Dr. Bob's Psychopharmacology Tips

Phentermine, fenfluramine, and SSRIs

Date: Tue, 25 Apr 1995 09:36:59 -0500
From: Stephen R Saklad <Saklad@uthscsa.edu>
Subject: Fenfluramine and fluoxetine

At 08:19 4/25/95, Sheldon Eisenman, MD <SHELLYE@aol.com> wrote:

I received a call from a 40-ish female patient who has had a good response to fluoxetine 20 mg/day and wants to know if she could take fenfluramine in order to lose weight... There was a good discussion recently on the use of stimulants for augmentation with SSRIs with generally good results.

I would not try fenfluramine since this has important pharmacodynamic effects on serotonin that might synergize with the fluoxetine, not to mention the pharmacokinetic effects at the CYP2D6 chokepoint.

Date: Tue, 25 Apr 1995 10:50:44 -0400 (EDT)
From: "Rona J. Hu" <hucares@helix.nih.gov>
Subject: Fenfluramine and fluoxetine

Anecdotally, heard from a colleague of just such a situation: pt doing well on fluoxetine added fenfluramine from her internist in order to lose weight, developed symptoms of serotonin syndrome.

Date: Tue, 25 Apr 1995 12:59:42 -0400
From: hrohan@pobox.upenn.edu (Mady Hornig-Rohan, M.D.)
Subject: Fenfluramine and fluoxetine

Although I have not seen anyone on this combination, I would be more concerned about this particular combination of an SSRI with fenfluramine due to fenfluramine's serotonin-releasing effects. On a theoretical basis, this would raise the risk of a potentially serious serotonin syndrome.

Date: Wed, 26 Jul 1995 21:52:29 -0700 (PDT)
From: Peter Forster <forster@itsa.ucsf.EDU>
Subject: Fenfluramine and fluoxetine

I recently started a patient with morbid obesity and refractory depression on a combination of phentermine, fenfluramine and an SSRI. The chief risk from this combination seemed to be induction of a "serotonin syndrome" reaction. Searches through Medline and inquiries of all the manafacturers of SSRIs lead to no information about the likelihood of the reaction. There have been no reports, but I don't know how many people have tried the combination. So I started after getting the patient's informed consent. She has had a fairly good response with no side effects.

That would be the end of my response except that at a lecture on depression in San Diego I ran a across a colleague who advised me that he had used the combination on at least 15 patients with no side effects or adverse reactions. Which is getting up to a large enough "n" that one would expect to see adverse reactions if they were common.

Date: 13 Dec 95 08:44:26 EST
From: Troy Caldwell <75112.1676@compuserve.com>
Subject: Fenfluramine and sertraline

I have tried Zoloft + fenfluramine at times in patients who were not responding to usual augmenting strategies and have had one or two remarkable turnarounds without any untoward effects. I do warn them about serotonin syndrome risks and to call if any of those symptoms occur.

Date: Sat, 16 Dec 1995 09:37:21 -0800 (PST)
From: Peter Forster <forster@itsa.ucsf.EDU>
Subject: Phentermine, fenfluramine, and SSRIs

I have [now] treated three patients with a combination of these two agents and an SSRI (after warning about the theoretical risk of serotonin syndrome and getting them to sign an experimental treatment form) with good results and no side effects. Still too small an "n" to say anything definitive.

Date: Sat, 16 Dec 1995 19:19:47 -0800 (PST)
From: Judith Lipton <jlipton@forest.net>
Subject: Phentermine and SSRIs

I have had five patients on phentermine plus an SSRI. One is bulimic, and she has had particularly good results, with moderate weight loss and complete cessation of binge/purge episodes, even under considerable stress. Another woman has OCD and was pleased with moderate weight loss without return of other symptoms. So far, no one has had side effects of note; I've gotten baseline EKGs and approval from the patients' family doctors before proceding and have not noted any cardiovascular changes.

