Stopping Antidepressants Research Articles

Society for Academic Primary Care Annual Scientific Meeting

What do GP specialists add to epilepsy care? How can polypharmacy be optimised? And how do clinicians feel about stopping antidepressants? These were just a small sample of questions that research presented at the 51st Annual Scientific Meeting of the Society for Academic Primary Care, held in Brighton in July 2023, tried to address.

Stopping antidepressants causes withdrawal symptoms in 15% of patients, meta-analysis finds

Stopping antidepressants causes withdrawal symptoms in 15% of patients, meta-analysis finds

Discontinuation strategies and long-term outcome of antidepressant medications

In terms of the treatment of depression, it is proven by many research that antidepressant drug has a significant impact on the treatment of depression patients. They can make them feel better and cope with their challenges. However, discontinuing these medications can be challenging due to concerns such as relapse, withdrawal symptoms, recurrence, and patient preferences. In this paper, we conducted a review of research on strategies for stopping antidepressants. Explored their long-term effects. By analyzing randomized controlled trials, cohort studies, systematic reviews, and meta-analyses, we gained insights into discontinuation methods and the extended impact of antidepressant use. Findings from quality evidence suggest that abruptly stopping antidepressants increases the risk of relapse or recurrence compared to reducing dosage or continuing with medication. Similarly, reducing dosage gradually helps in decreasing the risk and severity of withdrawal symptoms when compared to discontinuation or continued use without tapering off. Furthermore, psychological interventions like therapy or mindfulness-based cognitive therapy are identified as a best protocol for preventing relapse or recurrence after discontinuing antidepressants. These interventions are found to be particularly effective for patients experiencing symptoms or having risk factors. Additionally, although there is evidence regarding the long-term outcomes of using antidepressants beyond two years, some studies suggest that additional interventions such as patient education, shared decision-making processes monitoring progress, and providing feedback can assist in supporting successful discontinuation by improving adherence and patient satisfaction. In summary, stopping antidepressant medication is a process that necessitates assessment.

Designing withdrawal support services for antidepressant users: Patients’ views on existing services and what they really need

BackgroundPublic Health England has recommended that services be put in place to support people who choose to withdraw from antidepressants because of a current gap. This study aims to explore the views of members of online withdrawal peer-support groups about existing healthcare and what additional support is needed. MethodsThe administrators of 15 online support groups for people stopping antidepressants were asked to advertise an online survey to their members. The survey, which was online from May 2021 to April 2022, was completed by 1276 people from 49 countries. Results71% of respondents found their doctors' advice unhelpful (57% ‘very unhelpful’) regarding stopping an antidepressant; the main reasons being ‘Recommended a reduction rate that was too quick for me’, ‘Not familiar enough with withdrawal symptoms to advise me’ and ‘Suggested stopping antidepressants would not cause withdrawal symptoms’. One in three did not seek advice from their prescriber when deciding whether to withdraw, with the main reasons being ‘I felt they would not be supportive’ (58%) and ‘I felt that they didn't have the expertise to help me’ (51%). The most common prescriber responses to those who did seek advice was ‘Suggested a quick withdrawal schedule’ (56%) and ‘Not supportive and offered no guidance' (27%). The most common discontinuation periods recommended by doctors were one month (23%) and two weeks (19%). A range of potential professional services were rated ‘very useful’, most frequently: ‘Access to smaller doses (e.g. tapering strips, liquid, smaller dose tablets) to ensure gradual reduction’ (88%) and ‘A health professional providing a personalised, flexible reduction plan’ (79%). LimitationsThis was a convenience sample, which may have been biased towards people who took longer to withdraw, and experienced more withdrawal symptoms, than antidepressant users in general. Black and ethnic minority people, and people without access to the internet, were underrepresented. ConclusionsMost participants reported their prescribers were unable to help them safely stop antidepressants, compelling them to turn to online peer-support groups instead. Our findings indicate, in keeping with previous studies, that clinicians require upskilling in safe tapering of antidepressants, and that patients need specialised services to help them stop safely.

Draft NICE quality standard says adults stopping antidepressants should be supported to taper the dose slowly

Adults with depression who are stopping their antidepressants should have the dose reduced in stages, according to one of several new measures included in a draft quality standard published by the National Institute for Health and Care Excellence (NICE). The draft standard, which is expected to be published in June 2023, also states that adults […]

Integrative medicine approaches to chronic depression: case studies of the recovery process with a three-step path to recovery and significant cure.

