New research published at the European Congress on Obesity (ECO) shows that abrupt cessation after long-term use of the anti-obesity drug phentermine does not induce amphetamine-like withdrawal symptoms. The research is by Dr Ed Hendricks, Center for Weight Management*, Sacramento & Roseville, California, USA, and was funded by the American Society of Bariatric Physicians (ASBP).
Phentermine is a psychostimulant drug of the phenethylamine class, with pharmacology similar to amphetamine. It is approved as an appetite suppressant to help reduce weight in obese patients when used short-term and combined with exercise, diet, and behavioral modification. It is typically prescribed for individuals who are at increased medical risk because of their weight and works by helping to release certain chemicals in the brain that control appetite.
Phentermine was first approved by the U.S. FDA in 1959, prior to the time when the FDA decided obesity drug trials had to be conducted long-term for approval. Consequently American obesity medicine specialists currently prescribe phentermine long-term and have done so for the past 50+ years. While phentermine withdrawal syndrome has not been reported, due to its similarity to amphetamine there are concerns that such a syndrome might exist. This new study applied the stimulant withdrawal model for investigating abrupt phentermine treatment cessation.
In this new study, the duration of phentermine therapy in the study subjects ranged from one year to 21.5 years. This withdrawal study was nested in a larger study (reported separately as a poster at ECO2013: Abstract.
T5:P.114) in which the researchers looked for any sign or symptom of phentermine abuse, addiction (psychological dependence), or phentermine cravings in subjects on phentermine long-term and on phentermine short-term, and has been accepted for publication in the International Journal of Obesity.**
A total of 76 patients phentermine-treated for a mean of 8.4 years with a mean of 54 mg/day were tested with the 10-question Amphetamine Withdrawal Questionnaire (AWQ), modified for phentermine (PWQ), while taking phentermine (day zero [D0]) of the study). The drug was then withheld for 2 days, and the patients were tested with the PWQ on both days (D1 and D2), after which they resumed phentermine.
Total 10-item scores (out of a total maximum score of 40) were significantly different across the 3 days, going from 3.39 for day 0 to 3.55 for D1 and 2.99 for D2. EaHowever, the researchers found that the only individual question score that was significant was the hyperphagia (increased appetite) score, which increased from D0 to D1 and then went down again on D2. When hyperphagia scoring was deleted the remaining 9-item scores were not significantly different. Typically, AWQ total scores for methamphetamine (crystal meth)-dependent subjects are substantially higher than these, e.g. D0 scores of over 10, D1&D2 over 20. Dr Hendricks says:
“Other than hyperphagia, a symptom reflecting the loss of phentermine therapeutic effect after drug cessation, amphetamine-like withdrawal symptoms did not occur when phentermine was withheld. Abrupt cessation of phentermine after long-term treatment did not induce amphetamine-like withdrawal.”
He adds: “American obesity medicine specialists have found phentermine to be effective, safe and affordable. Recent surveys conform that this medicine is U.S. physicians’ first choice drug for treating obesity. Although the year 2000 European Union proscription of phentermine was lifted in 2002, the companies involved decided to not reintroduce the drug to the European market. As a result phentermine is not available for obesity treatment in Europe. Worldwide usage of phentermine has been curtailed because of persistent fears that the drug might induce addiction and that it might induce cardiovascular harm. However, this study suggests fears of causing addiction with long-term phentermine prescribing are exaggerated and present a needless barrier to better care for overweight and obese patients worldwide.”
Dr. Hendricks has previously published evidence from his practice that long-term phentermine treatment induces cardiovascular benefits rather than cardiovascular harm. The study (Hendricks EJ, Greenway FL, Westman EC, Gupta AK. Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity. Obesity (Silver Spring) 2011; 19(12): 2351-60) suggests that the fear that phentermine treatment increases cardiovascular risk is another needless barrier retarding use of an effective medicine for obesity treatment.***
Dr. Hendricks says: “Although some drugs used in the past to treat obesity did more harm than good, phentermine does not belong in that group. Phentermine and the other sympathomimetic drugs for weight loss are mistakenly stigmatised because their structures superficially resemble amphetamine. This structural similarity has led many to presume that phentermine should have the same adverse effects as crystal methamphetamine.
No evidence supporting such presumptions is to be found. On the contrary, the evidence strongly suggests phentermine is far safer than is commonly assumed. It is indeed unfortunate that these misconceptions hinder the availability of an effective, affordable medicine for treating obesity.”
* The Center for Weight Management is a private fee-for-service medical practice specialising in obesity medicine or bariatric medicine.
**The manuscript for the entire study has been accepted for publication by the International Journal of Obesity (Hendricks EJ, Greenway F, Srisurapanont M, Schmidt S, Haggard M, Souter S, et al. Addiction Potential of Phentermine prescribed during Long-term treatment of Obesity (APPLO Trial) International journal of Obesity. 2013;In Press (Manuscript # 2013IJO00126).
***extra info from Dr Hendricks: Dr. Richard Atkinson, co-editor of the International Journal of Obesity, suggested Dr Hendricks and his team conduct these addiction medicine studies being presented at ECO2013 after reviewing data from an earlier study presented at the Obesity Society meeting in 2009 and subsequently published in the American Journal of Therapeutics (Hendricks EJ, Greenway FL. A Study of Abrupt Phentermine Cessation in Patients in a Weight Management Program. American Journal of Therapeutics 2011; 18(4): 292-9).
Conflict of Interest: Dr. Hendricks has received honoraria from Akramax, Eurodrug Laboratories, Citius, and Vivus (all of which manufacture phentermine products). Abstract co-author Dr. Greenway has received honoraria from Baronova, Basic Research, Citius, Diabetic Living, Eisai, GNC, Jenny Craig, Lithera, Merck, Naturalpha, Nume Health, Orexigen, Plensat, Takeda, Thetis, Unigene, and Zafgen. Abstract co-authors Dr. Srisurapanont, Mr. De Marco, Ms. Hendricks, and Ms. Istratiy state no conflicts of interest.
Source: European Congress on Obesity (ECO)