RE: PAROXETINE WITHDRAWAL REACTIONS

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DATE      CITATION           DRUG                     REPORT                                      

1993 CSM & MCA Paroxetine "We have received 78 reports of symptoms occurring on withdrawal of paroxetine, including dizziness, sweating, nausea, insomnia, tremor and confusion. Such reactions have been reported more often with paroxetine than with other SSRIs. Reactions tended to start 1-4 days after stopping paroxetine and in several patients resolved on re-instating treatment. Paroxetine should not normally be discontinued abruptly". See also: Price et al, 1996.
1993 Inman et al Paroxetine See: Mackay et al., 1997
1994 Barr et al  Paroxetine  In the course of a 12-week double-blind trial of PRX versus placebo in OCD, it was noted that several patients experienced withdrawal symptoms after abrupt discontinuation. Investigators therefore decided on gradual withdrawal for patients involved in the open, continuation phase of the study. In spite of dose tapering over 7-10 days (from PRX 60mg/day) three out of six patients experienced withdrawal symptoms, including vertigo, gait instability, nausea and vomiting, diarrhea, insomnia, fatigue and visual phenomena.
1994 Keuthen et al Paroxetine Authors present case reports to illustrate their finding that, in spite of gradual dose reductions, five of 13 patients (38.5%) experienced new, "unexpected and sometimes disabling" withdrawal symptoms on discontinuation of PRX. The most commonly experienced effect was dizziness; headache, nausea and insomnia were reported too. Symptoms typically lasted from one and two weeks after discontinuation.
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".
1995 Bloch et al. Paroxetine Report of severe psychiatric symptoms associated with PRX withdrawal seen in two middle-aged men, neither with a history of major psychiatric disorders. Both men were involved in a six-week, controlled double-blind trial of PRX (50mg/day) for stuttering. The first patient developed marked hypomanic symptoms two days after abrupt PRX withdrawal and, after two weeks, exhibited impulsive behaviour, including "suicidal impulses and gestures." Symptoms abated spontaneously after two weeks. In the second case, PRX dose was tapered over 12 days. Initially, patient experienced uncharacteristic feelings of confidence and optimism. Later he experienced physical symptoms associated with PRX withdrawal, and felt angry, irritable and short-tempered "with some highly atypical vocal outbursts and tantrums. He became preoccupied with homicidal thoughts and plans, initially directed towards acquaintances and later towards his own children. These became so intense ... that he contemplated suicide." Symptoms lasted about 9 days and remitted spontaneously over 2-3 days.
1995 Debattista & Schatzberg Paroxetine Two cases are presented in which patients stabilised on a low dose of PRX (10mg/day) were then abruptly withdrawn and experienced symptoms including severe fatigue, dizziness, nausea and vomiting, headache, tremulousness and malaise. Both patients restarted PRX treatment; one later withdrew again and experienced substantial fatigue and nausea lasting six days. Authors conclude that some patients might need a dose tapering schedule extending for weeks rather than days.
1995 Dominguez & Goodnick Paroxetine Authors had previously noted no untoward effects after abrupt withdrawal of PRX "for numerous patients", even after longer exposures and with higher dosages. But here they report problems with three female patients who abruptly withdrew from PRX 40mg/day, after about 3- to 6-months treatment. All were "markedly to severely distressed by their symptoms" such that "immediate intervention was mandatory". All three were restarted on PRX and later successfully (gradually) withdrawn.
1995 Fava & Grandi Paroxetine (3 cases) and sertraline (1) Authors discuss four cases where depressed patients experienced symptoms similar to those in the cases reported in OCD patients, by Barr et al (1994) and Keuthen et al (1994) - indicating that withdrawal symptoms are therefore not specific in OCD.  These cases emerged from a total of four PRX patients, four on SRN and 19 patients treated with FLX. Authors conclude that "these serotonergically mediated  withdrawal syndrome raise concern about the possibility of the sensitizing of serotonergic systems by selective reputake inhibitors, leading to increased vulnerability to depressive relapse in the long run" (Fava, 1994)
1995 Frost & Lall Paroxetine (2 cases) Sertraline (1) Three cases are reported in this letter of withdrawal involving severe 'electric shock' like withdrawal symptoms similar to those reported by Ellison (1994). In one case, "five months of gradual paroxetine withdrawal led to cessation of the shocks"; in another case, "sertraline treatment was tapered over 8 weeks ... One day after the last 50mg dose of sertraline, he complained of 'electric shocks' ... They each lasted a second or so and occurred every 5-10 minutes. When his first attack occurred while he was in a swimming pool, he thought he 'was being electrocuted'. At times, his 'whole body would fly back', which once led to a brief loss of control of his car's steering wheel .... Less intense shocks persisted for 4 weeks and ceased 13 weeks after sertraline cessation."
