REPORTS OF SSRI WITHDRAWAL REACTIONS

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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'."
1992 Szabadi Fluvoxamine Single case. 30-year old woman treated for OCD with FVX 100mg/day, unable to stop when she became pregnant: "whenever she had tried to do so, she was overwhelmed by strong feelings of aggression (she felt that she 'could murder someone')." Later, when attempting withdrawal from FVX 150mg/day, patient initially felt pleasantly elated but, from second day after discontinuation, she again experienced what she described as 'unbearably distressing' aggressive feelings and thoughts.
1993 Black et al Fluvoxamine In an open-label study, fourteen patients were abruptly withdrawn from FVX, after 7-8 months of treatment for panic disorder. Twelve patients (86%) developed new symptoms, characteristic of a withdrawal syndrome - mostly dizziness, incoordination, headaches, nausea and irritability. Symptoms peaked on day 5 after withdrawal. One subject had a recurrence of panic, and other developed anxiety and depression; both were re-medicated.
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
1993 Mallya et al Fluvoxamine Four out of 17 OCD patients (28%) treated with FVX for at least one year developed symptoms (including dizziness, nausea, headaches, confusion, memory problems, low energy, weakness) during or after gradual drug discontinuation.
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 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 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 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 Lauterbach Fluoxetine Single case report of 62-year old woman who experienced pain several years after a thalamic infarct, following abrupt FLX discontinuation.
1994 Louie et al Sertraline Single case report of middle-aged woman, treated for 9 weeks with SRN, who experienced marked symptoms following both abrupt and gradual withdrawal. Patient experienced flu-like symptoms, also fatigue, insomnia headache and sore eyes. Symptoms resolved on restarting drug and a protracted withdrawal regimen was then begun. Patient reported similar but milder symptoms shortly after each of three dosage reductions; she was finally able to stop SRN treatment and became symptom free 14 weeks after the initial attempt at 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 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 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 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" . See also Fava, 1994, 1995
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 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 Kent & Laidlaw Sertraline Single case report of dependence seen in a neonate whose mother had taken SRN 200mg/day throughout her pregnancy and for three weeks after the birth, when it was stopped abruptly. "The baby, previously feeding and developing well, after one day developed symptoms of agitation, restlessness, poor feeding, constant crying, insomnia and an enhanced startle reaction. These symptoms were intense for 48 hours and then began to subside over the next few days. The mother remained well with no adverse symptoms after stopping sertraline." Comment. Fascinating, the contrast between what happened to mother and child. The mother was no longer depressed (perhaps elated by the birth) - while the never-depressed baby becomes hooked on an antidepressant drug. Makes you wonder what's going on
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 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).
1995 Lazowick & Levin Paroxetine Sertraline Fluvoxamine Review of ten published reports of SSRI withdrawal reactions. Authors note: "Withdrawal symptoms associated with the discontinuation of fluoxetine have not been established."
1995 Leiter al al Sertraline Report of two cases of withdrawal symptoms following SRN discontinuation, in one case after two weeks of dose tapering. Patients experienced deterioration of mood, cognition, energy levels, gait and balance, as well as headaches and gastrointestinal symptoms.Both patients "experienced significant discomfort due to paresthesias" (tingling, burning sensations under the skin).
