New Evidence: Obesity Drug Phentermine Is Not Addictive

Rachel Pugh

May 24, 2013

LIVERPOOL, United Kingdom — New research shows that sudden cessation of the antiobesity drug phentermine does not induce amphetaminelike withdrawal symptoms, even in patients who have been taking it for decades.

The work, by Ed Hendricks, MD, and colleagues, from the Center for Weight Management, Sacramento and Roseville, California, was presented at ECO2013, the 20th European Congress on Obesity, last week.

It revealed that other than a feeling of hunger — reflecting the removal of phentermine's therapeutic effect — patients experienced no symptoms of dependence.

"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," said Dr. Hendricks.

But 1 European expert greeted the study with reservation, despite the shortage of pharmacological treatment options for obesity in the European Union.

Asked to comment, Jason Halford, PhD, who runs the biggest center dedicated to eating behavior and appetite regulation in Europe, based at Liverpool University, United Kingdom, told Medscape Medical News: "While these data provide some reassurance, the problem is that the drug is old and the data are very limited. Phentermine is only ever used as a treatment for obesity in the United States."

Added to this, "there are a number of other potential effects such as cardiovascular problems that also need to be considered," he stressed.

And asked about the new combination product Qsiva (Vivus), which contains a low dose of phentermine and extended-release topiramate, he said he is still not convinced of its benefits. The product is available in the United States but has twice been rejected by the European Medicines Agency.

Phentermine "Far Safer Than Commonly Assumed"

Phentermine is a psychostimulant drug of the phenethylamine class. It has suffered from an association with heart-valve problems as part of the diet drug combination "fen/phen" (fenfluramine and phentermine), which was withdrawn worldwide a number of years ago.

On its own, phentermine is primarily used as an appetite suppressant in the United States, to help reduce weight in obese patients combined with exercise, diet, and behavioral modification. It was taken off the market in a number of countries, including many in Europe, but is still available in many others, although it is often restricted to short-term use.

Dr. Hendricks said concerns about withdrawal syndrome with phentermine are based on its similarity to amphetamines but that no study to date has provided conclusive evidence of this effect.

In his study, he took 76 subjects who had been taking phentermine for between 1 and 21.5 years (mean, 8.4 years), on a mean dosage of 54 mg/day. They were tested to establish a baseline with the 10-question Phentermine Withdrawal Questionnaire (PWQ) — a modification of the Amphetamine Withdrawal Questionnaire.

The drug was then withheld for 2 days, and the patients were retested with the PWQ on both days (D1 and D2) before resuming phentermine.

Total scores (out of 40) were significantly different across the 3 days, ranging from 3.39 on D0 to 3.55 for D1 and 2.99 for D2. But breaking down the score into its components, the only significantly difference was for hyperphagia — excessive hunger — 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. Typical expected AWQ total scores for methamphetamine-dependent subjects would be much higher (in the region of D0 more than 10 and D1 and D2 more than 20), Dr. Hendricks said.

He also noted that he has previously published evidence from his practice that long-term phentermine treatment induces cardiovascular benefits rather than harm.

"Phentermine and the other sympathomimetic drugs for weight loss are mistakenly stigmatized because their structures superficially resemble amphetamine. The evidence strongly suggests phentermine is far safer than is commonly assumed," he asserted.

But European Union Doesn't Think So; Stalls on Latest Obesity Drugs

The EU authorities, at least, are not convinced of phentermine's safety. Rejecting Qsiva for the second time in February, the European Medicines Agency said phentermine is known to increase heart rate and its long-term effects "are not clear." It also had concerns about the long-term psychiatric and cognitive effects of topiramate.

But the same product was cleared for marketing in the United States last year, where it is known as Qsymia. Despite initial enthusiasm, however, sales of Qsymia are below expectation there, industry analysts say.

Dr. Halford told Medscape Medical News that while there is some possible merit in combining phentermine with topiramate — the combination allows the amount of each individual drug to be reduced compared with the dose required when used alone (in phentermine's case from around 50 mg down to 7.5 mg) — he still feels there are not enough data on the side-effect profile of the 2-drug product to make it an attractive proposition for licensing in Europe.

"There are no robust data on eating behavior, either," he stressed. "Given that the phentermine/topiramate preparation is supposed to be helping people with problems with appetite, they need the evidence to support that, but the entire focus is on outcomes. For a drug to be successful worldwide, it needs US and European backing."

A second potential obesity drug, lorcaserin (Belviq, Arena Pharmaceuticals), has also failed to gain marketing approval in the European Union, where the company withdrew its application earlier this month. It too has been cleared in the United States, where it is due for launch shortly.

Belviq and Qsymia have both been classified as schedule IV drugs — the second-least-restrictive designation on a 5-step scale — by the US Drug Enforcement Agency.

The Center for Weight Management is a private fee-for-service medical practice specializing in obesity medicine or bariatric medicine. Dr. Hendricks has received honoraria from Akramax, Eurodrug Laboratories, Citius, and Vivus (all of which manufacture phentermine products). Disclosures for the coauthors are available in the abstract. Dr. Halford has received funding from a number of manufacturers as director of the European-wide SATIN project.

20th European Congress on Obesity. Abstract T5:OS2.3, presented May 15, 2013.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.