1995 Koopowitz & Berk Paroxetine In Case One, patient abruptly stopped PRX after 4 months at 20mg/day. She developed (inter alia) severe dizziness and vertigo. After four days, patient was able to return to work. Symptoms somewhat abated but brief episodes continued for about a month. In the Second Case, patient stopped PRX after two months because adverse effects (mainly akathisia) had become intolerable. A severe withdrawal reaction followed (vertigo, dizziness, ataxia, nausea, diplopia, heaviness in head and feelings of dissociation). Nine days after start of this withdrawal reaction patient took an overdose of oxazepam, resulting in three days hospitalisation. Withdrawal reactions subsided thereafter. In Case 3, patient asked to stop medication after 6 months on PRX 20mg/day. Dosage was then reduced to 10mg/day for one month, then 10mg on alternate days for two weeks. On alternate non-drug days patient experienced severe headache, very severe nausea, dizziness and vertigo, dry mouth and lethargy. Dose was then changed to 5mg/day but patient felt gradual withdrawal prolonged her agony: she therefore stopped abruptly. She experienced two weeks of withdrawal symptoms and then recovered fully.
1995 Oehrberg et al. Paroxetine The assessment of withdrawal symptoms, following 12-weeks treatment with either PRX (20mg/day to 60mg/day) or placebo, appears to be incidental in this manufacturer-sponsored study. Assessment was made two weeks after drug discontinuation and no detailed results are reported. Authors report that "only" 19 patients out of 55 (34.5%) on PRX reported an adverse event on stopping,  compared with seven out of 52 (13.5%) patients on placebo. "Most" adverse events (mainly dizziness) were rated "of mild or moderate severity".
1995 Phillips Paroxetine Single case report of patient who was abruptly withdrawn after taking PRX (20mg/day for about 6 weeks); she experienced headaches, nausea and vomiting, abdominal discomfort and agitation. No indication of severity was given. (Author noted, incidentally, that a fluoxetine withdrawal syndrome had been reported to the manufacturer [Lilly, personal communication], though the report by Einbinder, 1995 suggested otherwise).
1995 Pyke Paroxetine Single case report: patient discontinued abruptly after four months on PRX 10-20mg/day. Flu-like withdrawal symptoms with visual problems and "an unpleasant occipital feeling of movement" were incapacitating for three days and improved over the following week, though dizziness and diarrhea recurred intermittently for three weeks. Author notes deficiencies in manufacturer's prescribing information.
1996 Bhuamik & Wildgust Paroxetine Brief report of a retrospective case note analysis in which patients with learning difficulties were treated for depression either with PRX (average 30mg/day) or FLX (average 20mg/day), on average for months. Withdrawal symptoms ("agitation and restlessness") were reported in five out of 12 patients who discontinued PRX (41.6%), but in no patients on FLX.
1996 Arya Paroxetine Single case report of withdrawal symptoms following both abrupt and gradual discontinuation in middle-aged female treated with 20mg/day paroxetine for one year. On discontinuation she reported headache, extreme tiredness, fatigue, emotional lability, a 'floaty feeling' in her head and inability to concentrate. She restarted PRX 10mg/day and symptoms disappeared. After one week, dosage was reduced to 5mg/day for one week and then PRX was stopped. Symptoms of tiredness, fatigue and 'floaty feeling' returned and persisted for three days.
1996 Coupland et al. Paroxetine Fluvoxamine Sertraline Fluoxetine This paper reports the results of a retrospective chart review of patients treated with SSRIs (also clomipramine) in an outpatient clinic. In the 158 patients who were supervised during gradual tapering and discontinuation of SSRIs, the most common symptoms were dizziness, lethargy, paresthesia, nausea, vivid dreams, irritability and lowered mood.  The most common symptom, "dizziness" was variously described as having a "swimming, spaced-out, drunken or buzzing quality and was markedly exacerbated by movement". The next most common symptom was "paresthesia" which was described as "burning, tingling or like electric shocks". Symptoms occurred much more frequently in patients treated with shorter half-life SSRIs (FVX, PRX) than in patients on SRN or FLX. Symptoms persisted for up to three weeks (mean 11.8 days).
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."
1996 Pacheco et al Paroxetine Five cases are presented of withdrawal after   treatment with paroxetine 20mg/day for 12-14 months. In all cases, withdrawal symptoms appeared in spite of conservative tapering regimens  - over two weeks (2 cases) or one month (3). In two cases, symptoms demanded urgent treatment; in all cases, symptoms persisted for about a week. Authors say that, following this experience, they now apply a dosage reduction of 5mg/mg per week to try to avoid symptoms of withdrawal.
1996 Reeves & Pinkofsky Paroxetine Single case report of 39-year old woman being treated for depression "at a time of marital discord"; she took paroxetine 20mg/day for one year.  One day after abrupt withdrawal, she experienced nausea, hot and cold flashes, headaches and lightheadedness, plus what she described as electric shocks running through her back and limbs, precipitated by movement. Symptoms worsened markedly over the next two days; electric shock sensations became so severe she began sitting as still as possible. At this point, patient attended the hospital emergency department; withdrawal symptoms were reversed within three hours of taken paroxetine 20mg by mouth. Later she attempted gradual withdrawal (10mg/day for a week) but symptoms reappeared. Symptoms again abated on restarting paroxetine 10mg/day. Patient was subsequently withdrawn, with only minor and short-lived symptoms, on 10mg paroxetine every other day, for ten days.
