Specialist Pharmacy Service – 4th December 2023
This guidance highlights resources to help plan and support safe deprescribing of antidepressants in practice including NICE guidelines, CKS, Maudsley prescribing guidelines, and Royal College of Psychiatrists. Resources are also provided to signpost to patients.
NICE – 17th January 2023
Adults with depression who want to stop taking antidepressants should have the dose of their medication reduced in stages to reduce the likelihood and severity of withdrawal symptoms, NICE has said.
A new draft quality standard, which sets out priority areas for quality improvement for the care of adults with depression, includes a statement to help adults who want to come off the medication permanently.
The independent advisory committee, which includes experts in treating adults with depression, has recommended the staged withdrawal of antidepressants.
The committee said primary care and mental health professionals should follow the NICE guideline recommendations on stopping antidepressant medication, including agreeing with their patient whether it is right for them to stop taking the medication and if so, the speed and duration of withdrawal from it.
Reducing the dose of an antidepressant in stages over time, known as ‘tapering’, helps to reduce withdrawal effects and long-term dependence on the medication.
Any withdrawal symptoms need to have been resolved, or to be tolerable, before making the next dose reduction the committee has said.
Further information – Adults with depression who want to quit antidepressants should be given support on how to do it safely over time, says NICE
NIHR – 04 November 2022
The report analyses NIHR-funded research into antidepressant use in these age groups. It concludes GPs are prescribing antidepressants for children and teenagers without them seeing a psychiatrist first. NICE guidelines state this patient group should be treated with antidepressants only after seeing a psychiatrist.
Full article – New report on the use of antidepressants for children and young people
Background information – Antidepressants for children and teenagers: what works for anxiety and depression? – NIHR – 3rd November
NIHR | March 2022 | Almost half those on long-term antidepressants can stop without relapsing
The National Institute for Health Research (NIHR) provides a bite-sized summary of research into antidepressants and longer-term use
Taking long-term antidepressants can prevent depression recurring (relapse). But new research shows that almost half those who stop taking the medication do not relapse.
Depression is a major cause of ill health and disability worldwide. It causes emotional distress and interferes with everyday life. Many people with depression continue taking antidepressant drugs for months or even years after their symptoms have resolved. This so-called maintenance therapy aims to reduce the risk of relapse.
The numbers of people taking maintenance therapy for depression is increasing. However, there is little research to show how effective these drugs are in preventing relapse in people who have been taking them long-term.
This study included people who had two previous relapses of depression. Researchers compared rates of relapse in those who continued on antidepressants with those who stopped. They found that people who stopped medication were more likely to relapse. However, more than 4 in 10 people who stopped taking antidepressants had no relapse of their depression (Source: NIHR).
The Alert is available in full from NIHR
The original piece of research upon which this summary is based, is available from the NIHR’s Journals Library
Duffy L, Clarke CS, Lewis G, Marston L, Freemantle N, Gilbody S, et al. (2021). Antidepressant medication to prevent depression relapse in primary care: the ANTLER RCT. Health Technol Assess ;25(69). https://doi.org/10.3310/hta25690
Abstract
Background
There has been a steady increase in the number of primary care patients receiving long-term maintenance antidepressant treatment, despite limited evidence of a benefit of this treatment beyond 8 months.
Objective
The ANTidepressants to prevent reLapse in dEpRession (ANTLER) trial investigated the clinical effectiveness and cost-effectiveness of antidepressant medication in preventing relapse in UK primary care.
Design
This was a Phase IV, double-blind, pragmatic, multisite, individually randomised parallel-group controlled trial, with follow-up at 6, 12, 26, 39 and 52 weeks. Participants were randomised using minimisation on centre, type of antidepressant and baseline depressive symptom score above or below the median using Clinical Interview Schedule – Revised (two categories). Statisticians were blind to allocation for the outcome analyses.
Setting
General practices in London, Bristol, Southampton and York.
Participants
Individuals aged 18–74 years who had experienced at least two episodes of depression and had been taking antidepressants for more than or equal to 9 months but felt well enough to consider stopping their medication. Those who met an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of depression or with other psychiatric conditions were excluded.
Intervention
At baseline, participants were taking citalopram 20 mg, sertraline 100 mg, fluoxetine 20 mg or mirtazapine 30 mg. They were randomised to either remain on their current medication or discontinue medication after a tapering period.
Main outcome measures
The primary outcome was the time, in weeks, to the beginning of the first depressive episode after randomisation. This was measured by a retrospective Clinical Interview Schedule – Revised that assessed the onset of a depressive episode in the previous 12 weeks, and was conducted at 12, 26, 39 and 52 weeks. The depression-related resource use was collected over 12 months from medical records and patient-completed questionnaires. Quality-adjusted life-years were calculated using the EuroQol-5 Dimensions, five-level version.
