Duromine (phentermine) and its role in obesity management

Phentermine (Duromine) is an appetite suppressant used in the management of obesity.1 Phentermine works by altering the metabolism of serotonin and norepinephrine in the body.2 The use of pharmacotherapy in the treatment of obesity is recommended for those individuals whose health is impaired by their weight, when other interventions have failed, and for those individuals who are at risk of obesity related co-morbid conditions. Phentermine is one option for the short-term management of obesity.

Obesity and pharmacological management

Obesity is a growing problem in Australia. The 1999-2000 Australian Diabetes, Obesity and Lifestyle Study indicated that over seven million adult Australians (60% of the adult population) were overweight or obese. These seven million adults comprised 67% males and 52% females.³

Excess body weight is associated with a series of serious health risks including coronary heart disease, type-2 diabetes and stroke. A recent study found that life expectancies are 3-4 years lower in overweight individuals, 6 or 7 years lower in obese individuals and up to 13 years lower in obese individuals if they also smoke.⁴

The Australian Department of Health and Ageing recommends pharmacotherapy for weight loss when lifestyle interventions (i.e. diet or exercise) fail and where the body mass index (BMI) of an individual is 30 or more with no additional co-morbid conditions or where an individual has a BMI of ≥27 and the patient has additional obesity-related co-morbidities.⁵

Pharmacological agents cannot substitute for good nutrition, and exercise. However in the case of obese individuals, the use of appetite suppressants, in conjunction with caloric reduction, exercise and behavioural modification, may benefit the weight loss process.⁶

Phentermine

Phentermine is a symphathomimetic amine with significant anoretic activity.⁹ It increases norepinephrine levels within the synaptic cleft, resulting in stimulation of beta-2-adrenergic receptors.⁸ As a consequence, appetite is reduced and satiety is increased. Phentermine has also been reported increase the effects of serotonin by inhibiting its reuptake.⁸ Phentermine is typically orally administered in doses of 15-40mg/day.⁹

There is a common misconception that phentermine has the same chemical structure to amphetamine. However it is not the same and importantly, it lacks the dependency and abuse issues associated with amphetamine use.⁷

There is no strong evidence of serious adverse events associated with the use of phentermine (though see below for problems when it is combined with fenfluramine).¹⁰ However, common mild to moderate side-effects include insomnia, anxiety and increased blood pressure and tachycardia.¹⁰ It is therefore not recommended for individuals with cardiovascular problems or hypertension.¹¹

Short-term management of obesity

Dr Andrew Dean, Consultant Physician said "phentermine helps establish a break in the habit of over-eating. In doing so, it allows significant weight loss in the first week or two which can then encourage people to continue to eat healthily- it is particularly useful as part of a dietary and behaviour modification plan."

There has been little research interest in Phentermine in the last 10 years. Recent meta-analyses have reported that 9 studies examined the effects of Phentermine from 1968 until 1999,¹¹ with no further studies to 2006.¹² Only 6 of these studies were randomised controlled trials. The meta-analyses examined the effectiveness of obesity drugs, including phentermine, in the weight loss process. Both meta-analyses reported that, in 6 randomised controlled trials, Phentermine led to an average weight loss in the range of 6 or 7 kg over a period of 12 weeks or less (around 3kg more than placebo).^11,12

The longest Phentermine trial, and perhaps the most successful, was conducted in 1968.¹³ The trial involved 108 women who were asked to follow a low-carbohydrate calorie-controlled diet (1000kcal/day). Phentermine was administered to the treatment groups either continuously, or intermittently (4 weeks phentermine, 4 weeks placebo) for 36 weeks. While only 64 women completed the trial, an average weight reduction of 12.6 kg was reported for the treatment groups, as compared with 4.8kg for the placebo group.¹³ Notably, the mean difference in weight loss for the two treatment groups and the placebo group was driven by weight loss in the first 20 weeks of treatment. In the last 16 weeks of treatment, mean weight change was equivalent for the three groups.

