How long should a patient with recurrent major depressive disorder continue their antidepressant?

Your patient is a 40 year old woman with a history of recurrent major depressive disorder. When she presented initially, she was feeling low, with decreased motivation, poor concentration, low energy, trouble sleeping, and thoughts of death. She had no plans to hurt herself. You referred her to therapy and started escitalopram, titrated to 10mg daily. At a follow-up appointment 3 months later, she was satisfied with her therapist and her depressive symptoms were in remission.

Six months later, the same depressive symptoms recurred. She was not having any side effects from escitalopram, so you increased the dose to 20 mg daily. After a month, her depression was in full remission with the combination of therapy and escitalopram 20mg daily.

2 years later at your annual visit together, she is feeling well and asks about discontinuing the escitalopram. She ended her therapy sessions 6 months ago due to cost. What do you recommend?


How long should a patient with recurrent major depressive disorder continue their antidepressant?

On the one hand, we know surprisingly little about this question. A 2021 Cochrane review concluded that all trials comparing maintenance versus discontinuation of antidepressants for MDD were at high risk of bias due to confounding antidepressant withdrawal symptoms with depression relapse symptoms (Van Leeuwen, 2021). The authors concluded that no firm conclusions could be drawn from the data. On the other hand, there is some high quality data that can help us guide our patients in making this decision.   

A 2021 randomized, double-blinded, multi-center trial based in the UK compared the rate of MDD relapse among patients who continued antidepressant therapy versus those who received a matching placebo and had their antidepressant tapered over 2 months (Lewis, 2021). The study was limited in its patient population (95% white, UK only) and in the medications included (citalopram, fluoxetine, sertraline, and mirtazapine). All patients had recurrent depression (at least 2 episodes of MDD), had been on medication for at least 2 years, were not currently depressed, and were willing to stop their medications. The difference in rate of depression relapse was statistically significant. Relapse occurred in 39% of patients in the maintenance group compared with 56% of patients in the discontinuation group, as shown in the figure below.

Kaplan–Meier Estimates of the Primary Outcome. Shown are the results of Kaplan–Meier analysis of the first relapse of depression by 52 weeks (the primary outcome) among those who continued to receive their current antidepressant therapy (maintenance group) and those who tapered and discontinued such therapy (discontinuation group)* (Lewis, 2021).

*These data are applicable to adults with recurrent major depressive disorder, not adults with a single major depressive episode.



When talking with a patient, it is helpful to frame this discussion as a risk-risk conversation. What is the risk of continuing an antidepressant with a lower risk of depressive relapse vs the risk of stopping it with a higher risk of depressive relapse?  


Questions to understand the risk of continuing the antidepressant for this patient:

  • Are you experiencing adverse side effects? 
  • What about sexual side effects? [Ask specifically about sexual side effects, because patients often don’t spontaneously report these.] 
  • Has cost or access to the medication become an issue? 

Questions to understand the risk of tapering the medication for this patient:

  • Have you stopped antidepressants in the past? What happened?  
  • How severe have your prior major depressive episodes been? 
  • How would you feel about restarting a medication if you did have a relapse?  

Research summary for the patient:

  • We have limited, imperfect data on this topic. The data that we do have consistently shows that people with recurrent major depression who take antidepressants for at least 2 years and then decide to stop the medications have higher rates of relapse in the first year than those who do not stop medication (60 v. 40% in the study). To put these percentages another way, 2 out of 5 people with a history of recurrent major depression in remission who remain on their medications will experience a relapse of depression within the next year. 3 out of 5 people who stop their medication will experience a relapse, while 2 out of 5 people who stop their meds will not experience a relapse in the next year.  We unfortunately don’t have data about the impact of stopping medications on the longer-term course of MDD (5-10 years after stopping medications).

Is now the time?

  • Is your life at its baseline level of stress? I want you to have the best chance of staying off the medications when we stop them, so we should plan to taper them at a time that is not otherwise particularly stressful.  

Finally, I always offer myself as a support for the patient moving forward. Regardless of the choice today, I am available to discuss any questions or problems that arise.



References:

Lewis, Gemma, et al. “Maintenance or Discontinuation of Antidepressants in Primary Care.” New England Journal of Medicine, vol. 385, no. 14, Sept. 2021, pp. 1257–67. https://doi.org/10.1056/NEJMoa2106356

Van Leeuwen, Ellen, et al. “Approaches for Discontinuation versus Continuation of Long-Term Antidepressant Use for Depressive and Anxiety Disorders in Adults.” Cochrane Database of Systematic Reviews, edited by Cochrane Common Mental Disorders Group, vol. 2021, no. 4, Apr. 2021. https://doi.org/10.1002/14651858.CD013495.pub2


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