Incidence and Timing of Taper/Posttherapy–Emergent Adverse Events Following Discontinuation of Desvenlafaxine 50 mg/d in Patients With Major Depressive Disorder

Ninan, Philip T.; Musgnung, Jeff; Messig, Michael; Buckley, Gina; Guico-Pabia, Christine J.; Ramey, Tanya

doi:10.4088/pcc.14m01715

Cited by 11 publications

(10 citation statements)

References 17 publications

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“…In the study by Khan et al [7] the DESS total score increased during the first 2 weeks of the discontinuation phase compared to baseline in all of the treatment groups, without significant differences among groups. Ninan et al [37] conducted a post hoc analysis on these data, confirming that taper/posttherapy-emergent adverse events occurred in all 3 groups through week 4 of the discontinuation phase, regardless of whether the desvenlafaxine dose was tapered or not.…”

Section: Single Drug At Different Doses Comparisonsmentioning

confidence: 99%

Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review

Fava

Benasi

Lucente

et al. 2018

Psychother Psychosom

152

146

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Background: Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim of this paper is to identify the occurrence, frequency, and features of withdrawal symptoms after SNRI discontinuation. Methods: PRISMA guidelines were followed to conduct a systematic review. Electronic databases included PubMed, the Cochrane Library, Web of Science, and MEDLINE from the inception of each database to June 2017. Titles, abstracts, and topics were searched using a combination of the following terms: “duloxetine” OR “venlafaxine” OR “desvenlafaxine” OR “milnacipran” OR “levomilnacipran” OR “SNRI” OR “second generation antidepressant” OR “serotonin norepinephrine reuptake inhibitor” AND “discontinuation” OR “withdrawal” OR “rebound.” Only published trials in the English language were included. Results: Sixty-one reports met the criteria for inclusion. There were 22 double-blind randomized controlled trials, 6 studies where patients were treated in an open fashion and then randomized to a double-blind controlled phase, 8 open trials, 1 prospective naturalistic study, 1 retrospective study, and 23 case reports. Withdrawal symptoms occurred after discontinuation of any type of SNRI. The prevalence of withdrawal symptoms varied across reports and appeared to be higher with venlafaxine. Symptoms typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well. Conclusions: Clinicians need to add SNRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with other types of psychotropic drugs. The results of this study challenge the use of SNRI as first-line treatment for mood and anxiety disorders.

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Section: Single Drug At Different Doses Comparisonsmentioning

confidence: 99%

Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review

Fava

Benasi

Lucente

et al. 2018

Psychother Psychosom

152

146

View full text Add to dashboard Cite

show abstract

“…Type and course of the symptoms which the patient had developed 2 days after abrupt discontinuation of venlafaxine are characteristic of venlafaxine withdrawal (6,10,13,15). However, development of obsessive-compulsive symptoms after discontinuation of venlafaxine has not yet been reported (6).…”

Section: Discussionmentioning

confidence: 98%

“…In addition, severe forms of withdrawal phenomena appear to occur more frequently in association with venlafaxine, and abrupt discontinuation of venlafaxine is associated with a higher incidence for withdrawal symptoms than tapering (13). In principle, withdrawal symptoms related to venlafaxine/ desvenlafaxine resemble those of SSRI (7,10,13,15). Here we report on a patient with major depressive disorder who developed obsessive-compulsive symptoms following abrupt discontinuation of venlafaxine.…”

Section: Introductionmentioning

confidence: 94%

“…Discontinuation of selective serotonin-noradrenaline reuptake inhibitors as venlafaxine (and desvenlafaxine) or duloxetine may also cause withdrawal symptoms (6). There is even evidence that venlafaxine is associated with a higher risk for the occurrence of withdrawal symptoms (10), both in comparison with duloxetine (11) and SSRI (escitalopram, sertraline) (12)(13)(14). In addition, severe forms of withdrawal phenomena appear to occur more frequently in association with venlafaxine, and abrupt discontinuation of venlafaxine is associated with a higher incidence for withdrawal symptoms than tapering (13).…”

