Joshua D Rosenblat1, Ron Kakar1,2, Michael Berk3,4, Lars V Kessing5, Maj Vinberg5, Bernhard T Baune6, Rodrigo B Mansur1,7,8, Elisa Brietzke7,8, Benjamin I Goldstein9, Roger S McIntyre1. 1. Mood Disorders Psychopharmacology Unit, University Health Network, Department of Psychiatry and Pharmacology, University of Toronto, Toronto, Canada. 2. Department of Psychiatry, Western University, London and Windsor, ON, Canada. 3. IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Vic., Australia. 4. Department of Psychiatry, The Florey Institute of Neuroscience and Mental Health, and Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, University of Melbourne, Parkville, Vic., Australia. 5. Psychiatric Center Copenhagen, Faculty of Health and Medical Sciences and Department O, University of Copenhagen, Copenhagen, Denmark. 6. Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia. 7. Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Federal University of Sao Paulo, São Paulo, Brazil. 8. Program of Recognition and Intervention in Individuals in AT-Risk Mental States (PRISMA), Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil. 9. Departments of Psychiatry, Pharmacology, and Psychological Clinical Science, Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Abstract
OBJECTIVE: Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. METHODS: Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone. RESULTS: Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was -0.40 (95% confidence interval -0.14 to -0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. CONCLUSIONS: Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.
OBJECTIVE: Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. METHODS: Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone. RESULTS: Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was -0.40 (95% confidence interval -0.14 to -0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. CONCLUSIONS: Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.
Authors: Konstantinos N Fountoulakis; Lakshmi Yatham; Heinz Grunze; Eduard Vieta; Allan Young; Pierre Blier; Siegfried Kasper; Hans Jurgen Moeller Journal: Int J Neuropsychopharmacol Date: 2017-02-01 Impact factor: 5.176
Authors: Lakshmi N Yatham; Sidney H Kennedy; Sagar V Parikh; Ayal Schaffer; David J Bond; Benicio N Frey; Verinder Sharma; Benjamin I Goldstein; Soham Rej; Serge Beaulieu; Martin Alda; Glenda MacQueen; Roumen V Milev; Arun Ravindran; Claire O'Donovan; Diane McIntosh; Raymond W Lam; Gustavo Vazquez; Flavio Kapczinski; Roger S McIntyre; Jan Kozicky; Shigenobu Kanba; Beny Lafer; Trisha Suppes; Joseph R Calabrese; Eduard Vieta; Gin Malhi; Robert M Post; Michael Berk Journal: Bipolar Disord Date: 2018-03-14 Impact factor: 6.744
Authors: Alessio Squassina; Mirko Manchia; Claudia Pisanu; Raffaella Ardau; Carlo Arzedi; Alberto Bocchetta; Paola Caria; Cristina Cocco; Donatella Congiu; Eleonora Cossu; Tinuccia Dettori; Daniela Virginia Frau; Mario Garzilli; Elias Manca; Anna Meloni; Maria Antonietta Montis; Andrea Mura; Mariella Nieddu; Barbara Noli; Pasquale Paribello; Federica Pinna; Renato Robledo; Giovanni Severino; Valeria Sogos; Maria Del Zompo; Gian Luca Ferri; Caterina Chillotti; Roberta Vanni; Bernardo Carpiniello Journal: Neuropsychopharmacology Date: 2020-09-12 Impact factor: 7.853