Antidepressant Discontinuation Syndrome Research Articles

SSRI and SNRI withdrawal symptoms reported on an internet forum.

Antidepressant withdrawal symptoms are well-recognised, but their potential duration remains uncertain. We aimed to describe the characteristics of withdrawal associated with two popular classes of antidepressants, including duration. We analysed the content of a sample of posts on an antidepressant withdrawal website. We compared the characteristics of withdrawal associated with SSRIs and SNRIs, including time of onset, duration and nature of symptoms. 110 posts about SSRI withdrawal, and 63 concerning SNRI withdrawal, were analysed. The mean duration of withdrawal symptoms was significantly longer with SSRIs than SNRIs: 90.5 weeks (standard deviation, SD, 150.0) and 50.8 weeks (SD 76.0) respectively; p = 0.043). Neurological symptoms, such as 'brain zaps,' were more common among SNRI users (p = 0.023). Psychosexual/genitourinary symptoms may be more common among SSRI users (p = 0.054). The website aims to help people with antidepressant withdrawal, and is therefore likely to attract people who have difficulties. Length of prior use of antidepressants was long, with a mean of 252.2 weeks (SD 250.8). People accessing antidepressant withdrawal websites report experiencing protracted withdrawal symptoms. There are some differences in the characteristics of withdrawal associated with different classes of antidepressants.

Mental health experts weigh in on NYT analysis of SSRI withdrawal concerns

Mental Health WeeklyVolume 28, Issue 15 p. 1-3 Articles Mental health experts weigh in on NYT analysis of SSRI withdrawal concerns Valerie A. Canady, Valerie A. CanadySearch for more papers by this author Valerie A. Canady, Valerie A. CanadySearch for more papers by this author First published: 16 April 2018 https://doi.org/10.1002/mhw.31413Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume28, Issue1516 April 2018Pages 1-3 RelatedInformation

Antidepressant switching patterns in the elderly.

A cohort study of medication supply data from 6011 aged care residents in 60 long-term care facilities was conducted. Incident antidepressant users were followed for 12 months and their patterns of antidepressant use determined. The type of switching from and to different antidepressant classes was determined according to National and International recommendations for antidepressant switching. In total, 11% (n = 44) of the residents were initiated on an antidepressant medication (n = 402) switched to a different antidepressant agent within 12 months. Residents commenced on a SNRI or TCA were most likely to switch antidepressants (17% in each group). Almost half of the switches (n = 21, 48% of all switches) were not implemented according to guideline recommendations. Direct switch and taper followed by wash out and switch, accounted for all of the inappropriate switching (29% and 71%, respectfully), with half occurring to mirtazapine (N = 7) or from mirtazapine (N = 3). Over one in 10 long-term aged care residents who commence an antidepressant will switch to a different antidepressant within 12 months. Current antidepressant switching practices in long-term residential aged care may be increasing the risk of harm associated with antidepressant switching, with around half of all switches not following current guideline recommendations.

Effects of imipramine on cytokines panel in the rats serum during the drug treatment and discontinuation

Time dependent sensitization (TDS) - phenomenon described originally by Chiodo and Antelman (1980) in context of dopamine receptors, refers to cascade of events that continue to develop in the organism, after the initiating stimulus is no longer available. Treatment could be recognized as such a initiating stimulus (in case of depression, example of electroconvulsive therapy would be obvious, but some aspects of pharmacotherapy too). The process leads to improvement, but, on the other hand, phenomena of kindling in recurrent depression is well known (more relapses and therapies make heavier and longer lasting subsequent episodes). Hence our interest in delayed effects of treatment. Here we report alterations in rat immune system after Imipramine (IMI) treatment cessation.Wistar male rats were treated with IMI (10 mg/kg i.p. in 2 ml/kg of saline) repeatedly for 21 days or once - on the last day of drug administration period. Then the 3 weeks discontinuation phase begun, during which, at certain time points (3 h, 72 h, 7days, 21days) the trunk blood was collected. Tissue concentrations of IMI and its metabolite desipramine (DMI), as well as ACTH and various cytokines were measured.The IMI and DMI was detectable only 3 h after the last i.p. injection of the drug. Ever since the second time point (72 h of discontinuation) the levels of either compound were below detection threshold.There was no significant changes in ACTH levels between rat groups, although IMI seemed to attenuate alterations of the hormone level comparing to control groups. We observed differences between groups regarding certain cytokines at certain time points. Namely: at 72 h of discontinuation IL-2 and IL-4 were elevated in sera of rats treated with IMI acutely; at 7d of discontinuation levels of IL-1α, IL-5, IL-10 and IL-12 were affected in both acutely and chronically treated animals.Presented data support, regarding some cytokines in serum, the TDS theory. Furthermore they refer to important aspect of antidepressants (ADs) action – antidepressant discontinuation syndrome (ADS). The most frequently, ADS has been described in context of ADs-disrupted monoamine homeostasis. Here, the other principle (i.e. immunomodulation) of the syndrome is proposed.