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 Amsden & Georgian Sertraline Single case report: patient was a 29-year old man, who had taken SRN for 13 weeks before requesting discontinuation.  Dosage was then gradually decreased, to 50mg/day for five weeks, then 50mg every other day for six days, and stopped. Thereafter, patient developed dizziness and marked orthostatic hypotension on repeated attempts to withdraw the drug, using increasingly gradual regimens. After extensive examinations, all other organic factors were ruled out. Patient was finally successfully withdrawn, taking reducing doses over eight weeks.
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 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 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 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 Castaņeda et al. Nefazodone Report of three cases in which NFZ had been abruptly substituted for FLX, PRX and VFX, "with the emergence of anxiety, dysphoria, affective lability, agitation, restlessness, confusion and somatic complaints such as headaches, tremors and nausea", together with intense craving for opiates or cocaine in three "otherwise stably abstinent patients".
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 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 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."  
1996 Hamner & Huber Sertraline Letter discusses the implications of the common practice of discontinuing antidepressant drugs before giving ECT, in the light of experience with a patient whose depression markedly worsened (with development of spontaneous suicidal ideation) three days after discontinuing sertraline, prior to ECT. Patient "remained severely depressed after the first two ECT. Sertraline was then resumed and increased to 200mg daily. He progressively improved and by the fourth ECT had returned to his clinical status before discontinuing sertraline. With combined ECT and sertraline, he had full remission in major depressive symptoms after 10 additional treatments ..."
1996 Lane  (Pfizer Inc.) SSRIs Fairly detailed review (45 references) of withdrawal symptoms after discontinuation of SSRIs. Also reasonably dispassionate until it reaches the last sentence - which gives the kind of endorsement one might expect to see in quotes in a Lustral/Zoloft advertisement. It's not a bad example of  "advantage dredging". Click here. 
1996 Lejoyeux et al. SSRI and other antidepressants This is a detailed analysis and review of antidepressant withdrawal, and one the authors is a true world specialist in this field. Dilsaver has been a source of much good and wise intelligence over year years; much of it is still years ahead of its time in relation to general medical practice. In this paper, however, the key findings are buried in the body of the paper, which few read. By contrast, the Abstract of the paper, much more widely read - seems seriously bland. Click here.
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 Mareth & Brown SSRIs This is a query about the report by Ellison, 1994, with comments on the possible mechanism and origins of SSRI withdrawal symptoms. Dr Ellison replies.
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 Price et al., MCA & CSM SSRIs This report from the Medicines Control Agency and Committee on Safety of Medicines is discussed at some length both in The Antidepressant Web and in correspondence with the MCA. This paper is by no means devoid of acceptable evidence, but key parts of it are demonstrably based on confused, inadequate and/or sloppy research methodologies and interpretations. Therefore it reaches inaccurate conclusions, some of which  constitute a real risk to public health (eg in permitting lack of proper warnings), as well as signalling that regulatory standards may be as seriously deficient with other drugs.

