hypotension may be unresponsive to vasopressors that rely on catecholamine release, such as ephedrine. Therefore, the decision to perform surgery, especially elective surgery, in a patient taking phentermine should be made with caution. Because of the half-life of phentermine, we recommend discontinuing phentermine for at least 4 days prior to surgery. This differs from the classic 2-week discontinuation period recommended for "fen-phen." The patient should be made aware of the increased risk of surgery, and a skilled anesthesiologist should monitor intraoperative blood pressure and body temperature for signs of autonomic derailment.
The prevalence of obesity, measured by body mass index, has risen to unacceptable levels in both men and women in the United States and worldwide with resultant hazardous health implications. Genetic, environmental, and behavioral factors influence the development of obesity, and both the general public and health professionals stigmatize those who suffer from the disease. Obesity is associated with and contributes to a shortened life span, type 2 diabetes mellitus, cardiovascular disease, some cancers, kidney disease, obstructive sleep apnea, gout, osteoarthritis, and hepatobiliary disease, among others. Weight loss reduces all of these diseases in a dose-related manner—the more weight lost, the better the outcome. The phenotype of “medically healthy obesity” appears to be a transient state that progresses over time to an unhealthy phenotype, especially in children and adolescents. Weight loss is best achieved by reducing energy intake and increasing energy expenditure. Programs that are effective for weight loss include peer-reviewed and approved lifestyle modification programs, diets, commercial weight-loss programs, exercise programs, medications, and surgery. Over-the-counter herbal preparations that some patients use to treat obesity have limited, if any, data documenting their efficacy or safety, and there are few regulatory requirements. Weight regain is expected in all patients, especially when treatment is discontinued. When making treatment decisions, clinicians should consider body fat distribution and individual health risks in addition to body mass index.
В обзоре описана эволюция фармакотерапии ожирения – начиная от применения растительных средств, тиреоидных гормонов и симпатомиметиков, и заканчивая серотонинергическими препаратами, ингибиторами липазы, аналогами пептидов и комбинированными средствами. Описаны препараты, утвержденные в настоящее время для длительного лечения ожирения, такие как орлистат, лоркасерин, лираглутид, и комбинации фентермин/ топирамат и налтрексон/бупропион. Сделан вывод, что наиболее перспективными препаратами для лечения ожирения в будущем будут комбинации препаратов с различными механизмами действия.
This chapter examines the use of drugs as adjuncts to lifestyle in the treatment of the patient who is overweight or obese. There are two groups of approved drugs that can be used in this setting. The first are the four drugs currently approved for long-term treatment of obesity and a few others that can be used for short-term treatment. Orlistat partially blocks intestinal digestion of fat and produces weight loss of 5–8 kg. Its major limitations are associated gastrointestinal symptoms. Lorcaserin is a serotonin agonist that produces weight loss of 4–7 kg. It has few side effects. The combination of phentermine and topiramate in an extended release formulation produces weight loss of 8–10 kg but must be used only after showing a woman of child-bearing potential is not pregnant. The combination of bupropion 360 mg and naltrexone 60 mg in sustained release formulation is intermediate in weight loss efficacy compared to lorcaserin or phentermine/topiramate ER, but requires dose escalation over 3 weeks because of nausea and vomiting. Additionally, liraglutide has been under Food and Drug Administration (FDA) consideration for approval, and may be available in 2015. The short-term drugs are sympathomimetics with phentermine being most widely used. In obese patients being treated for type 2 diabetes, depression, convulsive disorders, migraine headaches, or psychiatric illnesses, it is important to select drugs, where possible, that, as part of their mechanism of action, reduce weight rather than drugs which increase weight.
Introduction: Few studies on combination therapies for the treatment of obesity had been conducted until recently, when two fixed-dose combinations, bupropion-naltrexone ER fixed-dose combination and phentermine-topiramate ER titrated-dose combinations were evaluated in clinical studies that ultimately led to FDA approval.
Areas covered: In this review, we discuss safety concerns about both combinations, the rationale and history of combination therapies for obesity (including phentermine plus fenfluramine), and possible future new combinations.
