ASK DR. BAUGHAN                                                         September 5, 1997

FEN-PHEN FALLOUT

I was quite disconcerted when I returned from vacation to have several patients ask me about the reports of heart problems associated with the use of the diet pills fenfluramine and phentermine.  I had prescribed these medications to patients, so my first reaction was, “Uh-oh, has anyone been harmed?”  My second reaction was, “I can’t go on vacation without becoming ignorant of important medical issues.”  Equally frustrating over the next two months was the inability to get details of these reports of heart problems.

Finally, last week’s edition of the New England Journal of Medicine published several articles with the findings that prompted the public health alert.  The lead article was by Dr. Connolly of the Mayo Clinic.  She and her associates found 24 women who had developed an unusual form of heart valve problems.  Five of the women had heart surgery, so the valves themselves could be examined.  These five all had heart valves that were covered with shiny plaques of fibrous tissue that made the valves thick and harder to open and close properly.  The other 19 had echocardiograms that gave pictures of the heart valves that looked similar in outline and action to the five who had surgery.  Dr. Connolly notified the Food and Drug Administration of her findings; then the FDA put out a call for other reports.  In this same issue, a letter from the FDA reports 28 additional similar cases have been identified around the country.  So far, all of the cases have been associated with the combination of fen-phen or with fenfluramine.  None of the cases have been women who took phentermine by itself.  Some of the cases improved after stopping the medicines, but some got worse even after stopping.  Most of the women had been taking the pills for a year, but a couple had only been taking them for  few months.  So far, no reported cases in men.

Why would a diet pill affect the heart valves?  Unfortunately, medicine goes throughout the body, not just where we want it to go.  The positive affect on appetite suppression may be in a small part of the brain, but the medicines stimulate the body to produce more serotonin, which is in the blood stream in your toes as well as your heart.  Serotonin is suspect because some of the only other known cases of this particular type of heart valve problem occur in a rare type of tumor (called carcinoid) that produces high levels of serotonin or with other uncommonly used medicines of the ergot-alkoloid family that also cause serotonin production.  Anti-depressant medications increase serotonin production, but the person was low in serotonin to begin with.  No such heart valve problems have been reported with anti-depressant medicines.

How big a risk is this?  In 1996, there were 18 million prescriptions for fen-phen.  With less than 100 cases identified, we cannot yet claim clear cause and effect.  Did these women have some unknown predisposing factor to this problem?  Did they already have a little bit of a valve problem that the medicine aggravated?  No easy answers.  What can we take away from this?  Will I still prescribe these medicines?  Certainly more cautiously and with more patient counseling.  I have been recommending trials of phentermine alone to begin weight loss, rather than starting with fen-phen routinely.  I have always reserved the medications for people more than 20% above their ideal body weight where the weight posed certain health risks.  I have discouraged use of medicines if someone hoped to lose 5-10 pounds for cosmetic reasons.  Once again, Nature has taught us that medical intervention must be done with respect for the balance of risks to benefits.  It’s a humbling business.