Paolo Olgiati1, Alessandro Serretti2, Daniel Souery3, Markus Dold4, Siegfried Kasper4, Stuart Montgomery5, Joseph Zohar6, Julien Mendlewicz7. 1. Department of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy. 2. Department of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy. Electronic address: alessandro.serretti@unibo.it. 3. Laboratoire de Psychologie Médicale, Université Libre de Bruxelles, and Centre Européen de Psychologie Médicale-PsyPluriel, Brussels, Belgium. 4. Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna, Austria. 5. University of London, Imperial College, London, United Kingdom. 6. Chaim Sheba Medical Center, Chaim Sheba Medical Center, Tel-Hashomer, Israel. 7. Université Libre de Bruxelles, Brussels, Belgium.
Abstract
BACKGROUND: Initial improvement in the first weeks of antidepressant (AD) treatment is a useful early predictor of complete AD response. We performed a meta-analysis of AD studies to investigate whether a partial decrease in depressive symptoms by week 4 was associated with response and remission by weeks 6-14 in major depressive disorder (MDD). Finally, we focused on treatment-resistant depression (TRD: lack of response to prior AD) to test the impact of early improvement on a second AD treatment outcome and to compare different switching strategies. METHODS: Meta-analysis was conducted on AD naturalistic studies published between 01.01.2000 and 06.30.2017. TRD was an exclusion criterion. TRD was analyzed in 407 MDD patients treated with venlafaxine for 6 weeks. The MADRS was used to define very early improvement (VEI: > 20% decrease at week 2), early improvement (EI: > 30% decrease at week 4) and remission (week 6 MADRS < 10). A theoretical model was used to simulate AD switch in TRD patients who failed to achieve remission (Algorithm A), VEI (Algorithm B) or EI (Algorithm C). RESULTS: Our meta-analysis (9 studies; N = 6185) showed significant associations between early improvement, response (OR: 3.28 95% C.I: 2.06-5.20) and remission (OR: 2.10 95% C.I: 1.53-2.87). 24.6% of TRD sample remitted. VEI was a poor outcome predictor: sensitivity = 0.52 (0.40-0.63); specificity = 0.82 (0.76-0.86); AUC = 0.67 (0.62-0.71). EI had a moderate predictive power: sensitivity = 0.87 (0.77-0.93); specificity = 0.71 (0.66-0.77); AUC = 0.76 (0.71-0.80). The best treatment scenario was Algorithm C (switch after 4 weeks) in which remission rate was marginally increased (35.1% vs 33.7% of Algorithm A). Algorithm B (switch after 2 weeks) led to a 4.3% decrease in remission compared to Algorithm A. LIMITATIONS: Inclusion of a naturalistic sample without a control arm; simulation of treatments. CONCLUSION: Although literature data suggest a correlation between an initial improvement of depressive symptoms and later response and remission during AD treatment, our analysis shows that such an early improvement is not a reliable outcome predictor in TRD. The nature of TRD is complex and different biological mechanisms and treatments might be necessary for TRD patients.
BACKGROUND: Initial improvement in the first weeks of antidepressant (AD) treatment is a useful early predictor of complete AD response. We performed a meta-analysis of AD studies to investigate whether a partial decrease in depressive symptoms by week 4 was associated with response and remission by weeks 6-14 in major depressive disorder (MDD). Finally, we focused on treatment-resistant depression (TRD: lack of response to prior AD) to test the impact of early improvement on a second AD treatment outcome and to compare different switching strategies. METHODS: Meta-analysis was conducted on AD naturalistic studies published between 01.01.2000 and 06.30.2017. TRD was an exclusion criterion. TRD was analyzed in 407 MDDpatients treated with venlafaxine for 6 weeks. The MADRS was used to define very early improvement (VEI: > 20% decrease at week 2), early improvement (EI: > 30% decrease at week 4) and remission (week 6 MADRS < 10). A theoretical model was used to simulate AD switch in TRDpatients who failed to achieve remission (Algorithm A), VEI (Algorithm B) or EI (Algorithm C). RESULTS: Our meta-analysis (9 studies; N = 6185) showed significant associations between early improvement, response (OR: 3.28 95% C.I: 2.06-5.20) and remission (OR: 2.10 95% C.I: 1.53-2.87). 24.6% of TRD sample remitted. VEI was a poor outcome predictor: sensitivity = 0.52 (0.40-0.63); specificity = 0.82 (0.76-0.86); AUC = 0.67 (0.62-0.71). EI had a moderate predictive power: sensitivity = 0.87 (0.77-0.93); specificity = 0.71 (0.66-0.77); AUC = 0.76 (0.71-0.80). The best treatment scenario was Algorithm C (switch after 4 weeks) in which remission rate was marginally increased (35.1% vs 33.7% of Algorithm A). Algorithm B (switch after 2 weeks) led to a 4.3% decrease in remission compared to Algorithm A. LIMITATIONS: Inclusion of a naturalistic sample without a control arm; simulation of treatments. CONCLUSION: Although literature data suggest a correlation between an initial improvement of depressive symptoms and later response and remission during AD treatment, our analysis shows that such an early improvement is not a reliable outcome predictor in TRD. The nature of TRD is complex and different biological mechanisms and treatments might be necessary for TRDpatients.
Authors: Katharine Dunlop; Sakina J Rizvi; Sidney H Kennedy; Stefanie Hassel; Stephen C Strother; Jacqueline K Harris; Mojdeh Zamyadi; Stephen R Arnott; Andrew D Davis; Farrokh Mansouri; Laura Schulze; Amanda K Ceniti; Raymond W Lam; Roumen Milev; Susan Rotzinger; Jane A Foster; Benicio N Frey; Sagar V Parikh; Claudio N Soares; Rudolf Uher; Gustavo Turecki; Glenda M MacQueen; Jonathan Downar Journal: Neuropsychopharmacology Date: 2020-07 Impact factor: 7.853
Authors: Paul B Hicks; Varadan Sevilimedu; Gary R Johnson; Ilanit Tal; Peijun Chen; Lori L Davis; Julia E Vertrees; Somaia Mohamed; Sidney Zisook Journal: Psychiatr Res Clin Pract Date: 2019-10-03