EFFEXOR

Life Sci 2001 May 25;69(1):37-46

Attenuation of morphine dependence and withdrawal in rats by venlafaxine, a serotonin and noradrenaline reuptake inhibitor.

Lu L, Su WJ, Yue W, Ge X, Su F, Pei G, Ma L.

National Laboratory of Medical Neurobiology, Fudan University Medical Center, Shanghai, People's Republic of China.

The effects of venlafaxine, a novel serotonin and adrenaline reuptake inhibitor, on the morphine withdrawal and activation of morphine conditioned place preference (CPP), were investigated in rats. Our results showed that the most morphine withdrawal signs, including jumping, writhing, shakes, exploring, lacrimation, piloerection, irritability, and diarrhea, were attenuated by pretreatment with 10 or 20 mg/kg venlafaxine. To investigate the effects of venlafaxine on relapse to opiate dependence, the morphine CPP was used and a dopamine D2 antagonist sulpiride was selected as a control drug. The morphine CPP disappeared following a 28-day drug-free period and appeared again after given a single injection of 1 mg/kg morphine. Acute treatment with sulpiride (25 or 50 mg/kg, i.p.) 30 min prior to 1 mg/kg morphine injection significantly blocked the reacquisition of CPP, while venlafaxine (10 or 20 mg/kg, i.p.) did not show significant effect. However, chronic treatment with venlafaxine (5 or 10 mg/kg, i.p. twice, daily, for seven consecutive days) significantly attenuated the reacquisition of morphine CPP, whereas chronic treatment with sulpiride (10 or 20 mg/kg, i.p.) have no significant effect. Our results demonstrated for the first time that venlafaxine strongly attenuates morphine withdrawal and morphine-induced reaquisition of

PMID: 11411809 [PubMed - indexed for MEDLINE]

Am J Respir Crit Care Med. 2003 Apr 1;167(7):958-61.

Drug-induced pneumonitis and heart failure simultaneously associated with venlafaxine.

Drent M, Singh S, Gorgels AP, Hansell DM, Bekers O, Nicholson AG, van Suylen RJ, du Bois RM.

Department of Respiratory Medicine, University Hospital of Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. mdr@slon.azm.nl

Two cases of interstitial pneumonia with cardiac failure developing in patients treated with the new antidepressant venlafaxine are presented. A strong relationship between the development of the patients' illness and the initiation of venlafaxine treatment was identified. The cytochrome P (CYP) 450 system is involved in the metabolism of venlafaxine, suggesting that alterations in the drug metabolic clearance might be, at least in part, responsible for the development of drug-induced damage in these cases. This might occur either as a consequence of a genetic factor or concomitant drug therapy with an inhibitor of the related CYP system. After identifying the causative agent in the first case, withdrawal of the antidepressant together with corticosteroid treatment led to a favorable outcome. In the other case, the multiorgan failure became fatal. These cases highlight a hitherto undescribed association of an adverse lung reaction and heart failure due to venlafaxine.

PMID: 12663337 [PubMed - indexed for MEDLINE]

Ned Tijdschr Geneeskd. 2002 Jun 29;146(26):1236-7.

[Delirium during withdrawal of venlafaxine]

[Article in Dutch]

van Noorden MS, Vergouwen AC, Koerselman GF.

Sint Lucas Andreas Ziekenhuis, afd. Psychiatrie, Postbus 9243, 1006 AE Amsterdam.

A 35-year-old man with anxiety and depression who was treated with venlafaxine, 300 mg a day, developed severe withdrawal symptoms in the form of a delirium during gradual tapering of the dosage. The symptoms resolved when the dosage was kept constant and did not recur when the dosage was reduced more gradually. Withdrawal symptoms are common during discontinuation of antidepressants, particularly after prolonged use of agents with a short half-life. The symptoms are usually mild and transient, especially in the case of selective serotonin reuptake inhibitors and venlafaxine. The occurrence of delirium as a result of the withdrawal of venlafaxine has not been reported previously. Even when antidepressants are being withdrawn with care, one should remain alert to the possible development of severe withdrawal symptoms.