The paper concludes that "overall, symptoms due to stopping SSRIs are rare" and that withdrawal symptoms "do not appear to be severe", but are "are relatively mild and do not have features of a physical drug dependency syndrome". Of the 27 reports on withdrawal cited above (through 1995), only five are cited in the MCA/CSM paper; some other citations are essentially spurious. 

When invited to withdraw these conclusions, the MCA said it found no "scientific grounds" for doing so. The MCA gave no indication of thinking it might improve matters by revising its views in any way, and no evidence of recognition that something might be wrong. Click here
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."  
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 Rosenstock Sertraline Two brothers, coincidentally being treated for depression with SRN up to 100mg/day, "experienced similar but unusual symptoms", in spite of gradual withdrawal. The main symptom was a "nearly immobilising disequilibrium". 
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 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 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 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 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 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 - as well as dizziness and G-I and other symptoms. "Remission occurred spontaneously without any pharmacologic intervention" after nine days
1997 Mackay et al Fluvoxamine Fluoxetine Sertraline Paroxetine Paper reports and discuss the results of four large-scale "Prescription Event Monitoring" surveys in which individual GPs are asked to report any "medically significant event" experienced by named patients for whom they had prescribed one of the reference drugs. Over ten thousand reports were received for each of the four reference SSRIs and there were 15 cases of withdrawal symptoms after stopping paroxetine and two with each of the other three SSRIs. Paper does not discuss possible limitations of the survey method as a basis for estimating incidence. In a survey large enough  to include reports of 1547 deaths including 110 suicides, these 21 reports of withdrawal problems indicate extremely high levels of under-recognition and/or under-reporting.
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".
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.
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 Therrien & Markowitz All SSRIs This report is based on a compilation of published reports (MEDLINE 1985-1996) of withdrawal symptoms following discontinuation of SSRIs. Brief summaries are given of 46 case reports and two discontinuation studies. This report "characterizes the withdrawal syndrome, discusses potential mechanisms of withdrawal, and makes recommendations for prevention and management".
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.
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. 
1997 Young & Currie SSRIs Authors note the huge discrepancy between the suspected incidence of SSRI withdrawal reactions (between about 30% to 80%) and the numbers of spontaneous adverse drug reaction reports sent to national agencies - 2 reports per million prescriptions for FLX, 30 reports per million for FVX and SRN, and  300 per million prescriptions for PRX. This observation prompted a survey of 100 psychiatrists and 100 GPs, to test their awareness of antidepressant withdrawal reactions. About half of each responded. The survey suggested "a sizeable minority of physicians denied being confidently aware of the existence of antidepressant withdrawal symptoms ...". The conclusion:   "Education  ... is needed for both psychiatrists and family practice physicians."   
1997 Zajecka et al SSRIs This useful review is based mainly on a MEDLINE search and  briefly summarises reports that allow systematic assessment of withdrawal symptoms following SSRI discontinuation.  SSRI withdrawal symptoms in adults are summarised in 24 case reports and 9 reports from controlled clinical trials, also in 3 case reports discussing neonatal withdrawal. "Percentages of patients reporting SRI discontinuation syndrome range from 5% to 86%". Authors propose the definition of an SSRI discontinuation syndrome as the onset of a cluster of somatic and psychic symptoms following drug withdrawal, which are not attributable to other causes (e.g., concomitant medication, illness). "These symptoms include dizziness, light-headedness, insomnia, fatigue, anxiety/ agitation, nausea, headache, and sensory disturbance. The syndrome may last up to 3 weeks and may be improved by restarting the antidepressant or starting an antidepressant with a similar pharmacologic profile." 
1998 Benazzi Fluvoxamine Patient was a 33-year old woman being treated for recurrent major depression and panic disorder, with fluvoxamine 200mg/day and clonazepam 2mg/day. After six months, fluvoxamine was slowly withdrawn. At 50mg/day, she began to suffer typical SSRI symptoms, but these worsened and were accompanied by severe depression and new, severe symptoms of aggressiveness, irritability and fatigue alternating with intense agitation. Patient had previously experienced typical symptoms after paroxetine  withdrawal "which lasted many weeks but disappeared within a few days after fluvoxamine was introduced".
1998 Benazzi Nefazodone Letter: thought to be the first published report (in the English- language literature) of nefazodone withdrawal problems. Patient was 27-year old male, with diagnosed "dysthymic disorder and social phobia". After three months on clomipramine and alprazolam, NFZ 250mg/day was added. One month later NFZ was abruptly withdrawn. Patient experienced similar withdrawal symptoms to those he had previous had when coming off  VFX. Symptoms spontaneous resolved after three days.
1998 Benazzi F Sertraline, venlafaxine

 

 In this letter, author describes two patients who had been unable to withdraw from sertraline and venlafaxine, because of severe withdrawal symptoms - who were later able to stop taking SSRIs "by adding, and later discontinuing, fluoxetine". 
1998

 

 Benazzi (4) Sertraline Patient was a 57 year old woman who had been taking sertraline 50mg/day for 10 months for recurrent major depressive disorder and panic disorder. Sertraline was slowly tapered but, after two days with sertraline 12.5mg/day, "she noted anxiety, irritability, compulsions (frequent cleaning and hand washing, which she had never had before), light/sound sensitivity, insomnia, nausea and headache."  Symptoms worsened during the second week: "she also noted depressed mood, fatigue, apathy (she spent many hour in bed), pessimistic and guilt ruminations, loss of appetite, difficulty concentrating and suicidal thoughts, of an intensity never had in the past". Symptoms soon cleared on restitution of sertraline 25mg/day.
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 Bryois et al Paroxetine Detailed case report and brief review (in German).
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

 

 Gram Citalopram, paroxetine, fluvoxamine Report, in Danish, gives brief details of reports of withdrawal reactions relating to citalopram (5 cases), paroxetine (5 cases) and fluvoxamine (1 case)
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 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

