NIHR Signal Staying on antidepressants may prevent a relapse of anxiety

Published on 17 January 2018

People with anxiety disorders who continued taking antidepressants after successful treatment were less likely to experience a relapse, and relapsed later, than people who stopped taking antidepressants. About 16% of people had a relapse if they remained on antidepressants for on average 44 weeks compared with 36% who stopped after 20 weeks.

Anxiety disorders are common and can interfere with people’s everyday work, family and social life. Antidepressants and psychological therapies are the mainstays of treatment. Reducing the likelihood of relapse after successful treatment is important for the individual and the cost of additional care. There remains a need for evidence about the effectiveness of continuing treatment beyond 12 months after remission.

Healthcare professionals discussing treatment continuation with people taking antidepressants should highlight the potential for relapse as well as the benefits of symptom reduction, to enable the person to make an informed decision.

Staying on antidepressants may prevent a relapse of anxiety

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Why was this study needed?

Anxiety disorders describe a range of mental health conditions where anxiety is the main symptom, including obsessive-compulsive disorder (OCD) and post-traumatic stress disorder. Around one in ten people in the UK may develop an anxiety disorder in their lifetime and it is estimated that around three million people in the UK have an anxiety disorder at any time.

People with anxiety often experience a relapse of their symptoms even after reaching remission – when their symptoms reach a manageable or sub-clinical level. Over half of people with anxiety disorders are treated using antidepressants, but – like all drugs – people taking them may experience side effects. In deciding how long to continue taking antidepressants, people need to be able to weigh up the benefits (if they relieve their symptoms) against the drawbacks (side effects) and risk of relapse if they stop too soon.

This review specifically looked at the longer-term effectiveness of antidepressants for preventing relapse in people with anxiety disorders.

What did this study do?

This systematic review included 28 randomised controlled trials of 5,233 people with various anxiety disorders: OCD (seven trials), generalised anxiety disorder (six), panic disorder (six), social phobia (five) and post-traumatic stress disorder (four). People had responded after, on average, 20 weeks of an antidepressant (range 8 to 52 weeks), before they were randomised to continue the antidepressant or switch to placebo.

Follow up ranged from 8 to 52 weeks. Thus people were on treatment for an average total of 44 weeks (range 16 to 80 weeks).

Participants were unaware of which treatment they were receiving, and the risk of bias was low in most trials, meaning we can feel confident in the results. However, the rate of dropout was high, with only 56% of people completing the trials.

What did it find?

  • Fewer people continuing on antidepressants experienced relapse (164%, 95% confidence interval [CI] 12.6% to 20.1%) compared to people who discontinued antidepressant treatment when switched onto placebo (364%, 95% CI 308% to 421%). This gives an absolute risk reduction of 20%, so five people would need to continue on antidepressants to prevent someone from relapsing.
  • People who were switched to placebo were three times more likely to relapse than those who continued on an antidepressant (odds ratio [OR] 311, 95% CI 248 to 389; 28 trials).
  • Stopping treatment meant that people relapsed sooner than if they continued antidepressants (hazard ratio [HR] 363, 95% CI 258 to 510; 11 trials).
  • Continuing antidepressants reduced relapse compared to placebo regardless of the type of anxiety disorder, antidepressant, immediate or gradual discontinuation, whether psychological therapy or if people had other illnesses.
  • Reporting of side-effects of anti-depressants or withdrawal symptoms was limited, so it was not possible to pool this data.

What does current guidance say on this issue?

NICE guidelines recommend a “stepped” approach to generalised anxiety disorder and panic disorder (2011), OCD and body dysmorphic disorder (2005), and other anxiety-related common mental health problems (2011). This means the type of treatment and its intensity is increased or decreased in line with the severity of symptoms.

NICE recommends the antidepressants selective serotonin reuptake inhibitors and tricyclic antidepressants for longer-term management of generalised anxiety disorder and panic disorder. Selective serotonin reuptake inhibitors are recommended for OCD or body dysmorphic disorder for at least 12 months after the person has reached remission and can be extended.

NICE highlights that informed patient choice – especially when weighing up the benefits and harms of taking antidepressants – is central to decision-making about whether to continue treatment.

What are the implications?