PMID: 12132141 [PubMed - indexed for MEDLINE]

Aust N Z J Psychiatry. 1998 Apr;32(2):291-4.

Withdrawal reactions associated with venlafaxine.

Parker G, Blennerhassett J.

University of New South Wales, Sydney, Australia.

OBJECTIVE: The aim of this paper is to describe discontinuation syndromes associated with abrupt and tapered withdrawal fo venlafaxine, and to document that withdrawal symptoms may occur after missing a single dose. CLINICAL PICTURE: We report on two patients prescribed venlafaxine. One developed a broad range of serious side effects after reaching a dose of 300 mg a day, and a severe withdrawal syndrome (including hallucinations) during a slow taper regime. The second had severe discontinuation symptoms during and aborting a slow taper regime, and described withdrawal responses after missing a single dose of venlafaxine. CONCLUSIONS: As for the short-acting selective serotonin re-uptake inhibitors, severe discontinuation reactions may occur with venlafaxine, seemingly marked most distinctly by headache, nausea, fatigue, dizziness and dysphoria, and may make cessation of the drug extremely difficult. Two strategies for addressing the concern are considered.

PMID: 9588310 [PubMed - indexed for MEDLINE]

Rev Med Liege. 1998 Feb;53(2):106-8.

[Pharma-Clinics. The drug of the month. Venlafaxine (Efexor)]

[Article in French]

Ansseau M.

Universite de Liege, Service de Psychiatrie et de Psychologie medicale.

Venlafaxine (Efexor) is the first representative of a new class of antidepressants: serotonin noradrenaline reuptake inhibitors. Its usual dose is 75 mg/d in two intakes but can be progressively increased until a maximal daily dose of 375 mg/d in severe or resistant depression, particularly among inpatients. The efficacy of venlafaxine is at least equivalent to reference antidepressants. At high doses, venlafaxine could even exhibit a better efficacy and a shorter latency than current compounds. Its profile of side-effects is quite similar to selective serotonin reuptake inhibitors with mainly nausea, with the exception if an increase in blood pressure which can appear at high doses. In total, venlafaxine represents an interesting innovation in the pharmacological treatment of depression.

PMID: 9564231 [PubMed - indexed for MEDLINE]

Rev Med Interne. 2000 Mar;21(3):282-4.

[Venlafaxine withdrawal syndrome: report of six cases and review of the literature]

[Article in French]

Pinzani V, Ginies E, Robert L, Peyriere H, Abbar M, Blayac JP.

Centre regional de pharmacovigilance, CHU de Montpellier, Montpellier, France.

INTRODUCTION: Venlafaxine is an antidepressant that selectively inhibits serotonin reuptake and is a norepinephrine inhibitor. Withdrawal syndromes can occur after abrupt drug discontinuation of long-term regimens. EXEGESIS: We report six cases of withdrawal symptoms after venlafaxine discontinuation. CONCLUSION: Physicians must be aware of the frequency, rapidity and potent severity of these withdrawal syndromes.

Publication Types:

Review

Review of Reported Cases

PMID: 10763190 [PubMed - indexed for MEDLINE]

Tidsskr Nor Laegeforen. 2000 Mar 20;120(8):913-4.

[Withdrawal syndrome after the use of serotonin reuptake inhibitors]

[Article in Norwegian]

Fagan M.

Kommunelegekontoret i Froland.

BACKGROUND: The use of serotonin reuptake inhibitors in the treatment of depression has increased significantly over the years since their introduction in Norway in the early 1990s. Reports of side effects have paralleled the increased use; one side effect is the withdrawal syndrome associated with serotonin reuptake inhibitors. MATERIAL AND METHODS: This article reports on two patients who discontinued paroxetine and experienced unusual shock-like symptoms consistent with this syndrome. RESULTS: There are numerous reports documenting withdrawal reactions caused by these antidepressants. Recently the first controlled studies have been published. INTERPRETATION: This syndrome is not well known and differs from the withdrawal syndrome caused by tricyclic antidepressants.

PMID: 10795494 [PubMed - indexed for MEDLINE]

J Clin Psychiatry. 1997;58 Suppl 7:37-40.