However, I still feel anxious about this combination, as good large-n data seems lacking, and there is no clearcut protocol. Also, I have not seen dramatic effects in those patients with morbid obesity (> 300 pounds).

I think that the full tale has yet to be unravelled.

Date: Fri, 16 Feb 1996 05:26:30 -0800
From: tgarton@ix.netcom.com (Theresa Garton )
Subject: Phentermine, fenfluramine, and SSRIs

I have had a good portion of mood disorder pts who begin crying constantly or become suicidal or affectively unstable when their "other doctor" adds these two, or even just the fenfluramine... Some pts have gone through this (fenfluramine) 2-3 times before they give the idea up. Some do OK, but my guess is the complication rate is between 25 and 50%. It is amazing how many people are taking these drugs, and they do not always admit it to their other caregivers.

From: LJGROLD@aol.com (L.James Grold M.D.)
Date: Fri, 16 Feb 1996 09:13:27 -0500
Subject: Phentermine, fenfluramine, and SSRIs

I have placed several overweight patients on the combo of phentermine and fenfluramine who are also on SSRIs or venlafaxine. So far the results are excellent. The patients find that a small dose (less than half the standard dose) works as an anorexiant and as a side benefit they find that they feel more energetic during the day without any insomnia at night. I plan to try this on a few more...

From: LJGROLD@aol.com (L.James Grold M.D.)
Date: Sun, 18 Feb 1996 23:12:47 -0500
Subject: Phentermine, fenfluramine, and SSRIs

I use phentermine 15 mg 1/2 hr. before breakfast. I give fenfluramine 20 mg 1/2 hr. before each meal. Many patients find that the phentermine acts as a mild energizer. The fenfluramine patients seem to find they don't need tid and quickly adjust to one or two times per day. So far I've seen no complications with any of the concomitant antidepressants. Many of the studies I've read have used these meds for years. I haven't used them that long. But if there aren't other weight-reducing techniques employed then once the meds are stopped it comes back.

Date: Tue, 2 Apr 1996 21:02:56 -0800 (PST)
From: Judith Lipton <jlipton@forest.net>
Subject: Phentermine, fenfluramine, and SSRIs

Alas, some problems have developed in my little cohort of patients on fluoxetine (Prozac) and phentermine, on whom I reported December 16. The lady with OCD stopped both her Prozac and phentermine as she became more involved with her work. Even her internist has not seen her in several months. The lady with bulimia indeed stopped vomiting, but began drinking rather heavily and I've had to stop the phentermine and confront the alcohol abuse. And a very nice woman with no axis II problems, just recurrent depression and obesity, stopped the phentermine because it didn't seem to do much good, and she preferred eating...

Date: Mon, 15 Apr 1996 22:21:56 -0500
From: talmadge@onramp.net (John M. Talmadge, M.D.)
Subject: Fenfluramine and SSRIs

Thanks to this list I am much more cautious than I was, say, a year ago. I not only check blood pressures and require a visit to the primary care physician (to inform and seek agreement that the approach is worth a try), but I also now ask the patient to write up briefly the outline of the proposed diet and exercise plan.

As far as combining the agents is concerned, I have not seen adverse side effects or serotonergic problems, even with doses of say 300 mg/day venlafaxine + 70 mg/day phendimetrazine + 20 mg/day fenfluramine. I am sure that adverse reactions do occur, and I go over potential problems carefully with the patients.

Date: Tue, 28 May 1996 19:34:38 -0500
From: Stephen R Saklad <Saklad@uthscsa.edu>
Subject: Serotonin syndrome

At 13:47 5/28/96, Randi Rubovits-Seitz wrote:

A situation that is of concern to me [is that] I have SSRI patients who were given fen/phen by an internist.

One expert I consulted suggested the risks were more theoretical than practical, and I haven't (yet) had a problem, but ... it seems that these drugs will be prescribed together fairly often, one way or another.

