Dr. Bob's Psychopharmacology Tips

Phentermine/fenfluramine adverse reactions

Date: Wed, 01 May 1996 11:32:56 -0400
From: Fumio Inoue <inouef@gov.on.ca>
Subject: Dexfenfluramine side effects and contraindications

PHILADELPHIA, April 29 /PRNewswire/ -- Wyeth-Ayerst Laboratories and Interneuron Pharmaceuticals Inc. announce clearance from the U.S. Food and Drug Administration to market Redux (dexfenfluramine hydrochloride capsules)...

The most commonly reported side effects in clinical trials included drowsiness, diarrhea and dry mouth. These side effects were usually mild and disappeared in a few weeks.

There is also a small risk of a serious, potentially life-threatening cardiovascular condition, primary pulmonary hypertension, associated with the use of all types of prescription weight loss drugs. This risk is estimated to be about 18 cases per 1,000,000 users per year. In the general population, the yearly occurrence of primary pulmonary hypertension is 1 to 2 cases per 1,000,000 people.

Dexfenfluramine should not be used in patients hypersensitive to dexfenfluramine or related compounds, in patients with diagnosed pulmonary hypertension or in patients taking (or within 14 days of discontinuing) monoamine oxidase inhibitors. Dexfenfluramine should not be administered to patients using other serotonergic drugs. Dexfenfluramine is not recommended for women who are pregnant or nursing or for pediatric patients. In animals receiving doses that resulted in brain concentrations approximately 10 times those observed in humans, neurochemical changes, which were generally reversible, were observed. The relevance of these findings to humans is not known...

Date: Thu, 9 May 1996 06:52:00 -0700
From: "Jim Ellison" <jellison@interserv.com>
Subject: Phentermine/fenfluramine primary pulmonary hypertension

There was a very alarming news special on TV last night about primary pulmonary hypertension resulting from diet pills that apparently included phentermine, fenfluramine and dexfenfluramine (the new one). The figure cited was "20-40 deaths per year in France." A young American woman was interviewed who claimed to have suffered from this. It certainly makes me reluctant to prescribe this combination...

Date: Thu, 09 May 1996 23:53:32 -0400
From: "Samuel L. Kent" <samkent@eznet.net>
Subject: No phentermine/fenfluramine adverse reactions

I have three patients on the combination of d-l fenfluramine and phentermine resin doing just fine and losing weight. Michael Weintraub, MD (used to be here at the University of Rochester, now, I think, with the FDA) studied a series of patients for 5 years on this combination with no serious side effects:

Weintraub M. Long-term weight control: the National Heart, Lung, and Blood Institute funded multimodal intervention study. Clinical Pharmacology & Therapeutics 1992 May, 51 (5):581-5. Erratum: Clin Pharmacol Ther 1992 Sep, 52 (3):323.

Date: Sun, 16 Feb 97 02:18:55 UT
From: "James Blake Jones" <JamesBlakeJones@msn.com>
Subject: Phentermine/fenfluramine psychosis

I have now seen two cases of new onset psychosis in association with use of dexfenfluramine (sorry, I don't know the dosage of dexfenfluramine in these cases). The staff on the inpatient psychiatric unit where I work say they have seen a number of cases. In fact, they say that the social workers screening new admissions in the emergency department now routinely determine if psychotic patients have been exposed to dexfenfluramine.

From: snagymd@mem.po.com (Stephen Nagy, M.D.)
Date: Tue, 25 Feb 1997 23:28:18 -0500
Subject: Dexfenfluramine withdrawal

After researching the pharmacology of dexfenfluramine for weight loss, I wondered when I would begin to see patients with withdrawal symptoms. I met my first patient this week with a problem related to dexfenfluramine withdrawal:

A 50 year old female had taken dexfenfluramine 15 mg daily for four months and, seeing no further weight loss, stopped the med. She had also been taking fluoxetine 20 mg daily, all prescribed by an internist.

Four days after discontinuing the dexfenfluramine she developed uncontrollable crying, a sense of "falling apart," irritability, insomnia, and feelings of depression.

Her history appeared to include a longstanding rapid cycling mood disorder with mild to moderate mood symptoms and a periodicity of three days up and three days down, a single episode of major depression after a painful separation years ago, and hypothyroidism treated with synthetic thyroid hormone.

A friend of hers, a patient of mine who had been interested in trying dexfenfluramine, contacted me to ask what to do. We decided to restart the dexfenfluramine at 15 mg daily and to increase the fluoxetine to up to 80 mg daily and observed that a short-term decrease in symptoms occurred. She was able to rest, had fewer affective symptoms. She is using a low dose of alprazolam to sleep, and we are more or less taking things one day at a time. I plan to stop the dexfenfluramine within a few days if her affective symptoms stabilize.

From: snagymd@mem.po.com (Stephen Nagy, M.D.)
Date: Thu, 27 Feb 1997 23:24:05 -0500
Subject: Dexfenfluramine withdrawal

After several days of taking fluoxetine 80 mg daily and dexfenfluramine 15 mg daily, the patient, a student now contemplating withdrawing from this semester's classes, is improved, with ongoing variable mood.

Date: Fri, 28 Feb 1997 10:55:58 -0600 (CST)
From: "Bonnie Spring Ph.D." <springb@mis.finchcms.edu>
Subject: Dexfenfluramine withdrawal

I have probably seen 3 cases of dexfenfluramine withdrawal, though I didn't recognize them as such at the time. In a study published in American Journal of Clinical Nutrition (1995, 62: 1181-1187) we gave 30 mg dexfenfluramine to 47 women to prevent weight gain after quitting smoking. As had been the case in my early study of dexfenfluramine (Health Psychol, 1991, 10: 216-223), quit rates were slightly better on dex than on placebo, and the drug virtually eliminated the irritability and anxiety that usually characterize the first week after quitting smoking. Many patients commented that this was the most effortless, least painful quit process they'd ever had. We maintained the patients on meds (or placebo) for 1 month in one study and 3 months in the other and then tapered them off. Pooling both studies, 3 women became profoundly depressed with suicidal ideation after drug withdrawal.

At the time I inferred that these women had underlying depressive vulnerabilities that they had accidentally learned how to self-medicate at age 11 or 12. Now we had removed their antidepressant of choice (nicotine), transiently substituted another med that had some antidepressant properties (dexfenfluramine), and then withdrawn that. It seemed to me that the women were, perhaps for the first time [since age 11 or 12], experiencing their unmedicated depressive diatheses. But now, as we hear progressively more about "withdrawal-like syndromes" following abrupt discontinuation of some of the shorter half-life SSRIs, I've wondered whether "withdrawal" offers a better explanation of what was going on.

Date: Wed, 19 Mar 1997 22:54:39 -0800
From: "Kathleen Schilli, PharmD." <DrRx@ix.netcom.com>
Subject: Dexfenfluramine primary pulmonary hypertension

The original reports of primary pulmonary hypertension from dexfenfluramine seemed to be study specific. When the drug was released into the general population, it was found that this problem was underestimated by the study, and therefore new recommendations had to be set forth as to the drug's duration of therapy.

Date: Thu, 05 Jun 1997 21:38:35 -0700
From: DMREISS <DMREISS@Prodigy.Net>
Subject: Phentermine/fenfluramine depresson or irritability

I do about ten new patient evaluations per week (all outpatient), and over the last couple of months, I've been averaging one per week for whom I trace acute depresson or irritability to starting or stopping fen-phen, or mixing fen-phen with an SSRI. (Often, the treating psychiatrist is unaware that the patient is even receiving fen-phen from a GP). A controlled study it is not, but it sure doesn't seem like coicidence.

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