RE: FLUOXETINE WITHDRAWAL REACTIONS

DATE      CITATION           DRUG                     REPORT                                      

1988 Cooper Fluoxetine "A single patient has reported untoward effects related to discontinuation of fluoxetine; agitation, inability to concentrate, and insomnia were experienced within 48 hours of discontinuation." This case is mentioned in a review by Eli Lilly's Director of Clinical Research Europe of adverse events in 2938 patients who received FLX in pre-marketing comparative studies. Not stated: details of dosages, duration of treatment and numbers of patients observed during drug discontinuation.
1991 Stoukides & Stoukides Fluoxetine Single case involving a 32 year old male who had discontinued FLX  after six months treatment for depression. On the day after discontinuation he experienced some stiffness in his neck; the following morning he awoke with painful extensor muscle spasms and protruding tongue movements. Patient was seen in hospital emergency room: he was sweating and tremulous, still with protuberant tongue movements.  He was treated with 50mg i.m. diphenhydramine; symptoms resolved within 45 minutes.
1992 Breggin Fluoxetine This is a short report of suicidal ideation associated with stimulant effects and a subsequent "crash" during fluoxetine treatment. "The patient suffered apparently increasing tolerance to the medication's stimulant effects, producing a withdrawal reaction ('crashed') twice while being maintained on constant dose levels. The suicidal ideation was abrupt in onset and was associated with a feeling of 'crashing'."
1993 Spencer Fluoxetine Single case. Neonatal withdrawal symptoms reported in infant born to mother who had been prescribed FLX 20mg/day during most of her pregnancy. Onset of symptoms noted at 4hrs of age (marked acrocyanosis, jitteriness, rapid breathing, followed by temperature instability and signs of impending seizures). Infant transferred to intensive care unit; symptoms peaked at 36hrs (continuous crying, irritability, tremors, increased muscle tone, hyperactive startle reflex, and some vomiting). Symptoms diminished at 83hrs and had disappeared by 96hrs.
1994 Ellison Fluoxetine Fluvoxamine Paroxetine Author reported "peculiar and distinctive withdrawal phenomena" in about 5% of patients treated with SSRIs - following either rapid or gradual withdrawal and persisting for several weeks. This "withdrawal buzz" is described as a distractingly intense sensation in the head, like a 'jolt', a 'rush', a 'shock' or brief moment of disorientation and dizziness". Author notes that "no specific SSRI has appeared to predominate in causing this phenomenon, although one might expect an SSRI with a longer elimination half-life to produce fewer and milder withdrawal symptoms".
1994 Lauterbach Fluoxetine Single case report of 62-year old woman who experienced pain several years after a thalamic infarct, following abrupt FLX discontinuation.
1994 Rosenblat Fluoxetine & other SSRIs Preliminary report of the two cases of FLX withdrawal symptoms, subsequently published as Berlin (1996), plus a review of communications reported on the Internet of withdrawal reactions to other SSRIs.
1995 Einbinder Fluoxetine Single case involving a young woman who made repeated, unsuccessful attempts at withdrawal after three months on FLX (initially 40mg/day). Each time she experienced extreme dizziness. and instability. "Examinations by a neurologist and an otorhinolaryngologist, a magnetic resonance imaging of the head and tests for Lyme disease provided no explanation for her complaints". Symptoms were relieved each time by restarting the drug. She was finally withdrawn over a 12-week period, eventually tapering the dosage of FLX to 2.5mg/day for two weeks. "Author noted: "The manufacturer is unaware of any reports of withdrawal symptoms upon cessation of fluoxetine", but earlier reports  (Phillips, 1995; Berlin, 1996) indicate otherwise.   
1995 Kasantikul Fluoxetine The paper reports on a patient who experienced acute episodes of reversible delirium after twice attempting to discontinue long term fluoxetine therapy for depression. Author concludes it is "apparent that fluoxetine can have dependence and withdrawal potential."
1995 Kreider et al Fluoxetine This study from SmithKline Beecham (manufacturers of PRX) investigated what happened when depressed patients, stabilised on fluoxetine, were switched to PRX under double-blind conditions. Patients were randomised into two groups: 123 pts were switched immediately from FLX to PRX; and 119 pts were switched to placebo for two weeks before starting PRX. Lack of baseline data confounds analysis of adverse effects: were they due to either stopping FLX or to starting PRX? However, in group switched from FLX to placebo, there is some evidence of withdrawal effects (increased depression, nervousness and diarrhea) in the two-week off-drug period. Also in this group, one patient was hospitalised for drug and alcohol abuse (though study excluded patients who met DSM-III criteria for substance abuse).
