"Effect of Antidepressant Discontinuation vs. Maintenance on Relapse in Primary Care Patients". The New England Journal of Medicine.

Clinical Question

Does discontinuation of antidepressants in primary care patients who have been treated for depression and feel well enough to stop medication increase the risk of relapse as compared to maintenance of therapy?

Bottom Line

Antidepressant discontinuation in primary care patients who felt ready to stop increased the risk of depression relapse compared to maintenance therapy over 52 weeks. Quality of life, and symptoms of depression and anxiety, were worse in patients who discontinued their antidepressant therapy.

Major Points

Guidelines

This trial contributes to discussions on guidelines for managing long-term antidepressant therapy in primary care, specifically the potential risks of discontinuation in patients who feel well enough to consider stopping the medication.

Design

- Randomized, double-blind trial
- N=478 (238 in maintenance group, 240 in discontinuation group)
- Setting: 150 general practices in the United Kingdom
- Follow-up: 52 weeks
- Analysis: Intention-to-treat
- Primary outcome: First relapse of depression by 52 weeks

Population

- Adult patients in primary care practices
- History of at least two depressive episodes or taking antidepressants for 2 years or longer
- Felt well enough to consider stopping antidepressants
- Most commonly prescribed antidepressants: citalopram, fluoxetine, sertraline, mirtazapine

Interventions

- Maintenance group continued current antidepressant therapy
- Discontinuation group tapered and discontinued therapy with placebo replacement

Outcomes

- Relapse occurred in 39% of maintenance group vs. 56% of discontinuation group (HR 2.06; P<0.001)
- Secondary outcomes generally favored the maintenance group; patients in the discontinuation group had more depressive, anxiety, and withdrawal symptoms
- 39% of patients in the discontinuation group returned to prescribed antidepressant use by end of the trial

Criticisms

- Not generalizable to all antidepressants as only specific types were included
- Excluded patients on doses different from standard U.K. maintenance doses
- Limited patient participation rate
- Findings applicable only to patients ready to cease medication
- Method used to define depression relapse adapted for the study, which may not be generalized
- Lack of diversity among trial participants

Funding

- National Institute for Health Research

Further Reading

- Full text of the article at NEJM.org

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.