Withdrawal reaction associated with venlafaxine
BMJ 1998; 317 doi: https://doi.org/10.1136/bmj.317.7161.787a (Published 19 September 1998) Cite this as: BMJ 1998;317:787
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I read with intense interest your article regarding the syndrome
associated with withdrawal of Venlafaxine. The article answered some
rather pressing questions as to why I was experiencing a plethora of
rather horrid symptoms.I have been on this medication 300mg/day for approx
6 months, and a lower dosage (175mg) generally for the last 5 years.
I experience occasional breakthrough depressive symptoms which seem
related to daylight changes-occurring in autumn and abating in spring. The
symptoms are at their worst in December-February. It is at these times
when my dosage is increased, to a maximum of 300mg. When I drop back down
in Spring to a lower dosage I experience the withdrawal affects, albeit to
a lesser degree than that I imagine would occur should I withdraw
completely from the medication. The most troubling symptoms seem to be
fluctuating blood pressure-flushing,tachycardia and sweating. I have
suffered the gamut of recorded symptomatology though except for
fasciculation. I suspect this medication has a sufficiently short half-
life in-vivo that even 1 dose missed can cause the syndrome.
Of interest to me was that at no time has any General Practitioner (or
Psychiatrist for that matter) ever mentioned the possibility of these
affects, in fact, I noted them to my most recent Physician, and he
researched the issue from there for his own knowledge. Fairly scary if one
doesn't know whats going on.
Competing interests:
None declared
Competing interests: No competing interests
I, personally, have witnessed first-hand the severe withdrawal
syndrome, associated with venlafaxine.
I had been on 225mg XL for 2 years. If I ever missed a dose, I would
experience onset of withdrawal within a few hours, consisting of
dizziness, headache and nausea.
Recently I took the decision to discontinue venlafaxine altogether.
My psychiatrist recommended tapering the dose by 75mg on a weekly basis
but I was unable to tolerate this
regime. I experienced severe vertigo, dizziness, headache, nausea and
vomiting and sweating within hours of taking the 75mg reduction. I
persisted with this and was given painkillers and antiemetics.
Unfortunately, these did not relieve the symptoms at all and I became
quite incapacitated. I was unable to move without feeling dizzy and
suffered relatively severe nausea and vomiting as a result. I was confined
to my bed and my blood pressure also became significantly raised on
numerous occasions. I ended up being admitted to hospital as a result of
this severe withdrawal syndrome.It was suggested then that I taper the
dose by 37.5mgs (using the
regular effexor tablets alongside the modified release)on a weekly basis.
I still, however, suffered the symptoms listed afore and was prescribed
numerous medications including stemetil, betahistine and
cyclizine, with no effect. I was unable to read, watch TV, use the
computer or drive due to the vertigo and effectively had to spend my time
in bed.
The triad of vertigo, nausea/vomiting and
headache lasted well after my dose tapering regime was finshed. Even
after a month of being without any venlafaxine altogether, I still was
troubled by vertigo and nausea. My doctors refused to acknowledge that
venlafaxine (or lack of it) was causing this and preferred to put my
symptoms down to a "mystery virus". It was decided that I should restart
an antidepressant as I was feeling rather down (perhaps not surprisingly)
and I was commenced on sertraline. Within a day of starting it, my
headache and dizziness stopped. My doctor's explanation of this was that
my virus must have run its course or that it was actually stress causing
my headache all along, or sertraline was acting as a placebo!
One characteristic of the withdrawal I noted was that it came in
"waves", with symptoms peaking around 2-5pm (i used to take my venlafaxine
in the morning). Taking a small
amount of venlafaxine (18.75mg) at these times alleviated the symptoms
within a few hours. My doctor's explanation of this was that taking the
venlafaxine at these times acted as a placebo and took away the withdrawal
simply because I was convinced it would. She also stated that i
experienced withdrawal from venlafaxine as I was waiting for it to occur
but when I accidentally forgot to take my venlafaxine in the past, it was
only after I managed to link this with the lack of venlafaxine on at least
5 occasions, that I realised that I was experiencing withdrawal. I
propose that the very short half life of venlafaxine (6 hours)means that
missing a dose or reducing a dose will result in the onset of withdrawal
symtoms within a matter of hours.
Clearly more studies are required to determine the exact nature of
venlafaxine withdrawal including drug-tapering regimes and symptom control
during the withdrawal period. Education of doctors on the severity and
nature of withdrawal also needs to be employed as clearly many, even
psychiatrists, do not even believe that this exists and prefer often to
put symptoms down to a "mystery virus" or patient neruroses.
Competing interests:
None declared
Competing interests: No competing interests
There are some rare evidences in the literature, which suggest that
venlafaxine may cause balance and motor coordination problems by
interfering with not only the vestibular system but also with the
cerebellum. I have witnessed a case that developed a severe pancerebellar
syndrome (but not vertigo, nausea or tinnitus) and resolved promptly
within one week after stopping the treatment. Interestingly, there are two
reports, which suggest that venlafaxine may have receptors on cerebellum
(1) and that regional cerebellar glucose metabolism rate is reduced
especially in non-responders (2).