Effect of Abrupt Discontinuation of Antidepressants in Critically Ill Hospitalized Adults.

To determine whether discontinuation of chronic antidepressant therapy is associated with a higher risk of antidepressant discontinuation syndrome (ADS) symptoms in patients admitted to the intensive care unit (ICU) when compared with those who were continued on therapy and to identify factors associated with increased risk of ADS in this population. Single-center retrospective observational cohort study. ICUs in a tertiary care hospital. A total of 106 adult patients, admitted to the ICU between September 2013 and August 2014, who had a length of stay of 72 hours or longer and who were receiving chronic selective serotonin inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) before admission. Patients were classified as continued or discontinued from therapy based on initiation of home SSRI/SNRI therapy within 48 hours of admission. The primary end point was incidence of ADS symptoms. Type of symptoms, receipt of symptom-related therapies, and length of stay were also assessed. Sequential logistic regression analysis was used to determine the impact of discontinuation while controlling for other risk factors. Therapy was discontinued in 38.7% of patients. The risk of developing ADS symptoms was higher in discontinued patients (unadjusted odds ratio [OR] 2.6, 95% confidence interval [CI] 1.12-6.07, p=0.024). After adjusting for covariates, the odds of ADS increased (adjusted OR 3.8, 95% CI 1.3-11.7, p=0.018). Female sex was associated with an increase in risk of ADS (OR 3.4, 95% CI 1.2-10.0, p=0.026). Affective symptoms were the most prevalent type reported (34.1% vs 10.8%, p=0.005). Use of symptom-related therapies and length of stay did not differ between groups. Abrupt discontinuation of SSRI/SNRI therapy increases the risk of ADS symptoms in critically ill patients, particularly in females. These results underscore the importance of continuation of home antidepressant therapy even in the setting of critical illness.

Paroxetine 10mgからの退薬で生じ, 診断や治療に難渋したSSRI退薬症候群の1例

Paroxetine 10mgからの退薬で生じ, 診断や治療に難渋したSSRI退薬症候群の1例

Antidepressant discontinuation syndrome.

About 20% of patients develop antidepressant discontinuation syndrome following an abrupt stoppage of or marked reduction in the dose of an antidepressant taken continuously for one month.[1][1] Symptoms are usually mild and may occur following treatment with any type of antidepressant. Symptoms

Are antidepressants a double-edged sword? Treatment emergent affective switch or antidepressant discontinuation syndrome.

Are antidepressants a double-edged sword? Treatment emergent affective switch or antidepressant discontinuation syndrome.

Characteristics of Escitalopram Discontinuation Syndrome

Antidepressant discontinuation syndrome (ADS) frequently occurs in patients who undergo an abrupt discontinuation of their antidepressant medication. We evaluated 25 consecutive outpatients with depression who discontinued their use of escitalopram. The presence of ADS was evaluated according to the Antidepressants Discontinuation Syndrome checklist. Antidepressant discontinuation syndrome was observed in 14 of 25 patients. Frequent symptoms were dizziness (44%), muscle tension (44%), chills (44%), confusion or trouble concentrating (40%), amnesia (28%), and crying (28%). The treatment doses and plasma concentrations of escitalopram were significantly higher in patients with ADS than in patients without ADS. No group differences were observed regarding age, sex, or duration of escitalopram treatment before the discontinuation. These findings suggest that a higher dose and lower clearance of escitalopram lead to a higher risk of ADS. Very slow tapering is recommended for all patients.

