INTRODUCTION

Recently, the desire for weight loss, in particular in women has increased around the world. There are some ways to lose weights, such as eating habit modification, exercise, anorectics and bariatric surgery¹. Among them, anorectic drugs were originally designed to cure people suffering from obesity or complications of obesity. However, some studies have reported the problems with the abuse of anorectics^2-18.

In this narrative review, it investigated anorectic drugs used worldwide (amfepramone, amphetamine, benzphetamine, diethylpropion, fenproporex hydrochloride, liraglutide, lorcaserin, naltrexone/bupropion, orlistat, phendimetrazine, phentermine, rimonabant, sibutramine and topiramnate)^1-7,19-23 and several supplements (α-amylase inhibitor, α-lipoic acid, caffeine, chitin, cocoa, dietary fiber, green tea, Phyillyrea latifolia leaves and rimonabant)^2,21,24-26.

Although anorectic drugs, such as, orlistat should only be used by overweight adults, Alli (OTC name of orlistat) can be purchased online regardless age or weight in the USA²⁶. Accordingly, it focused on drugs likely to be misused or abused (e.g., fenfluramine, orlistat, phendimetrazine, phentermine and sibutramine) and investigated their abuse and side effects. To prevent the misuse and abuse of anorectic drugs, the roles of health professionals are indispensable. Pharmacists deliver interventions for weight management, help select and monitor anorectics and provide patients with comprehensive dietary advice and information^19,26-34. Doctors assess patient’s habits and provide counseling regarding weight loss^1,35-39 and nurses provide weight-related interventions and conduct training and organizational support for obesity management^40-42.

The objectives of this narrative review were to identify types of anorectic drugs (anorectics) likely to be misused or abused, to define the roles of health professionals, to determine levels of cooperation between health professionals and to suggest appropriate policies and programs. This narrative review will be able to stimulate health professionals, who have continued to make efforts to protect people from abuse of anorectics and will give an opportunity for health professionals to be more interested in the abuse of anorectics than now.

APPROACH TO A NARRATIVE REVIEW

It was conducted comprehensive study to obtain information on types of anorectics, their abuse and roles of health professionals in the context of anorectic abuse. Searches of PubMed, Science Direct and Google Scholar were conducted to identify documents published between 1996 and 2016. To identify overall information about anorectics including types and abuse aspects, it searched the following keywords: "Anorectics", "Anorectic drug abuse", "Weight control drug", "Weight loss" and "Drug abuse". After collecting information about anorectics, it focused on the roles of health professionals in the prevention of anorectic abuse and then, it searched for the following keywords: "Anorectic abuse", "Health professional", "Pharmacist", "Doctor", "Nurse" and "Intervention". In particular, a search for "Obesity" plus "Pharmacist" identified 153 papers, including 75 papers published during the last 5 years. Among 153 papers, it excluded duplicates from difference sites and checked the relevance with our narrative review. The criteria for choosing references was the roles of pharmacists, doctors, nurses and other health professionals about the abuse of anorectics and then 92 papers were excluded in the final reference list and it referred to four studies to figure out characteristics about narrative reviews^43-46. Finally, it selected a total of 65 papers as references.

TYPES OF ANORECTICS

Anorectic drugs are being used worldwide (Table 1). Amfepramone is a schedule 3 controlled drug in the UK⁴⁷ and has been used to treat obesity for more than 50 years, but is abused due to its low-cost in Brazil⁴⁸. In fact, about 1,277 adults who were using amfepramone in Southern Brazil, 81% had an anorectic prescription. Mean period of usage was 8.7 months⁴⁹.

Benzphetamine and diethylpropion are used for short term treatment and approved by FDA as schedule III and IV drug, respectively. They are used much less than phentermine, though they tend to suppress the appetite of patients. Also, they are possible to cause side effects and have considerable problems from latent ability about abuse¹.

In 1999, fenproporex was withdrawn from market in France because it is inefficient for treating obesity. At time of discontinuation, users experienced withdrawal syndromes including anxiety and nightmares followed by depression Pelissier-Alicot et al.⁵⁰.

Some anorectics, including phentermine are recommended for short term use. The US Food and Drug Administration (FDA) had approved 5 anorectic drugs, that were orlistat, lorcaserin, phentermine/topiramate, naltrexone/bupropion and liraglutide for long term use^1,19. Although some weight loss drugs have been withdrawn because of severe side effects, the FDA and the European Medicines Agency (EMA) differ in terms of approvals and/or withdrawals of anorectics.

Table 1:	Several kinds of anorectic drugs and supplements

Sibutramine, orlistat and rimonabant have been used as anorectics for 15 years in Sweden and although sibutramine was withdrawn from the European market, it can be purchased on the web and is considered as a main drug for weight loss². In Brazil, the drugs most used for weight loss are amphetamine, sympathomimetic amines (40.5%), amfepramone, fenproporex hydrochloride and sibutramine²³.