Expert commentary: Combination therapies are a promising new area in obesity treatment, similar to what occurs with diabetes and hypertension. Safety assessment is highly important due to the high number of potential users on a chronic basis.
The dramatic rise in the prevalence of obesity in the Western world over the last four decades (Global Strategy on Diet, Physical Activity and Health, WHO. http://www.who.int/dietphysicalactivity/strategy/eb11344/strategy_english_web.pdf. Accessed December 10, 2012) unfortunately has not been followed by effective measures for its long-term treatment, which still mainly relies on lifestyle modification through diet and exercise. Few medications are available for its treatment and surgical treatment, although growing considerably in the last decades, is only indicated for extreme obesity (BMI over 40 kg/m²) or in patients with considerable comorbidities.
Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to short-term treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds.
Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners like diethylpropion(DEP), phentermine(PHEN) and bupropion(BUP) whose effects are mediated through serotonin, norepinephrine and dopaminergic pathways. The nucleus accumbens shell(NAc-shell) receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc-shell responses to short-term treatments of DEP, PHEN and BUP. These compounds caused a transient decrease in weight and food-intake while increasing locomotion, stereotypy and insomnia and evoked a large inhibitory imbalance in NAc-shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials(LFPs) showed that all three drugs modulated beta, theta and delta oscillations. These oscillations do not reflect an aversive-malaise brain state as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric(and intraNAc-shell) infusions of dopamine antagonists SCH23390(D1-receptor) or raclopride(D2-receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP's oscillations and partially restored the imbalance in NAc-shell activity. These data revealed that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc-shell depend on to various extents on dopaminergic activation thus point to an important role for D1/D2-like receptors(in the NAc-shell) in the mechanism of action for these anorexic compounds.
Copyright © 2015, Journal of Neurophysiology.
Children with persistent Chlamydia pneumoniae infection may be at increased risk for atherosclerosis. The impact of antimicrobial therapy for primary prevention of atherosclerotic cardiovascular disease is unsolved.
The purpose of this study was to determine whether treatment with antimicrobial agents effective against C pneumoniae during childhood, regardless of indication, has a favorable influence on the arterial wall-thickness in children by the time they reach adolescence.
The association of macrolide, tetracycline, quinolone, and rifamycin use (number of exposure events) between ages 5 and 13 years with carotid and aortic intima-media thickness at age 13 years was investigated among 508 healthy children. Information about the use of medications was obtained from the Finnish prescription register. Arterial intima-media thickness was measured with a high-resolution ultrasound.
Mean aortic intima-media thickness showed a significant direct association with the number of antichlamydial antimicrobial exposure events also after controlling for established atherosclerotic risk factors. Elevated C-reactive protein level had an additional effect on aortic intima-media thickness in a multivariable model. Carotid intima-media thickness was not associated with the number of preceding antichlamydial treatments.
Recurrent antichlamydial treatments in childhood have no favorable influence on early vascular changes but are associated with increased intima-media thickness in the abdominal aorta. These findings suggest that the use of antimicrobial agents does not offer protection against the potential atherogenicity of repeated infectious insults.
5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Therapeutic use of 5-HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. 5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.
