In primary care, people with a history of depression often choose to take antidepressant medication; National Institute for Health and Care Excellence (NICE) guidance recommends antidepressant medication for those at risk of recurrence of depression for up to 2 years (NICE, 2022).
When someone reaches a point where they want to stop taking protective antidepressant medication, a natural thought is to think about it. risk of recurrence of depression (Maund et al., 2019). However, there is limited understanding of the clinical risk factors that may make someone in primary care vulnerable to relapse.
Currently, there is some evidence that the number of previous depressive episodes (Conradi et al., 2008), residual depressive symptoms, and comorbid anxiety (Gopinath et al., 2007) are all associated with an increased risk of relapse in this condition. group. By further understanding these individual factors, clinicians can provide more informed clinical advice to those seeking to discontinue maintenance antidepressants.
In the current study, Duffy and colleagues (2023) aimed to address this knowledge gap by assessing clinical factors that may be associated with depression relapse risk for people who feel better and are considering stopping antidepressant treatment.
Little is known about the clinical risk factors associated with relapse of depression in primary care patients receiving long-term antidepressants.
Methods
Data were used double-blind, randomized controlled trial (ANTLER) randomized people to continue or taper antidepressant use for 2 months.
A Cox proportional hazards model was used that examined how long it took to reach a stable event—in this case, time to relapse (measured using the modified Clinical Interview Schedule-Revised (CIS-R) at 12, 16, 39, and 52 weeks). It is often difficult to distinguish between “relapse” (reliving the current episode) and “relapse” (a new episode, after recovery), so the authors defined it as relapse. “any new recurrence of depressive symptoms”.
Clinical factors (age of onset of depression, number of episodes, residual depression (PHQ-9) and anxiety (GAD-7) symptoms) were examined as predictors of time to relapse, adjusting for baseline sociodemographic confounders (age, sex, ethnicity, education). , marital status, employment status, and housing) and alcohol consumption, financial difficulties, and whether someone received psychological therapy.
Results
The sample included 477 individuals who were predominantly female (73%) and white British (94%). There was little difference between relapsers (n = 204) compared to non-recidivists (n = 273) in relation to baseline socio-demographic and clinical characteristics, except for people with higher education, relapse was more frequent.
The authors performed 3 separate models adjusting for (1) randomized treatment group assignment, (2) clinical factors, or (3) sociodemographic factors, group allocation, therapy status, and clinical factors.
The Model 3 had it strong evidence that the number of previous depressive episodes and residual depression increase the risk of relapse. If someone had more than 5 episodes of depression, the risk of recurrent depression increased by 57% (HR = 1.57, 95% CI (1.01–2.43), p = .025) compared to people with up to 2 depressive episodes. For a 1-point change in PHQ-9 depression scores, individuals had a 6% greater chance of relapse (HR = 1.06, 95% CI (1.01–1.12), p = .023).
However, as the authors acknowledge, the clinician cannot “adjust” these factors when making clinical decisions, so it makes sense to also look at a model without the adjusted factors (model 1). Here, in addition to a greater number of previous depressive episodes (>5 episodes, HR = 1.84, 95% CI (1.23 to 2.75), p = .002) and residual depression (HR = 1.05, 95% CI (1.01 to 1.09), p = .010), Age of onset of depression was also a risk factor for relapse (p = .024). Compared to older age (40-75 years), there was one If the age of onset of depression is between 23 and 39 years, the risk of recurrence increased by 62%. (HR = 1.62, 95% CI (1.13 to 2.43) and If it occurs between the ages of 18 and 22, the risk of relapse is increased by 37% (HR = 1.37, 95% CI (0.90 to 1.97)).
There was no statistical evidence regarding the duration of the current depressive episode (p = 0.172) or residual anxiety symptoms (p = 0.547) was associated with depression relapse risk in this sample.
More previous depressive episodes, higher residual depressive symptoms, and younger age have been identified as risk factors for recurrence of depression during long-term antidepressant treatment.
Results
This secondary analysis of the ANTLER trial data is highlighted three clinical factors After long-term use of maintenance antidepressants may contribute to an increased risk of relapse of depression:
- Greater number of previous depressive episodes (>5);
- More residual depressive symptoms;
- Younger age of onset of depression (under 40 compared to over 40).
