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Psychopharmacology Tips

Antidepressant discontinuation reactions

Date: Sun, 26 Mar 1995 12:51:06 -0800 (PST)
From: Ivan Goldberg <psydoc@psycom.net>
Subject: Antidepressant discontinuation reactions

About 20% of my patients who discontinue sertraline have told me (spontaneously) that they experience a "flu-like" syndrome -- feeling "crummy", tired, achy, etc. -- for about one week after discontinuation. I've heard it enough that I now tell my patients ahead of time this might happen.


The flu-like syndrome following discontinuation is most likely to happen following the sudden discontinuation of paroxetine or venlafaxine. In addition to the flu-like symptoms, visual phenomena (e.g., "moustaches on men and women but only smudges on the upper lips of babies") are not rare.


Any thought about how to mitigate the discontinuation syndrome.


The administration of a single 20 mg capsule of fluoxetine usually does the job. The withdrawal symptoms are relieved within hours and the patient goes through a slow fluoxetine withdrawal that is usually symptomless. If the individual had been on a high dose of paroxetine or venlafaxine, a second 20 mg of of fluoxetine may be needed.

Date: Sat, 10 Jun 1995 11:28:30 -0700 (PDT)
From: Ivan Goldberg <psydoc@psycom.net>
Subject: Antidepressant discontinuation reactions

I hear from my colleagues of withdrawal reactions in about 20% of their patients abruptly stopping 20 mg/day of paroxetine, and in much higher percentages of those who abruptly stop higher doses. A similar reaction is seen in pholks who abruptly stop venlafaxine. Both of these antidepressants have short half-lives (t-1/2) as opposed to fluoxetine whose active metabolites remain in the plasma for weeks after administration of the drug has been stopped.

The withdrawal reaction which may be seen within 8-hours in some people (occasionally necessitating q.i.d. administration of paroxetine or venlafaxine) often includes:

There is no risk of such withdrawal symptoms when going between SSRIs or between an SSRI and venlafaxine. You can go from fluoxetine to just about anything, but an MAOI, and not worry because of that drugs long t-1/2.

From: "Chris"
Date: Fri, 28 Jul 1995 14:05:30 +0000
Subject: Diphenhydramine for venlafaxine discontinuation reactions

As a patient I found that Benadryl helped me get through the very uncomfortable withdrawals from Effexor. I only took it for a month. I was very surprised at the intensity of the withdrawal. The worst withdrawal effect for me was a sense of my nerves jangling when I moved my eyes and continuous indigestion, sort of a migraine-like feeling without the headache. When the Benedryl finally started to make me sleepy I switched to Dimetapp. The withdrawal took almost six weeks to get through, but I am now drug-free with tolerable levels of [chronic neck and back] pain [which was being treated with the Effexor].

From: "George Nasra" <nasdoc@penn.com>
Date: Mon, 9 Oct 1995 09:33:07 -0400
Subject: Venlafaxine discontinuation reactions

I was tapering a patient off Effexor a few weeks ago and he had what I considered a severe withdrawal reaction with nausea and vomiting and flu-like symptoms although he was already started on fluoxetine. A slower tapering worked better.

Date: Sun, 22 Oct 1995 20:46:43 -0700 (PDT)
From: Judith Lipton <jlipton@forest.net>
Subject: Venlafaxine discontinuation reactions

Of particular note with venlaxafine is the severe withdrawal syndrome that may occur with dose reduction.

Date: Wed, 11 Oct 1995 18:14:23 -0700 (PDT)
From: Ivan Goldberg <psydoc@psycom.net>
Subject: Venlafaxine discontinuation reactions

On Wed, 11 Oct 1995, Charles S Berlin wrote:

In my experience with Effexor [the] main drawback is that -- like Xanax -- it seems easy to get on, but very hard to get off. Many of my patients on this med start to have some withdrawal symptoms after missing even a few doses, or when tapering down.

From: "D. Fegg"
Date: Tue, 9 Jan 1996 22:12:14 -0500
Subject: Diphenhydramine for venlafaxine discontinuation reactions

I want to reply/confirm regarding a listing for Effexor withdrawl symptoms that Benadryl is a great help getting through some of the rougher symptoms -- whoda thunkit?!

I tapered off my Effexor from 150 mg/day to 75 mg/day for a few wks, then to 37.5 mg/day for 2 wks, and then off. For the first 48 hrs, I had no symptoms, but then I was socked with the "electrical shock" phenomena someone else mentioned -- with any movement at all. There were also concentration difficulties and gastrointestinal upset and just general crumminess. About 4 days into this, I read the post about Benadryl and got some, with quick reduction in a lot of the symptoms -- enough so that I could return to work. It didn't eliminate all of the problems, but it did a good job. I took it for about two weeks and then was over virtually all problems.

My doctor was not familiar enough with this medication to have advice regarding the type/length of withdrawl symptoms, so I passed on the above info and hope it will help someone else.

By the way, I am one of those people who do miss the great dreams I had on Effexor -- very detailed vivid and downright interesting dreams -- oh well.