Section: Introductionmentioning

confidence: 99%

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Development of Obsessive-Compulsive Symptoms Following Abrupt Discontinuation of Venlafaxine

2020

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Withdrawal symptoms after discontinuation of antidepressants are common and have long been known. Typical symptoms after dose reduction or discontinuation of antidepressants are dizziness, drowsiness, headache, flu-like symptoms, hyperarousal, imbalance, insomnia, irritability, and nausea. Rebound, relapse, or recurrence associated with the underlying mental disorder may also occur. The occurrence of obsessivecompulsive symptoms (OCS) following abrupt discontinuation of antidepressants have not yet been reported. Here we report the development of OCS (obsessional suicidal thoughts) in a patient with major depressive disorder and absence of a previous obsessive-compulsive disorder following abrupt discontinuation of venlafaxine. Treatment with escitalopram facilitated remission of OCS. We discuss a possible causal link between abrupt discontinuation of venlafaxine and development of OCS under consideration of pathophysiologic aspects regarding obsessive compulsive disorders, the chronological sequence of symptoms in the present case, and pharmacodynamic and-kinetic aspects. Our case report suggests the possibility of the occurrence of obsessivecompulsive symptoms following abrupt discontinuation of venlafaxine.

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“…Given their intermediate half-life, we expect them to display moderate withdrawal and rebound symptoms [20,90,91], which should on average trigger more cognitive impairments than drugs with a long halflife. In contrast, antidepressants with a short half-life like MAOIs [92] and TCAs [93], the SNRI drug venlafaxine (commercialized as Effexor) [25,94], and the SSRI drug paroxetine (better known as Paxil and Seroxat) [95], should be associated with strong withdrawal and rebound symptoms, which are most likely to produce severe Thieme Review cognitive impairments, as compared to substances with a longer half-life.…”

Section: Antidepressant Types Are Likely To Determine Which Cognitive Processes Will Be Impaired By Withdrawal and Rebound Effectsmentioning

confidence: 99%

An Oppositional Tolerance Account for Potential Cognitive Deficits Caused by the Discontinuation of Antidepressant Drugs

et al. 2021

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Depression is the leading cause of disability worldwide, making antidepressant drugs the most used psychiatric drugs in the USA. Withdrawal effects and rebound symptoms frequently occur after the reduction and/or discontinuation of these drugs. Although these phenomena have been investigated with respect to the clinical symptomatology, no studies have systematically investigated the effects of withdrawal/rebound on general cognition. We present a novel framework based on the idea of allostatic adaptation, which allows to predict how different antidepressants likely impair different cognitive processes as a result of withdrawal and rebound effects. This framework relies on the assumptions that the type of cognitive impairments evoked by an antidepressant is determined by the targeted neurotransmitter systems, while the severity of deficits depends on its half-life. Our model predicts that the severity of detrimental cognitive withdrawal and rebound effects increases with a shorter half-life of the discontinued antidepressant drug. It further proposes drug-specific effects: antidepressants mainly targeting serotonin should primarily impair aversive and emotional processing, those targeting norepinephrine should impair the processing of alerting signals, those targeting dopamine should impair motivational processes and reward processing, and those targeting acetylcholine should impair spatial learning and memory. We hope that this framework will motivate further research to better understand and explain cognitive changes as a consequence of antidepressant discontinuation.

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Incidence and Timing of Taper/Posttherapy–Emergent Adverse Events Following Discontinuation of Desvenlafaxine 50 mg/d in Patients With Major Depressive Disorder

Abstract: ClinicalTrials.gov identifier: NCT01056289.

Cited by 11 publications

References 17 publications

Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review

Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review

Development of Obsessive-Compulsive Symptoms Following Abrupt Discontinuation of Venlafaxine

An Oppositional Tolerance Account for Potential Cognitive Deficits Caused by the Discontinuation of Antidepressant Drugs

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