Rituparna Maiti1, Archana Mishra2, Biswa Ranjan Mishra3, Monalisa Jena4. 1. Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India. pharm_rituparna@aiimsbhubaneswar.edu.in. 2. Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi, India. 3. Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India. 4. Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India.
Abstract
RATIONALE: Mitochondrial dysfunctions have emerged as new biological hypothesis and therapeutic target for bipolar disorder. This network meta-analysis has been done to evaluate the comparative efficacy of mitochondrial agents in bipolar depression. METHODS: After a comprehensive literature search on PubMed/MEDLINE, Cochrane databases, and International Trials Registry Platform, efficacy data were extracted from 15 randomized controlled trials. Random-effects meta-analysis was done following both frequentist and Bayesian approaches to pool the effects across the interventions. A network graph was built, relative effects of interventions in respect to one another and placebo were calculated, and treatments were ranked as per P- and SUCRA scores. Change in depression rating score was the primary outcome. Data was entered in contrast level and arm level for frequentist and Bayesian approaches, respectively. RESULTS: Amongst mitochondrial agents, N-acetylcysteine (NAC) was shown to have the highest probability of being the best treatment, followed by coenzyme Q10 and combination therapy of alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALCAR) as depicted by P- and SUCRA scores. In the Bayesian approach, none of the treatments had better efficacy than placebo, but in the frequentist approach, NAC (effect estimate: - 1.18 (95% CI: - 2.05; - 0.31)) was significantly better than placebo. CONCLUSION: Methodically, there may be a difference of magnitude in frequentist and Bayesian approaches, but the direction of effect and ranking probabilities do not differ. We conclude that none of the existing mitochondrial agents showed better efficacy than placebo in bipolar depression regarding depression rating scores.
RATIONALE: Mitochondrial dysfunctions have emerged as new biological hypothesis and therapeutic target for bipolar disorder. This network meta-analysis has been done to evaluate the comparative efficacy of mitochondrial agents in bipolar depression. METHODS: After a comprehensive literature search on PubMed/MEDLINE, Cochrane databases, and International Trials Registry Platform, efficacy data were extracted from 15 randomized controlled trials. Random-effects meta-analysis was done following both frequentist and Bayesian approaches to pool the effects across the interventions. A network graph was built, relative effects of interventions in respect to one another and placebo were calculated, and treatments were ranked as per P- and SUCRA scores. Change in depression rating score was the primary outcome. Data was entered in contrast level and arm level for frequentist and Bayesian approaches, respectively. RESULTS: Amongst mitochondrial agents, N-acetylcysteine (NAC) was shown to have the highest probability of being the best treatment, followed by coenzyme Q10 and combination therapy of alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALCAR) as depicted by P- and SUCRA scores. In the Bayesian approach, none of the treatments had better efficacy than placebo, but in the frequentist approach, NAC (effect estimate: - 1.18 (95% CI: - 2.05; - 0.31)) was significantly better than placebo. CONCLUSION: Methodically, there may be a difference of magnitude in frequentist and Bayesian approaches, but the direction of effect and ranking probabilities do not differ. We conclude that none of the existing mitochondrial agents showed better efficacy than placebo in bipolar depression regarding depression rating scores.
Authors: Anne M Cataldo; Donna L McPhie; Nicholas T Lange; Steven Punzell; Sarah Elmiligy; Nancy Z Ye; Michael P Froimowitz; Linda C Hassinger; Emily B Menesale; Laura W Sargent; David J Logan; Anne E Carpenter; Bruce M Cohen Journal: Am J Pathol Date: 2010-06-21 Impact factor: 4.307
Authors: Michael Berk; David L Copolov; Olivia Dean; Kristy Lu; Sue Jeavons; Ian Schapkaitz; Murray Anderson-Hunt; Ashley I Bush Journal: Biol Psychiatry Date: 2008-06-05 Impact factor: 13.382
Authors: Brian P Brennan; John Eric Jensen; James I Hudson; Caitlin E Coit; Ashley Beaulieu; Harrison G Pope; Perry F Renshaw; Bruce M Cohen Journal: J Clin Psychopharmacol Date: 2013-10 Impact factor: 3.153
Authors: Michael Berk; Olivia M Dean; Sue M Cotton; Clarissa S Gama; Flavio Kapczinski; Brisa Fernandes; Kristy Kohlmann; Susan Jeavons; Karen Hewitt; Kirsteen Moss; Christine Allwang; Ian Schapkaitz; Heidi Cobb; Ashley I Bush; Seetal Dodd; Gin S Malhi Journal: BMC Med Date: 2012-08-14 Impact factor: 8.775
Authors: Michael Berk; Alyna Turner; Gin S Malhi; Chee H Ng; Susan M Cotton; Seetal Dodd; Yuval Samuni; Michelle Tanious; Claire McAulay; Nathan Dowling; Jerome Sarris; Lauren Owen; Astrid Waterdrinker; Deidre Smith; Olivia M Dean Journal: BMC Med Date: 2019-01-25 Impact factor: 8.775