title: Treatment implications of predominant polarity and the polarity index: a comprehensive review.
abstract: BACKGROUND
  Bipolar disorder (BD) is a serious and recurring condition that affects approximately 2.4% of the global population. About half of BD sufferers have an illness course characterized by either a manic or a depressive predominance. This predominant polarity in BD may be differentially associated with several clinical correlates. The concept of a polarity index (PI) has been recently proposed as an index of the antimanic versus antidepressive efficacy of various maintenance treatments for BD. Notwithstanding its potential clinical utility, predominant polarity was not included in the DSM-5 as a BD course specifier.
  
  
  METHODS
  Here we searched computerized databases for original clinical studies on the role of predominant polarity for selection of and response to pharmacological treatments for BD. Furthermore, we systematically searched the Pubmed database for maintenance randomized controlled trials (RCTs) for BD to determine the PI of the various pharmacological agents for BD.
  
  
  RESULTS
  We found support from naturalistic studies that bipolar patients with a predominantly depressive polarity are more likely to be treated with an antidepressive stabilization package, while BD patients with a manic-predominant polarity are more frequently treated with an antimanic stabilization package. Furthermore, predominantly manic BD patients received therapeutic regimens with a higher mean PI. The calculated PI varied from 0.4 (for lamotrigine) to 12.1 (for aripiprazole).
  