1996 Berlin Fluoxetine Three cases are presented involving withdrawal reactions with FLX (one after gradual withdrawal) to illustrate the author's view that "if and when withdrawal occurs from fluoxetine, it may be more prolonged than with other SSRIs, and vertiginous symptoms may predominate". The predominant symptoms were recurrent bursts of dizziness and vertigo lasting a few seconds each and exacerbated by movement, plus symptoms of dysphoria, lasting four to eight weeks after discontinuation. In one case, patient twice remained without medication for a month each time, but symptoms did not abate. He resumed FLX treatment, with rapid relief of symptoms, and appeared unable to withdraw. Author noted that Eli Lilly had received 101 reports of suspected FLX withdrawal reactions by June 1994. (See Einbinder, 1995).
1996 Chambers et al. Fluoxetine This paper reports the results of a prospective examination of outcomes of pregnancies in 228 women who took FLX during pregnancy (and 254 women in a control group). Pregnancies were identified between 1989 and 1995, and infants were delivered in 109 different hospitals. Report concludes that women who take fluoxetine in the third trimester are at increased risk of perinatal complications, with an adjusted relative risk of 8.7 (2.9 - 26.6) of poor neonatal adaptation, including respiratory difficulty, cyanosis on feeding and jitteriness.  
1996 Mathew (Ed) Paroxetine Sertraline Fluoxetine Note from the Australian Adverse Drug Reactions Advisory Committee re reports received of withdrawal reactions with PRX (22 reports), SRN (7) and FLX (3). A total of 51 different symptoms had been reported. In addition to hallucinations (3 cases) and depersonalisation (3), there was "a wide range of other neurological and psychiatric symptoms including amnesia, ataxia, blurred vision, confusion, dysarthria, delirium, fatigue, hyperacusis, hypertonia, meningism, mood swings, neurosis, nervousness, nightmares, paresthesia, rigors, sensory disturbance, tinnitus and twitching. There was also a report of a neonatal withdrawal reaction."
1997 Blomgren et al. Paroxetine Sertraline Fluoxetine This report presents preliminary data from a multi-site study using an open-label, controlled, parallel design with a double-blinded interruption period to compare mean incidence of discontinuation-emergent signs and symptoms (DESS) in three demographically comparable treatment groups. Patients were clinically stable on maintenance doses (4 - 24 months) of FLX (20 - 60 mg/d), SRN (50 - 200 mg/d), or PRX (20 - 60 mg/day). For a five-to-eight-day blinded period, placebo was substituted for active drug. Brief interruptions of sertraline and paroxetine therapy produced significantly more adverse events than interruption of fluoxetine therapy.   The study design would greatly bias results in favour of fluoxetine. Given the short interruption period, one would not expect to see DESS in patients on fluoxetine, which has a significantly longer half-life than either paroxetine or sertraline. See detailed review.
1997 Mathew (Ed) Fluoxetine Sertraline Note from the Australian Adverse Drug Reactions Advisory Committee re eight reports received of withdrawal reactions in neonates whose mothers had taken with PRX (1 report), SRN (4) or FLX (3) in pregnancy, four of whom went on to breast feed the infant. "One case, in which the mother had taken fluoxetine involved a three day old baby who developed tachypnoea, irritability, jitteriness, fever, anorexia, cyanosis and possible fitting." In the other cases reported symptoms included jittery, irritable and unsettled behaviour, rapid breathing, lethargy and poor feeding. The effects "appeared to resolve spontaneously".
1998 Macdonald Paroxetine(17) sertraline (4) fluoxetine (3) fluvoxamine(2) This short report summarises the 26 reports of withdrawal reactions reported to the Canadian Adverse Drug Reaction Monitoring Programme, for the four available SSRIs.  In 15 cases, drug was restarted; in 10 cases symptoms abated. Of particular interest: three of the 26 cases (drug not specified) resulted in hospitalisation or prolonged hospitalisation;  and in one case, "electric shock-like" symptoms (paresthesia) persisted for four years after discontinuation of paroxetine.
1997 Mhanna et al Fluoxetine Case report (letter). Authors conclude "that although fluoxetine produces no identifiable malformations during pregnancy, pediatricians should be aware of the increased hemorrhagic tendency and jitteriness in infants who have been exposed to fluoxetine" in utero.
1998 Rosenbaum, Fava et al Fluoxetine, Paroxetine & Sertraline This paper is the subject of detailed review and gives important clues about withdrawal from fluoxetine.
1998 Zajecka et al Fluoxetine How to avoid following up clues - while still managing to give the game away. See detailed review.
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 Mahendran & Chan Fluoxetine, fluvoxamine Interviews with nine Asian patients, treated in Singapore, who had spontaneously and abruptly discontinued treatment with an SSRI suggested that seven had experienced withdrawal symptoms - three of the four patients taking fluoxetine and all four patients on fluvoxamine
2000 Green Paroxetine (2) Fluoxetine (1) This Psychiatry On-Line full-text report briefly describes experience with three patients (ages 29-35) who all suffered prolonged neurological symptoms for months after stopping SSRI medication ...... Mrs C experienced problematic nocturnal twitching (sudden myoclonic jerks), continuing eight months after stopping fluoxetine ...
2000 Mohan and Moore Fluoxetine Case report of a premature baby with marked automatism and skin manifestations after exposure to fluoxetine in utero. Neurological symptoms were reported resolved by 7 days and neurodevelopment was found normal at 4-month follow-up.
2001

