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In primary care, people with a history of depression often choose to take maintenance antidepressant medications; National Institute for Health and Care Excellence (NICE) guidance recommends antidepressant medication for those at risk of depression relapse for up to 2 years (NICE, 2022).
When someone is at a point where they want to stop taking maintenance antidepressant medication, it is natural to consider the risk of depression relapse (Mound et al., 2019). However, there is limited understanding of the clinical risk factors that predispose those in primary care to relapse.
Currently, there is some evidence to suggest 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 relapse risk. group. By better understanding these individual factors, clinicians can provide more informed medical advice to those looking to stop taking maintenance antidepressants.
In the present study, Duffy and colleagues (2023) aimed to address this knowledge gap by assessing clinical factors associated with depression relapse risk for individuals considering discontinuation of maintenance antidepressant treatment.
Little is known about the clinical risk factors associated with depression relapse in primary care patients on long-term maintenance antidepressants.
methods
Data were used from a double-blind, randomized group-controlled trial (ANTLER) of individuals randomized to continue or gradually reduce their antidepressant use for 2 months.
Cox proportional hazards modeling was used to examine how long it would take to reach a stable event – in this case the time to relapse (measured at 12, 16, 39 and 52 weeks using the Modified Clinical Interview Schedule-Revised (CIS-R)). Because it is difficult to distinguish between ‘relapse’ (re-experiencing the current episode) and ‘recurrence’ (a new episode, after recovery), the authors defined relapse as “Resurgence of any new depressive symptoms”,
Clinical factors (age of depression onset, number of episodes, residual depression (PHQ-9) and anxiety (GAD-7) symptoms) were examined to predict time to relapse, adjusting for baseline sociodemographic confounders (age, sex, race, education). , marital status, employment status, and housing) and alcoholism, financial difficulties, and whether one was receiving psychiatric treatment.
Results
The sample consisted of 477 individuals who were predominantly female (73%) and White British (94%). There was little difference between those who returned (n = 204) compared to those who did not return (n = 273) with respect to baseline sociodemographic and clinical characteristics, except for persons with higher educational qualifications who were more likely to return.
The authors conducted 3 separate models that adjusted for (1) random treatment group assignment, (2) clinical factors, or (3) sociodemographic factors, group assignment, treatment status, and clinical factors.
In Model 3, there is There is strong evidence that the number of previous depressive episodes and residual depression increase the risk of relapsesomeone who experienced more than 5 episodes of depression had a 57% increased risk of depression relapse (HR = 1.57, 95% CI (1.01 to 2.43), p = .025) compared with individuals who had 2 depressive episodes. For depression scores, with a 1-point unit change in the PHQ-9, individuals were 6% more likely to relapse (HR = 1.06, 95% CI (1.01 to 1.12), p = .023).
However, as the authors acknowledge, the clinician cannot ‘adjust’ for these factors when making clinical decisions, so it also makes sense to look at the model without the adjustment factors (Model 1). Here, along with the 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 at onset of depression is also a risk factor for relapse ,p = .024). Compared to the elderly (aged 40–75 years), a Age of onset of depression between 23-39 years has a 62% risk of recurrence (HR = 1.62, 95% CI (1.13 to 2.43), and Onset between 18-22 years has a 37% risk of recurrence (HR = 1.37, 95% CI (0.90 to 1.97)).
There is no statistical evidence for the duration of the current depressive episode (p = 0.172) or residual anxiety symptoms (p = 0.547) were associated with depression risk in this sample.
A greater number of previous depressive episodes, higher residual depressive symptoms, and younger age have all been identified as risk factors for depression relapse among long-term maintenance antidepressants.
Conclusions
This secondary analysis of the ANTLER trial data is highlighted Three clinical factors Long-term use of maintenance antidepressants may contribute to a higher risk of depression relapse following:
- a greater number (>5) of previous depressive episodes;
- more residual depressive symptoms;
- Younger age of onset of depression (compared to those under 40).
Clinicians can take these factors into account when assessing the risk of relapse in adults who are taking long-term antidepressant medications but feel better and are considering stopping them.
This study lays the groundwork for future research to explore other factors that might be considered when considering discontinuation of maintenance antidepressant medication.
Strengths and limitations
Strengths
A major strength of this study is the ANTLER trial data, which a A high quality randomized controlled trialas the authors note, there is little research in this area and this study adds to the evidence using a large, primary care sample from England.
limitations
The authors accept that The final sample is a subset of a much larger sample who contacted (n = 23,553) and performed for the trial and the The representativeness of the sample is limited Because of this.
The authors adjust for sociodemographic factors in the analyses, but what really stands out? Lack of diversity in the sample, 447 (94%) of the 477 individuals included in the trial were white. The ANTLER trial is not alone in its lack of representation, with a review of 36 years of randomized controlled trials for depression including few trials from ethnic minority backgrounds (among other groups, including low socioeconomic backgrounds and younger age groups). 18s; Polo et al., 2019). Caution is warranted because the factors the authors found to be associated with depression relapse in this sample may not be the same for those from different sociodemographic backgrounds, and these results are not generalizable. The sample size did not allow the authors to conduct analyses. Future research is needed to see if sociodemographic factors interact with clinical factors to influence recovery time and to further understand the risk of relapse in this population group.
It is also worth noting Participants with residual depressive symptoms in the sample were in the moderate-severe range (The highest PHQ-9 depression score is 19, out of a possible 27). Therefore, the risk of relapse for those with more residual depressive symptoms should be further investigated.
Greater diversity among trials is needed to fully understand how sociodemographic factors influence the risk of depression relapse.
Implications for practice
Until now, Doctors have little guidance on who is at risk for depression relapse while on maintenance antidepressants., thus making it difficult to make informed decisions regarding discontinuation. This paper contributes to the limited evidence available in this field.
As the authors note, Clinicians can ask patients about previous depressive episodes, assess for residual depressive symptoms, and consider age during consultations where discontinuation of maintenance antidepressants is discussed.,
However, there is still a long way to go in fully understanding the clinical factors associated with relapse in this population before it can be fully incorporated into practice. Future research should build on this work to understand how other different clinical (eg, co-morbid physical and mental health conditions, number of previous psychiatric treatments), sociodemographic (eg, ethnic diversity, employment, housing, and income) and interpersonal factors. Factors may influence relapse risk in this population.
Clinicians can use this research to advise on discontinuing antidepressant medication, but future research is needed to explore other factors (eg, clinical, sociodemographic, interpersonal) associated with depression relapse risk.
Declaration of Interests
There is none.
Links
Primary paper
Duffy, L., Lewis, G., Marston, L., et al. (2023) Clinical factors associated with relapse in depression in a sample of UK primary care patients on long-term antidepressant treatment. Psychological Medicine, 1-11.
Other references
Conradi, HJ, De Jonge, P., & Ormel, J. (2008). Assessment of 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). Stopping antidepressants: patient perspectives on barriers and facilitatorsThe Mental Elf.
Maund, E., Dewar-Haggart, R., Williams, S., Bowers, H., Geraghty, W., Laydon, 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 for Health Care and Excellence. (2022) Depression in Adults: A Complete Guide to Treatment and Management. London: NICE. www.nice.org.uk/guidance/ng222 (April).
Polo, AJ, Makol, BA, Castro, AS, Colon-Quintana, N., Wagstaff, AE, & Guo, S. (2019). Variation in randomized clinical trials of depression: a 36-year review. Clinical Psychology Review, 6722-35.
Rifkin-Zibutz, R., & Jouharm S. (2021). Should antidepressants be maintained or discontinued for depression? Findings from the ANTLER trialThe Mental Elf.