 

 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 Maixner et al Unspecified SSRIs See abbreviated abstract. Notable for suggesting that, when antidepressants are discontinued, tapering over three to six months may be needed.
1998 Markowitz Unspecified SSRIs Following an earlier report on the controversial but common practice of discontinuing antidepressant drugs before treatment with ECT  (Hamner & Huber, 1996) also a review of SSRI withdrawal reactions (Therrien & Markowitz, 1997), the author suggests in this letter that: "It is possible that in some cases, side effects that are presently attributed to the ECT treatment itself may be partially (if not entirely) the result of abrupt discontinuation of an SSRI ..."
1998 Mourad et al Unspecified SSRIs In French with English abstract. Sixteen patients on antidepressants (including six on SSRIs) "were submitted to a brutal discontinuation" of drug, and 14 "presented modifications of their somatic or psychic state three days after the interruption" of treatment. With SSRIs, the most frequent symptoms were increased anxiety and irritability and headache, with reduced levels of nausea and anorexia in two patients. 
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".
1998 Rosenbaum, Fava et al Paroxetine Sertraline and Fluoxetine This paper is the subject of detailed review. Briefly, it gives excellent evidence in relation to withdrawal from paroxetine and sertraline, but only clues about fluoxetine.
1998 Zajecka et al Fluoxetine How to avoid following up clues - while still managing to give the game away. See detailed review.
1999 Bakker A Paroxetine In Dutch.  Letter re: "Severe withdrawal symptoms with fever upon stopping paroxetine"
1999 Epelde et al Fluoxetine Letter: in Spanish, describes "Seizures crisis following abrupt withdrawal of fluoxetine"
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

 

 Kotlyar et al Nefazodone This case report concerns a healthy 28-year old male volunteer, given up to 400mg/day NFZ (the usual therapeutic dose) for nine days. Following abrupt discontinuation, subject reported "electric shock-like symptoms, dizziness, and nausea". Symptoms began to subside 72-hours after stopping and ceased shortly thereafter.
1999

 

 Lauber Nefazodone After four weeks of treatment at the usual therapeutic dose (400mg/day), this young woman patient abruptly stopped treatment and 48 hours later experienced "nausea, vomiting, fatigue, headache, myalgia, sweating, restlessness, dizziness, sleeping disturbances with vivid nightmares, severely depressed mood, emotional lability and anxiety" plus "brief moments of disorientation and shock-like sensations". Four days later treatment was restarted and symptoms promptly resolved. Author comments that, in view of the relatively short half-life of NFZ, it seemed surprising that the onset of the withdrawal syndrome occurred only 48 hours after discontinuation.
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
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).
1999

 

 Rajagopalan and Little Nefazodone Case report: 41 year old patient took nefazodone 100mg/day for three weeks, but her conditioned worsened and it was decided to reduce and then stop the NFZ (after 3 days on 50mg/day). Severe withdrawal symptoms began two days off drug and lasted another week ... "she became frightened by what she described as the worst feeling throughout. Although she found the experience difficult to describe, she reported that her head felt itchy inside, had racing thoughts, felt anxious and hyped up to the point that she wanted to hit her head on the wall in order to make it stop ..."
1999

 

 Sierra Santos et al Venlafaxine In Spanish. Single case-history of severe reactions experienced in spite of gradual withdrawal and brief review.
1999 Vergouwen and Kuipers Paroxetine In Dutch.  Letter re: "Severe withdrawal symptoms with fever upon stopping paroxetine"
1999

 

