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

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.

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.

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]).

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.