All you need is cognitive behaviour therapy?
1.Smith DF, Jensen PN, Gee AD, Hansen SB, Danielsen E, Andersen F,
Saiz PA, Gjedde A. PET neuroimaging with [11C]venlafaxine: serotonin
uptake inhibition, biodistribution and binding in living pig brain. Eur
Neuropsychopharmacol 1997;7(3):195-200.
2.Little JT, Ketter TA, Kimbrell TA, Danielson A, Benson B, Willis MW,
Post RM. Venlafaxine or bupropion responders but not nonresponders show
baseline prefrontal and paralimbic hypometabolism compared with controls.
Psychopharmacol Bull 1996;32(4):629-35.
Competing interests: No competing interests
There are some rare evidences in the literature, which suggest that
venlafaxine may cause balance and motor coordination problems by
interfering with not only the vestibular system but also with the
cerebellum. I have witnessed a case that developed a severe pancerebellar
syndrome (but not vertigo, nausea or tinnitus) and resolved promptly
within one week after stopping the treatment.
Interestingly, there are two reports, which suggest that venlafaxine
may have receptors on cerebellum (1) and that regional cerebellar glucose
metabolism rate is reduced especially in non-responders (2).
1.Smith DF, Jensen PN, Gee AD, Hansen SB, Danielsen E, Andersen F,
Saiz PA, Gjedde A. PET neuroimaging with [11C]venlafaxine: serotonin
uptake inhibition, biodistribution and binding in living pig brain. Eur
Neuropsychopharmacol 1997;7(3):195-200.
2.Little JT, Ketter TA, Kimbrell TA, Danielson A, Benson B, Willis
MW, Post RM. Venlafaxine or bupropion responders but not nonresponders
show baseline prefrontal and paralimbic hypometabolism compared with
controls. Psychopharmacol Bull 1996;32(4):629-35.
Competing interests: No competing interests
Sir
In response to the paper by Johnson et al. entitled "Withdrawal
reaction associated with Venlafaxine" (BMJ 1998; 317:787)
Physicians should note that on 3 March 2000 the US Food and Drug
Administration approved important safety related drug labelling changes
which acknowledge the existence of a Venlafaxine withdrawal syndrome.
The drug labelling changes also confirm that the likelihood and
severity of withdrawal reactions on Venlafaxine discontinuation or dose
reduction increase with both dose and time.
The drug labelling changes are reproduced below and are available on
the Medwatch web site at:
http://www.fda.gov/medwatch/safety/2000/mar00.htm#effexo
Physicians should further note that Venlafaxine withdrawal reactions
have been reported after missing just a single dose. [1] and [2].
FDA DRUG LABELLING CHANGES
EFFEXOR & EFFEXOR XR (venlafaxine HCl) Tablets
[March 3, 2000: Wyeth-Ayerst]
DRUG ABUSE AND DEPENDENCE:
Physical and Psychological Dependence: New third paragraph -
"Discontinuation effects have been reported in patients receiving
venlafaxine (see DOSAGE AND ADMINISTRATION)."
DOSAGE AND ADMINISTRATION:
Discontinuing Effexor (venlafaxine HCl): First sentence revised -
"When discontinuing Effexor after more than 1 week of therapy, it is
generally recommended that the dose be tapered to minimize the risk of
discontinuation symptoms. Patients who have received Effexor for more than
6 weeks or more should have their dose tapered gradually over at least a 2
-week period."
New second paragraph -
"Discontinuation symptoms have been systematically evaluated in
patients taking venlafaxine, to include prospective analyses of clinical
trials in Generalized Anxiety Disorder and retrospective surveys of trials
in depression. Abrupt discontinuation or dose reduction of venlafaxine at
various doses has been found to be associated with the appearance of new
symptoms, the frequency of which increased with increased dose level and
with longer duration of treatment. Reported symptoms include agitation,
anorexia, anxiety, confusion, coordination impaired, diarrhoea, dizziness,
dry mouth, dysphoric mood, fasciculation, fatigue, headaches, hypomania,
insomnia, nausea, nervousness, nightmares, sensory disturbances (including
shock-like electrical sensations), somnolence, sweating, tremor, vertigo,
and vomiting. It is therefore recommended that the dosage of Effexor be
tapered gradually and the patient monitored. The period required for
tapering may depend on the dose, duration of therapy and the individual
patient. Discontinuation effects are well known
to occur with antidepressants."
Discontinuing Effexor XR:
"When discontinuing Effexor XR after more than 1 week of therapy, it
is generally recommended that the dose be tapered to minimize the risk of
discontinuation symptoms. In clinical trials with Effexor XR, tapering was
achieved by reducing the daily dose by 75 mg at one week intervals.
