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Original Research

Acceptability of Second-Line Antidepressant Medications Using Filled Prescription Sequences in a Nationwide Cohort Study

Charles Ouazana-Vedrines, MDa,*; Thomas Lesuffleur, MScb; Pierre Denis, MScb; Nicolas Hoertel, MD, PhDc; Romain Olekhnovitch, PhDd; Mark Olfson, MD, PhDe; Carlos Blanco, MD, PhDf; Frédéric Limosin, MD, PhDc; Antoine Rachas, MD, PhDb; Philippe Tuppin, MD, PhDb; and Cédric Lemogne, MD, PhDa

Published: October 17, 2022


Background: Although about half of patients do not respond to a first-line antidepressant medication, there is no consensus on the best second-line option. The aim of this nationwide population-based study was to rank antidepressants according to their relative acceptability (ie, efficacy and tolerability) using filled prescription sequences after failure of first treatment.

Methods: About 1.2 million people were identified as new antidepressant users in the French national health data system in 2011. The inclusion criterion was having at least 2 filled prescriptions of a second-line treatment after a filled prescription of a first-line treatment, resulting in 63,726 participants. The outcome was clinical acceptability as measured by the continuation/change ratio for second-line treatment. Continuation sequence was defined as at least 2 refills of the same treatment. Change sequence was defined as at least 1 filled prescription of another antidepressant. Adjusted odds ratios (aORs) were computed through multivariable binary logistic regressions.

Results: Intraclass switch had a better acceptability than interclass switch (aOR [95% CI]: 1.23 [1.20–1.28]). According to the first-line treatment, intraclass switch remained more acceptable for selective serotonin reuptake inhibitors only (1.37 [1.31–1.42]). For α2 blockers and tricyclic agents, combination antidepressant therapy was the most acceptable second-line option (1.59 [1.27–2.01] and 2.53 [1.53–4.04], respectively), whereas for serotonin-norepinephrine reuptake inhibitors there was no significant difference between the strategies. For other antidepressants, intraclass switch had lower acceptability than interclass switch (0.70 [0.51–0.95]).

Conclusions: Administrative claim databases may help with ranking acceptability of second-line treatments in real world settings and complement randomized controlled trials in informing clinicians about the most acceptable second-line options according to the first-line treatment.

Volume: 83

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