STUDY 329 SUGGESTS TO EXERT AN EFFECT IN CHILDREN AND ADOLESCENTS Alexander Lisinski, Fredrik Hieronymus, Staffan Nilsson, Elias Eriksson Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden

Background In a recent paper in BMJ (1), Le Noury and co-workers reanalysed the results of a previously published (Study 329) (2) addressing the tolerability and efficacy of paroxetine in adolescent depression. Noting that paroxetine did not outperform with respect to the primary effect variable, the total score of the Hamilton depression rating scale (HDRS 17-sum), they concluded that paroxetine did not show efficacy. In order to shed further light on this issue, we have undertaken additional analyses of the data from Study 329.

Methods Effect sizes and p-values for the difference between paroxetine and placebo were assessed using linear mixed models for each individual HDRS 17 item i) in all subjects, ii) after excluding subjects reporting <1 on the item in question at baseline and iii) after also excluding those below age 13. Figure 1 Results As reported in the original report by All subjects >= 1p baseline >= 1p, > 13 years Keller and co-workers, paroxetine 0.8 outperformed placebo with respect to * * p < 0.05 reduction in depressed mood, the * * * effect size being relatively large (0.61); 0.6 * in addition, a significant difference was obtained also in the item guilt (ES * * * 0.47). After exclusion of subjects 0.4 * displaying baseline rating <1 for the item in question, no further Effect Size differences were revealed between 0.2 the groups. However, after exclusion also of subjects <13 years of age, 0.0 significant reductions in depressed

mood, guilt, psychomotor retardation Guilt and psychic anxiety as well as in HDRS Retardation 17-sum were revealed. HDRS 17-sum Psychic anxiety Depressed mood Conclusions We have recently reported that SSRIs often outperform placebo in reducing important items in the HDRS 17 even when no significant difference is found with respect to HDRS 17-sum (3). This re-analysis of trial 329 yielded very similar results, suggesting HDRS 17-sum being a suboptimal measure for detecting an antidepressant signal also in the young. Moreover, leaving the formal aspect that HDRS 17-sum was named primary effect parameter in Study 329 aside, the results do not support the conclusion by Le Noury and co-workers that paroxetine lacks efficacy in adolescent depression. The study was supported by the Swedish Medical Research Council, Bertil Hållsten’s Foundation, Söderberg’s Foundation, the Sahlgrenska References University Hospital and the Swedish Brain Foundation. We thank GSK for kindly providing us with patient-level data from the included trial. 1. Le Noury et al, BMJ 2015;351:h4320 Conflicts of interest: FH has received speaker’s fees from Servier. EE has 2. Keller et al, J Am Acad Child Adolesc Psychiatry 2001;40:7;762-772 previously been on advisory boards and/or received speaker's honoraria and/or research grants from Eli Lilly, Servier and H Lundbeck. SN and AL 3. Hieronymus et al, Molecular Psychiatry 2016;21;523–530. report no conflicts of interest.

For additional information, please contact Det gick inte att hitta bilddelen med relations-ID rId3 i filen. Dr. Alexander Lisinski [email protected]