This is not F.D.A. approved; however, preliminary research shows it is effective short term. The long term benefits and problems are not know at the time, because it has not been in use long enough to draw any significant conclusions.

Treatment for obesity with the fenfluramine-Phentermine combination (fenphen) was widespread until about a year ago. However, reports of fenfluramine-related primary pulmonary hypertension have been disturbing. Fluoxetine has a similar chemical structure to fenfluramine, but has not been associated with this complication.

The author of this report describes 557 patients he has treated for more than 2 years using fluoxetine instead of fenfluramine in the fen-phen combination. The patients each lost an average of over 14 pounds; there were only 7 patients who did not lose weight. Treatment in eight patients had to be discontinued for the following reasons; three got insomnia, 2 experienced palpitations, one became nausiasted, and two diabetic patients had increased hyperglycemia (high blood sugar). However, glycemic control was improved in other patients with diabetes, and blood pressure was reduced in patients with hyperten-sion. After completing treatment and reaching their ideal weight, one fourth of patients maintained their weight loss with no additional treatment. The other three-fourths continued on low-dose therapy.

The effective fluoxetine dosage used in these patients was 10 mg./day. According to the authors of the report, initial stimulant side effects can be avoided by starting at 15 mg/day (half the usual dosage), and increasing it to the full 30mg/day dosage after 1 week. Other Serotonin-enhancing drugs that seem to be safe and effective in combination with phentermine are; sertraline (Zoloft), fluvoxamine (Luvox), and trazodone (Desyrel). Paroxetine (Paxil), bupropion (Wellbutrin), and the TCA's have not been shown to be effective for weight loss.

Brand Names

Wellbutrin

Pondimin

Prozac

Luvox

Fastin, lonamin

Zoloft

Trazodone

Generic Names

Buprorion

Fenfluramine

Fluoxetine/Fluvoxamine

Phentermine

Sertraline

Desyrel

Alternatives to Phen/Fen

Now that Pondimin (fenfluramine) and Redux have been the subject of a voluntary recall by their manufacturer, Wyeth-Ayerst, the question has arisen regarding safe and effective alternatives.

Phentermine is still viable for use. It has the effect of increasing the metabolism by raising the levels to two neurotransmitters (brain chemicals), dopamine and norepinephrine, in the spaces between neurons, or nerve cells. This is accomplished by blocking absorption of these two chemical messengers, thus allowing them to stay in this space longer and be more readily available for use. Phentermine also has the effect of causing a decreased appetite- Because it increases metabolism, some people experience side effects; such as headaches, insomnia, dry mouth, jitteriness, and constipation- However, by carefully metering the dose that is taken, these side effects can be diminished.

Since the recall of Pondimin and Redux, the challenge has been to find a replacement for fenfluramine. The replacement must raise levels of serotonin (a chemical naturally found in the body) while diminishing the risk of PPH (primary pulmonary hypertension) and the possibility of heart valve damage. This increased serotonin level will result in a decrease in appetite. and patients will require much smaller amount of food in order to feel full. The way this normally works is that food intake, especially carbohydrates, increases the level of serotonin, which produces a feeling of fullness. By using a chemical agent to increase the serotonin level available, this feeling of fullness can. be achieved with minimal amounts of food- Side effects of serotonin-increasing agents include diarrhea and drowsiness.

As mentioned above, the two medications in question have opposite side effects (phenter-mine increases metabolism, thereby causing jitteriness and constipation, and serotonin-increasing agents slow you down, which causes drowsiness and diarrhea). Therefore, if the two medications are "balanced" against each other, it should "cancel out" most of the side effects while retaining the effectiveness of the weight loss characteristics of both medications.

Fortunately, there has a great deal of research done on serotonin-increasing agents. The ones mentioned here have a long track record, and there is a wealth of data supporting their safety. That is why Trazodone (Desyrel) and Prozac were chosen first. Each has been used extensively (some say the latter too much in the 1980's) and a myriad number of studies was conducted on each is the past- I advocate that Trazodone should be the primary replacement for Pondimin. This medication has previously been prescribed as an antidepressant at doses over three times as great as those needed for the weight loss combination. Though Trazodone effectively raises serotonin levels, it also can cause drowsiness, and has often been prescribed for insomnia. This is a beneficial side effect in the first days of an individual's treatment with Phentermine when insomnia can be a problem for patients trying to adjust to the medication.

Prozac ran also be substituted for fenfluramine. It is an excellent alternative, but one which is has gotten the reputation of being over-prescribed and often abused. There are also more side effects involved with this combination, than with Trazadone when equivalent doses are used. Drowsi-ness usually occurs at high doses, and can lead to more side effects. Therefore, even though Prozac is just as tenable a replacement as Trazodone, I tend to prefer the latter.

An obvious question that many people may be wondering is, "Why do these medications, which work just as effectively as fenfluramine, not pose the same health risks?" One reason lies in the way fenfluramine effects the amount of serotonin in the body. Instead of inhibiting the absorp-tion of seronotin, the way phentermine does with dopamine and norepinephron, fenfluramine causes more serotonin to be released. This raise in serotonin is not as well controlled as it is with Trazadone or Prozac. Another reason is that fenfluramine mobilizes serotonin in the platelets, special blood cells that are involved in clotting. Because of this, there is a dangerous excess of serotonin in the lungs and heart, which has been hypothesized to be the factor responsible for PPH and possible heart valve damage. Previous studies by Eli Lily, the manufacturer of Prozac, have found only 8 cases of PPH in an estimated 19 million users. This figure is actually lower than the number of cases expected to occur naturally in a population of that size.

Having established the superiority of Trazodone and Prozac over fenfluramine, one might ask, 'Why weren't these medications used before?" Due to the wild popularity of Phen/Fen, multitudes of patients refused to even consider them. Why use something else, when you are sure of something that works? This thinking was usually fostered by stories of friends or relatives who had successfully lost weight on Phen/Fen. Now the time for something new has arrived!

Physicians today should gather a lot more clinical evidence on a medication before they feel comfortable with it. This is usually accomplished by varying dosages of individual medications until they find one that produces minimal side effects. However, this doesn't always happen- Many prac-titioners "misbalance" the medications, which results in excessive side effects. Therefore, it is imperative that patients find a practitioner that is well trained in the daily use of these medications and their risks.