 Wisner et al Antidepressants Review of results from prospective studies (1989 - 1999), in which antidepressants were presecribed during pregnancy, found that "direct drug effects and withdrawal syndromes occurred in some neonates whose mothers were treated with antidepressants near term".
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.
2000 Fernando & Schwader Citalopram Case report in which a 45-year woman, taking 40mg/day citalopram experienced rapid-onset dizziness a few hours after missing her morning dose. On the second occasion this resulted in a minor car accident
2000 Friedman Paroxetine Letter: Neurobiology of behavioural changes after prenatal exposure to paroxetine (Paxil)
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 ... Mrs C experienced problematic nocturnal twitching (sudden myoclonic jerks), continuing eight months after stopping fluoxetine ... 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 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 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 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.
2000 Nuss & Kinkaid SSRIs Authors note that "very little is discussed about discontinuing treatment" though there is "growing evidence" of a withdrawal syndrome with SSRIs. Article describes two cases and reviews  the literature.
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".
2000 Sempere et al Citalopram Letter re: withdrawal problems with citalopram (in Spanish)
2000 Strickland and Hough Paroxetine Letter: case report involving facial numbness and visual blurring associated with withdrawal from paroxetine
2000 Yapp et al Nefazodone Case report involving admission of breast-fed premature baby found "drowsy, lethargic, unable to maintain normal body temperature and feeding poorly". Authors report their data "suggest a putative association between maternal nefazodone ingestion and adverse effects" in this infant.  The measured amount of drug exposure would normally be considered safe in a full-term infant; however, adverse effects in the infant resolved when breastfeeding was stopped.
2001

 

 Carrazana et al Sertraline Letter reporting case in which 62-year old woman experienced withdrawal symptoms, quitting after 6 months on sertraline 100mg/day - which she then attempted to treat with an anti-anxiety drug, buspirone. This apparently intensified symptoms of withdrawal, producing 'intense nausea, anxiety, dizziness and vertigo'.
2001 Einarson et al antidepressants/  benzodiazepines Important and disturbing report detailing the experiences of 36 participants in a study of women who stopped taking antidepressants or tranquillisers when their pregnancies were confirmed. See author abstract
2001

 

 Favaro et al Sertraline Long letter reporting a small retrospective study details sertraline withdrawal syndrome observed in 6/24 (25%) patients treated for anorexia nervosa (AN). Authors note that "neither high doses of medication nor specifically, abrupt discontinuation, seem to be linked to the presence of discontinuation symptoms ... Our data suggest that discontinuation syndrome in AN is related more to the psychologic and temperamental characteristics of the patients than to their underweight condition."
2001 Hirose Fluvoxamine Case report - believed to be the first published report of SSRI withdrawal in Japan - in which abrupt drug discontinuation produced marked symptoms of restlessness. Symptoms soon disappeared when patient was put back on drug.
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'.
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). SSRIs have been found to degrade sleep quality more than other antidepressants. In this study, 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. See later comment by Ibister et al, 2001.
2001 WHO/Uppsala Monitoring Centre SSRIs, BDZs and other drugs The print-out reproduced elsewhere on this website identifies four SSRIs - paroxetine, venlafaxine, sertraline and fluoxetine - among the top ten drugs with most reports of withdrawal problems indicative of dependence. See Table and comment relating to the posture of the European regulators and the pharmaceutical industry.
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

 

 Trenque, et al All SSRIs This is a brief review of the 60 cases of withdrawal reactions reported for SSRI/SRNI drugs, on the French national pharmacovigilance database, to May 2000. They included seven neonatal withdrawal reactions. Paroxetine and venlafaxine top the list; this report acknowledges that the delayed onset of withdrawal reactions to fluoxetine (due to extended half-life) "explains the relatively few reported withdrawal reactions."
2002

 

 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

 

 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).
2002 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.
2003

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 ADRAC Sertraline, Paroxetine, Fluoxetine, Citalopram This short report summarises notifications, to the Australian Adverse Drug Reactions Advisory Committee, of adverse effects in neonates, following maternal ingestion of SSRIs - also adverse effects probably resulting from breast-milk transfer. The full report is available online.

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Abbreviations  -  and links to reports on individual SSRIs

FLX

=

fluoxetine

FVX

=

fluvoxamine

NFZ

=

nefazodone

PRX

=

paroxetine

SRN

=

sertraline

VFX

=

venlafaxine
CTL   =

citalopram

OCD

=

Obsessive-compulsive disorder

 

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