Taking antidepressants for on average 44 weeks reduced relapse rates compared to stopping after on average 20 weeks. However, this only applies to people who had an initial positive response and were willing to remain on them. Due to the high dropout rate, we don’t know how many people stopped taking them due to recovery, side effects or lack of improvement.

These findings support NICE recommendations that the risk of relapse should be factored into discussions between individuals and their doctors about how long to continue antidepressant treatment for anxiety disorders. As only two studies randomised people after 52 weeks of taking antidepressants and the rest did so after a maximum of 26 weeks, it remains unclear whether it is safe to stop antidepressants after one year regarding the risk of relapse.

Citation and Funding

Batelaan NM, Bosman RC, Muntingh A, et al. Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials. BMJ. 2017;358:j3927.

No funding information was provided for this study.

Bibliography

NICE. Generalised anxiety disorder and panic disorder in adults: management. CG113. London: National Institute for Health and Care Excellence; 2011.

NICE. Obsessive-compulsive disorder and body dysmorphic disorder: treatment. CG31. London: National Institute for Health and Care Excellence; 2005.

NICE. Common mental health problems: identification and pathways to care. CG123. London: National Institute for Health and Care Excellence; 2011.

Why was this study needed?

Anxiety disorders describe a range of mental health conditions where anxiety is the main symptom, including obsessive-compulsive disorder (OCD) and post-traumatic stress disorder. Around one in ten people in the UK may develop an anxiety disorder in their lifetime and it is estimated that around three million people in the UK have an anxiety disorder at any time.

People with anxiety often experience a relapse of their symptoms even after reaching remission – when their symptoms reach a manageable or sub-clinical level. Over half of people with anxiety disorders are treated using antidepressants, but – like all drugs – people taking them may experience side effects. In deciding how long to continue taking antidepressants, people need to be able to weigh up the benefits (if they relieve their symptoms) against the drawbacks (side effects) and risk of relapse if they stop too soon.

This review specifically looked at the longer-term effectiveness of antidepressants for preventing relapse in people with anxiety disorders.

What did this study do?

This systematic review included 28 randomised controlled trials of 5,233 people with various anxiety disorders: OCD (seven trials), generalised anxiety disorder (six), panic disorder (six), social phobia (five) and post-traumatic stress disorder (four). People had responded after, on average, 20 weeks of an antidepressant (range 8 to 52 weeks), before they were randomised to continue the antidepressant or switch to placebo.

Follow up ranged from 8 to 52 weeks. Thus people were on treatment for an average total of 44 weeks (range 16 to 80 weeks).

Participants were unaware of which treatment they were receiving, and the risk of bias was low in most trials, meaning we can feel confident in the results. However, the rate of dropout was high, with only 56% of people completing the trials.

What did it find?

  • Fewer people continuing on antidepressants experienced relapse (164%, 95% confidence interval [CI] 12.6% to 20.1%) compared to people who discontinued antidepressant treatment when switched onto placebo (364%, 95% CI 308% to 421%). This gives an absolute risk reduction of 20%, so five people would need to continue on antidepressants to prevent someone from relapsing.
  • People who were switched to placebo were three times more likely to relapse than those who continued on an antidepressant (odds ratio [OR] 311, 95% CI 248 to 389; 28 trials).
  • Stopping treatment meant that people relapsed sooner than if they continued antidepressants (hazard ratio [HR] 363, 95% CI 258 to 510; 11 trials).
  • Continuing antidepressants reduced relapse compared to placebo regardless of the type of anxiety disorder, antidepressant, immediate or gradual discontinuation, whether psychological therapy or if people had other illnesses.
  • Reporting of side-effects of anti-depressants or withdrawal symptoms was limited, so it was not possible to pool this data.

What does current guidance say on this issue?

NICE guidelines recommend a “stepped” approach to generalised anxiety disorder and panic disorder (2011), OCD and body dysmorphic disorder (2005), and other anxiety-related common mental health problems (2011). This means the type of treatment and its intensity is increased or decreased in line with the severity of symptoms.

NICE recommends the antidepressants selective serotonin reuptake inhibitors and tricyclic antidepressants for longer-term management of generalised anxiety disorder and panic disorder. Selective serotonin reuptake inhibitors are recommended for OCD or body dysmorphic disorder for at least 12 months after the person has reached remission and can be extended.