Results
Between 9 March 2017 and 1 March 2019, we randomised 238 participants to antidepressant continuation (the maintenance group) and 240 participants to antidepressant discontinuation (the discontinuation group). The time to relapse of depression was shorter in the discontinuation group, with a hazard ratio of 2.06 (95 per cent confidence interval 1.56 to 2.70; p less than 0.0001). By 52 weeks, relapse was experienced by 39 per cent of those who continued antidepressants and 56 per cent of those who discontinued antidepressants. The secondary analysis revealed that people who discontinued experienced more withdrawal symptoms than those who remained on medication, with the largest difference at 12 weeks. In the discontinuation group, 37 per cent (95 per cent confidence interval 28 per cent to 45 per cent) of participants remained on their randomised medication until the end of the trial. In total, 39 per cent (95 per cent confidence interval 32 per cent to 45 per cent) of participants in the discontinuation group returned to their original antidepressant compared with 20 per cent (95 per cent confidence interval 15 per cent to 25 per cent) of participants in maintenance group. The health economic evaluation demonstrated that participants randomised to discontinuation had worse utility scores at 3 months (–0.037, 95 per cent confidence interval –0.059 to –0.015) and fewer quality-adjusted life-years over 12 months (–0.019, 95 per cent confidence interval –0.035 to –0.003) than those randomised to continuation. The discontinuation pathway, besides giving worse outcomes, also cost more [extra £2.71 per patient over 12 months (95 per cent confidence interval –£36.10 to £37.07)] than the continuation pathway, although the cost difference was not significant.
Conclusions
Patients who discontinue long-term maintenance antidepressants in primary care are at increased risk of relapse and withdrawal symptoms. However, a substantial proportion of patients can discontinue antidepressants without relapse. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants and improve shared decision-making. The participants may not have been representative of all people on long-term maintenance treatment and we could study only a restricted range of antidepressants and doses. Identifying patients who will not relapse if they discontinued antidepressants would be clinically important.
Horowitz, M. & Wilcock, M. | 2021| Newer generation antidepressants and withdrawal effects: reconsidering the role of antidepressants and helping patients to stop | Drug and Therapeutics Bulletin| 60 | P. 7-12.
This review published in the Drug and Therapeutics Bulletin, considers some of the issues relating to the evidence of efficacy of antidepressants and discuss the problems associated with withdrawing from antidepressant treatment.
This review makes the following key learning points:
Abstract
In England, the prescribing of antidepressants, primarily the newer generation antidepressant classes, has steadily increased over recent years. There is ongoing debate about how the efficacy of these drugs is viewed, their place in therapy and the harms associated with stopping them. Much of the evidence of their efficacy comes from short-term placebo-controlled trials which tend not to include outcomes that are of greatest relevance to patients, such as social functioning or quality of life, but rather restrict outcomes narrowly to symptom measures. On such measures these studies do not demonstrate clinically significant differences from placebo for depression. A range of adverse effects are also recognised, often greater in naturalistic studies of long-term antidepressants users than those measured in short-term efficacy studies, including emotional numbing, sexual difficulties, fatigue and weight gain. There is increasing recognition that withdrawal symptoms from antidepressants are common and that these symptoms can be severe and long-lasting in some patients. Recent guidance on how to stop antidepressants in a tolerable way has been presented by the Royal College of Psychiatrists. We believe that increasing awareness about the difficulty that some patients have in stopping antidepressants should lead to more cautious prescribing practice, with antidepressants given to fewer patients and for shorter periods of time. This article discusses the perceived benefits and harms of antidepressant use.
Mental Elf | 30 November 2021 | Antidepressants, autism diagnosis & self-harm
The Mental Elf is producing ‘Golden Nuggets’ which are videos that present key ideas from mental health research that professionals can use in practice.
This ‘Golden Nugget’ covers antidepressants, autism diagnosis & self-harm.
The Mental Elf | 17 November 2021 | Maintenance or discontinuation of antidepressants for depression? Findings from the ANTLER trial
This blog post from The Mental Elf considers the findings his study was a multicentre, computer randomised, double blind, placebo-controlled trial based in 150 GP practices across England (Bristol, London, Southampton and York).
Maintenance or discontinuation of antidepressants for depression? Findings from the ANTLER trial [Blog post]
Lewis, G. et al | 2021 | Maintenance or Discontinuation of Antidepressants in Primary Care | N Engl J Med | Sep 30 | 385| 14 | P.1257-1267. doi: 10.1056/NEJMoa2106356. PMID: 34587384.
Abstract
Background: Patients 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.
Methods: We 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.
Results: A 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 per cent in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39 per cent) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95 per cent 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.
Conclusions: Among 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.).