If the patient gets the prescriptions filled at the same pharmacy, the pharmacist should not fill the second prescription without discussing this with the prescribers. I asked several colleagues if they would permit this [combination] to be filled, and they all thought about it and said no.

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

On Wed, 17 Jul 1996 Freud1@aol.com wrote:

I want to start using dexfenfluramine in my obese depressed patients but most of them are on an SSRI. How relative is the contraindication to use these drugs together? I understand the drug company needs to be conservative and state the possibility of serotonin syndrome, but isn't that also an issue whe you prescribe fenfluramine?

My question is why continue the SSRI -- for its effect on depression? You might actually find that DF has an antidepressant action on the patients you describe.

Date: Mon, 22 Jul 1996 17:24:09 -0500 (CDT)
From: "Dr. Bonnie Spring" <springb@mis.finchcms.edu>
Subject: Phentermine, fenfluramine, and SSRIs

As a clinical psychologist who offers behavioral weight control treatment, I'm concerned about the number of recent patients who report the following. They are in psychiatric treatment with Dr. X, who prescribes an SSRI for their depression. Simultaneously, they are being seen at a weight loss clinic where they are receiving dexfenfluramine (Redux) or the fen-phen (fenfluramine-phentermine) combination. They may not think to tell Dr. X about their weight loss treatment or they may deliberately withold that information for fear of having to do without or with less of either treatment. I have been told of two cases involving professionals who withheld from their psychiatrist the fact that they were being treated with fen-phen. Both underwent hypomanic episodes when the psychiatrist introduced or increased their dosage of SSRI.

The fen-phen combination is widely available at commercial weight loss centers, and Redux is becoming more available in that context. I used to feel some reassurance that the harm patients could do to themselves by seeking this kind of dual prescription was minimized by the fact that the fen-phen side effect profile was sufficiently unpleasant that patients weren't tempted to increase their dosage above what had been prescribed. Dexfenfluramine is pretty sedating, so maybe that will continue to reduce the risk. Still, it might be a good idea to bear in mind that some patients manage to acquire a surprising number of pharmacotherapists.

Date: Thu, 08 Aug 1996 21:12:55 -0400
From: "Samuel L. Kent" <samkent@eznet.net>
Subject: Phentermine, fenfluramine, and SSRIs

I have treated two patients with racemic fenfluramine, phentermine, and an SSRI (in one case fluoxetine 80 mg/day and in the other fluvoxamine 300 mg/day). Maybe I haven't seen the serotonin reactions because I start them on the lowest dose of fenfluramine and increase slowly. On the other hand maybe it's related to using the racemic mixture rather than the dex stereoisomer, which I understand is far more potent for serotonin release. Maybe I have yet to see the serotonin reactions.

Date: 08 Aug 96 22:53:39 EDT
From: Troy Caldwell <75112.1676@CompuServe.COM>
Subject: Phentermine, fenfluramine, and SSRIs

I would point out that the literature on resistant OCD encourages the use of the serotonin agonist fenfluramine (Pondimin) to augment SSRIs. Of course one must educate their patients about the serotonin syndrome. I would, however, consider the combination a cause for caution and education and not a contraindication.

Date: Sat, 10 Aug 1996 19:47:27 -0400
From: Ereshefsky@uthscsa.edu (Larry Ereshefsky)
Subject: Fenfluramine and SSRIs

From the neurochemical side, Stahl has presented data showing that SSRIs block the uptake of fenfluramine into the cell, suggesting that if the SSRI is on board first then fenfluramine has little if any effect on the neuron at all.

From: MZSHRINK@aol.com (Victoria Codispoti,M.D.)
Date: Tue, 19 Nov 1996 23:50:58 -0500
Subject: Dexfenfluramine and SSRIs

I have a patient on fluoxetine 40 mg and dexfenfluramine and she has had no problems whatsoever. I attempted to take her off the fluoxetine and she became very depressed so I reinstated it with the knowledge that it was contraindicated by the company. She is doing very well and needs less fluoxetine than previously (60-80 mg).