Date: Thu, 1 Feb 1996 16:00:29 -0800
From: kerridc@ix.netcom.com (Kerri D. Carter )
Subject: Venlafaxine discontinuation reactions

A female patient in her 50s is currently taking Effexor tid in addition to blood pressure medication. She recently had a routine surgery for nasal passage blockage and discontinued her Effexor for approximately 3 days. She states that she experienced ringing in her ears and throbbing in her head that she associates with the absence of the Effexor -- and this has been sufficiently severe for her to seriously question continuing to take it. This patient is typically very treatment receptive and compliant. This patient experienced this on one other occasion, when first taking the medication, and decided to continue after reassurance from her doctor of its benefits. The patient has had an excellent response to Effexor.

Subject: Venlafaxine discontinuation reactions
Date: Thu, 1 Feb 1996 21:02:45 -0500 (EST)
From: "Jeffrey R. Stenzel" <jstenzel@polar.Bowdoin.EDU>

I have a patient that suffered the symptoms you describe. Both times she discontinued venlafaxine (dose <= 37.5 mg) she described tinnitus and a vertiginous-like experience that lasted up to a week. Both times the symptoms completely resolved. BTW, she liked everything about the antidepressant except decreased libido and anorgasmia, hence the reason for the switches.

Date: Thu, 1 Feb 1996 22:59:23 -0500
From: bret@vnet.net (Bret Burquest)
Subject: Paroxetine discontinuation reactions

Your trouble with venlafaxine reminds me of the increasing problems I've had in withdrawal from paroxetine. My first was very dramatic, with transient ophthalmopolegia while driving his car after independently stopping paroxetine 40/d suddenly. The man called me in a rage. Subsequently I've had several less serious problems including the "electric shocks" repeatedly reported in letters to the editor of the Am J Psychiatry. The manufacturer gave me a nice summary, showing the same shocks from other SSRIs... but they occur mostly with higher doses, and I've see them with Paxil at 20/d. I'm still trying to get 2 patients off, weeks after they would be off other SSRIs. It's almost like stopping Xanax, except I don't believe paroxetine is fun to take.

Date: Sat, 3 Feb 1996 13:08:32 -0800
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Fluoxetine for antidepressant discontinuation reactions

When a patient is having a severe discontinuation syndrome following the too rapid discontinuation of paroxetine (Paxil) or venlafaxine (Effexor), the treatment I prefer is fluoxetine (Prozac) 20 mg. q.o.d. until the reaction disappears. It is seldom necessary to give more than 2 or 3 doses, and because of the long t-1/2 of fluoxetine, no additional doses are necessary.

From: RMRich1@aol.com (Roberta M. Richardson, M.D.)
Date: Sun, 4 Feb 1996 15:27:49 -0500
Subject: Fluoxetine for antidepressant discontinuation reactions

Dr. Sheldon Preskorn has also suggested using fluoxetine to treat paroxetine withdrawal, and I have used it successfully for both paroxetine and venlafaxine withdrawal. As per Dr. Preskorn's advice, I give the fluoxetine for several consecutive days, then stop it and let the natural taper occur.

Date: Sun, 4 Feb 1996 16:46:21 -0500
Subject: Fluoxetine for antidepressant discontinuation reactions
From: cwolfman@pipeline.com (Cyrus Wolfman)

I have found the use of fluoxetine a better approach in treating the so-called "discontinuation" symptoms on withdrawing SSRIs with short half-lives. In the past, I had raised the SSRI dose back up and simply reduced it more slowly, often with the symptoms reappearing on the more gradual withdrawal. Now, I lower the dose a second time, as in the past, but if the symptoms appear, I switch to fluoxetine 20 mg per day. As soon as the symptoms remit (in two or three days) I stop the fluoxetine. So far, no problems.

From: DrMargery@aol.com (Margery Johnson, M.D.)
Date: Thu, 30 May 1996 20:43:59 -0400
Subject: Sertraline discontinuation reactions

I have been treating a teenaged boy who presented with some symptoms of depression and also psychological problems, especially difficulty with authority figures that goes way beyond the usual adolescent stuff. I decided to try him on sertraline, and the dose was gradually increased to 150 mg, with modest benefit. He decided abruptly to stop taking the medication and didn't tell me or his parents. Three days later he got in a disagreement with a security guard at his high school. The patient didn't remove his cap upon entering the school, as is required by the school to limit gang-associated clothing, and the guard knocked the cap off his head. The patient reacted by knocking the guard's eyeglasses off, breaking them. The guard pressed charges, and the patient now has an assault charge pending. The patient has no history of any aggressive behavior and admits that he "overreacted". After this incident, he resumed the medication until a month or so later, when he again stopped taking it and this time he told me and his parents. The patient and his parents noticed a marked irritability and a tendency to overreact and generally to be too emotional beginning 2 or 3 days after stopping the sertraline. The patient then began to wonder if his previous episode was in any way related to going "cold turkey". His lawyers as well as his family would like to use this in his defense.