  
  CONCLUSIONS
  This review supports the clinical relevance of predominant polarity as a course specifier for BD. Future studies should investigate the role of baseline, predominant polarity as an outcome predictor of BD maintenance RCTs.
authors.affiliation: Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil (Dr Carvalho); Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX (Dr Quevedo); Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil (Dr Quevedo); Departments of Psychiatry and Pharmacology and Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON, Canada (Dr McIntyre); Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil (Dr Souza); 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Thessaloniki, Greece (Dr Fountoulakis); IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia (Dr Berk); Department of Psychiatry, the Florey Institute of Neuroscience and Mental Health, and Orygen Youth Health Research Centre, University of Melbourne, Parkville, Australia (Dr Berk); Department of Psychiatry, Medical School, University of Ioaninna, Ioaninna, Greece (Dr Hyphantis); Bipolar Disorders Unit, Clinical Institute of Neurosciences, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERSAM, Barcelona, Catalonia, Spain (Dr Vieta) andrefc7@terra.com.br.
authors.forename: Andre F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil (Dr Carvalho); Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX (Dr Quevedo); Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil (Dr Quevedo); Departments of Psychiatry and Pharmacology and Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON, Canada (Dr McIntyre); Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil (Dr Souza); 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Thessaloniki, Greece (Dr Fountoulakis); IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia (Dr Berk); Department of Psychiatry, the Florey Institute of Neuroscience and Mental Health, and Orygen Youth Health Research Centre, University of Melbourne, Parkville, Australia (Dr Berk); Department of Psychiatry, Medical School, University of Ioaninna, Ioaninna, Greece (Dr Hyphantis); Bipolar Disorders Unit, Clinical Institute of Neurosciences, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERSAM, Barcelona, Catalonia, Spain (Dr Vieta).
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.affiliation: Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil (Dr Carvalho); Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX (Dr Quevedo); Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil (Dr Quevedo); Departments of Psychiatry and Pharmacology and Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON, Canada (Dr McIntyre); Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil (Dr Souza); 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Thessaloniki, Greece (Dr Fountoulakis); IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia (Dr Berk); Department of Psychiatry, the Florey Institute of Neuroscience and Mental Health, and Orygen Youth Health Research Centre, University of Melbourne, Parkville, Australia (Dr Berk); Department of Psychiatry, Medical School, University of Ioaninna, Ioaninna, Greece (Dr Hyphantis); Bipolar Disorders Unit, Clinical Institute of Neurosciences, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERSAM, Barcelona, Catalonia, Spain (Dr Vieta).
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
authors.affiliation: Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil (Dr Carvalho); Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX (Dr Quevedo); Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil (Dr Quevedo); Departments of Psychiatry and Pharmacology and Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON, Canada (Dr McIntyre); Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil (Dr Souza); 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Thessaloniki, Greece (Dr Fountoulakis); IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia (Dr Berk); Department of Psychiatry, the Florey Institute of Neuroscience and Mental Health, and Orygen Youth Health Research Centre, University of Melbourne, Parkville, Australia (Dr Berk); Department of Psychiatry, Medical School, University of Ioaninna, Ioaninna, Greece (Dr Hyphantis); Bipolar Disorders Unit, Clinical Institute of Neurosciences, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERSAM, Barcelona, Catalonia, Spain (Dr Vieta).
authors.forename: Márcio G
authors.initials: MG
authors.lastname: Soeiro-de-Souza
authors.affiliation: Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil (Dr Carvalho); Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX (Dr Quevedo); Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil (Dr Quevedo); Departments of Psychiatry and Pharmacology and Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON, Canada (Dr McIntyre); Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil (Dr Souza); 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Thessaloniki, Greece (Dr Fountoulakis); IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia (Dr Berk); Department of Psychiatry, the Florey Institute of Neuroscience and Mental Health, and Orygen Youth Health Research Centre, University of Melbourne, Parkville, Australia (Dr Berk); Department of Psychiatry, Medical School, University of Ioaninna, Ioaninna, Greece (Dr Hyphantis); Bipolar Disorders Unit, Clinical Institute of Neurosciences, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERSAM, Barcelona, Catalonia, Spain (Dr Vieta).
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Fountoulakis
authors.affiliation: Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil (Dr Carvalho); Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX (Dr Quevedo); Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil (Dr Quevedo); Departments of Psychiatry and Pharmacology and Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON, Canada (Dr McIntyre); Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil (Dr Souza); 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Thessaloniki, Greece (Dr Fountoulakis); IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia (Dr Berk); Department of Psychiatry, the Florey Institute of Neuroscience and Mental Health, and Orygen Youth Health Research Centre, University of Melbourne, Parkville, Australia (Dr Berk); Department of Psychiatry, Medical School, University of Ioaninna, Ioaninna, Greece (Dr Hyphantis); Bipolar Disorders Unit, Clinical Institute of Neurosciences, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERSAM, Barcelona, Catalonia, Spain (Dr Vieta).
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.affiliation: Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil (Dr Carvalho); Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX (Dr Quevedo); Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil (Dr Quevedo); Departments of Psychiatry and Pharmacology and Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON, Canada (Dr McIntyre); Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil (Dr Souza); 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Thessaloniki, Greece (Dr Fountoulakis); IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia (Dr Berk); Department of Psychiatry, the Florey Institute of Neuroscience and Mental Health, and Orygen Youth Health Research Centre, University of Melbourne, Parkville, Australia (Dr Berk); Department of Psychiatry, Medical School, University of Ioaninna, Ioaninna, Greece (Dr Hyphantis); Bipolar Disorders Unit, Clinical Institute of Neurosciences, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERSAM, Barcelona, Catalonia, Spain (Dr Vieta).
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Hyphantis
authors.affiliation: Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil (Dr Carvalho); Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX (Dr Quevedo); Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil (Dr Quevedo); Departments of Psychiatry and Pharmacology and Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON, Canada (Dr McIntyre); Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil (Dr Souza); 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Thessaloniki, Greece (Dr Fountoulakis); IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia (Dr Berk); Department of Psychiatry, the Florey Institute of Neuroscience and Mental Health, and Orygen Youth Health Research Centre, University of Melbourne, Parkville, Australia (Dr Berk); Department of Psychiatry, Medical School, University of Ioaninna, Ioaninna, Greece (Dr Hyphantis); Bipolar Disorders Unit, Clinical Institute of Neurosciences, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERSAM, Barcelona, Catalonia, Spain (Dr Vieta).
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D018692:Antimanic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents
keywords: bipolar disorder; maintenance; polarity index; predominant polarity; treatment