The aim of this study was to evaluate decrease in waist circumference in obese patients receiving different anti-obesity treatments. The study was designed as a short-term (12 weeks), open-label, and randomized trial. Eighty six patients (70 females, 81.4%; mean age 41.09+/-8.73 years, mean BMI 36.1+/-4.3 kg/m2) were randomized to four different therapy groups. The primary outcome parameters were waist circumference and body mass index (BMI). The therapy groups were a) diet+sibutramine 1 x 10 mg/d (n=22), b) diet+orlistat 3 x 120 mg/d (n=25), c) combination of diet+sibutramine+orlistat (n=20) and d) diet (n=19). Combination therapy was more effective than diet and orlistat mono-therapy (p<0.0001 for all), but not significantly superior to sibutramine mono-therapy (p=0.072) in decreasing BMI. Sibutramine mono-therapy was significantly more effective in inducing BMI decrease compared with orlistat mono-therapy (p=0.039). The association between change in BMI and change in waist circumference was strongest in the orlistat mono-therapy group (P interaction=0.003). This means that patients taking orlistat experienced more decrease in waist circumference (3.4 cm, R2=0.29) per unit decrease in BMI compared to patients under combination therapy (2.6 cm, R2=0.25, P interaction = 0.015) and patients taking sibutramine (1.8 cm, R2=0.19, P interaction=0.026). In the diet therapy group decline in waist circumference was independent of BMI (1.9 cm, R2=0.02, P interaction=0.076). Although combination therapy and sibutramine mono-therapy were more effective in decreasing BMI, reduction in waist circumference and BMI was most significantly associated with the orlistat mono-therapy group. This may hint at the possibility of orlistat inducing weight loss mainly in the abdominal area targeted to reduce cardiovascular risk.
Sibutramine and orlistat are currently used for weight loss. We aimed to investigate the effect of orlistat and sibutramine combination therapy in treatment of obese women.
Study population consisted of 89 obese women who had a body mass index > or = 30 kg/m2, were normotensive, and had normal glucose tolerance. All patients were placed on a diet which contained fat approximately 30% of total calorie intake and the diet was designed to cause an energy deficit of approximately 2.51-3.56 megajoule/day. At the first month of diet (baseline), all patients were randomly divided into three therapy groups: Diet + Orlistat (group 1; n = 30 patients), Diet + Sibutramine (group 2; n = 29 patients), Diet + Orlistat + Sibutramine (group 3; n = 30 patients). Body weight, body fat distribution and serum lipid levels were evaluated baseline and after six months in all subjects.
Mean weight loss was 5.5 +/- 4.9 kg (p = 0.024) in group 1, 10.1 +/- 3.6 kg (p < 0.001) in group 2, 10.8 +/- 6.6 kg (p < 0.001) in group 3 after the six months. Weight loss was significantly greater in group 2 (p = 0.003) and group 3 (p = 0.002) when compared with group 1. Percentage of mean weight loss was 5.5 +/- 3.1% in group 1, 10.2 +/- 4.8% in group 2, 10.6 +/- 5.7% in group 3. Percentage of weight loss was higher in group 2 (p = 0.01) and group 3 (p = 0.009) when compared with group 1. Weight loss and percentage of weight loss were not different between group 2 and group 3.
These three regimens had different results on weight loss in obese women. Combination drug therapy and sibutramine therapy were both more effective than orlistat therapy alone. However, no significant difference was noted between combination drug therapy and sibutramine treatment groups.
In response to the increase in obesity, pharmacologic treatments for weight loss have become more numerous and more commonly used.
To assess the efficacy and safety of weight loss medications approved by the U.S. Food and Drug Administration and other medications that have been used for weight loss.
Electronic databases, experts in the field, and unpublished information.
Up-to-date meta-analyses of sibutramine, phentermine, and diethylpropion were identified. The authors assessed in detail 50 studies of orlistat, 13 studies of fluoxetine, 5 studies of bupropion, 9 studies of topiramate, and 1 study each of sertraline and zonisamide. Meta-analysis was performed for all medications except sertraline, zonisamide, and fluoxetine, which are summarized narratively.
The authors abstracted information about study design, intervention, co-interventions, population, outcomes, and methodologic quality, as well as weight loss and adverse events from controlled trials of medication.
All pooled weight loss values are reported relative to placebo. A meta-analysis of sibutramine reported a mean difference in weight loss of 4.45 kg (95% CI, 3.62 to 5.29 kg) at 12 months. In the meta-analysis of orlistat, the estimate of the mean weight loss for orlistat-treated patients was 2.89 kg (CI, 2.27 to 3.51 kg) at 12 months. A recent meta-analysis of phentermine and diethylpropion reported pooled mean differences in weight loss at 6 months of 3.6 kg (CI, 0.6 to 6.0 kg) for phentermine-treated patients and 3.0 kg (CI, -1.6 to 11.5 kg) for diethylpropion-treated patients. Weight loss in fluoxetine studies ranged from 14.5 kg of weight lost to 0.4 kg of weight gained at 12 or more months. For bupropion, 2.77 kg (CI, 1.1 to 4.5 kg) of weight was lost at 6 to 12 months. Weight loss due to topiramate at 6 months was 6.5% (CI, 4.8% to 8.3%) of pretreatment weight. With one exception, long-term studies of health outcomes were lacking. Significant side effects that varied by drug were reported.