Comment in:

J Clin Psychiatry. 1998 Oct;59(10):535-7.

Clinical management of antidepressant discontinuation.

Rosenbaum JF, Zajecka J.

Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston 02114, USA.

To minimize the symptoms of antidepressant discontinuation, gradual tapering is necessary for all serotonin reuptake inhibitors (SRIs) except fluoxetine, which has an extended half-life. Agents with shorter half-lives such as venlafaxine (effexor), fluvoxamine, and paroxetine should be tapered gradually. Discontinuation symptoms, which frequently emerge after abrupt discontinuation or intermittent non-compliance and, less frequently, during dose reduction, are generally mild, short-lived, and self-limiting but can be distressing and may lead to missed work days and decreased productivity. The symptoms may be somatic (e.g., dizziness and light-headedness; nausea and vomiting; fatigue, lethargy, myalgia, chills, and other flu-like symptoms; sensory and sleep disturbances) or psychological (anxiety and/or agitation, crying spells, irritability). Mild symptoms can often be treated by simply reassuring the patient that they are usually transient, but for more severe symptoms, it may be necessary to reinstitute the dosage of the original antidepressant and slow the rate of taper. Symptoms of discontinuation may be mistaken for physical illness or relapse into depression; misdiagnosing the symptoms may lead to unnecessary, costly tests and treatment. Thus, health care professionals need to be educated about the potential adverse effects of SRI discontinuation.

Publication Types:

Review

Review, Tutorial

PMID: 9219493 [PubMed - indexed for MEDLINE]

J Clin Psychiatry. 1997;58 Suppl 7:5-10.

Comment in:

J Clin Psychiatry. 1998 May;59(5):255.

Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. Discontinuation Consensus panel.

Schatzberg AF, Haddad P, Kaplan EM, Lejoyeux M, Rosenbaum JF, Young AH, Zajecka J.

Department of Psychiatry, Stanford University School of Medicine, Calif 94305, USA.

Adverse events following discontinuation from serotonin reuptake inhibitors (SRIs) are being reported in the literature with increasing frequency; the frequency and severity of these symptoms appear to vary according to the half-life of the SRI, e.g., the incidence appears higher with the shorter half-life agents than with fluoxetine, which has an extended half-life. Yet, there have been no systematic studies of the phenomenon to date. Therefore, a group of experts convened in Phoenix, Arizona, to develop a clear description or definition of the phenomenon based on these reports. The SRI discontinuation syndrome, referred to as "withdrawal symptoms" in many anecdotal case reports, is distinctly different from the classic withdrawal syndrome associated with alcohol and barbiturates. Anti-depressants are not associated with dependence or drug-seeking behavior. SRI discontinuation symptoms tend to be short-lived and self-limiting, but can be troublesome. They may emerge when an SRI is abruptly discontinued, when doses are missed, and less frequently, during dosage reduction. In addition, the symptoms are not attributable to any other cause and can be reversed when the original agent is reinstituted, or one that is pharmacologically similar is substituted. SRI discontinuation symptoms, in most cases, may be minimized by slowly tapering antidepressant therapy, but there have been several case reports where symptoms occurred consistently even through repeated attempts to taper therapy. Physical symptoms include problems with balance, gastrointestinal and flu-like symptoms, and sensory and sleep disturbances. Psychological symptoms include anxiety and/or agitation, crying spells, and irritability. Further analyses of data bases and clinical studies are needed to define this proposed syndrome more clearly.

Publication Types:

Review

Review, Tutorial

PMID: 9219487 [PubMed - indexed for MEDLINE]

Med Hypotheses. 2002 Jul;59(1):92-4.

Prevention of the serotonin reuptake inhibitor discontinuation syndrome.

Sher L.

