Efficacy of antidepressants in children and adolescents with depression – results from a large scale patient-level meta-analysis
F. Hieronymus1, A. Lisinski1, J. Näslund1
1Sahlgrenska Academy, University of Gothenburg, Pharmacology, Gothenburg, Sweden
Background: In this symposium, we show that the effects of different antidepressants may be moderated by different factors, including trial design, age and sex of the participant, and the rating scale used.
Aims & Objectives: Using data from large-scale study- and patient-level analyses, we provide foundations for better understanding study results, and improving trial design.
Method: Can blinded interventions be fairly compared to unblinded ones in depression? Contrasting classical antidepressants to psychotherapy, exercise and psilocybin
Fredrik Hieronymus, MD, PhD
Treatment guidelines in depression are increasingly focused on contrasting different treatment modalities against one another, e.g., psychotherapy versus pharmacotherapy or exercise versus pharmacotherapy. However, while pharmacotherapy with classical antidepressants can be trialled under blinded conditions, the same is not true for exercise or psychotherapy - which cannot be administered in a blinded fashion - and likely also not for the psychedelic compound psilocybin. Fredrik Hieronymus will critically review the available literature on how blinding impacts efficacy in depression treatment trials across active interventions and control groups, and discuss how this impacts assessments of the relative efficacy of different treatment modalities in depression.
Fredrik Hieronymus, MD, PhD
Treatment guidelines in depression are increasingly focused on contrasting different treatment modalities against one another, e.g., psychotherapy versus pharmacotherapy or exercise versus pharmacotherapy. However, while pharmacotherapy with classical antidepressants can be trialled under blinded conditions, the same is not true for exercise or psychotherapy - which cannot be administered in a blinded fashion - and likely also not for the psychedelic compound psilocybin. Fredrik Hieronymus will critically review the available literature on how blinding impacts efficacy in depression treatment trials across active interventions and control groups, and discuss how this impacts assessments of the relative efficacy of different treatment modalities in depression.
Results: Efficacy of antidepressants in children and adolescents with depression – results from a large scale patient-level meta-analysis
Alexander Lisinski, MD, PhD
The effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) for child and adolescent depression are generally considered to be small. Here, Alexander Lisinski will present data from a novel patient-level meta-analysis of 21 drug trials in non-adults, focusing on the impact of age and sex on treatment outcome compared to placebo, analysed both using rating scale sum-scores as well as individual symptoms of depression. Other key issues include potential differences between different SSRIs, or between SSRIs and SNRIs, as well as the impact of placebo response on drug-placebo differences. Further, the possibility of treatment-emergent suicidal ideation will be addressed. The results from this meta-analysis, representing currently available data from randomised, placebo-controlled drug trials on child and adolescent depression, are likely to impact treatment guidelines and clinical practice.
Alexander Lisinski, MD, PhD
The effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) for child and adolescent depression are generally considered to be small. Here, Alexander Lisinski will present data from a novel patient-level meta-analysis of 21 drug trials in non-adults, focusing on the impact of age and sex on treatment outcome compared to placebo, analysed both using rating scale sum-scores as well as individual symptoms of depression. Other key issues include potential differences between different SSRIs, or between SSRIs and SNRIs, as well as the impact of placebo response on drug-placebo differences. Further, the possibility of treatment-emergent suicidal ideation will be addressed. The results from this meta-analysis, representing currently available data from randomised, placebo-controlled drug trials on child and adolescent depression, are likely to impact treatment guidelines and clinical practice.
Discussion & Conclusions: Augmentation with atypical antipsychotics in treatment resistant depression
Jakob Näslund, MD, PhD
Augmentation with atypical antipsychotics is a common strategy when managing treatment-resistant depression (TRD). As these drugs generally are both sedative and orexigenic, it is possible that the reported efficacy in clinical trials partly reflects outsized improvements in sleep and appetite, that need not generalise to other depressive symptoms such as depressed mood or anhedonia. Jakob Näslund will present on a novel patient-level meta-analysis examining whether this is the case for adjunctive olanzapine treatment in combination with fluoxetine. By contrasting outcomes from the whole Montgomery-Åsberg Depression Rating Scale (MADRS) to results obtained with a subscale excluding sleep and appetite items (MADRS-8), as well as by performing item-level analyses, sedative and orexigenic effect can be isolated from more general antidepressant effects. Dr. Näslund will also present results from other recent patient-level meta-analyses comparing SSRIs and SNRIs to mirtazapine, an atypical antidepressant that, similar to atypical antipsychotics, also displays sedative and orexigenic properties.
Jakob Näslund, MD, PhD
Augmentation with atypical antipsychotics is a common strategy when managing treatment-resistant depression (TRD). As these drugs generally are both sedative and orexigenic, it is possible that the reported efficacy in clinical trials partly reflects outsized improvements in sleep and appetite, that need not generalise to other depressive symptoms such as depressed mood or anhedonia. Jakob Näslund will present on a novel patient-level meta-analysis examining whether this is the case for adjunctive olanzapine treatment in combination with fluoxetine. By contrasting outcomes from the whole Montgomery-Åsberg Depression Rating Scale (MADRS) to results obtained with a subscale excluding sleep and appetite items (MADRS-8), as well as by performing item-level analyses, sedative and orexigenic effect can be isolated from more general antidepressant effects. Dr. Näslund will also present results from other recent patient-level meta-analyses comparing SSRIs and SNRIs to mirtazapine, an atypical antidepressant that, similar to atypical antipsychotics, also displays sedative and orexigenic properties.
In sessions