Dr. Bob's Psychopharmacology Tips

Antidepressant action of dexfenfluramine

Date: Wed, 17 Jul 1996 22:46:46 -0500 (CDT)
From: "Dr. Bonnie Spring" <springb@mis.finchcms.edu>
Subject: Antidepressant action of dexfenfluramine

The issue is controversial because depression has been listed as a possible side effect of DF. But if you look at the research literature on how it affects seasonal affective disorder, premenstrual depression, carbohydrate craving [in] obesity, and nicotine withdrawal, the action is clearly antidepressant.

Date: Sun, 21 Jul 1996 11:34:13 -0700 (PDT)
From: rlam@unixg.ubc.ca (Dr. Raymond W. Lam)
Subject: Antidepressant action of dexfenfluramine

Could you send a short reference list supporting the d-fenfluramine therapeutic profile for seasonal affective disorder, PMS, etc.?

--Larry Ereshefsky

I also know of clinicians who routinely combine d-fenfluramine with SSRIs in the treatment of bulimia nervosa. It makes some sense to use the combination in refractory depression if you believe increasing serotonergic transmission helps, since they work by different mechanisms. Unfortunately, as predicted by the 5HT1a presynaptic autoreceptor model, the increase in synaptic serotonin from the combination might be negated by the autoreceptor effects, thus explaining the negative result found in Larry Price's study (2).

1. Guy-Grand B. Clinical studies with d-fenfluramine. American Journal of Clinical Nutrition 55 (1 suppl):173S-176S, 1992 Jan.

2. Price LH, Charney DS, Delgado PL, Heninger GR. Fenfluramine augmentation in tricyclic-refractory depression. Journal of Clinical Psychopharmacology 10 (5):312-7, 1990 Oct.

3. Brzezinski AA, Wurtman JJ, Wurtman RJ, Gleason R, Greenfield J, Nader T. d-Fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual depression. Obstetrics & Gynecology 76 (2):296-301, 1990 Aug.

4. O'Rourke D, Wurtman JJ, Wurtman RJ, Chebli R, Gleason R. Treatment of seasonal depression with d-fenfluramine. Journal of Clinical Psychiatry 50 (9):343-7, 1989 Sep.

5. O'Rourke DA, Wurtman JJ, Brzezinski A, Nader TA, Chew B. Serotonin implicated in etiology of seasonal affective disorder. Psychopharmacology Bulletin 23 (3):358-9, 1987.

Date: Sun, 21 Jul 1996 20:46:33 -0500 (CDT)
From: "Dr. Bonnie Spring" <springb@mis.finchcms.edu>
Subject: Antidepressant action of dexfenfluramine

Raymond Lam has cited most of the studies I know. An additional one appears below.

Unless anyone knows something to the contrary, the fairest appraisal may be that dexfenfluramine has never been specifically tested for efficacy as an antidepressant. I think that in all of the studies except Price's the focus was weight and appetite control; dysphoric mood was a secondary outcome.

Given the generally antidysphoric effects, I've often wondered why dexfenfluramine wasn't studied as a potential antidepressant. I have 2 guesses. One is that the pharmaceutical company was already marketing another antidepressant and preferred to follow a 1 disorder-1 drug marketing strategy. The other is that depression was sometimes reported as a side effect of dexfenfluramine. My clinical experience was that I never saw depression when patients were taking dexfenfluramine, though I saw plenty of sedation. I did see depression in patients who had successfully quit smoking after we terminated their medication. My guess about the explanation had always been that we'd weaned these folks from their antidepressant of choice (nicotine) and had now taken away the pharmacotherapy that had continued to hold their affective disorder in check. In retrospect, I now wonder whether we were observing a more straightforward drug withdrawal reaction.

Spring B, Wurtman J, Gleason R, Wurtman R, Kessler K (1991). Weight gain and withdrawal symptoms after smoking cessation: A preventive intervention using d-fenfluramine. Health Psychology, 10 (3), 216-223.

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