Threat components for despair relapse whereas on long-term upkeep antidepressant therapy


Inside major care, individuals with a historical past of despair usually select to take upkeep antidepressant treatment; the Nationwide Institute for Well being and Care Excellence (NICE) steerage recommends antidepressant treatment for these liable to despair relapse for as much as 2 years (NICE, 2022).

When somebody will get to some extent of eager to cease taking upkeep antidepressant treatment, a pure consideration is to consider the threat of despair relapse (Maund et al., 2019). Nevertheless, there’s a restricted understanding of the medical threat components which may make somebody in major care susceptible to relapse.

Presently, there’s some proof to counsel that the variety of earlier despair episodes (Conradi et al., 2008), residual despair signs, and comorbid nervousness (Gopinath et al., 2007) are all related to an elevated threat of relapse on this group. By understanding these particular person components additional, clinicians might be able to present extra knowledgeable medical recommendation to these trying to cease taking upkeep antidepressants.

Within the present research, Duffy and colleagues (2023) aimed to deal with this data hole by assessing medical components that could be related to a threat of despair relapse for individuals who really feel higher and are contemplating discontinuing upkeep antidepressant therapy.

Little is known about the clinical risk factors that are associated with depression relapse in primary care patients on long-term maintenance antidepressants.

Little is understood concerning the medical threat components which might be related to despair relapse in major care sufferers on long-term upkeep antidepressants.


Knowledge was used from a double blind, randomised group-controlled trial (ANTLER) of individuals randomised to both proceed or regularly taper their antidepressant use over 2 months.

Cox proportional hazards modelling was used, which examines how lengthy it takes to achieve a hard and fast occasion – on this case time to relapse (measured utilizing a modified Medical Interview Schedule- Revised [CIS-R] at 12, 16, 39 and 52 weeks). It’s usually troublesome to untangle ‘relapse’ (re-experience present episode) and ‘recurrence’ (new episode, after restoration) so the authors outlined relapse as “any new reappearance of depressive signs”.

Medical components (age of despair onset, variety of episodes, residual despair [PHQ-9] and nervousness [GAD-7] signs) had been examined as predictors of time to relapse, adjusting for baseline sociodemographic confounders (age, gender, ethnicity, schooling, marital standing, employment standing, and housing) and alcohol consumption, monetary difficulties and whether or not somebody was receiving psychological remedy.


The pattern included 477 people who had been predominately feminine (73%) and White British (94%). There was little distinction between those that relapsed (n = 204) in comparison with those that didn’t relapse (n = 273) in relation to baseline sociodemographic and medical traits, besides individuals with increased academic attainment had been extra more likely to relapse.

The authors performed 3 separate fashions adjusting for (1) randomised therapy group allocation, (2) medical components, or (3) sociodemographic components, group allocation, remedy standing, and medical components.

In mannequin 3, there was robust proof that the variety of earlier depressive episodes and residual despair elevated the chance of relapse. If somebody had skilled greater than 5 episodes of despair, they’d a 57% elevated threat of despair relapse (HR = 1.57, 95% CI [1.01 to 2.43], p = .025) in comparison with individuals who had as much as 2 depressive episodes. For despair scores, with 1-point unit change on the PHQ-9, people had a 6% higher probability of relapse (HR = 1.06, 95% CI [1.01 to 1.12], p = .023).

Nevertheless, as the authors acknowledge, a clinician can’t ‘alter’ for these components when making medical selections, so it is smart to additionally have a look at a mannequin with out adjusted components (mannequin 1). Right here, along with the higher variety of earlier depressive episodes (>5 episodes, HR = 1.84, 95% CI [1.23 to 2.75], p = .002) and residual despair (HR = 1.05, 95% CI [1.01 to 1.09], p = .010), age of despair onset was additionally a threat issue for relapsing (p = .024). In comparison with older age (40–75-year-olds), there was a 62% elevated threat of relapse if age of despair onset was between the ages of 23-39 years (HR = 1.62, 95% CI [1.13 to 2.43), and a 37% increased risk of relapse if onset was between 18-22 years (HR = 1.37, 95% CI [0.90 to 1.97]).

There was no statistical proof that the length of the present depressive episode (p = 0.172) or residual nervousness signs (p = 0.547) had been related to the chance of despair relapse on this pattern.

Greater number of previous depressive episodes, higher residual depressive symptoms, and younger age were all identified as risk factors for depression relapse whilst on long-term maintenance antidepressants.

Better variety of earlier depressive episodes, increased residual depressive signs, and youthful age had been all recognized as threat components for despair relapse while on long-term upkeep antidepressants.


This secondary evaluation of the ANTLER trial knowledge highlighted three medical components that will contribute to an elevated threat of despair relapse following long-term use of upkeep antidepressants:

  • Better quantity (>5) of earlier despair episodes;
  • Extra residual despair signs;
  • Youthful age of despair onset (underneath 40 in comparison with over 40).

