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. 2024 Dec 5;226(5):1-10.
doi: 10.1192/bjp.2024.194. Online ahead of print.

Real-world effects of antidepressants for depressive disorder in primary care: population-based cohort study

Franco De Crescenzo  1 , Riccardo De Giorgi  2   3 , Cesar Garriga  4 , Qiang Liu  2   5 , Seena Fazel  2   3 , Orestis Efthimiou  2   6   7 , Julia Hippisley-Cox  4 , Andrea Cipriani  8   9
Affiliations

Real-world effects of antidepressants for depressive disorder in primary care: population-based cohort study

Franco De Crescenzo et al. Br J Psychiatry. .

Abstract

Background: Antidepressants' effects are established in randomised controlled trials (RCTs), but not in the real world.

Aims: To investigate real-world comparative effects of antidepressants for depression and compare them with RCTs.

Method: We performed a cohort study based on the QResearch database. We included people with a newly recorded diagnosis of depression, exposed to licensed antidepressants in the UK. We assessed all-cause dropouts (acceptability), dropouts for adverse events (tolerability), occurrence of at least one adverse event (safety), and response and remission on the Patient Health Questionnaire (PHQ)-9 (effectiveness) at 2 and 12 months. Logistic regressions were used to compute adjusted-odds ratio (aOR) with 99% CIs, assessing the associations between exposure to each antidepressant against fluoxetine (comparator) and outcomes of interest. We compared estimates from the real world with RCTs using ratio-of-odds ratio (ROR) with 95% CI.

Results: A total of 673 177 depressed people were studied: females 57.1%, mean age 42.8 (s.d. 17.7) years, mean baseline PHQ-9 17.1 (s.d. 5.0) (moderately severe depression). At 2 months, antidepressant acceptability was 61.4%, tolerability 94.4%, safety 54.5%, PHQ-9 decreased to 12.3 (s.d. 6.5). At 12 months, acceptability was 12.3%, tolerability 87.5%, safety 28.8%, PHQ-9 12.9 (s.d. 6.8). In the short and long term, tricyclics, mirtazapine and trazodone were worse than fluoxetine for most outcomes; citalopram had better acceptability than fluoxetine (aOR 0.95; 99% CI 0.92, 0.97), sertraline had lower tolerability (aOR 1.12; 99% CI 1.06, 1.18), and both citalopram and sertraline had lower safety (aOR 1.17 and 1.25, respectively). In the long term, citalopram had better acceptability (aOR 0.78; 99% CI 0.76, 0.81) and effectiveness (aOR 1.12 for both response and remission), but worse tolerability (aOR 1.09; 99% CI 1.06, 1.13) and safety (aOR 1.12; 99% CI 1.08, 1.16). Observational and randomised data were similar for citalopram and sertraline, while there was some difference for drugs less prescribed in the real world.

Conclusions: Antidepressants showed low acceptability, moderate-to-high tolerability and safety, and small-to-moderate effectiveness in the real world. Real-world and RCT estimates showed similar findings only when the analyses were carried out using large datasets; otherwise, the results diverged.

Keywords: Antidepressants; depressive disorders; general adult psychiatry; observational study; register-based epidemiology.

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Conflict of interest statement

F.D.C. was supported by the NIHR Research Professorship to A.C. (grant RP-2017-08-ST2–006) and by the NIHR Oxford Health Biomedical Research Centre (grant BRC-1215-20005), and he is now an employee of Boehringer-Ingelheim International. A.C. has received research, educational and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), Cariplo Foundation, Lundbeck and Angelini Pharma. He is supported by the NIHR Oxford Cognitive Health Clinical Research Facility, by an NIHR Research Professorship (grant RP-2017-08-ST2-006), by the NIHR Oxford and Thames Valley Applied Research Collaboration, by the NIHR Oxford Health Biomedical Research Centre (grant NIHR203316) and by the Wellcome Trust (Global Alliance for Living Evidence on Anxiety, Depression and Psychosis [GALENOS] Project). The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR or the UK Department of Health and Social Care. R.D.G. is a member of the British Journal of Psychiatry editorial board, and did not take part in the review or decision-making process of this paper. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of the study cohort.
Figure 2
Figure 2
Forest plot showing ratio-of-odds ratios (ROR) with 95% CI for each antidepressant, with fluoxetine as index comparator, comparing real-world versus clinical trials (Group of Researchers Investigating Specific Efficacy of Individual Drugs for Acute Depression [GRISELDA] study) data. For acceptability and tolerability, a ROR >1 for drug X indicates that the effect of X versus fluoxetine is larger in randomised controlled trials (RCTs) as compared with the real world. For response and remission, a ROR <1 for drug X indicates that the effect of X versus fluoxetine is larger in RCTs as compared with the real world.
See this image and copyright information in PMC

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