Publication bias may exist despite a comprehensive search and despite the lack of statistical evidence for the existence of bias. Evidence of heterogeneity was observed for all meta-analyses.
Sibutramine, orlistat, phentermine, probably diethylpropion, bupropion, probably fluoxetine, and topiramate promote modest weight loss when given along with recommendations for diet. Sibutramine and orlistat are the 2 most-studied drugs.
To formulate EULAR recommendations for the management of early arthritis.
In accordance with EULAR's "standardised operating procedures", the task force pursued an evidence based approach and an approach based on expert opinion. A steering group comprised of 14 rheumatologists representing 10 European countries. The group defined the focus of the process, the target population, and formulated an operational definition of "management". Each participant was invited to propose issues of interest regarding the management of early arthritis or early rheumatoid arthritis. Fifteen issues for further research were selected by use of a modified Delphi technique. A systematic literature search was carried out. Evidence was categorised according to usual guidelines. A set of draft recommendations was proposed on the basis of the research questions and the results of the literature search.. The strength of the recommendations was based on the category of evidence and expert opinion.
15 research questions, covering the entire spectrum of "management of early arthritis", were formulated for further research; and 284 studies were identified and evaluated. Twelve recommendations for the management of early arthritis were selected and presented with short sentences. The selected statements included recognition of arthritis, referral, diagnosis, prognosis, classification, and treatment of early arthritis (information, education, non-pharmacological interventions, pharmacological treatments, and monitoring of the disease process). On the basis of expert opinion, 11 items were identified as being important for future research.
12 key recommendations for the management of early arthritis or early rheumatoid arthritis were developed, based on evidence in the literature and expert consensus.
To evaluate the long-term impact of Medifast meal-replacement supplements (MMRS) combined with appetite suppressant medication (ASM) among participants who received 52 weeks of treatment.
We conducted a systematic program evaluation of weight loss data from a medically-supervised weight control program combining the use of MMRS and ASM. Data were obtained and analyzed from 1,351 patient (BMI> or =25) medical charts who had participated for at least 12 weeks of treatment. Outcomes included weight loss (kg) and percent weight loss from baseline and at 12, 24, and 52 weeks. Both completers and intention-to-treat analyses were conducted. Completers' (i.e., those with complete data for 52 weeks) outcomes were evaluated after stratification for reported adherence to the MMRS and ASM.
Participants who completed 52 weeks of treatment experienced substantial weight losses at 12 (-9.4+/-5.7 kg), 24 (-12.0+/-8.1 kg), and 52 weeks (-12.4+/-9.2 kg) and all measures were significantly different from baseline weight (p<0.001 for all contrasts) for both true completers (n=324) and for ITT analysis (n=1,351). Fifty percent of patients remained in the program at 24 weeks and nearly 25% were still participating at one year.
This weight loss program using a combination of MMRS and ASM produced significant and sustained weight losses at 52 weeks. Results were better than those typically reported for obesity pharmacotherapy in both short- and long-term studies and also better than those reported for partial meal replacement programs. Program retention at one year was similar to that reported in many controlled drug trials and better than most commercial programs reported in the literature.
To use medications properly for treatment of the overweight patient, it is important to start with a framework based on the realities of its treatment. The following is a brief summary:
• Overweight results from an imbalance between energy intake and energy expenditure.
• Drugs can either reduce food intake or increase energy expenditure.
• Drug treatment does not cure the overweight patient.
• The therapeutic armamentarium of physicians is limited to only a few drugs.