These factors can be considered by clinicians when assessing relapse risks for adults who have been taking antidepressants for a long time but feel well and are considering stopping them.
This study lays the groundwork for future research to examine other factors that may be considered when considering discontinuation of antidepressant medication.
Strengths and limitations
Strengths
A major strength of this study was the ANTLER trial data high-quality randomized controlled trial. As the authors acknowledge, there is little research in this area and this study adds to the evidence base using a large, primary care sample from England.
Restrictions
The authors acknowledge this the final sample was a subset of a larger sample who did they approach (N = 23,553) and screened for testing and the representativeness of the sample is limited therefore.
In the analyses, the authors adjusted for sociodemographic factors, but this is what really stands out lack of diversity in the sample; of the 477 people in the trial, 447 (94%) were white British. The ANTLER trial, which reviewed 36 years of randomized controlled trials on depression, found few trials that included a range of people from ethnic minority backgrounds (among other groups, including those from low socioeconomic backgrounds and low income). 18; Polo et al., 2019). The factors that the authors found to be associated with depression relapse in this sample may not be the same for those from different sociodemographic backgrounds, and caution should be exercised because these findings may not be generalizable. The sample size did not allow the authors to perform analyses future research is needed to see whether sociodemographic factors interact with clinical factors to influence recovery time and to further understand the risk of relapse in this group of people.
It should also be noted that participants with residual depressive symptoms in the sample were in the moderate-to-severe range (the highest PHQ-9 depression score was 19 out of a possible 27). Thus, the risk of relapse for people with more residual depressive symptoms remains to be investigated.
More diversity in trials is needed to fully understand how sociodemographic factors may influence depression recurrence risk.
Implications for practice
Until now, there is little guidance for clinicians on who is at risk of relapse of depression during antidepressant maintenance., therefore making it difficult to make informed decisions about termination. This paper contributes to the limited evidence available in this area.
As the authors point out, clinicians can ask patients about previous episodes of depression, assess for residual depressive symptoms, and consider age during consultations where antidepressant discontinuation is discussed..
However, a full understanding of the clinical factors associated with relapse in this population still has a long way to go before it can be fully incorporated into practice. Future research should build on this work to examine whether a variety of other clinical (e.g., comorbid physical and mental health conditions, number of prior psychological treatments received), sociodemographic (e.g., ethnic diversity, employment, housing, and income), and interpersonal factors influence relapse risk in this population. can have an effect.
Clinicians can use this study to advise on discontinuation of antidepressant medications, but future research is needed to examine other factors (eg, clinical, sociodemographic, interpersonal) associated with depression relapse risk.
Statement of interest
None.
Connections
Primary paper
Duffy, L., Lewis, G., Marston, L., et al. (2023). Clinical factors associated with relapse of depression in a sample of UK primary care patients receiving long-term antidepressant treatment. Psychological Medicine, 1-11.
Other references
Conradi, HJ, de Jonge, P., & Ormel, J. (2008). Predicting the three-year course of recurrent depression in primary care patients: Different risk factors for different outcomes. Journal of Affective Disorders, 105(1–3), 267–271.
Gopinath, S., Cotton, WJ, Russo, JE, & Ludman, EJ (2007). Clinical factors associated with relapse in primary care patients with chronic or recurrent depression. Journal of Affective Disorders, 101(1–3), 57–63.
Katsampa, D., & Nguyen, T. (2020). Antidepressant discontinuation: patient perspectives on barriers and facilitators. Mental Elf.
Maund, E., Dewar-Haggart, R., Williams, S., Bowers, H., Geraghty, AW, Leydon, G., … & Kendrick, T. (2019). Barriers and facilitators to discontinuing antidepressant use: a systematic review and thematic synthesis. Journal of Affective Disorders, 24538-62.
National Institute of Health and Excellence. (2022). Depression in Adults: A Complete Guide to Treatment and Management. London: EXCELLENT. www.nice.org.uk/guidance/ng222 (April).
Polo, AJ, Makol, BA, Castro, AS, Columbus-Quintana, N., Wagstaff, AE, & Guo, S. (2019). Diversity in randomized clinical trials of depression: a 36-year review. Clinical Psychology Review, 6722-35.
Rifkin-Zybutz, R. and Jauharm S. (2021). Maintaining or Discontinuing Antidepressants for Depression? Results of the ANTLER trial. Mental Elf.