RE VENLAFAXINE WITHDRAWAL REACTIONS

DATE      CITATION           DRUG                     REPORT                                      

1996 Benazzi Venlafaxine Single case report of withdrawal symptoms after abrupt cessation of four week treatment with VFX 150mg/day. Patient experienced "brief   'bursts' of dizziness, which lasted for a few seconds and occurred numerous times throughout the day", also with headache, nausea, fatigue, sweating and worsening of depression. Symptoms cleared when VFX 75mg/day was restarted and did not reappear during the gradual drug tapering that followed.
1996 Farah & Lauer Venlafaxine Single case report of a 32-year old woman, originally on VFX 300mg/day, treated for eight months for depression. On each of three occasions she failed to withdraw from the drug, after abrupt discontinuation: she "experienced headache, gastro-intestinal distress, fatigue and other symptoms ... She remains on a regimen of venlafaxine, 100mg t.i.d."  
1966 Louie et al Venlafaxine Three cases are reported of VFX withdrawal, following both abrupt (2 cases) and very gradual cessation. Main symptoms were dizziness and G-I distress, but one patient also experienced auditory hallucinations and bizarre dreams. It took her ten weeks from the initial attempt at withdrawal to discontinue VFX. Neither of the two other patients was reported to have achieved withdrawal.
1996 Rauch et al Venlafaxine Four out of nine patients involved in an open 12-week trial of VFX for OCD "developed a troublesome withdrawal syndrome", in spite of gradual withdrawal of medication over four days to two weeks. Symptoms included "a flu-like syndrome with muscle aches, fatigue, headache, nausea and dizziness. In three cases, symptoms were relieved by resuming venlafaxine, followed by a more gradual discontinuation. Interestingly, the fourth patient developed withdrawal symptoms despite having initiated fluoxetine."  
1997 Agelink et al. Venlafaxine Two cases reported, both involving elderly women. In one case, patient was taken off VFX venlafaxine after 26 days because of persistent insomnia. Withdrawal symptoms included confusion, nausea, agitation, sweating, anxiety, visual hallucinations and fluctuation of blood pressure and heart rate. The severity of symptoms required close monitoring for eight hours in the psychiatric intensive care unit; symptoms resolved 24 hours after last dose. In the second case, VFX was stopped after 42 days because of lack of efficacy and unwanted effects. Withdrawal symptoms included nausea, feelings of abdominal distension, headache, restlessness, agitation, sweating and also visual hallucinations. Symptoms resolved within two to three hours after VFX was reinitiated. Thereafter, the drug was gradually withdrawn over four days, with no recurrence of symptoms. 
1997 Cunningham Venlafaxine & Venlafaxine XR This Wyeth-Ayerst sponsored study included measurements of withdrawal reactions in 127 patients treated with VFX but did not report them. Remarkable. Patients had been treated for 12 weeks with VFX (either the usual or Extended-Release version) in a double-blind, placebo-controlled trial, following which "study medications were tapered over a period of up to two weeks". The report states that patients were evaluated 4 to 10 days after medication was discontinued, but results are not reported.
1997 Fava et al Venlafaxine XR Twenty adult outpatients were randomly assigned to receive either an extended-release formulation of VFX or placebo. After eight weeks of double-blinded treatment, doses were tapered or stopped   (tapered by 75mg/week for patients taking 150mg/day or 225mg/day - but not for patients on 75mg/day, or on PBO). Seven of the nine patients previously on VFX (78%) reported adverse effects on withdrawal (and became significantly more depressed), compared with two out of nine patients (22%) on placebo. The  relationship between frequency and severity of effects and dosage of VFX was not recorded, but severity of withdrawal effects was significantly greater in the VFX group than for the group on placebo. See also: Cunningham, 1997.  
1997 Giakas & Davis Venlafaxine Fluoxetine Three consecutive cases reported of  26-35 year old women who experienced severe withdrawal after discontinuing venlafaxine, following treatment ranging from a week or two to seven months: "Repeated attempts at gradually tapering the dosage were unsuccessful and led to intolerable withdrawal sensations."  In these and other cases, authors noted appearance of withdrawal symptoms within a few hours of patient missing a dose. Although, symptoms they saw "are not identical to a fully-fledged psychedelic experience or a true migraine headache, similarity is evident..."  In all cases, venlafaxine was eventually discontinued under cover of fluoxetine, which itself was later withdrawn uneventfully in one of the three cases.
1997 Moore Venlafaxine "The investigators who were testing Effexor observed that 'clusters of symptoms sometimes occurred at or shortly after the discontinuation of Effexor treatment'. As a result, Wyeth-Ayerst did a survey of all the patients in the clinical trial's testing program. Overall, 35 per cent of the Effexor patients experienced withdrawal symptoms ranging from a flu-like syndrome to insomnia, nausea, nervousness and loss of energy. In five patients, Wyeth-Ayerst reported, withdrawal symptoms were so severe and prolonged that medical treatment was required. Two patients could not be withdrawn from the drug, and treatment was resumed. One patient was hospitalised. Two others had to be treated with another antidepressant. These five cases suggest a risk of severe addiction in some patients." Click for Moore
1997 Thase Venlafaxine XR Report of a manufacturer-sponsored, randomised, double-blind, placebo-controlled, multicentre evaluation of venlafaxine (extended release version) versus placebo. In this 8-week study, 91 patients were treated with VFX-XR and 100 with placebo. The medications were then tapered for up to two weeks, with a post- study evaluation made 4-10 days after discontinuation. In the 'Results' section of the paper, author noted: "Importantly, no clinically significant withdrawal syndromes were observed during double-blind discontinuation of study medications".  However, the term "clinically significant" is not defined, and this finding was not considered sufficiently important to be mentioned in the Abstract of the paper.  
1997 Wolfe Sertraline Venlafaxine Review including brief reports of two patients who had experienced withdrawal symptoms on discontinuing SRN and VFX respectively. The patient on VFX experienced severe restlessness (akathisia) which abated within hours of restarting the drug. The drug was later gradually tapered and withdrawn. 
1998 Benazzi F Sertraline, venlafaxine