These components will be considered by clinicians when assessing the dangers of relapse for adults who’ve been on long-term antidepressant treatment, however are feeling properly and contemplating stopping them.

This study lays the foundation for future research to explore other factors that could be taken into consideration when thinking of discontinuing maintenance antidepressant medication.

This research lays the muse for future analysis to discover different components that could possibly be considered when considering of discontinuing upkeep antidepressant treatment.

Strengths and limitations


The primary energy of this research was the ANTLER trial knowledge, which was a prime quality randomised managed trial. Because the authors acknowledge, there’s little analysis on this space and this research provides to the proof base utilizing a big, major care pattern from England.


The authors acknowledge that the ultimate pattern was a subset of a a lot bigger pattern who had been approached (N = 23,553) and screened for the trial, and the representativeness of the pattern is restricted due to this.

Throughout the analyses the authors alter for sociodemographic components, however what actually stands out is the lack of range within the pattern; out of 477 people included within the trial 447 (94%) had been White British. The ANTLER trial will not be alone in its lack of illustration, with a overview of randomised managed trials for despair throughout 36 years discovering few trials that included a variety of individuals from ethnic minority backgrounds (amongst different teams, together with these from low socioeconomic backgrounds and underneath 18’s; Polo et al., 2019). The components the authors discovered to be related to despair relapse on this pattern might not be the identical as for individuals who are from totally different sociodemographic backgrounds and warning is required as these findings aren’t generalisable. The pattern dimension didn’t enable the authors to conduct analyses to see whether or not sociodemographic components work together with medical components to affect time to restoration, and future analysis is required to additional perceive threat of relapse on this group of individuals.

It’s also of notice that individuals with residual despair signs within the pattern had been within the moderate-severe vary (the best PHQ-9 despair rating was 19, out of a potential 27). So, the hazard of relapse for these with higher residual despair signs nonetheless must be investigated.

Greater diversity in trials is needed to fully understand how sociodemographic factors might influence risk of depression relapse.

Better range in trials is required to completely perceive how sociodemographic components would possibly affect threat of despair relapse.

Implications for follow

Till now, there was little steerage for clinicians as to who could also be liable to despair relapse when on upkeep antidepressants, due to this fact making it troublesome to make knowledgeable selections relating to discontinuation. This paper contributes to the restricted out there proof on this discipline.

Because the authors notice, clinicians can ask sufferers about earlier despair episodes, assess residual despair signs, and think about age throughout consultations the place discontinuation of upkeep antidepressants are being mentioned.

Nevertheless, there’s a nonetheless a protracted technique to go in totally understanding the medical components related to relapse on this inhabitants earlier than this may be totally embedded into follow. Future analysis ought to construct on this work to know how different totally different medical (e.g., co-morbid bodily and psychological well being situations, earlier variety of psychological therapies obtained), sociodemographic (e.g., ethnic range, employment, housing, and revenue), and interpersonal components could affect threat of relapse on this inhabitants.

Clinicians can use this research to help advise about discontinuing antidepressant medication, but future research is needed to explore other factors (e.g., clinical, sociodemographic, interpersonal) related to risk of depression relapse.

Clinicians can use this analysis to assist advise about discontinuing antidepressant treatment, however future analysis is required to discover different components (e.g., medical, sociodemographic, interpersonal) associated to threat of despair relapse.

Assertion of pursuits



Main paper

Duffy, L., Lewis, G., Marston, L., et al. (2023). Medical components related to relapse in despair in a pattern of UK major care sufferers who’ve been on long-term antidepressant therapy. Psychological Medication, 1-11.

Different references

Conradi, H. J., de Jonge, P., & Ormel, J. (2008). Prediction of the three-year course of recurrent despair in major care sufferers: Completely different threat components for various outcomes. Journal of Affective Issues, 105(1–3), 267–271.

Gopinath, S., Katon, W. J., Russo, J. E., & Ludman, E. J. (2007). Medical components related to relapse in major care sufferers with persistent or recurrent despair. Journal of Affective Issues, 101(1–3), 57–63.

Katsampa, D., & Nguyen, T. (2020). Stopping antidepressants: affected person views on limitations and facilitators. The Psychological Elf.

Maund, E., Dewar-Haggart, R., Williams, S., Bowers, H., Geraghty, A. W., Leydon, G., … & Kendrick, T. (2019). Boundaries and facilitators to discontinuing antidepressant use: a scientific overview and thematic synthesisJournal of Affective Issues245, 38-62.

Nationwide Institute for Well being Care and Excellence. (2022). Despair in adults: Therapy and administration full guideline. London: NICE. (April).

Polo, A. J., Makol, B. A., Castro, A. S., Colón-Quintana, N., Wagstaff, A. E., & Guo, S. (2019). Variety in randomized medical trials of despair: A 36-year overviewMedical Psychology Overview67, 22-35.

Rifkin-Zybutz, R., & Jauharm S. (2021). Upkeep or discontinuation of antidepressants for despair? Findings from the ANTLER trial. The Psychological Elf.

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