I have had several patients -- all children and adolescents -- who have developed extreme irritability, often very unlike their usual personality, beginning a few days after abruptly discontinuing a short-acting serotonergic antidepressant. I'm aware of reports of withdrawal symptoms from paroxetine and sertraline, but I've not seen anything about exclusively behavioral symptoms in the absence of physical sxs.

From: JEFKMD@aol.com (jeffrey kramer)
Date: Fri, 31 May 1996 06:37:06 -0400
Subject: SSRI discontinuation reactions

I definitely have seen variations on this, most specifically with sertraline, but also with fluoxetine.

Date: Fri, 31 May 1996 08:15:05 -0300
From: "marcelo.caixeta" <marcelo.caixeta@netline.com.br>
Subject: SSRI discontinuation reactions

Some of my adolescent patients have developed the sort of withdrawal symptoms you describe.

Some of them have what I call "irritable depressive" thoughts and acts. One of them has narcissistic personality disorder and becomes irritable and has depressive (suicidal) thoughts whenever he doesn't get something he thinks he deserves. He blames an affront and sometimes assaults people, mainly his relatives, because of this. These episodes are augmented by alchool + SSRI and by SSRI withdrawal. (By the way: he only had consistent improvement when I added neuroleptics.)

Speculation: perhaps there is a sort of "irritable depression" with very oppositional features that does not respond very well to 5HT augmentation strategies alone.

Date: Fri, 31 May 1996 22:20:42 -0500
From: gsdavids@niagara.com (George Davidson)
Subject: Antidepressant discontinuation reactions

I see all sorts of strange complaints from stopping SSRIs too soon. These include mood disturbance, psychotic features such as illusions or frank hallucinations, extreme agitation, and severe malaise.

Irritability and "over-reacting" don't suprise me in the least, and I find the story as you present it quite consistent with SSRI sudden-withdrawal syndrome. Having learned the hard way how terrible the effects of suddenly stopping SSRIs and venlafaxine (Effexor) can be I now routinely urge all my patients to come off these drugs gradually. I have seen the worst reactions from paroxetine (Paxil), but I have seen them in all the SSRIs. It is claimed that they ar more frequent in drugs with a short half-life -- certainly it doesn't seem to happen with fluoxetine (Prozac), to my knowledge. I have seen the withdrawal sydrome at low doses, like Paxil 20 mg and even Zoloft 50 mg.

If in doubt that a symptom is due to SSRI withdrawal, just give a test dose and see if the symptoms soon disappear. It has been said on Psychopharmacology Tips that one dose of Prozac, due to its long half-life, can stop the SSRI withdrawal syndrome. The one time I tried this, it did not work, and I needed to give the Prozac daily for a week, then once every 2 days, etc.

Date: Fri, 31 May 1996 13:30:27 -0700 (PDT)
From: Joseph Barrett <jbarrett@u.washington.edu>
Subject: Sertraline discontinuation reactions

I too have had experience with sertraline withdrawal. The two patients that come to mind complained of general dysphoria, derealization, and somatic sensations that led to a panic attack in one of them.

Date: Fri, 31 May 1996 22:45:03 -0700 (PDT)
From: Rafael Gray <rafael@itsa.ucsf.edu>
Subject: Anticipating medication discontinuation reactions

One thing that I've found helpful is to ask patients whether they have over the course of treatment "accidentally forgot" the med or "experimented" to see if they could do without it. This helps me predict how sensitive they may be during a taper off the med. If they definitely had symptoms during a brief med hiatus then of course I can be more conservative in the taper and the patient is usually more appreciative and understanding because they know what to expect.

Date: Sat, 24 May 1997 12:57:57 -0400
From: Ivan Goldberg <Psydoc@PsyCom.Net>
Subject: Antidepressant discontinuation reactions

Because of Depression Central I receive many emails from patients who are experiencing SSRI or venlafaxine withdrawal. I respond with:

Many of my patients who decided to simply stop Paxil or Effexor have developed syndromes identical to yours. I let them know that there are two ways to control the symptoms of the discontinuation syndrome:

  1. to restart the Paxil or Effexor and then lower the dose slowly, or

  2. to start taking 10 mg of Prozac a day for about 5 days longer than it takes to control the symptoms of the discontinuation syndrome. The Prozac can then be stopped. Because of its long half life the Prozac leaves the blood over a few weeks and the discontinuation symptoms generally do not recur.

From: TStinn1959@aol.com (Thomas C. Stinnett, M.D.)
Date: Thu, 5 Jun 1997 01:49:02 -0400 (EDT)
Subject: Venlafaxine discontinuation reactions

Several months ago I was referred a patient with a history of chronic, recurrent depression who had been maintained on 450 mg. of venlafaxine for approximately one year. The nature of the referral was that the patient had begun to manifest "breakthrough" symptoms of depression. After trying various augmentation strategies, the patient was started on a trial of bupropion with good results. The tapering process of the venlafaxine was very difficult, with very intense (but typical) symptoms. After several months, the patient continues to manifest withdrawl symptoms every 3 to 4 days. These respond to 37.5 mg. of venlafaxine.

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[dr. bob] Dr. Bob is Robert Hsiung, MD, dr-bob@uchicago.edu

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