Off-label drugs for weight management.

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 approved 208 drugs for cancer, 118 for cardiovascular diseases, 168 for neurological diseases, 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.

Pharmacotherapy for Obesity and Changes in Eating Behavior: a Patient and Physician's Perspective.

This article, co-authored by a patient with obesity, diabetes, and hypertension, and an obesity medicine specialist, discusses the patient's experience with the onset of diabetes complicating obesity and with her frustration living with these diagnoses until finding an obesity medicine specialist physician who helped her lose weight and reverse her diabetes. The patient continues to maintain a significant weight loss and is diabetes free for 5.5 years after treatment initiation. The physician discusses the application of combination treatment that can be effective in diabetes reversal in such cases. He also discusses salient clinical lessons exemplified by this case.

How physician obesity medicine specialists treated obesity before 2012 new drug approvals.

BACKGROUND: A survey of obesity medicine specialists was conducted before the approval of new obesity medications in 2012. METHODS: An Internet survey was sent to obesity medicine specialists inquiring about their practice and prescribing habits. RESULTS: Twenty-five percent of 1992 obesity medicine specialists responded. They used stimulant obesity medication for longer and at higher doses than recommended in the package insert. Medications for other indications were used off-label alone and in combination for obesity treatment. Only 15 % saw surgical patients. CONCLUSIONS: The survey is a baseline for when more obesity medications exist in 5 years. We hope discovering a lack of collaboration between obesity medical specialists and obesity surgeons will stimulate more team work that will benefit obese patients contemplating or undergoing obesity surgery.

Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity.

There is a perception that phentermine pharmacotherapy for obesity increases blood pressure and heart rate (HR), exposing treated patients to increased cardiovascular risk. We collected data from phentermine-treated (PT) and phentermine-untreated (P0) patients at a private weight management practice, to examine blood pressure, HR, and weight changes. Records of 300 sequential returning patients were selected who had been treated with a low-carbohydrate ketogenic diet if their records included complete weight, blood pressure, and HR data from seven office examinations during the first 12 weeks of therapy. The mean time in therapy, time range, and mode was 92 (97.0), 12-624, and 52 weeks. 14% were normotensive, 52% were prehypertensive, and 34% were hypertensive at their first visit or had a previous diagnosis of hypertension. PT subjects systolic blood pressure/diastolic blood pressure (SBP/DBP) declined from baseline at all data points (SBP/DBP -6.9/-5.0 mm Hg at 26, and -7.3/-5.4 at 52 weeks). P0 subjects' declines of SBP/DBP at both 26 and 52 weeks were -8.9/-6.3 but the difference from the treated cohort was not significant. HR changes in treated/untreated subjects at weeks 26 (-0.9/-3.5) and 52 (+1.2/-3.6) were not significant. Weight loss was significantly greater in the PT cohort for week 1 through 104 (P = 0.0144). These data suggest phentermine treatment for obesity does not result in increased SBP, DBP, or HR, and that weight loss assisted with phentermine treatment is associated with favorable shifts in categorical blood pressure and retardation of progression to hypertension in obese patients.

A study of abrupt phentermine cessation in patients in a weight management program.

Phentermine is the most widely used antiobesity drug in the United States. Although no evidence of phentermine addiction has been published, fear that phentermine has addiction potential has contributed to curtailment of its worldwide use in clinical practice. The aim of this study was to evaluate the abuse and addiction potential of long-term phentermine pharmacotherapy in patients in a weight management program. Thirty-five patients in a weight management program who abruptly stopped taking prescribed phentermine on their own initiative were examined using the 18-item Kampman Cocaine Selective Severity Assessment scale modified for phentermine. The Kampman Cocaine Selective Severity Assessment scale has also been modified by McGregor for amphetamines to assess withdrawal from amphetamine in amphetamine-addicted subjects. For comparison, 35 new patients were examined with the same scale before any treatment was initiated. Data from the treated and untreated groups were compared by t test with each other and with published data from amphetamine-addicted subjects. There were no significant differences in individual items or total scores between the patients who stopped phentermine abruptly and the patients who had never taken phentermine. There was a striking and significant difference in individual and total scores between the phentermine-treated subjects and the amphetamine-dependent subjects. Cravings for the substance abused, the hallmark characteristic of substance dependence and withdrawal, were entirely absent in the phentermine-treated subjects. Abrupt cessation of long-term phentermine therapy does not induce amphetamine-like withdrawal. Long-term phentermine therapy does not induce phentermine cravings. Symptoms observed after abrupt phentermine cessation represent loss of therapeutic effect and are not withdrawal.

Phentermine cardiovascular safety II: response to Yosefy Int J Cardiol. 2009 Epub Mar 19.

This is the fourth in a series of letters-to-the-editor discussing phentermine and cardiovascular safety. Yosefy et al., in reporting a case of aortic cusp tear in a 28 year-old woman with a bicuspid aortic valve, attributed the tear to previous phentermine therapy. Evidence of mitral and tricuspid valve thickening was noted at echocardiography. In replying we pointed out that phentermine-induced valvular heart disease has not been reported and suggested that, since the reference cited for support referred to fenfluramine-induced valvulopathy, the attribution of the cusp tear to phentermine was incorrect. Yosefy replied, asserting that since the patient had no other cardiac risk factor, the tear had to be due to phentermine. In support of his presumption that phentermine therapy can induce cardiac risk he cited only the PDR warnings for phentermine. In this reply we point out that a congenital bicuspid valve should not be ignored as a cardiac risk factor, that aortic valve cusp tears have been associated with bicuspid valves but never with phentermine or with valve thickening no matter the etiology, and that there is no published data implicating phentermine as a cause of valve thickening (or any other valve pathology). Evidence of phentermine safety in the peer-reviewed medical literature is discussed in the context of the cardiovascular warnings for phentermine in the PDR.

How physician obesity specialists use drugs to treat obesity.

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.