Duration of Antidepressant Drug Treatment and Its Influence on Risk of Relapse/Recurrence: Immortal and Neglected Time Bias
Abstract
Several observational studies have found a higher risk of recurrence/relapse of depression for patients who discontinue antidepressant use compared with those who continue. This study demonstrated that measurement of follow-up time can be subject to immortal and neglected time bias. Data were obtained from the 2001 Second Dutch National Survey of General Practice. The study population was composed of antidepressant users with a registered depression diagnosis, divided into early discontinuers and continuing users. Two methods were used to measure time to relapse/recurrence. Method 1, used in previously mentioned studies, measured the beginning of follow-up 6 months after starting antidepressant therapy. Method 2 constructed individual treatment episodes for each patient and measured follow-up from actual end-of-treatment episode. The Cox proportional hazards model produced a risk ratio of 1.58 (95% confidence interval: 1.02, 2.45) for method 1, suggesting a higher risk of relapse/recurrence for early discontinuers. In method 2, a statistically nonsignificant risk ratio of 0.77 (95% confidence interval: 0.49, 1.21) was produced, indicating no difference in risk of relapse/recurrence. The authors found the method used in previous studies subject to bias. Applying a different method, accounting for immortal and neglected time bias, eliminated the protective effects of longer treatments.
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In naturalistic studies of patients treated with SSRIs, longer duration of antidepressant treatment was associated with greater likelihood of recurrence.
“In naturalistic studies of patients treated SSRI,70,71 the longer the duration of antidepressant treatment, the more likely were the patients to recur.”
From May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance (2020) · cites this paper as [71]
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- Authors
- Gardarsdottir, H., Egberts, T. C., Stolker, J. J., & Heerdink, E. R.
- Affiliations
- Utrecht University (NL)
- Corresponding author
- Heerdink, E. R.
- Venue
- American Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-06-04
- Volume
- 170
- Issue
- 3
- Pages
- 280-285
- ISSN
- 0002-9262 (ISSN-L)
- 1476-6256
- OpenAlex
- W2159553172
- Cited by
- 47
- References
- 26
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 1 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 6 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 6
- FWCI
- 4.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universiteit Utrecht
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Keywords
- antidepressant treatment duration, depression relapse, depression recurrence, antidepressant discontinuation, immortal time bias, treatment episodes, general practice patients
- MeSH terms
- Antidepressive Agents, Depressive Disorder, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Male, Middle Aged, Netherlands, Research Design, Time Factors, Cohort Studies, Bias, Confidence Intervals, Proportional Hazards Models, Odds Ratio, Treatment Outcome, Pharmacoepidemiology, Medication Adherence, Secondary Prevention
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