• The use of drugs labors under the negative halo of treatment mishaps.
• Drugs do not work when they are not taken.
• Weight-loss plateaus during continued treatment occur when compensatory mechanisms come into play to counterbalance the effect of the drug.
• Monotherapy usually produces weight loss in the range of 10% (5% better than placebo).
• Frustration with the failure to continue to lose weight often leads to discontinuation of therapy and weight regain, with the drug labeled as a failure.
I. Introduction II. Criteria for Evaluating the Efficacy of Antiobesity Treatment III. Physiological and Pharmacological Mechanisms to Reduce Food Intake A. Peripherally acting agents B. Centrally acting agents IV. Drugs That Alter Metabolism A. Preabsorptive agents B. Postabsorptive modifiers of nutrient metabolism V. Drugs That Increase Energy Expenditure A. Thyroid hormone B. Adrenergic thermogenic drugs VI. Conclusion
Objective: To assess the safety and efficacy of minocycline in the treatment of rheumatoid arthritis. Design: A double-blind, randomized, multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo. Setting: 6 clinical centers in the United States. Patients: 219 adults with active rheumatoid arthritis who had previous limited treatment with disease-modifying drugs. Measurements: As the primary outcomes, 60 diarthrodial joints were examined for tenderness, and 58 joints were examined for swelling (hips excluded). Grip strength, evaluator's global assessment, morning stiffness, Modified Health Assessment Questionnaire, patient's global assessment, hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels were also assessed; radiographs of both hands and wrists were taken. Results: 109 and 110 patients were randomly assigned to receive minocycline and placebo, respectively. At entry, demographic, clinical, and laboratory measurements were similar in both groups. Most patients had mild to moderate disease activity and some evidence of destructive disease. At the week 48 visit, 79% of the minocycline group and 78% of the placebo group continued to receive the study medication. At 48 weeks, more patients in the minocycline group than in the placebo group showed improvement in joint swelling (54% and 39%) and joint tenderness (56% and 41 %) (P<0.023 for both comparisons). The minocycline group also showed greater improvement in hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels (all P values <0.001), and more patients receiving minocycline had laboratory values within normal ranges at 48 weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all greater than the critical value of 0.005 (Bonferroni adjustment for multiple comparisons). The frequency of reported side effects was similar in both groups, and no serious toxicity occurred. Conclusions: Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis. Its mechanisms of action remain to be determined
The increasing prevalence of obesity in the United States is widely recognized as a complex problem with significant public health implications, morbidity, mortality, and costs. Pharmacotherapy can contribute to the treatment of obesity. The regulation of appetite and body weight involves multiple parallel neuronal and bodily mechanisms. Not surprisingly, experience has shown that a medication that targets any one mechanism produces weight loss of 5%-10%. Although weight loss of this magnitude may produce significant reductions in risk factors associated with cardiovascular morbidity and mortality, patients expect cosmetically meaningful reductions in weight (~20%-25%). Combining 2 medications that work via different mechanisms, that is, "combination pharmacotherapy," is an approach to obtaining cosmetically relevant reductions in weight. The most effective example of this approach was the combination of phentermine and fenfluramine. This article will describe a novel combination pharmacotherapy developed in clinical practice: the combination of phentermine with the serotonin precursor L-5-hydroxytryptophan plus the peripheral decarboxylase inhibitor, carbidopa. Observational data on the efficacy and safety of this combination pharmacotherapy will be presented. In conclusion, combination pharmacotherapy can make important contributions to the treatment of obesity. Controlled clinical trials should be done before such combination treatments are widely adopted.