Antidepressant Discontinuation Syndrome in Clinical Practice

Antidepressant Discontinuation Syndrome – (995.29 in DSM-5, 2013) particularly if treatment is stopped suddenly, is common, but modern times they have no common evidence. According to the pathophysiological studies, the Antidepressant Discontinuation Syndrome may be as the result from a temporary shortage of synaptic transmission of serotonin or other violations of the interaction of neurotransmitters such as norepinephrine, dopamine, GABA. (C. Damsa et al . (2004). Adverse events as the Antidepressant Discontinuation Syndrome we observed in our clinical practice, at 33% patients treated with serotonin and norepinephrine reuptake inhibitors. The most frequent reactions were dizziness, sleep disturbances (insomnia, vivid dreams), agitation, anxiety, headache. Typically, these symptoms were mild. They usually occurred within the first few days after treatment cessation. Long-term antidepressant discontinuation syndromes, which include psychiatric disorders – excitement, anxiety, dysphoric reactions, fatigue, cognitive impairment can last from month or to six years (S. Belaise, 2012). The absence of diagnostic criteria were need further study of short and long-term syndromes termination of the different classes of antidepressants and the development of methodological recommendations for their prevention.

New classification system to diagnose SSRI withdrawal proposed

New classification system to diagnose SSRI withdrawal proposed

New insights on the antidepressant discontinuation syndrome.

Antidepressants are at best 50–55% effective. Non-compliance and the antidepressant discontinuation syndrome (ADS) are causally related yet poorly appreciated. While ADS is associated with most antidepressants, agomelatine seems to be devoid of such risk. We review the neurobiology and clinical consequences of antidepressant non-compliance and the ADS. Agomelatine is presented as a counterpoint to learn more on how ADS risk is determined by pharmacokinetics and pharmacology. The relevant literature is reviewed through a MEDLINE search via PubMed, focusing on agomelatine and clinical and preclinical research on ADS. Altered serotonergic dysfunction appears central to ADS so that how an antidepressant targets serotonin will determine its relative risk for inducing ADS and thereby affect later treatment outcome. Low ADS risk with agomelatine versus other antidepressants can be ascribed to its unique pharmacokinetic characteristics as well as its distinctive actions on serotonin, including melatonergic, monoaminergic and glutamatergic-nitrergic systems. This review raises awareness of the long-term negative aspects of non-compliance and inappropriate antidepressant discontinuation, and suggests possible approaches to “design-out” a risk for ADS. It reveals intuitive and rational ideas for antidepressant drug design, and provides new thoughts on antidepressant pharmacology, ADS risk and how these affect long-term outcome.

SSRI Discontinuation Syndrome Following Bariatric Surgery: A Case Report and Focused Literature Review

SSRI Discontinuation Syndrome Following Bariatric Surgery: A Case Report and Focused Literature Review

Manic Symptoms as a Symptom of Antidepressant Discontinuation Syndrome in a Child

Manic Symptoms as a Symptom of Antidepressant Discontinuation Syndrome in a Child

A Case of Amelioration of Venlafaxine-Discontinuation “Brain Shivers” With Atomoxetine