1996 Stein et al Paroxetine Sixteen patients who had responded well to PRX for "generalised social phobia" were randomised, on a double-blind basis, either to continue taking PRX, or (after tapering) to placebo. One of the eight patients (13%) continuing with paroxetine relapsed within 12 months versus five of the eight patients on placebo. Authors interpret these results as evidence of the superiority of PRX over PBO. They noted: "In retrospect, it seems that two patients randomised to placebo were experiencing withdrawal symptoms (ie dizziness and nausea) at the time of relapse".
1997 Dahl et al Paroxetine This letter reports a suspected case of paroxetine withdrawal in a neonate, following maternal exposure during the last trimester of pregnancy. The newborn initially appeared alert. Aged 12 hours he was referred for observation of increased respiratory rate, jitteriness, increased muscle tone and tremor, but with no convulsions. Except for sustained jitteriness, symptoms decreased during third and fourth days, when close observation ceased. A four week follow-up showed normal neurological status. 
1997 Landry & Roy Paroxetine Single case of a 33-year old woman treated for a first episode of depression with panic attacks. Over nine weeks, she was treated with increasing doses of paroxetine, up to 50mg/day. "On a few occasions", her symptoms remitted for several days after the dosage was increased, but then she relapsed. Paroxetine was then discontinued and replaced by desipramine. Three days later, she became irritable, dysphoric, restless and hyperactive - a dramatic change from her previous state - and experienced dizziness and G-I and other symptoms. "Remission occurred spontaneously without any pharmacologic intervention" after nine days
1997 Walker-Kinnear Paroxetine Patient was a physically healthy 30-year old man, treated with paroxetine 20mg/day (for depression) and sertindole (for paranoid psychosis). He had previously taken PRX and stopped without ill-effects but, when it was stopped on this second occasion, he had a severe reaction lasting for two weeks. Authors suggest that sertindole increased severity of withdrawal reaction and recommend against concurrent use.
1998 Bryois et al Paroxetine Detailed case report and brief review (in German).
1998 Huffstutler Paroxetine, other SSRIs Illustrative single case report in general review - emphasising management of antidepressant withdrawal reactions - prompted inter alia by the view that "discontinuation of antidepressant medications has received minimal attention" in the medical literature.
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.
1998 User views Paroxetine Thanks to correspondent, H.Evans, for identifying an interesting off-site source of user comments on withdrawal problems. You may need to explore, but try: http://www.lexmall.com/HEALTH/HBOARD/wwwboard.html
1998 Rosenbaum, Fava et al Paroxetine This paper is the subject of detailed review. It gives excellent evidence about withdrawal from paroxetine (and sertraline).
1999 Bakker A Paroxetine In Dutch.  Letter re: "Severe withdrawal symptoms with fever upon stopping paroxetine"
1999 Peeters & Zandbergen Paroxetine Case history of 30-year-old man, being treated for depression, who experienced "violent withdrawal symptoms with fever while tapering off paroxetine" (In Dutch with English Abstract).
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 F. continued to suffer from tardive dystonia, 8 months after stopping paroxetine ... and one year after stopping paroxetine, Mr B still suffered intermittent episodes, lasting hours to days at a time, comprising paresthesiae, dizziness, unsteadiness and slurred speech.
2000 Patients' reports Paroxetine See also these busy US websites: http://paxil.bizland.com and http://bbs.onecenter.com/paxil
2000 Hindmarch et al Paroxetine and other SSRIs "Abrupt discontinuation of treatment with paroxetine leads to deterioration in various aspects of health and functioning", but data on comparative effects appears to be of limited value
2000 Strickland and Hough Paroxetine Letter: case report involving facial numbness and visual blurring associated with withdrawal from paroxetine
2000 Friedman Paroxetine Letter: Neurobiology of behavioural changes after prenatal exposure to paroxetine (Paxil)
2000 Haddad and Qureshi Paroxetine Single case report: when a woman patient was switched from paroxetine to another (non-SSRI) antidepressant (dothiepin) she developed symptoms her doctor interpreted as an adverse reaction to dothiepin. A second opinion was obtained when it was realised she was in fact suffering from paroxetine withdrawal. Authors conclude: "Increased professional awareness of discontinuation symptoms is necessary to prevent misdiagnosis and inappropriate treatment". 
2000 Belloeuf et al Paroxetine In French. Aim of this report is "to stress the main clinical features of this syndrome", which is described as being "largely unknown to most physicians".
2000 Diler et al Paroxetine Letter: Withdrawal symptoms associated with paroxetine discontinuation in a nine-year-old boy.
2001 Nijhuis et al Paroxetine Letter reporting case of withdrawal reaction in a premature baby after maternal use of paroxetine (40mg/day) during the pregnancy.
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."
2001 Silvestri et al Fluvoxamine
Paroxetine