 

 In this letter, author describes a patient who had been unable to withdraw from sertraline because of severe withdrawal symptoms - who was later able to discontinue "by adding, and later discontinuing, fluoxetine".  
1998 Boyd Venlafaxine Brief review of the 13 reports of withdrawal reactions to VFX received by the Australian Adverse Drug Reaction Advisory Committee (ADRAC) between early 1996 and early 1998. "Four of the 13 patients recovered from their symptoms within two weeks and two required return to venlafaxine and a tapered withdrawal. Three patients had not recovered at the time the report was submitted to ADRAC and information on time to recovery was not available for three patients, while outcome was unknown for one patient."
1998 Dallal & Chouinard Venlafaxine Letter reports that, on completion of  an 8-week open label study of venlafaxine, six of eight patients required gradual dose reduction (over 7-15 days, mean 11 days) because of severe withdrawal symptoms. In addition, two patients in the study had complained of a withdrawal symptom (nausea) shortly after missing a single dose. Authors advise: "clinicians should be aware of the potential for serious psychiatric and physical sumptoms that should not be confounded with the original illness when venlafaxine is abruptly discontinued".
1998 Johnson et al Venlafaxine Case report. Patient was a 42-year old man, successfully treated for depression with VFX 75mg/day for six months. Dosage was then halved (for an unspecified period) and stopped. Within 36 hours of stopping, patient "developed positional vertigo, which caused him significant incapacity, in addition to nausea and light- headedness". Symptoms soon resolved on reintroduction of drug. Dosage was reduced to 18.75mg/day for three weeks and then discontinued: "He had ongoing symptoms of vertigo which resolved slowly over three weeks. The patient's determination enabled him to discontinue ... but he did so with difficulty."
1998 Macbeth and Rajagopalan Venlafaxine Case report: After two year's unsuccessful treatment for depression, Mr Y (51) was tried on venlafaxine, to 300mg/day. "After four weeks on this dose, depressive symptoms continued unabated and Mr Y began to make active suicidal plans". A course of ECT was therefore planned, so the VFX was rapidly reduced, over two days. After 72 hrs, Mr Y developed severe nausea, anorexia, dizziness, unsteady gait, tinnitus and headache - all new symptoms which resolved when VFX was restarted at 75mg.day. Shortly after, Mr Y was withdrawn uneventfully from this dosage, over one week.
1998 Parker & Blennerhasset Venlafaxine Paper describes withdrawal problems associated with abrupt and tapered withdrawal of VFX and documents withdrawal symptoms occurring after missing a single dose. Two cases are discussed, including one where severe symptoms (including hallucinations) were experienced during slow tapering. Authors conclude that withdrawal "make make cessation of the drug extremely difficult", and they consider two strategies for addressing the problem.
1998 Raby Venlafaxine Case report in which odansetron was successfully used to relieve somatic symptoms (but not anxiety) of venlafaxine withdrawal. Patient (29 year old woman with 12-year history of bipolar I disorder)  had been treated with VFX for 10 weeks without response. Dosage was decreased with difficulty: "when receiving less than 75mg/day of venlafaxine, Ms. A would experience nausea, headaches, diarrhea, and anxiety so severe that she was forced to remain at home" and "this proved to be a dose below which the tapering schemedule could not be continued".
1999 Goldstein et al Sertraline (2), fluoxetine (1), venlafaxine (1)