The support provided by conventional treatments centered on the administration of medication for chronic or other types of depression is limited. Integrative medicine, which is based on both modern Western medicine and a range of complementary and alternative medicine practices, is patient-centered and promotes natural healing in patients to achieve significant cure. Thisreport focuses on the indications of recovery fromdepression using integrative medicine, especially homeopathy. Thirty-one patients (9 males and 22 females) with depression underwent homeopathic treatment using various strategies over 3months, in addition to antidepressants. All patients were diagnosed with Major Depressive Disorders, except bipolar disorders. Three steps were used to model indications of their recovery from depression: reducing difficulties in everyday life, reducing and stopping antidepressants, and reducing and stopping the homeopathic remedies. Patients were considered to have recovered when antidepressants had been stopped for 6months or more and 3 or more months had passed since homeopathic medicines were stopped. Of the 31 patients with depression, 13 recovered within 2years of starting homeopathic treatment, and 11 completely recovered from chronic depression. This study suggests that integrative medicine can be a useful strategy for depression, including the use of a three-step strategy for reducing all dependence on clinical treatment. As most patients, especially chronic patients, significantly recovered from depression through homeopathy over 2years, this model can help understand recovery from depression through integrative medicine.

EVALUATION OF SEXUALITY AND ITS IMPACT ON 80 OUTPATIENTS FOLLOWED FOR A DEPRESSIVE DISORDER

Sexual disorders are a major part of depression, making patient care difficult to manage by stopping antidepressants due to their unwanted sexual effects. We aim in this study to assess sexual function in patients with a major depressive disorder and study the sociodemographic, clinical, and sexual characteristics associated with sexual dysfunction, through a descriptive and analytical cross-sectional study involving 80 outpatients followed in a psychiatric hospital in Ibn RochdUniversity Hospital and having been evaluated through the Female Sexual Function Index (for sexual function) scale and the Hamilton Depression Scale (for the severity of depression).The mean age was 37.1 years with extremes ranging from 18 to 58 years. The majority of women were aged between 29 and 39 years old, having a level of secondary education 53% and 47.5% with average socio-economic conditions. The depression was of medium intensity for most patients (50%), with an average duration of 5.8 months. Marital discord was reported by 48,7% of patients. No patient reported any sexual dysfunction in her partner. Sexual function was impaired in 60% of patients. Sexual desire is the most impaired phase in our patients 77,5%, followed by orgasm disorder among 60% of patients, then sexual dissatisfaction in 53.33% of patients. We found that the alteration of the overall sexual function and other phases were significantly correlated with the severity and duration of the depressive episode but not with the existence of marital discord.Satisfaction with sexual life is an important factor affecting the quality of life. Patients rarely deal with problems in sexual life, so questions about this area of life should not be overlooked during a medical and psychiatric interview.

Discontinuing antidepressants: Pearls and pitfalls.

Stopping antidepressants can be challenging due to the high rate of discontinuation symptoms. Patients with antidepressant discontinuation syndrome (ADS) commonly experience insomnia, flu-like symptoms, mood disturbances, dizziness, and paresthesias, but a broad array of adverse effects is possible. Symptoms can last for days to months, and different symptoms have different durations. Patient education, identification of patients most at risk for developing symptoms, and a slow antidepressant taper or cross-taper are important steps in mitigating the risk of ADS and managing patient concerns about ADS. Tapers should be carried out over weeks to months. Discontinuation symptoms should be managed with restarting the prior dose of antidepressant and then tapering even more slowly, with additional symptomatic management as needed.