 

 Investigation of sleep disruption induced by SSRI use in 14 healthy volunteers, in a 31-day protocol (7 days pre-drug, 19 days on drug and 5 days of acute withdrawal). Paroxetine disrupted sleep more than fluvoxamine and paroxetine-induced sleep disturbance persisted into the withdrawal phase
2001 Stiskal et al Paroxetine Short report describing four cases with neonatal complications, consistent with neonatal SSRI (paroxetine) withdrawal syndrome. Authors call for the SSRI neonatal withdrawal syndrome to be clearly characterised.
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.
2002

 

 Costei et al Paroxetine Prospective controlled cohort study: of 55 neonates exposed to paroxetine in late gestation, 12 had complications necessitating intensive treatment and prolonged hospitalisation - respiratory distress (n=9), hypoglycaemia (n=2) and jaundice (n=1).
2002new.bmp (454 bytes) Diler & Avci Paroxetine, Fluvoxamine Sertraline Six case reports describing withdrawal symptoms (following abrupt and gradual discontinuation) in children (mean age 11.33 +/- 1.75 years) taking paroxetine (3 cases), fluvoxamine (2 cases) and sertraline. The withdrawal syndrome in children is described as similar to that experienced by adults; supportive strategies are discussed.

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

Paroxetine (Seroxat/Paxil): "Symptoms, including dizziness, sensory disturbance (eg paraesthesia), anxiety, sleep disturbances, (including vivid dreams), agitation, tremor, nausea, sweating and confusion have been reported following abrupt discontinuation of Seroxat. They are usually self-limiting and symptomatic treatment is seldom warranted. No particular patient group appears to be at higher risk of these symptoms; it is therefore recommended that when antidepressant treatment is no longer required, gradual discontinuation by dose-tapering or alternate day dosing be considered".

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