 

 Manic symptoms following antidepressant withdrawal have mainly been reported in unipolar depression. These cases involved bipolar patients, treated for an average 6.5 months, before taper (average 20 days, range 1-43). The first manic symptoms emerged, on average, 2 weeks into the taper period (range 1-23 days), and mean length of manic episode was 28 days (range 12-49 days).
1999

 

 Sierra Santos et al Venlafaxine In Spanish. Single case-history of severe reactions experienced in spite of gradual withdrawal and brief review.
2000

 

 Pinzani et al Venlafaxine In French. Short report of six cases of withdrawal reactions and a brief literature review. Authors conclude that "physicians must be aware of the frequency, rapidity and potent severity of these withdrawal syndromes".
2001 Luckhaus and Jacob Venlafaxine Case report involving 'marked, distressing and on-going' symptoms pecipitated by withdrawal of venlafaxine. Symptoms were resolved by sertraline (but not prevented by concurrent maprotiline) and included agitation, perspiration, nausea, vomiting, tinnitus and insomnia, but 'there was no relapse of depression'.
2002

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 van Noorden
et al		 Venlafaxine Article in Dutch. Case report of a 35-year-old man with anxiety and depression, treated with venlafaxine 300mg/day who developed severe withdrawal symptoms during a gradual taper of the dosage. Authors state this is the first published case of delirium following venlafaxine withdrawal
2002 Patients' reports Venlafaxine See this well-established, much visited US website operated by Belynda Warner at   http://members.tripod.com/bwarner/effexor.html   See also new UK website  at:  http://www.effexorfx.freeuk.com
operated by Steve Whiting.

The following are the recommendations and warnings relating to withdrawal reactions for SSRI antidepressants in the Data Sheet Compendium 1998/99:

Venlafaxine (Efexor/Effexor):  "Discontinuing Efexor: No definitive withdrawal syndrome has been observed with Efexor. During clinical trials, symptoms reported on abrupt discontinuation of Efexor from daily doses of 150mg or more included fatigue, nausea and dizziness and one episode of hypomania. Discontinuation effects are well known to occur with antidepressants; therefore, when Efexor has been administered for more than one week and is then stopped, it is generally recommended that the dose be reduced gradually over a few days and the patient monitored in order to minimise the risk of discontinuation symptoms. Patients who have received Efexor for six weeks or more should have their dose reduced gradually over at least a one-week period."

Contents page
  Pencil_and_PaperE190.gif (245 bytes) References
Table: all reports of SSRI withdrawal