To the Editor: Antidepressant discontinuation syndrome is a common syndrome seen following abrupt termination of treatment with a serotonin reuptake inhibitor.1 It occurs at rates ranging from 17.2% to as high as 78% with venlafaxine.2,3 There is, however, little literature on “brain shivers,”4,5 a common antidepressant-discontinuation symptom described by patients taking venlafaxine, duloxetine, citalopram, and paroxetine. Much of the information comes from Internet blogs and Web sites.6–8 The symptom is described variously as “an electrical shock–like sensation in the brain,” “the sensation of the brain shivering,” “brain zaps,” “brain shocks,” “brain shivers,” “head shocks,” or “cranial zings.” The etiology of the symptom is not known, and there is no known treatment for this distressing symptom. We describe a case in which “brain shivers” occurred as part of venlafaxine discontinuation syndrome and abated with atomoxetine treatment. Case report. Mr A, a 34-year-old man, presented with DSM-IV major depressive disorder (MDD) that responded well to venlafaxine (300 mg/d). He achieved remission except for seasonal exacerbations during autumn during the next 4 years. In view of a family history of bipolar disorder, it was decided to add lamotrigine and taper venlafaxine. Mr A maintained remission on venlafaxine (37.5 mg/d) and lamotrigine (200 mg/d) without seasonal exacerbations. Mr A abruptly discontinued venlafaxine 37.5 mg/d. On the second day following discontinuation, he reported feeling an unpleasant sensation of “electricity in the head” that “felt like the brain was shaking inside the skull.” Mr A was also noticed to demonstrate emotional incontinence and complained of anhedonia, anxiety, tinnitus, headache, nausea, and increased sensitivity to noise. Since the “brain shivers” were the most distressing symptom, a trial of atomoxetine 40 mg/d was attempted based on the hypothesis that the symptom was a result of noradrenergic imbalance.9 An immediate improvement in “brain shivers” was reported within 2 or 3 hours of taking the first dose. Over the next 3 days, Mr A reported further improvement in “brain shivers” and anhedonia although emotional incontinence and increased sensitivity to noise persisted. Given the severity of other withdrawal symptoms, venlafaxine (37.5 mg/d) was reinstated and atomoxetine was stopped. All withdrawal symptoms disappeared during the next day. The case adds to the interesting speculation about the noradrenergic imbalance as the basis of “brain shivers.”9 “Brain shivers,” conceptually related to Lhermitte’s phenomenon,10 have also been reported with the noradrenergic drug 3,4-methylenedioxy-N-methylamphetamine (MDMA). The psychotropic effects of MDMA are mediated via norepinephrine transporter11 and results in an increase in synaptic norepinephrine levels. Venlafaxine’s affinity for norepinephrine transporter (K[i] = 2,984 nM),12 is 103-fold lower than that of atomoxetine (K[i] = 5 nM),13 yet venlafaxine causes an increase (242%)14 in synaptic norepinephrine levels comparable to that by atomoxetine (290% ± 33%).13 Curiously, chronic treatment with venlafaxine does not reduce norepinephrine transporter binding sites.15 These facts point to the possibility that increases in synaptic norepinephrine are due to norepinephrine transporter reversal, akin to dopamine transporter reversal associated with amphetamine.16 Abrupt withdrawal of venlafaxine would hence result in paradoxical increase in synaptic norepinephrine via efflux through norepinephrine transporter channels, which is normalized by atomoxetine’s norepinephrine transporter blockade. This speculation of the noradrenergic basis of “brain shivers” warrants further study.

1764 – Case report: antidepressant withdrawal mania

Introduction Antidepressant withdrawal mania is a rare paradoxical event. It was initially reported in unipolar patients but it can also occur in bipolar patients, despite adequate mood-stabilizing treatment. It has been described with all antidepressant classes and may be self-limited or require medical hospitalization. Tapered withdrawal doesn’t seem to prevent the condition, though most reported cases developed after abrupt antidepressant discontinuation. Chronic antidepressant therapy enhances dopaminergic neurotransmission in the mesolimbic system. Noradrenergic hyperactivity and cholinergic overdrive secondary to antidepressant cessation are the most accepted theoretical mechanisms proposed. Objectives Case report, discussion and literature review. Aims We report a case of fluoxetine withdrawal mania and discuss its implications on clinical practice. Methods Case report and non systematic literature review. Results We present a case of a divorced 59-year-old woman who developed a manic episode shortly after antidepressant discontinuation. She was under antidepressant therapy since 2001, due to an unipolar chronic depressive disorder. She was put on fluoxetine 20 mg q.d. since 2005. On May 2012, she discontinued the antidepressant therapy upon misunderstanding medical advice. Few weeks later, she was involuntarily admitted to our inpatient unit presenting a manic episode with psychotic features. She started valproic acid 1000 mg q.d. and risperidone 4 mg q.d. and a complete remission was quickly obtained. Conclusions This case illustrates the potential for mania related to antidepressant discontinuation. Differential diagnosis includes spontaneous mania, antidepressant withdrawal syndrome and antidepressant induced mania. Finally, the authors discuss the adequacy of categorizing this entity in bipolar spectrum disorders.

Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome: A Review of the Clinical Evidence and the Possible Mechanisms Involved

Besides demonstrated efficacy, selective serotonin reuptake inhibitors (SSRIs) hold other advantages over earlier antidepressants such as greater tolerability and a wider range of clinical applications. However, there is a growing body of clinical evidence which suggests that SSRIs could, in some cases, be associated with a withdrawal reaction upon cessation of regular use. In addition to sensory and gastrointestinal-related symptoms, the somatic symptoms of the SSRI discontinuation syndrome include dizziness, lethargy, and sleep disturbances. Psychological symptoms have also been documented, usually developing within 1–7 days following SSRI discontinuation. The characteristics of the discontinuation syndrome have been linked to the half-life of a given SSRI, with a greater number of reports emerging from paroxetine compared to other SSRIs. However, many aspects of the neurobiology of the SSRI discontinuation syndrome (or SSRI withdrawal syndrome) remain unresolved. Following a comprehensive overview of the clinical evidence, we will discuss the underlying pathophysiology of the SSRI discontinuation syndrome and comment on the use of animal models to better understand this condition.

Hippocampal Agenesis in an Individual who Engaged in Violent Criminal Behaviors After Discontinuing Carbamazepine and Paroxetine Treatment

Antidepressant discontinuation syndrome (ADS) occurs after abrupt discontinuation of an antidepressant medication. A 23-year-old man with right hippocampal agenesis demonstrated sexual crime (hypersexuality) since the age of eight and had been successfully treated with carbamazepine since the age of 13. He had required increased doses of paroxetine and carbamazepine owing to the development of an unstable affect after quitting his job. He abruptly stopped taking his medication for 3 days and his criminal behaviors re-emerged. We examined changes in brain structure and activity before and after medication cessation, using MRI and functional MRI (fMRI). The image of a girl in a swimsuit increased activity in the thalamus only after medication discontinuation. The alteration in thalamic activity might induce hypersexuality. We conclude that a primary hypersexuality had been suppressed with carbamazepine and paroxetine treatment, and the discontinuation of the medication caused the hypersexuality.

A Case Report of Onset of Tinnitus Following Discontinuation of Antidepressant and a Review of the Literature

This case report describes a 46-year-old woman with long-standing episodic severe depression (ICD-10 code F33) who discontinued venlafaxine over a 4-week taper after taking the antidepressant for 8 years. Severe discontinuation syndrome was experienced. Panic and relapse of depression occurred 2 months after achieving discontinuation, and the development of tinnitus took place concurrently to the discontinuation. The experience of the tinnitus as a side effect of discontinuation is different from cases reported in the literature in which the tinnitus was experienced when the antidepressant was started and ceased when the antidepressant was stopped. Here, the patient experienced the tinnitus as a discontinuation symptom, and it persisted even after the antidepressant was reintroduced. A review of the literature on antidepressant discontinuation syndrome is also provided.

Dapoxetine: a novel treatment for premature ejaculation.

Premature ejaculation (PE) is a common problem worldwide and has significant impact not only on the sufferer but on the partner in terms of self-esteem, interpersonal distress and sexual satisfaction. A variety of psychological, topical and oral therapies have been tried in this condition with varying degrees of success. The selective serotonin reuptake inhibitors (SSRIs) are known to cause delayed ejaculation but require daily administration, have a relatively slow onset of action and may cause SSRI discontinuation syndrome on withdrawal. In addition, they are currently unlicensed for PE. Dapoxetine hydrochloride, an SSRI, has been specifically developed for on-demand use in PE. Its pharmacokinetic profile is characterized by rapid absorption, a short initial half-life of 1.3-1.4 h and rapid elimination with minimal accumulation even after multiple dosing. Several large phase III studies have demonstrated that dapoxetine can increase intravaginal ejaculatory latency time and improve several patient-reported outcomes relevant to control of ejaculation and satisfaction with intercourse. Dapoxetine is generally well tolerated with a low incidence of discontinuations due to adverse events. There were no signals for treatment-emergent anxiety or SSRI discontinuation syndrome after abrupt withdrawal.