Limitations of Phentermine Use

Phentermine has limited use in the long-term treatment of obesity.⁵ Due to a lack of research evidence, it is recommended that phentermine be used only in the short term (up to three months).

Used in combination with another appetite suppressant – fenfluramine – phentermine was found to increase the risk of cardio valvular problems.¹⁴ As a result, fenfluramine is no longer available in Australia. When used alone, phentermine has not been associated with the same cardiac problems.¹⁵ In both Australia and the US, phentermine is currently approved for use in short term weight management but not for long-term use.^9,15 Phentermine is not currently available under the Pharmaceutical Benefits Scheme in Australia.

References

1. Appetite suppressant drugs. The Royal Society of Medicine Health Encyclopedia; 2000. London: Bloomsbury Publishing Ltd. Retrieved 2008 August 10, from http://www.credoreference.com.ezproxy.library.uwa.edu.au/entry/2226581/
2. Phentermine. In The American Heritage Dictionary of the English Language; 2007. Boston, MA: Houghton Mifflin. Retrieved 2008 August 10, from http://www.credoreference.com.ezproxy.library.uwa.edu.au/entry/7113432/
3. Australian Institute of Health and Welfare. Overweight and Obesity. [document on the internet]. Canberra: The Institute; [updated 2004 Dec 8; cited 2008 Aug 20]. Available from: http://www.aihw.gov.au/riskfactors/overweight.cfm
4. Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A,  Bonneux L. Obesity in adulthood and its consequences for life expectancy:  a life-table analysis. Ann Intern Med, 2003;138:24–32
5. Department of Health and Aging. NHMRC Clinical Practice Guidelines for the Management of Overweight and Obesity in Adults. Canberra; Commonwealth Government of Australia; [updated 2004 Mar 19; cited 2008 Aug 20]. Available from: http://www.health.gov.au/internet/main/publishing.nsf/Content/obesityguidelines-guidelines-adults.htm
6. Dieting. New Harvard Guide to Women’s Health; 2004. Cambridge, MA: Harvard University Press. Retrieved 2008 August 10, from http://www.credoreference.com.ezproxy.library.uwa.edu.au/entry/7878388/
7. Langlois KJ, Forbes JA, Bell GW, Grant, GF. A double-blind clinical evaluation of the safety and efficacy of phentermine hydrochloride (fastin) in the treatment of exogenous obesity. Curr Ther Res 1974; 16; 289-296.
8. Ioannides-Demos LL, Proietto J, McNeil JJ. Pharmacotherapy for Obesity. Drugs 2005; 65 (10): 1391-1418.
9. Duromine (Phentermine) Product Information. Thornleigh NSW: iNova Pharmaceuticals (Australia) Pty Limited, 2007 May 18.
10. National Task Force on the Prevention and Treatment of Obesity. Long-term pharmacotherapy in the management of obesity. JAMA 1996; 276(23):1907–15.
11. Schnee DM, Zaiken K, McCloskey WW. An update on the pharmacological treatment of obesity. Curr Medical Research and Opinion 2006; 22;1463-1474.
12. Haddock CK, Poston WS, Dill PL, Foreyt JP, Ericsson M. Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomised clinical trials. Int J Obes Relat Metab Disord 2002; 26:262–73.
13. Munro JF, MacCuish AC, Wilson EM, Duncan LJP. Comparison of continuous and intermittent anorectic therapy in obesity. BMJ, 1968, 1, 352-354.
14. Connolly HM, Crary JL, McGoon MD et al. Valvular heart disease associated with fenfluramine-phentermine. New Engl J Med 1997; 337: 581-8.
15. Centre for Drug Evaluation and Research. “FEN-PHEN" UPDATE. Maryland USA; United States Food and Drug Administration [updated 1997 August 27; cited 2008 August 20]. Available from: http://www.fda.gov/cder/news/phen/fenphenupdate.htm