Phen-Pro article in Family Practice News

The following article about Phen-Pro was published in the February 15, 2004 issue of Family Practice News.

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Phentermine + Prozac May Offer Safe Obesity Tx

Patrice G.W. Norton
Contributing Writer

CHICAGO — Although it's unlikely to gain federal approval, the combination of phentermine and fluoxetine was shown to be a safe treatment for obesity in a study presented at a symposium on obesity sponsored by the American Society of Bariatric Physicians.

Since 1995, Dr. Michael Anchors has given “phen-pro”—a combination of phentermine and Prozac (fluoxetine)—to 2,360 obese patients, some for as long as 8 years. Only one serious side effect was reported: acute psychosis after 1 week on phen-pro in a patient with a family history of manic-depressive illness.

A total of 615 patients reached a body mass index of 25 kg/m2, and the rest lost an average of 32 pounds. With only four exceptions, no one seen for regular visits gained back more than 10 pounds, said Dr. Dennis Padla, who presented the findings on behalf of Dr. Anchors, who did not attend the meeting. Dr. Anchors operates two Web sites on phen-pro.

Phentermine, approved by the Food and Drug Administration for the treatment of obesity, suppresses appetite by releasing norepinephrine in the hypothalamus. Adding low doses of certain selective serotonin reuptake inhibitors enhances the anorexiant effect.

The “fen-phen” combination of fenfluramine and phentermine was taken off the market in September 1997 because of its association with heart valve disease.

The phen-pro combination does not cause heart valve disease, as neither phentermine nor Prozac binds to the 5-HT2B receptor, Dr. Anchors commented in an interview. It is believed that overexpression of the serotonin 5-HT2B receptor in the heart leads to abnormal mitochondrial function and cardiac hypertrophy.

Neither drug is a substrate for the membrane serotonin transporter, and thus neither causes primary pulmonary hypertension as fenfluramine did, said Dr. Anchors of Georgetown University, Washington.

Cardiograms were conducted on Dr. Anchors' patients from 1997–1999, but he no longer orders the test. “It costs $500 for a cardiogram, and I can't get patients to do those,” he said. “I don't see the purpose. There were no problems.”

The phen-pro combination will never be approved by the Food and Drug Administration, Dr. Anchors predicted. “These are generic drugs and no pharmaceutical company has the financial incentive in presenting it,” he said. “I begged [Eli] Lilly to do it back then, but they were afraid of the backlash from the media.”

Dr. Anchors prescribes phen-pro for patients who have not responded to previous weight-loss therapies, and who have a body fat percentage greater than 20% for men and greater than 25% for women.

Patients typically receive a combination of 30 mg of phentermine and 10 mg of Prozac, as high doses of SSRIs block the action of phentermine. Patients are started at 15 mg of phentermine because many people can't tolerate the higher dose initially. Weight loss averages 2 pounds a week for the first 6 weeks, followed by an average of 1 lb/wk. The most common side effects are dry mouth, insomnia, rapid heartbeat, and sweating, usually during the first 10 days of treatment.

About two-thirds of patients taking phen-pro stop losing weight after a few weeks or months. When patients plateau, Dr. Anchors adds 100 mg of 5-hydroxytrytophan (5-HTP) to the regimen. About 50% of these patients return to an average weight loss of 1 lb/wk, with women more likely to respond than men.

All patients are advised to use phen-pro in combination with a healthy, low-calorie diet and exercise. “It is completely effective in lowering hunger, but hunger isn't the only reason people are overweight,” he said. “It may be that the medicine works less and less well because as they get leaner they are less hungry.”

Overall, 75% of patients need to continue taking a small dose of phen-pro to maintain their lower weight.

Dr. Anchors has found phentermine to be effective when combined with other antidepressants, including citalopram hydrobromide, sertraline, as well as venlafaxine (but not paroxetine, bupropion, or nefazone).

Few studies have been conducted on phen-pro. A 1999 study by Eli Lilly was based on an independent review of records from the private practices of Dr. Anchors, Dr. Padla, and Dr. Bonnie Lee.

No cases of primary pulmonary hypertension or cardiac valvulopathy were found in 711 obese patients treated with phentermine 30 mg and either 10 mg or 20 mg of fluoxetine once a day, or in a control group of 154 patients given phentermine 30 mg alone.

The phen-pro group lost an average of 11% of their starting weight by 18 months, and 20% reached a body mass index of 25 kg/m2.

On average, patients in the phentermine-only group lost 3% of their weight during the first 6 months of therapy, but by the end of the study they had returned to baseline and had even gained weight.

REFERENCE

Norton PGW. Phentermine + Prozac May Offer Safe Obesity Tx. 2004 Feb 15, 34(4):81.

I just heard of this combination of drugs today. I have been taking phentermine 37.5 mg qam and effexor xr 75mg at HS. Appetite was suppressed for about 2-3 weeks. I've been on this for 2 months. I have the same cravings and appetite that I had before taking the drugs. The only perk is that I feel a little more alert during the day.

I have been reading about the Phen-Pro Cocktail, and I happened to have started today on it. I am on 37.5mg of Phentermine and 20mg of Prozac daily. I hope this is a rational dose that I am, and hope to notice a difference soon.