Maintenance or Discontinuation of Antidepressants in Primary Care [abstract only]
If you’d like to read the full paper, contact your Library
NIHR | September 2021 | Staying on long-term antidepressants reduces risk of relapse
This NHIR Alert summarises the research findings of a trial that studied 478 adult patients in primary care who had a history of depressive episodes or who had been prescribed antidepressants for two years or more and felt able to consider stop taking depressions. They found that over half of participants (56 per cent) who discontinued antidepressants experienced a relapse (a new episode of depression), compared to a more than a third (39 per cent) of participants who kept taking them. Of the 56 per cent who experienced relapse after discontinuation, only half then chose to return to an antidepressant prescribed by their clinician. The researchers say that some relapses, as well as possible withdrawal symptoms, might not have been severe enough for the person to decide they needed to return to their medication.
Those who discontinued their antidepressants were more likely to experience withdrawal symptoms. Despite this, by the end of the study, 59 per cent of the discontinuation group were not taking antidepressants.
They now report their findings in a paper published in the NEJM
Our findings add to evidence that for many patients, long-term treatment is appropriate, but we also found that many people were able to effectively stop taking their medication when it was tapered over two months.
As 44 per cent of those who discontinued their antidepressants did not relapse after a full year, our findings suggest that some patients might decide to stop their antidepressant, knowing the risk of relapse but we recommend discussing this with your doctor.”
Lead author of the study Dr Gemma Lewis, UCL Psychiatry
Paul Lanham, lived experience co-researcher, said: “Many patients taking antidepressants long term have absolutely no idea what they would be like without antidepressants. Some will not want to find out, but others will. These results show that staying on antidepressants does reduce the risk of relapse, but it does not guarantee well-being, and some people can stop antidepressants without a relapse.” (Source: NIHR & Lewis et al 2021).
Lewis, G. et al | 2021| Maintenance or Discontinuation of Antidepressants in Primary Care | NEJM | DOI: 10.1056/NEJMoa2106356
Abstract
Background
Patients 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.
Methods
We 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.
Results
A 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 per cent were women. Adherence to the trial assignment was 70 per cent in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39 per cent ) in the maintenance group and in 135 of 240 (56 per cent) in the discontinuation group (hazard ratio, 2.06; 95 per cent confidence interval, 1.56 to 2.70; P less than 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.
Conclusions
Among 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.
Maintenance or Discontinuation of Antidepressants in Primary Care [abstract only]
Contact the Library & Knowledge Service for a copy
Maguire, M.J., Marson, A.G., & Nevitt, S.J. | 2021 | Antidepressants for people with epilepsy and depression| Cochrane Database of Systematic Reviews | Issue 4| Art. No.: CD010682 | DOI: 10.1002/14651858.CD010682.pub3.
This systematic review reviewed 10 studies that researched antidepressants for people with epilepsy and depression. The reviewers found existing evidence on the effectiveness of antidepressants in treating depressive symptoms associated with epilepsy is still very limited.
Abstract
Background
Depressive disorders occur in approximately one-third of people with epilepsy, often requiring antidepressant treatment. However, depression often goes untreated in people with epilepsy, partly due to fear that antidepressants might cause seizures. There are different classes of antidepressants, however they all aim to increase key nerve chemicals in the brain, thereby alleviating depressive symptoms.
Characteristics of studies
We found ten studies that included 626 patients with epilepsy and depression treated with an antidepressant. Four were randomised controlled trials, and six were non-randomised prospective cohort studies. The studies observed the effect of different antidepressants, mainly a class of antidepressant called a selective serotonin reuptake inhibitor (SSRI). One randomised controlled trial and one prospective study also observed the effect of cognitive behavioural therapy on depression.
Results
Taking all the evidence into account, the review found that there is very limited evidence that antidepressants decrease depressive symptoms more than other treatments, placebo, or no treatment in epilepsy. There was limited information on the effect of antidepressants on seizure control, however in the studies reporting this outcome there did not appear to be any significant worsening of seizures. The evidence is current to February 2021.
Quality of the studies
We assessed the studies with regard to bias and quality. Overall, the quality of the evidence was rated as moderate to low for the clinical trials and low to very low for the non-randomised prospective cohort studies. Large, high quality trials of antidepressants are needed to examine how different classes of antidepressant compare, and what impact they are likely to have on seizure control.
Calls to mental health helplines and prescriptions for antidepressants have reached an all-time high, while access to potentially life-saving talking therapies has plunged during the coronavirus pandemic, a Guardian investigation has found.
More than 6 million people in England received antidepressants in the three months to September, part of a wider trend and the highest figure on record.
The fall in referrals to NHS psychological therapies services (IAPT) is thought to have been down to counselling services going online, which some doctors have deemed inappropriate for certain patients, while some patients were reluctant to seek face-to-face help or add extra pressure to health services.
Concerns have been raised that vital early intervention treatment will not have been given, with experts saying the longer people wait for appropriate help the “more severe and complex their difficulties and their lives can become”.
Full detail: Antidepressant use in England soars as pandemic cuts counselling access
Mental Health News 