Stopping antidepressants: withdrawal symptoms and rebound effects : Review and practical recommendations

Stopping antidepressants can cause withdrawal (discontinuation) symptoms, the return of the original illness, and rebound. The latter means that the disease will return stronger, faster, or with greater likelihood than if it had not been treated with medication. The Psychiatry Working Group of the Drug Commission of the German Medical Association (AkdÄ) presents the scientific findings and provides practical recommendations for action. Withdrawal symptoms are multiform; unspecific physical symptoms are predominant. Distinguishing them from the recurrence of depressive symptoms can be difficult. Most of them are mild and self-limiting. There is insufficient evidence on the extent and frequency of rebound depression. The rebound risk implies that when establishing the medication, the short-term benefit must be weighed against the possible long-term risk of chronic depression or the possible need for long-term medication. Patients should be informed about the risk of withdrawal both as early as the joint decision-making process about treatment initiation and regularly during the course of treatment. Withdrawal should take place gradually, except in emergency situations, whereby small steps should be taken, especially in the low-dose range.

Maintenance or Discontinuation of Antidepressants in Primary Care

BackgroundPatients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting.MethodsWe conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings.ResultsA total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group.ConclusionsAmong patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.)

The relationship between resting-state functional connectivity, antidepressant discontinuation and depression relapse

The risk of relapsing into depression after stopping antidepressants is high, but no established predictors exist. Resting-state functional magnetic resonance imaging (rsfMRI) measures may help predict relapse and identify the mechanisms by which relapses occur. rsfMRI data were acquired from healthy controls and from patients with remitted major depressive disorder on antidepressants. Patients were assessed a second time either before or after discontinuation of the antidepressant, and followed up for six months to assess relapse. A seed-based functional connectivity analysis was conducted focusing on the left subgenual anterior cingulate cortex and left posterior cingulate cortex. Seeds in the amygdala and dorsolateral prefrontal cortex were explored. 44 healthy controls (age: 33.8 (10.5), 73% female) and 84 patients (age: 34.23 (10.8), 80% female) were included in the analysis. 29 patients went on to relapse and 38 remained well. The seed-based analysis showed that discontinuation resulted in an increased functional connectivity between the right dorsolateral prefrontal cortex and the parietal cortex in non-relapsers. In an exploratory analysis, this functional connectivity predicted relapse risk with a balanced accuracy of 0.86. Further seed-based analyses, however, failed to reveal differences in functional connectivity between patients and controls, between relapsers and non-relapsers before discontinuation and changes due to discontinuation independent of relapse. In conclusion, changes in the connectivity between the dorsolateral prefrontal cortex and the posterior default mode network were associated with and predictive of relapse after open-label antidepressant discontinuation. This finding requires replication in a larger dataset.

Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives from a large internet forum.

Background:Protracted withdrawal syndrome (PWS) after stopping antidepressants (frequently also referred to as post-acute withdrawal syndrome or PAWS) has been described in a few case reports. However, a detailed quantitative analysis of specific symptom manifestations in antidepressant PWS is still lacking.Methods:We extracted patient narratives from a large English-language internet forum SurvivingAntidepressants.org, a peer support site concerned about withdrawal from antidepressants. PWS was ascertained based on diagnostic criteria proposed by Chouinard and Chouinard, specifically ⩾6 months of continuous antidepressant use, with emergence of new and/or more intense symptoms after discontinuation that last beyond the initial 6 weeks of acute withdrawal. We assessed medication history, outcome of PWS, and the prevalence of specific symptoms.Results:In total, n = 69 individual reports of protracted withdrawal were selected for analysis. At time of the subjects’ most recent reports, duration of PWS ranged from 5 to 166 months, mean = 37 months, median = 26 months. Length of time on the antidepressant causing protracted withdrawal ranged from 6 to 278 months, mean = 96 months, and median = 79 months. Throughout the withdrawal experience, affective symptoms, mostly anxiety, depression, emerging suicidality and agitation, were reported by 81%. Somatic symptoms, mostly headache, fatigue, dizziness, brain zaps, visual changes, muscle aches, tremor, diarrhea, and nausea were reported by 75%. Sleep problems (44%) and cognitive impairments (32%) were mentioned less frequently. These broad symptom domains were largely uncorrelated.Conclusion:PWS or PAWS from antidepressants can be severe and long-lasting, and its manifestations clinically heterogeneous. Long-term antidepressant exposure may cause multiple body system impairments. Although both somatic and affective symptoms are frequent, they are mostly unrelated in terms of occurrence. Proper recognition and detection of PWS thus requires a comprehensive assessment of medication history, duration of the withdrawal syndrome, and its various somatic, affective, sleep, and cognitive symptoms.