Prevention of the serotonin reuptake inhibitor discontinuation syndrome (SRIDS) is an important issue. The author suggests: (1) serotonin reuptake inhibitors (SRIs) should be used only when they are necessary. Sometimes tablets should be replaced with other treatment modalities; (2) patients should be given the lowest dosage of SRIs possible; (3) patients who have a history of medication noncompliance, who have experienced the discontinuation symptoms in the past, or who have treatment-emergent anxiety are at highest risk for experiencing the SRIDS and need closer monitoring; (4) SRIs should be tapered prior to stoppage; (5) generic drugs are allowed up to a 20% difference in bioequivalence from the brand original. Patients should receive continuity of supply from the dispenser, with no intermanufacturer switching; (6) patients and healthcare professionals should be educated to ensure that SRIs are not stopped abruptly; (7) neonatal SRIDS can follow maternal use of antidepressants during pregnancy and possibly breast feeding. The patient and physician should take this into consideration when making treatment decision.

PMID: 12160689 [PubMed - indexed for MEDLINE]

Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria

Kathy Black, MB ChB; Cathy Shea, MD; Serdar Dursun, MD, PhD; Stanley Kutcher, MD

J Psychiatry Neurosci 2000;25(3):255-61.

[résumé]

Abstract

Objective: To establish specific criteria by which selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome may be identified.

Data sources: MEDLINE and PSYCHLIT databases were searched for case reports published from 1986 to 1997 inclusive, and references of relevant articles were also searched.

Study selection: Forty-six case reports of symptoms following the discontinuation of fluoxetine, fluvoxamine, paroxetine or sertraline were selected. Three studies of SSRI discontinuation were also reviewed.

Data extraction: Demographic and treatment information, as well as the timing, duration, number, nature and frequency of dicontinuation symptoms.

Data synthesis: Paroxetine was most frequently implicated. The drug had been tapered in half of the cases. In some cases, symptom onset began during taper, whereas, in most cases, symptoms began within 1 to 3 days of drug discontinuation. Fifty-three different symptoms were reported, with dizziness being the most common. Other common symptoms were nausea or emesis, fatigue, headache, gait instability and insomnia. Shock-like sensations, paresthesia and visual disturbances were the most rare. Without intervention, symptoms persisted for more than a week in half of the cases. In cases in which the SSRI was restarted, symptoms resolved within 72 hours. In some cases, withdrawal symptoms recurred when the same SSRI was again discontinued.

Conclusions: Findings were used to construct diagnostic criteria for the SSRI discontinuation syndrome. These criteria are 2 or more of the following symptoms developing within 1 to 7 days of discontinuation or reduction in dosage of an SSRI after at least 1 month's use, when these symptoms cause clinically significant distress or impairment and are not due to a general medical condition or recurrence of a mental disorder: dizziness, light-headedness, vertigo or feeling faint; shock-like sensations or paresthesia; anxiety; diarrhea; fatigue; gait instability; headache; insomnia; irritability; nausea or emesis; tremor; and visual disturbances.

J Clin Psychiatry. 1997;58 Suppl 7:23-7.

Comment in:

J Clin Psychiatry. 1998 Oct;59(10):535-7.

Possible biological mechanisms of the serotonin reuptake inhibitor discontinuation syndrome. Discontinuation Consensus Panel.

Schatzberg AF, Haddad P, Kaplan EM, Lejoyeux M, Rosenbaum JF, Young AH, Zajecka J.

Department of Psychiatry, Stanford University School of Medicine, California 94305, USA.

Although the number of documented serotonin reuptake inhibitor (SRI) discontinuation reactions is increasing, to date no systematic studies have been completed; therefore the mechanism of action for these reactions is not clearly understood. However, several hypotheses have been proposed. Researchers have postulated that discontinuation events result from a sudden decrease in the availability of synaptic serotonin in the face of down-regulated serotonin receptors. In addition, other neurotransmitters, such as dopamine, norepinephrine, or gamma-aminobutyric acid (GABA), may also be involved, although little research in this area has been published. Individual patient sensitivity, i.e., genetics or cognitive mindset, may also be a factor in SRI discontinuation phenomena. Finally, experts have hypothesized that since some symptoms associated with paroxetine withdrawal are similar to those of tricyclic antidepressant discontinuation, they may be caused by cholinergic rebound.

Publication Types:

Review

Review, Tutorial

PMID: 9219490 [PubMed - indexed for MEDLINE]