 

 Nordeng et al Paroxetine
Fluoxetine
Citalopram		 "Neonatal withdrawal syndrome commonly occurs in infants exposed during the third trimester to drugs known to cause addiction. We report five cases of neonatal withdrawal syndrome after third trimester in utero SSRI exposure. In three cases the mother used paroxetine in doses from 10mg to 40mg, one mother used citalopram 30mg, and one mother used fluoxetine 20mg. Withdrawal symptoms occurred within few days after birth and lasted up to one month after birth. Four of the infants needed treatment with chlorpromazine. Symptoms were irritability, constant crying, shivering, increased tonus, eating and sleeping difficulties and convulsions."
2002 Bogetto et al Paroxetine Fluoxetine Report of a study of 97 outpatients diagnosed with dysthymic disorder who responded to 8-weeks or more of treatment with fluoxetine or paroxetine, who were studied at the time of drug discontinuation - the purpose being to investigate the incidence and characteristics of the withdrawal syndrome and to identify clinical predictors of the syndrome. A withdrawal syndrome was identified in 22/52 patients (42%) stopping paroxetine and  in 4/45 patients (9%) stopping fluoxetine. Authors believe this to be the first systematic investigation of the incidence of withdrawal symptoms in patients who either abruptly stopped their drugs or underwent slow tapering. In contrast to other reports, authors reported no significant difference in incidence of withdrawal symptoms between these two groups.

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

Fluoxetine (Prozac) "When dosing is stopped, active drug substances will persist in the body for weeks. This should be borne in mind when starting or stopping treatment".

 

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