Outcome of antidepressant drug discontinuation with taperingstrips after 1-5 years.

Background:Stopping antidepressants is often difficult due to withdrawal. Taperingstrips were developed to facilitate antidepressant discontinuation according to the recently described Horowitz-Taylor method, allowing for personalised titration of discontinuation to the intensity of withdrawal. A taperingstrip consists of antidepressant or other medication, packaged in a 28-day roll of small daily pouches, each with the same or slightly lower dose than the one before it. We previously reported that the short-term success rate of antidepressant taperingstrips was 71%. Here, we examine longer-term outcome after 1–5 years.Methods:Patients whose doctor had ordered taperingstrips between January 2015 and December 2019 were sent a questionnaire for participation in anonymised research in January 2020. Of 1012, 483 participated, of whom 408 (85%) had attempted antidepressant tapering.Results:Of the 408 patients included, 192 (47%) had used strips for tapering venlafaxine, 142 (35%) for paroxetine and 74 (18%) for other antidepressants. Median length of antidepressant use was 4 years, and most (61%) had tried to come off without taperingstrips at least once. After 1–5 years, 270 patients (66%) remained off antidepressants after tapering their antidepressant, 6 (2%) had successfully reduced their medication, 87 (21%) had restarted due to (self-reported) relapse, 35 had restarted for another indication (9%), and 10 (3%) reported another outcome. People with more severe experience of withdrawal prior to tapering, and people who had been on antidepressants for a shorter period of time, were more likely to remain off medication after 1–5 years.Conclusion:The previously reported 71% short-term success rate of taperingstrips in the most severely affected group, was matched by a 68% rate after 1–5 years. The evidence-based approach of personal tapering to counter withdrawal, as used for drugs causing withdrawal, for example, benzodiazepines, may represent a simple solution for an important antidepressant-related public health problem, without extra costs.

The 'patient voice': patients who experience antidepressant withdrawal symptoms are often dismissed, or misdiagnosed with relapse, or a new medical condition.

Background:Stopping antidepressants commonly causes withdrawal symptoms, which can be severe and long-lasting. National Institute for Health and Care Excellence (NICE) guidance has been recently updated to reflect this; however, for many years withdrawal (discontinuation) symptoms were characterised as ‘usually mild and self-limiting over a week’. Consequently, withdrawal symptoms might have been misdiagnosed as relapse of an underlying condition, or new onset of another medical illness, but this has never been studied.Method:This paper outlines the themes emerging from 158 respondents to an open invitation to describe the experience of prescribed psychotropic medication withdrawal for petitions sent to British parliaments. The accounts include polypharmacy (mostly antidepressants and benzodiazepines) but we focus on antidepressants because of the relative lack of awareness about their withdrawal effects compared with benzodiazepines. Mixed method analysis was used, including a ‘lean thinking’ approach to evaluate common failure points.Results:The themes identified include: a lack of information given to patients about the risk of antidepressant withdrawal; doctors failing to recognise the symptoms of withdrawal; doctors being poorly informed about the best method of tapering prescribed medications; patients being diagnosed with relapse of the underlying condition or medical illnesses other than withdrawal; patients seeking advice outside of mainstream healthcare, including from online forums; and significant effects on functioning for those experiencing withdrawal.Discussion:Several points for improvement emerge: the need for updating of guidelines to help prescribers recognise antidepressant withdrawal symptoms and to improve informed consent processes; greater availability of non-pharmacological options for managing distress; greater availability of best practice for tapering medications such as antidepressants; and the vital importance of patient feedback. Although the patients captured in this analysis might represent medication withdrawal experiences that are more severe than average, they highlight the current inadequacy of health care systems to recognise and manage prescribed drug withdrawal, and patient feedback in general.

How effective are antidepressants for depression over the long term? A critical review of relapse prevention trials and the issue of withdrawal confounding.