Individualization of tapering may be necessary. [The remainder of the
paragraph beginning with "While the discontinuation effects of Effexor XR
have not been systematically evaluated in controlled clinical trials,
retrospective..." has been deleted] and replaced with -
"Discontinuation symptoms have been systematically evaluated in
patients taking venlafaxine, to include prospective analyses of clinical
trials in Generalized Anxiety Disorder and retrospective surveys of trials
in depression. Abrupt discontinuation or dose reduction of venlafaxine at
various doses has been found to be associated with the appearance of new
symptoms, the frequency of which increased with increased dose level and
with longer duration of treatment. Reported symptoms include agitation,
anorexia, anxiety, confusion, coordination impaired, diarrhoea, dizziness,
dry mouth, dysphoric mood, fasciculation, fatigue, headaches, hypomania,
insomnia, nausea, nervousness, nightmares, sensory disturbances (including
shock-like electrical sensations), somnolence, sweating, tremor, vertigo,
and vomiting. It is therefore recommended that the dosage of Effexor XR be
tapered gradually and the patient monitored. The period required for
tapering may depend on the dose, duration of therapy and the individual
patient. Discontinuation effects are well known to occur with
antidepressants."
References.
1. Parker G, Blennerhassett J. Withdrawal reactions associated with
venlafaxine. Aust N Z J Psychiatry 1998; 32:291-4
2. Pinzani V, Ginies E, Robert L, Peyriere H, Abbar M, Blayac J.P.
Venlafaxine withdrawal syndrome: Report of six cases and literature
review. Rev Med Interne 2000; 21:282-4
Competing interests: No competing interests
Dear Sir,
Johnson etal. (1) report a withdrawal reaction associated with
venlafaxine at low dose . I have personally experienced a withdrawal
reaction after taking 37.5mg. twice a day for two weeks. The reaction was
identical to that experienced with paroxetine in the past and consisted of
insomnia, vivid dreams and sweating. The symptoms subsided immediately on
reintroduction of medication. Previous experience with paroxetine would
suggest that such symptoms can take up to a week to subside.
Competing interests: No competing interests
I recently reviewed you article by Johnson, Bouman, and Lawton with
regard to withdrawal reaction to venlaxafine. I have seen similar
reactions in a single patient on withdrawal of sertraline, fluoxetine, and
nefazadone. All of these including the venlaxafine have some
SSRI(selective serotonin reuptake inhibitor) activity. It is further of
interest that these symptoms resolved in a much shorter timeframe than the
three weeks as described in the aforementioned article when she was
withdrawn from one SSRI and started on another. Most recently however,
she was weaned from venlaxafine to bupropion, the symptoms were much more
persistent. Bupropion is not an SSRI.
This suggests a common withdrawal syndrome to SSRI medication and not just
venlaxafine. Clearly larger scale and preferably randomized studies need
to be done to obtain a clearer answer.
My patient is a 38 year old woman who was initially started on fluoxetine
in May 1995 for an episode of major depression. As no clinical response
was obtained at a dose of 40 mg for four weeks(July 1995), she was then
gradually withdrawn and started on sertraline. The positional vertigo
resolved in two or three days of starting the new medication. In July of
1996 she was withdrawn from the sertraline and started on nefazadone over
a period of two weeks. Again two or three days only of positional vertigo
occurred. Because of recent clinical ineffectiveness at 600 mg per day of
nefazadone she was again gradually withdrawn and restarted on venlaxafine
again over a two week period. The venlaxafine was effective, but again
because of side effect issues, she was started on bupropion. As the
bupropion approached therapeutic doses the effexor was gradually tapered
over two weeks, the last four days having a single daily dose of 37.5 mg.
The positional vertigo recurred but was more persistent. The symptoms
rapidly disappeared with a single dose of 37.5 mg of venlaxafine.
This is an issue of concern given the liberty with which SSRI medications
are prescribed.
Competing interests: No competing interests
Venlafaxine withdrawal syndrome: needs more time for discontinuation
I came to know about article by Johnson, Bouman, and Lawton (1) with
regard to withdrawal reaction to venlaxafine. I have witnessed a case that
developed neurological (diffuse headache, dizziness and sinking sensation)
and gastrointestinal (abdominal distress and nausea) on discontinuation of
venlafaxine. The symptoms resolved completely on re-initiation of
venlafaxine. After that, withdrawals were attempted several times over a
period of 2 to 4 weeks. Finally, venlafaxine gradually tapered over a
period of 10 weeks successfully.
It seems that venlafaxine should be withdrawn cautiously may be more than
recommended 2weeks (2) probably 6 to 10 weeks so that withdrawal symptoms
can be minimized.
References:
1.H Johnson, W P Bouman, and J Lawton
Drug points: Withdrawal reaction associated with venlafaxine BMJ 1998;
317: 787a
2.Steven Whiting. Withdrawal reactions associated with Venlafaxine - an
update. Rapid response to BMJ(26 May 2000)
Competing interests:
None declared
Competing interests: No competing interests