To assess continued efficacy of anorexiants after 3 years of use, 52 participants (43% of those starting) entered a second double-blind trial to compare 60 mg sustained-release fenfluramine plus 15 mg phentermine resin versus placebo added to behavior modification, caloric restriction, and exercise. Although participants in both the active medication and placebo groups gained weight, participants receiving fenfluramine plus phentermine (n = 27) gained significantly (p less than 0.01) less (4.4 +/- 0.5 kg or 5.3% +/- 0.5% of initial weight) than participants receiving placebo (n = 24) (6.9 +/- 0.8 kg or 8.5% +/- 1.1% of initial weight). At week 190, both groups were still below their initial weight (fenfluramine plus phentermine group, 5.0 +/- 1.4 kg; placebo group, 2.1 +/- 1.2 kg; p less than 0.01). Overall, 12 participants (23.5% of those still in the study) were greater than or equal to 10% below initial weight. One participant dropped out during this phase because of personal reasons and loss of medication efficacy. During the 30 weeks, participants receiving fenfluramine plus phentermine had 26 moderate or severe complaints versus eight participants receiving placebo. Fenfluramine plus phentermine provided better appetite control and only slightly more bother. Analysis of participant response in this phase by treatment assignment in the first double-blind phase (weeks 6 to 34) indicated that initial receipt of medication did not have negative learning effects. Eleven participants receiving active medication between weeks 6 and 34 and receiving placebo between weeks 160 to 190 gained 5.1 +/- 1.0 kg. In contrast, 13 participants originally taking placebo gained 8.3 +/- 9 kg in this second double-blind phase.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent (type II) diabetes.
Randomised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet, followed by randomised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction.
Patients attending diabetic outpatient clinic of city hospital.
Thirty four patients with established type II diabetes complicated by mild hypertension (systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions). Patients already taking antihypertensive agents (but not diuretics) not barred from study provided that criteria for mild hypertension still met. Conditions precluding patients from study were diabetic or hypertensive nephropathy, cardiac failure, and pregnancy.
After run in phase with recordings at seven weeks, three weeks, and time zero patients were allocated at random to receive moderate dietary sodium restriction for three months (n = 17) or to continue with usual diabetic diet. Subsequently nine patients in sodium restriction group continued with regimen for a further two months, during which they completed a randomised double blind crossover trial of sustained release preparation of sodium (Slow Sodium 80 mmol daily) for one month versus matching placebo for one month.
Reduction in blood pressure in type II diabetics with mild hypertension.
Supine and erect blood pressure, body weight, and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies. After parallel group study sodium restriction group showed significant reduction in systolic blood pressure (supine 19.2 mm Hg, erect 21.4 mm Hg; p less than 0.001) and mean daily urinary sodium excretion (mean reduction 60 mmol/24 h). There were no appreciable changes in weight, diabetic control, or diastolic pressure. No significant changes occurred in controls. In double blind crossover study mean supine systolic blood pressure rose significantly (p less than 0.005) during sodium supplementation (to 171 mm Hg) compared with value after three months of sodium restriction alone (159.9 mm Hg) and after one month of placebo (161.8 mm Hg).
Moderate dietary restriction of sodium has a definite hypotensive effect, which may be useful in mild hypertension of type II diabetes.
To assess the safety and efficacy of minocycline in the treatment of rheumatoid arthritis.
A double-blind, randomized, multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo.
6 clinical centers in the United States.
219 adults with active rheumatoid arthritis who had previous limited treatment with disease-modifying drugs.
As the primary outcomes, 60 diarthrodial joints were examined for tenderness, and 58 joints were examined for swelling (hips excluded). Grip strength, evaluator's global assessment, morning stiffness, Modified Health Assessment Questionnaire, patient's global assessment, hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels were also assessed; radiographs of both hands and wrists were taken.
109 and 110 patients were randomly assigned to receive minocycline and placebo, respectively. At entry, demographic, clinical, and laboratory measurements were similar in both groups. Most patients had mild to moderate disease activity and some evidence of destructive disease. At the week 48 visit, 79% of the minocycline group and 78% of the placebo group continued to receive the study medication. At 48 weeks, more patients in the minocycline group than in the placebo group showed improvement in joint swelling (54% and 39%) and joint tenderness (56% and 41%) (P < 0.023 for both comparisons). The minocycline group also showed greater improvement in hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels (all P values < 0.001), and more patients receiving minocycline had laboratory values within normal ranges at 48 weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all greater than the critical value of 0.005 (Bonferroni adjustment for multiple comparisons). The frequency of reported side effects was similar in both groups, and no serious toxicity occurred.
Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis. Its mechanisms of action remain to be determined.
This study assessed whether adding orlistat to sibutramine would induce further weight loss in patients who previously had lost weight while taking sibutramine alone.
Patients were 34 women with a mean age of 44.1 +/- 10.4 years, weight of 89.4 +/- 13.8 kg, and body mass index (BMI) of 33.9 +/- 4.9 kg/m2 who had lost an average of 11.6 +/- 9.2% of initial weight during the prior 1 year of treatment by sibutramine combined with lifestyle modification. Patients were randomly assigned, in double-blind fashion, to sibutramine plus orlistat or sibutramine plus placebo. In addition to medication, participants were provided five brief lifestyle modification visits during the 16-week continuation trial.
Mean body weight did not change significantly in either treatment condition during the 16 weeks. The addition of orlistat to sibutramine did not induce further weight loss as compared with treatment by sibutramine alone (mean changes = +0.1 +/- 4.1 kg vs. +0.5 +/- 2.1 kg, respectively).
These results must be interpreted with caution because of the study's small sample size. The findings, however, suggest that the combination of sibutramine and orlistat is unlikely to have additive effects that will yield mean losses > or =15% of initial weight, as desired by many obese individuals.
Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes.
We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups.
The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin.
Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.
Since passage of the Dietary Supplement Health and Education Act of 1994, the sale of herbal dietary supplements containing caffeine and ephedrine for weight loss has become widespread in the United States. Reports of adverse events associated with the use of these non-prescription supplements have raised concerns in the United States regulatory community. Restricting the use of these products is now being considered. Such restriction should be based upon controlled clinical trials. This review of the literature in Medline relative to the use of caffeine and ephedrine in the treatment of obesity concludes that caffeine and ephedrine are effective in causing weight loss. Caffeine and ephedrine give equivalent weight loss to Diethylpropion and superior weight loss compared to dexfenfluramine. Caffeine and ephedrine have a long history of safe, non-prescription use. The adverse events accompanying acute dosing are mild and transient. Adverse events with caffeine and ephedrine reach and remain at placebo levels after 4-12 weeks of continuous treatment, but data from randomized trials up to 6 months only are available. Obesity is chronic, requires chronic treatment, its incidence is increasing and it has few effective treatments. The benefits of caffeine and ephedrine in treating obesity appear to outweigh the small associated risks. Restriction of dietary herbal supplements containing caffeine and ephedrine, often with other ingredients, should be based on controlled clinical trials of these products.
In 1999, the American College of Physicians (ACP), then the American College of Physicians-American Society of Internal Medicine, and the American College of Cardiology/American Heart Association (ACC/AHA) developed joint guidelines on the management of patients with chronic stable angina. The ACC/AHA then published an updated guideline in 2002, which ACP recognized as a scientifically valid review of the evidence and background paper. This ACP guideline summarizes the recommendations of the 2002 ACC/AHA updated guideline and underscores the recommendations most likely to be important to physicians seeing patients in the primary care setting. This guideline is the second of 2 that provide guidance on the management of patients with chronic stable angina. This document covers treatment and follow-up of symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months. Sections addressing asymptomatic patients are also included. Asymptomatic refers to patients with known or suspected coronary disease based on a history or electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests. A previous guideline covered diagnosis and risk stratification for symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months and asymptomatic patients with known or suspected coronary disease based on a history or electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests.
To compare changes in anthropometric measures [body mass index (BMI), body weight] of obese patients treated with diet and exercise alone or additionally sibutramine, orlistat or the combination of both drugs, respectively. To describe encountered adverse effects.
Short-term (12 weeks), randomized, open-labeled trial. A total of 86 patients (18.6% male, age 41.1 +/- 8.7 years, BMI: 36.11 +/- 4.34 kg/m(2)) were randomized to (1) sibutramine group (10 mg/d, n = 22), or (2) orlistat group (3 x 120 mg/d, n = 25), or (3) combination group (10 mg sibutramine/d + 3 x 120 mg orlistat/d, n = 20), or (4) diet group (n = 19). The primary outcome parameter was a decrease in BMI. Additionally patient-reported adverse effects were reported.