The aim of this article is to discuss the validity of relapse prevention trials and the issue of withdrawal confounding in these trials. Recommendations for long-term antidepressant treatment are based almost exclusively on discontinuation trials. In these relapse prevention trials, participants with remitted depression are randomised either to have the antidepressant abruptly discontinued and replaced by inert placebo or to continue active treatment. The drug–placebo difference in relapse rates at the end of the maintenance phase is then interpreted as a prophylactic drug effect. These trials consistently produce remarkable benefits for maintenance treatment. However, the internal validity of this trial protocol is compromised, as research has shown that abruptly stopping antidepressants can cause severe withdrawal reactions that lead to (or manifest as) depression relapses. That is, there is substantial withdrawal confounding in discontinuation trials, which renders their findings uninterpretable. It is not clear to what degree the drug–placebo separation in relapse prevention (discontinuation) trials is due to withdrawal reactions, but various estimations suggest that it is presumably the majority. A review of findings based on other methodologies, including real-world long-term effectiveness trials like STAR*D and various naturalistic cohort studies, do not indicate that antidepressants have considerable prophylactic effects. As absence of evidence does not imply evidence of absence, no definitive conclusions can be drawn from the literature. To enable a thorough risk–benefit evaluation, real-world effectiveness trials should not only focus on relapse prevention, but also assess antidepressants’ long-term effects on social functioning and quality of life. Thus far, reliable long-term data on these outcome domains are lacking.

Switching and stopping antidepressants.

Switching from one antidepressant to another is frequently indicated due to an inadequate treatment response or unacceptable adverse effects. All antidepressant switches must be carried out cautiously and under close observation. Conservative switching strategies involve gradually tapering the first antidepressant followed by an adequate washout period before the new antidepressant is started. This can take a long time and include periods of no treatment with the risk of potentially life-threatening exacerbations of illness. Clinical expertise is needed for more rapid or cross-taper switching as drug toxicity, including serotonin syndrome, may result from inappropriate co-administration of antidepressants. Some antidepressants must not be combined. Antidepressants can cause withdrawal syndromes if discontinued abruptly after prolonged use. Relapse and exacerbation of depression can also occur. Gradual dose reduction over days to weeks reduces the risk and severity of complications.

Stopping antidepressants: Clinical considerations

Stopping antidepressants: Clinical considerations

Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database

Objective To assess the associations between different antidepressant treatments and the rates of suicide and attempted suicide or self harm in people with depression.Design Cohort study.Setting Patients registered with UK...

Pregnancy as a Major Determinant for Discontinuation of Antidepressants

Potential adverse effects of antidepressants during pregnancy have caused concern about their use. There are, however, very limited detailed data on patterns of antidepressant prescribing in pregnancy. To examine secular trends in prescribing during pregnancy, to assess whether pregnancy is a major determinant for stopping antidepressants, and to identify characteristics of those who stopped antidepressants during pregnancy. In this cohort study, we obtained data on 114,999 pregnant women (median age at delivery, 30.5 years [interquartile range, 26-34 years]) who had a live birth between 1992 and 2006 and 22,677 nonpregnant women from The Health Improvement Network primary care database, one of the largest sources of continuous anonymized primary care data in the United Kingdom and broadly representative of UK general practice. This database includes information on age, sex, medical diagnosis and symptoms, health promotion activities, referrals to secondary care, and prescriptions for each registered individual. The database also holds information about social deprivation as measured using quintiles of the Townsend score. We used Cox regression analysis to compare time to last prescription in pregnant versus nonpregnant women and to identify characteristics of those women who stopped antidepressants during pregnancy. Antidepressant prescribing in pregnancy increased nearly 4-fold from 1992 to 2006 (relative risk = 3.87; 95% CI, 1.73-8.66; P < .001). Since 2001, approximately 3% of the cohort received antidepressants at some stage during pregnancy. Selective serotonin reuptake inhibitors accounted for approximately 80% of the prescribed antidepressants. Antidepressants were more likely to be stopped in pregnant than in nonpregnant women, in particular during the first 6 weeks of pregnancy (hazard ratio = 5.19; 95% CI, 4.85-5.56; P < .001). Only 10% of women treated before pregnancy still received antidepressants at the start of the third trimester. In contrast, 35% of nonpregnant women were still treated after a similar time period. Although antidepressant prescribing in pregnancy increased nearly 4-fold from 1992 to 2006, pregnancy was a major determinant of cessation of antidepressant medication, and most women did not receive further antidepressant prescriptions beyond 6 weeks of gestation. This finding may be explained by concerns about potential adverse effects of the medications, even though these concerns need to be balanced against the potential harm of inadequate treatment of depression during pregnancy.

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