Some Cochrane reviews investigate the effects of different ways of stopping, rather than starting treatments. A new review in April 2021 does this for adults who have been taking antidepressants for some time. One of the authors, Mieke van Driel from The University of Queensland in Australia tells us more in this podcast.
Monaz: Hello, I'm Monaz Mehta, editor in the Cochrane Editorial and Methods department. Some Cochrane reviews investigate the effects of different ways of stopping, rather than starting treatments. A new review in April 2021 does this for adults who have been taking antidepressants for some time. One of the authors, Mieke van Driel from The University of Queensland in Australia tells us more in this podcast.
Mieke: Antidepressants are frequently prescribed for patients with depression or anxiety and it is recommended that patients should continue to take them for six months after their symptoms have improved if it is their first episode, or for two years if they are at high risk.
However, many people continue taking antidepressants for several years or even decades and this long-term use is driving much of the internationally observed rise in antidepressant consumption. Surveys of antidepressant users suggest that there is no evidence-based indication for 30% to 50% of long-term antidepressant prescriptions. This puts people at high risk of adverse events, such as sleep disturbance, weight gain, sexual dysfunction, low blood sodium and gastrointestinal effects (for instance diarrhoea and constipation). It can also make them feel emotionally numb and unable to deal with problems in life without medication. Therefore, it is important to consider discontinuing antidepressants when they are no longer indicated and our review tries to identify ways to do so.
We looked for evidence to inform clinicians and their adult patients about effective and safe approaches to discontinue long-term antidepressants. Our searches revealed 33 randomised trials including a total of just under 5000 participants, with all the studies having a high risk of bias. Nearly all the studies recruited patients from specialist mental healthcare services and most of the participants had had two or more episodes of depression.
In 13 studies, the antidepressant was stopped abruptly, while 18 studies used a ‘tapered’ approach, reducing the dose gradually over usually about 4 weeks or less. Four studies offered psychological support during the discontinuation process and in one general practice study, stopping was prompted by a letter to the GP providing guidance on tapering.
We looked at benefits (such as successful stopping rates) and harms (such as return of the depressive or anxiety episodes, side effects and withdrawal symptoms). This provided very low certainty evidence that abrupt stopping or short tapering schedules may have a higher risk of relapse. There was also very low to low certainty evidence that providing psychological support may help some people to stop their antidepressant but there was no difference in relapse rates.
In general, studies did not report on the occurrence of withdrawal symptoms, and because these can resemble the symptoms of relapse of depression, it is possible that the reported ‘relapse’ could have been related to the impact of withdrawal, which is a temporary phenomenon.
There is emerging evidence that, when discontinuing long-term antidepressants, a very slow tapering scheme should be used over many months with very small dose reductions at each step, rather than the more rapid reduction over just a few weeks as used in the studies included in our review.
In conclusion, there is an urgent need for trials that adequately address withdrawal confounding bias, and distinguish relapse from withdrawal symptoms by using very slow and gradual tapering schemes. Future studies should include participants who have had only one or no depression episode in the past because these are the patients commonly seen in primary care where most antidepressant prescribing occurs. The lack of research for older people and those taking antidepressants for anxiety also needs to be filled by new studies, to provide evidence to support discontinuation in these groups.
Monaz: If you would like to read more about the trials that have been done, and watch for updates of the review if these evidence gaps are filled, the full review is available online. If you go to Cochrane Library dot com and search 'approaches for discontinuation of antidepressants', you’ll see a link to the review.