The four interventional groups displayed decreases in BMI as follows: (1) -4.41 +/- 1.26 kg/m(2); (2) -3.64 +/- 0.97 kg/m(2); (3) -5.12 +/- 1.44 kg/m(2) and (4) -2.52 +/- 1.36 kg/m(2); with the diet group showing the significantly lowest decrease in BMI compared to the orlistat (P = 0.004), sibutramine (P < 0.001) or the combination groups (P < 0.001), respectively. Decreases in BMI did not statistically differed between the sibutramine group and the combination therapy group (P = 0.072). However, both treatment groups were significantly more efficient in decreasing BMI than the orlistat group (P < 0.001). In addition to well-known side effects, such as gastrointestinal disturbances, headache and dry mouth, newly described adverse effects were self-reported hypermenorrhea (13.6%, n = 3) with sibutramine and forgetfulness with orlistat (24%, n = 6).
In our study pharmacotherapy showed significant better results in the short-term management of obesity than dietary regimens alone. Sibutramine and sibutramine in combination with orlistat seemed to be equally effective in terms of weight reduction compared to orlistat monotherapy. Attention should be paid to the possibility of adverse effects.
Long-term, possibly lifetime, use of medications for the management of obesity may be thought to be similar to the use of pharmacotherapy for other chronic diseases such as hypertension or diabetes. Because there have been no systematic studies of this extended use, the experience of eight patients who have used obesity medications in a sustaining manner was studied.
The clinical characteristics of eight adult patients, each of whom has experience with long-term (more than 10 years) use of medications for weight loss and weight maintenance, were studied.
The clinical experience of these eight patients was analyzed. Each chose to sustain the use of weight management medications for more than 10 years because of perceived benefit, comfort, and the absence of significant side effects. There has been no evidence of the development of tolerance, addiction, or misuse and no adverse events related to the medication. The beneficial effects of the medication have not diminished with time.
The clinical characteristics of eight patients, each of whom has used obesity pharmacotherapy for more than 10 years, are described. The experience of these eight individuals cannot be generalized to the entire population of overweight or obese patients. It does suggest, however, that some patients respond successfully to this form of therapy and that they will derive value from it for the management of this disease. Efforts should be made to identify these patients, and consideration should be given to the use of chronic medications for the continuing management of obesity.
This paper reviews the preclinical and clinical evidence regarding the use of the dietary supplement 5-hydroxytryptophan (5-HTP) for the treatment of depression. In the absence of supplementation with exogenous 5-HTP, the amount of endogenous 5-HTP available for serotonin synthesis depends on the availability of tryptophan and on the activity of various enzymes, especially tryptophan hydroxylase, indoleamine 2,3-dioxygenase, and tryptophan 2,3-dioxygenase (TDO). Factors affecting each of these are reviewed. The amount of 5-HTP reaching the central nervous system (CNS) is affected by the extent to which 5-HTP is converted to serotonin in the periphery. This conversion is controlled by the enzyme amino acid decarboxylase, which, in the periphery, can be blocked by peripheral decarboxylase inhibitors (PDIs) such as carbidopa. Preclinical and clinical evidence for the efficacy of 5-HTP for depression is reviewed, with emphasis on double-blind, placebo-controlled (DB-PC) trials. Safety issues with 5-HTP are also reviewed, with emphasis on eosinophilia myalgia syndrome (EMS) and serotonin syndrome.
National Institutes of Health: NIH Consensus Development Conference Statement, Health Implications of Obesity
National Institutes of Health: NIH Consensus Development Conference
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Blood and Lung Institute Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults-the evidence report
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Cases of myxoedema and acromegalia treated with benefit by sheep's thyroids
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Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults-the evidence report
- National Institutes of Health, National Heart, Blood and Lung Institute