Subject: Dexfenfluramine and SSRIs
Date: Wed, 20 Nov 96 05:36:28 -0500
From: "Samuel L. Kent" <samkent@eznet.net>

I have a patient on 80 mg/day of fluoxetine doing well on 30 mg/day of dexfenfluramine. She's been losing about 8 lbs/month over the last two months.

Date: Sat, 23 Nov 1996 22:06:14
From: wstnmllr@gnn.com (Warren Steinmuller)
Subject: Dexfenfluramine and SSRIs

An endocrinologist friend, who specializes in the treatment of obesity, told me he has seen 5 people become ill with serotonin syndrome symptoms to the point of needing hospitalization when they had been prescribed Redux (dexfenfluramine) and Prozac (fluoxetine).

From: Cdbojrab@aol.com (Christopher D. Bojrab, M.D.)
Date: Fri, 7 Mar 1997 08:13:44 -0500 (EST)
Subject: Dexfenfluramine and SSRIs

I had one patient who was on Redux (dexfenfluramine) and Prozac (fluoxetine) prescribed by other physicians. She developed severe headaches, elevated blood pressure, and mild confusion after the fluoxetine was added to the dexfenfluramine. The symptoms remitted within about a day after I advised her to discontinue the Redux.

Date: Tue, 25 Mar 1997 23:04:55 -0800
From: Michael Kenin <MKENIN@pol.net>
Subject: Phentermine, fenfluramine, and antidepressants

I have combined phen-fen with all categories of antidepressant meds with no problems and sometimes with improved mood or energy. As always when combining meds, start low 'n' go slow, i.e. start at a low dose and slowly titrate up, one med at a time.

Date: Fri, 28 Mar 1997 20:19:47 -0800 (PST)
From: "Sanford R. Pepper" <peppers@itsa.ucsf.edu>
Subject: Phentermine and SSRIs

I have just had the experience of treating an indivdual who was hospitalized thrice in a couple of months using the combination of paroxetine and phentermine. She presented with delusions and hallucinations which cleared rapidly upon admission each time. Sad to say, the psychiatrist did not recognize that the combination was behind the psychotic epsiodes.

I am cautioning my patients against taking SSRIs and diet pills.

If prescribed, I would follow the patients closely.

Date: Sat, 29 Mar 1997 10:54:09 -0500
From: "Jonathan A. Slater, M.D." <jas14@columbia.edu>
Subject: Phentermine and SSRIs

I have used phentermine with SSRIs many times in obese patients, most commonly phentermine and fluoxetine, with some weight loss (10-40 lbs). Unfortunately for these patients, medication alone is not the answer. I often work in conjunction with behavioral programs for obesity with physicians on staff who monitor BP, weight, and labs.

Date: Thu, 05 Jun 1997 21:38:35 -0700
From: DMREISS <DMREISS@Prodigy.Net>
Subject: Phentermine, fenfluramine, and SSRIs

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.

From: FLerro@aol.com
Date: Fri, 6 Jun 1997 18:57:15 -0400 (EDT)
Subject: Phentermine, fenfluramine, and SSRIs

This is a very controversial issue. I don't believe phentermine plus an SRI would cause a problem since phentermine is a noradrenergic agonist. The problem is with the use of an SRI and a serotonin agonist such as fenfluramine. This double barreled stimulation of serotonin risks development of a serotonin syndrome. I've stayed away from this combo for this reason, but a number of psychiatrists feel the risk is tolerable.

Date: 07 Jun 97 23:05:01 EDT
From: Leslie Gise <76106.413@compuserve.com>
Subject: Phentermine, fenfluramine, and SSRIs

I have had several patients on SRIs who have gone on phen-fen without consulting me. Nothing bad happened.

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