NICE highlights that informed patient choice – especially when weighing up the benefits and harms of taking antidepressants – is central to decision-making about whether to continue treatment.

What are the implications?

Taking antidepressants for on average 44 weeks reduced relapse rates compared to stopping after on average 20 weeks. However, this only applies to people who had an initial positive response and were willing to remain on them. Due to the high dropout rate, we don’t know how many people stopped taking them due to recovery, side effects or lack of improvement.

These findings support NICE recommendations that the risk of relapse should be factored into discussions between individuals and their doctors about how long to continue antidepressant treatment for anxiety disorders. As only two studies randomised people after 52 weeks of taking antidepressants and the rest did so after a maximum of 26 weeks, it remains unclear whether it is safe to stop antidepressants after one year regarding the risk of relapse.

Citation and Funding

Batelaan NM, Bosman RC, Muntingh A, et al. Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials. BMJ. 2017;358:j3927.

No funding information was provided for this study.

Bibliography

NICE. Generalised anxiety disorder and panic disorder in adults: management. CG113. London: National Institute for Health and Care Excellence; 2011.

NICE. Obsessive-compulsive disorder and body dysmorphic disorder: treatment. CG31. London: National Institute for Health and Care Excellence; 2005.

NICE. Common mental health problems: identification and pathways to care. CG123. London: National Institute for Health and Care Excellence; 2011.

Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials

Published on 15 September 2017

Batelaan, N. M.,Bosman, R. C.,Muntingh, A.,Scholten, W. D.,Huijbregts, K. M.,van Balkom, Ajlm

Bmj Volume 358 , 2017

Objectives To examine the risk of relapse and time to relapse after discontinuation of antidepressants in patients with anxiety disorder who responded to antidepressants, and to explore whether relapse risk is related to type of anxiety disorder, type of antidepressant, mode of discontinuation, duration of treatment and follow-up, comorbidity, and allowance of psychotherapy.Design Systematic review and meta-analyses of relapse prevention trials.Data sources PubMed, Cochrane, Embase, and clinical trial registers (from inception to July 2016).Study selection Eligible studies included patients with anxiety disorder who responded to antidepressants, randomised patients double blind to either continuing antidepressants or switching to placebo, and compared relapse rates or time to relapse.Data extraction Two independent raters selected studies and extracted data. Random effect models were used to estimate odds ratios for relapse, hazard ratios for time to relapse, and relapse prevalence per group. The effect of various categorical and continuous variables was explored with subgroup analyses and meta-regression analyses respectively. Bias was assessed using the Cochrane tool.Results The meta-analysis included 28 studies (n=5233) examining relapse with a maximum follow-up of one year. Across studies, risk of bias was considered low. Discontinuation increased the odds of relapse compared with continuing antidepressants (summary odds ratio 3.11, 95% confidence interval 2.48 to 3.89). Subgroup analyses and meta-regression analyses showed no statistical significance. Time to relapse (n=3002) was shorter when antidepressants were discontinued (summary hazard ratio 3.63, 2.58 to 5.10; n=11 studies). Summary relapse prevalences were 36.4% (30.8% to 42.1%; n=28 studies) for the placebo group and 16.4% (12.6% to 20.1%; n=28 studies) for the antidepressant group, but prevalence varied considerably across studies, most likely owing to differences in the length of follow-up. Dropout was higher in the placebo group (summary odds ratio 1.31, 1.06 to 1.63; n=27 studies).Conclusions Up to one year of follow-up, discontinuation of antidepressant treatment results in higher relapse rates among responders compared with treatment continuation. The lack of evidence after a one year period should not be interpreted as explicit advice to discontinue antidepressants after one year. Given the chronicity of anxiety disorders, treatment should be directed by long term considerations, including relapse prevalence, side effects, and patients' preferences.

Expert commentary

While it’s not obvious in name, it is common for antidepressants to be prescribed for anxiety. We know little about how they are used best in the long term after an acute episode. The key question is, does continued use prevent relapse?

Current clinical guidance suggests that it is best to slowly decrease medication. This study shows that relapse is lower when people continue antidepressants for up to a year.

I am hopeful this information will strengthen opportunities for dialogue between individuals with anxiety and clinicians early on about what is the best individual treatment choice when thinking about the long term. 

Josefien Breedvelt, Research Manager, Mental Health Foundation