Rimonabant has been used for treatment of anti-obesity in Sweden. Rimonabant was reported that it had potential for malformation and health problems, such as pes equinovarus and coarctation of aorta in case study for infants from mothers who took rimonabant in early pregnancy².

Some agents, not medicines are also available for weight loss. For example, α-lipoic acid induced weight loss in over-weight diabetes mellitus type 2 patients²⁵ and Phillyrea latifolia leaves are considered weight loss agents due to their ability to reduce obesity associated with cellular problems²⁴.

Caffeine, cocoa and green tea have also been used to induce weight loss. Dietary fiber not digested carbohydrates can reduce weight by disturbing energy intake²¹. To lose weight, youths have abused OTC drugs and supplements including laxatives in the USA. However, these agents are not used to lose weight and abuse can cause severe health problems²⁶. Though there is no evidence about losing weight, α-amylase inhibitor and chitin are used to decrease calorie intake by inhibiting nutrients, such as carbohydrates and fat, from absorption in the body²¹.

ABUSE OF ANORECTICS

Young women in particular misuse and abuse drugs to reduce weight despite having a normal body weight after purchasing drugs illegally online. For this reason, it focused on anorectics likely to be misused or abused (e.g., fenfluramine, orlistat, phendimetrazine, phentermine and sibutramine) and investigated their abuse and side effects (Table 2).

In one Brazilian study, 31.1% of college students took anorectics prescribed by doctors (31.1%) and 17.8% took non-prescribed drugs²³. After long-term treatment, abrupt cessation of fenfluramine and its derivative (dexfenfluramine) can induce depressive withdrawal symptoms^6,21. The seriousness of the side effects of fenfluramine and its derivatives have been well discussed and include a significant risk of heart disease. For this reason, they were withdrawn from market in 1997^6-9.

In the case of orlistat, western countries, including the USA have mostly reported results of orlistat abuse, which is viewed as a compensatory behavior in those with an eating disorder. In India, orlistat is an abused OTC drug due to its availability, peer pressure and the desire to wear western dress¹⁰. Orlistat has also been misused among normal weight patients with bulimia nervosa and caused severe problems. Patients who took Alli (OTC name of orlistat) at ten times recommended doses, which surpasses the intensity of prescription orlistat, experienced more serious side effects.

Table 2:	Abuse and side effects of anorectic drugs

Also, patients that misused orlistat with laxatives experienced fluid and electrolyte imbalances, which sometimes resulted in a heart accident of medical concern or death¹². Main side effects of orlistat are associated with the gastrointestinal tract and include fatty/oily stools, fecal incontinence, repeated or sudden bowel movements and flatulence^7,11,12.

Phendimetrazine is a prodrug for the monoamine releaser phenmetrazine and an anorectic that has an analogous process with norepinephrine^14,21. Phendimetrazine is known as a treatment for patients with cocaine use disorder and has been reported to be associated with abuse in cocaine-dependent patients⁵. It was mentioned that sympathomimetric drugs, including phendimetrazine have potential for adverse effects similar to amphetamine, such as insomnia. Therefore, phemdimetrazine was used for short-term treatment (less than 12 weeks)²¹.

Although some researchers have reported that phentermine does not induce dependence or withdrawal syndrome after short or long-term treatment^3,4 and through several studies, it is recommended that phentermine be taken for less than 12 weeks due to the possibility of addiction and uncertain long-term safety^7,15. However, phentermine is often prescribed as off label and sold in the market as obermine, phenterex, obephe and etc., in US.¹ Phentermine has been associated with serious health problems, such as, hypertension, vasculopathy and mental illness¹⁵.

Sibutramine is an anorectic and a serotonin and noradrenalin re-uptake inhibitor in the hypothalamus^17,18. One Korean patient who ingested 280 mg of sibutramine presented thyrotoxicosis with thyroiditis¹⁷. In addition, sibutramine has been associated with elevations in blood pressure, heart rate and adverse heart events^7,18. Also, it was reported that babies from mother who used sibutramine for anti-obesity tend to have high potential for serious malformation². In 2010, sibutramine was withdrawn by the FDA and in European market due to the risk of cardiovascular events^7,9. However, sibutramine is still sold through the internet and used for making some items which are not medical drugs but products related to anti-obesity².

Roles of pharmacists, doctors and nurses and the prevention of the abuse of anorectic drugs: To prevent the misuse and abuse of anorectic drugs, the roles of the health professionals are indispensable. Health professionals should pay attention to anorectic drugs because these drugs have often been abused by patients with an Eating Disorder (ED)¹⁰. In one case, a person with an ED misused Alli and experienced diarrhea. To prevent this type of accident, health professionals should monitor orlistat because it can be accessed easily and is prone to abuse in the short and long-term⁵¹. Attitudes of health professionals are also important because they effect obese patients⁵².

Although guidelines have been established to support health professionals regarding the treatment of obesity in USA, UK and Europe²² several barriers remain with respect to the counseling of obese patients. The main barriers are lack of time (76.8%), lack of patient interest (55.8%) and lack of reward/return (49.3%)⁵³. Actually, many patients are not prepared to pay pharmacists for management of obesity⁵⁴.

Health professionals make efforts to ensure the appropriate use of anorectics. The roles of individual health professionals are shown in Table 3.

Roles of pharmacists: In Australia, pharmacists educate consumers about prevalently used anorectics²⁸. As consumers regarded pharmacists as important health professionals for weight management, pharmacists are able to deliver appropriate advice about weight management. They can provide female consumers who need to manage weight with proper advice and knowledge about meal replacement products and herbal products²⁷. In USA, to meet the need to manage weight effectively³², pharmacists help consumers to choose and monitor anorectics properly¹⁹ and reclassify anorectics by developing regulations regarding 3rd class of BTC (behind-the-counter) drugs²⁶. In addition, they provide interventions for preventive health services in rural areas on a clinic basis with follow-up to manage weight loss extensively³⁰. In USA, it would be better for pharmacists to combine both behavioral and pharmacological treatment. Also, there was a need to determine how to combine treatments properly, because many efficient, secure anorectic drugs were available on prescription and as OTC drugs³¹. In UK, many services for public health are provided including telephone counseling, which is efficient and cost-effective for long-term weight management²⁹. Individuals can use a telephone or request person-to-person care, which is a more efficient approach for maintaining weight loss than education alone³⁰. In Thailand and Kuwait, obese patients are provided with programs to improve behavior and knowledge about weight and obesity^33,34. In Thailand, Primary Care Units (PCUs) provided pharmacists with the opportunity of establishing weight loss programs. Also, PCUs enable various health professionals, such as, doctors, nurses and community staff, to offer health services to satisfy needs related to local health³³. In Kuwait, plans were proposed to create behavioral changes to increase physical performance and improve aspects related to eating. Some of these proposals included improving of information regarding obesity, counseling skills and raising patient awareness of the value of communicating with pharmacists³⁴.

Table 3:	Roles of pharmacists, doctors and nurses against the abuse of anorectics

Roles of doctors: Doctors can contribute to reduce the obesity epidemic by adopting pharmacotherapies that meet consumer’s needs, comorbidities and drug safety criteria. Doctors should inform patients when and how to cease therapy if weight loss is not achieved or if side effects outweigh drug benefits. In USA, doctors provide information on effective drugs for weight loss and help to manage obese patients with a comorbid status¹. It is important that patients are provided with accurate information about obesity and the opportunity to lose weight with the assistance of doctors³⁸. To prevent and treat obesity, advice from doctors is important for obese patients³⁸. If a chronic care model is adapted to treat obesity, it is expected to facilitate effective treatment and provide patients with scientific information suitable for the management of obesity⁵⁵. Doctors can encourage obese patients to lose weight through counseling³⁹. In Australia, doctors check and counsel patients about lifestyles and dietary habits. While many efficient ways have been developed to address obesity, doctors did not consider obesity treatment as their roles³⁵. However, in UK, although doctors considered their advice useless, they were found to be critical for the treatment of obesity³⁶.

Roles of nurses: In UK, nurses involved in primary care also participate in interventions targeting obesity^40,42. To conduct intervention efficiently, it has been suggested that there is a need to develop an education program for nurses and to inform nurses and patients that self-assessment is important for treating obesity⁴⁰. According to a study conducted in the UK, Chinese nurses conduct weight management programs better than English nurses⁴². Also, nurses who display confidence and a proper attitude when conducted weight counseling provide patients with organizational assistance⁴¹. It is important that patients consider interventions through nurses important for weight control and management⁴⁰. To support nurses who are familiar with skills required for successful intervention, there are needs to establish standardized guidelines for obesity-related care, educate nurses to treat obesity properly and encourage nurses to provide appropriate intervention^41,42.

Systematic programs against anorectics: There is a need for efficient educational programs to prevent the abuse of anorectic drugs by obese patients.

As obesity has increased among children, the Centers for Disease Control (CDC) and other related authorities have promoted increasing time spent on physical activities to prevent obesity^56,57. Web-based programs are more efficient for teens with respect to changing dietary habits and health conditions^58,59 and nutrition-related education is needed to encourage obese adults to consume more fruits and vegetables⁶⁰. Also, there is a need to prepare programs for the illiterate and individuals with a poor educational background, because in one Iranian study it was found educational levels were related to obesity⁶¹. Some programs for health promotion are important for mothers to provide them with information about the risk of stillbirth, which is strongly related to maternal obesity and to encourage them to increase physical activity levels and take measures to prevent their children from becoming obese^62-64. In USA, community based nutritional intervention programs have been reported to improve female health and reduce waist circumferences and depression⁶⁵.