The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm.
The current paper includes a systematic search of the literature, a detailed presentation of the results, and a grading of treatment options in terms of efficacy and tolerability/safety.



The PRISMA method was used in the literature search with the combination of the words 'bipolar,' 'manic,' 'mania,' 'manic depression,' and 'manic depressive' with 'randomized,' and 'algorithms' with 'mania,' 'manic,' 'bipolar,' 'manic-depressive,' or 'manic depression.' Relevant web pages and review articles were also reviewed.



The current report is based on the analysis of 57 guideline papers and 531 published papers related to RCTs, reviews, posthoc, or meta-analysis papers to March 25, 2016. The specific treatment options for acute mania, mixed episodes, acute bipolar depression, maintenance phase, psychotic and mixed features, anxiety, and rapid cycling were evaluated with regards to efficacy. Existing treatment guidelines were also reviewed. Finally, Tables reflecting efficacy and recommendation levels were created that led to the development of a precise algorithm that still has to prove its feasibility in everyday clinical practice.



A systematic literature search was conducted on the pharmacological treatment of bipolar disorder to identify all relevant random controlled trials pertaining to all aspects of bipolar disorder and graded the data according to a predetermined method to develop a precise treatment algorithm for management of various phases of bipolar disorder. It is important to note that the some of the recommendations in the treatment algorithm were based on the secondary outcome data from posthoc analyses.
3rd Department of Psychiatry, School of Medicine, Aristotle University, Thessaloniki, Greece; Department of Psychiatry, University of British Columbia, Mood Disorders Centre of Excellence, Djavad Mowafaghian Centre for Brain Health, Canada; Paracelsus Medical University, Salzburg, Austria; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; The Royal Institute of Mental Health Research, Department of Psychiatry, University of Ottawa, Ottawa, Canada; Department of Psychiatry and Psychotherapy, Medical University Vienna, MUV, AKH, Vienna, Austria; Psychiatric Department Ludwig Maximilians University, Munich, Germany.
Konstantinos N
KN
Fountoulakis
3rd Department of Psychiatry, School of Medicine, Aristotle University, Thessaloniki, Greece; Department of Psychiatry, University of British Columbia, Mood Disorders Centre of Excellence, Djavad Mowafaghian Centre for Brain Health, Canada; Paracelsus Medical University, Salzburg, Austria; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; The Royal Institute of Mental Health Research, Department of Psychiatry, University of Ottawa, Ottawa, Canada; Department of Psychiatry and Psychotherapy, Medical University Vienna, MUV, AKH, Vienna, Austria; Psychiatric Department Ludwig Maximilians University, Munich, Germany.
Lakshmi
L
Yatham
3rd Department of Psychiatry, School of Medicine, Aristotle University, Thessaloniki, Greece; Department of Psychiatry, University of British Columbia, Mood Disorders Centre of Excellence, Djavad Mowafaghian Centre for Brain Health, Canada; Paracelsus Medical University, Salzburg, Austria; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; The Royal Institute of Mental Health Research, Department of Psychiatry, University of Ottawa, Ottawa, Canada; Department of Psychiatry and Psychotherapy, Medical University Vienna, MUV, AKH, Vienna, Austria; Psychiatric Department Ludwig Maximilians University, Munich, Germany.
Heinz
H
Grunze
3rd Department of Psychiatry, School of Medicine, Aristotle University, Thessaloniki, Greece; Department of Psychiatry, University of British Columbia, Mood Disorders Centre of Excellence, Djavad Mowafaghian Centre for Brain Health, Canada; Paracelsus Medical University, Salzburg, Austria; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; The Royal Institute of Mental Health Research, Department of Psychiatry, University of Ottawa, Ottawa, Canada; Department of Psychiatry and Psychotherapy, Medical University Vienna, MUV, AKH, Vienna, Austria; Psychiatric Department Ludwig Maximilians University, Munich, Germany.
Eduard
E
Vieta
3rd Department of Psychiatry, School of Medicine, Aristotle University, Thessaloniki, Greece; Department of Psychiatry, University of British Columbia, Mood Disorders Centre of Excellence, Djavad Mowafaghian Centre for Brain Health, Canada; Paracelsus Medical University, Salzburg, Austria; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; The Royal Institute of Mental Health Research, Department of Psychiatry, University of Ottawa, Ottawa, Canada; Department of Psychiatry and Psychotherapy, Medical University Vienna, MUV, AKH, Vienna, Austria; Psychiatric Department Ludwig Maximilians University, Munich, Germany.
Allan
A
Young
3rd Department of Psychiatry, School of Medicine, Aristotle University, Thessaloniki, Greece; Department of Psychiatry, University of British Columbia, Mood Disorders Centre of Excellence, Djavad Mowafaghian Centre for Brain Health, Canada; Paracelsus Medical University, Salzburg, Austria; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; The Royal Institute of Mental Health Research, Department of Psychiatry, University of Ottawa, Ottawa, Canada; Department of Psychiatry and Psychotherapy, Medical University Vienna, MUV, AKH, Vienna, Austria; Psychiatric Department Ludwig Maximilians University, Munich, Germany.
Pierre
P
Blier
3rd Department of Psychiatry, School of Medicine, Aristotle University, Thessaloniki, Greece; Department of Psychiatry, University of British Columbia, Mood Disorders Centre of Excellence, Djavad Mowafaghian Centre for Brain Health, Canada; Paracelsus Medical University, Salzburg, Austria; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; The Royal Institute of Mental Health Research, Department of Psychiatry, University of Ottawa, Ottawa, Canada; Department of Psychiatry and Psychotherapy, Medical University Vienna, MUV, AKH, Vienna, Austria; Psychiatric Department Ludwig Maximilians University, Munich, Germany.
Siegfried
S
Kasper
3rd Department of Psychiatry, School of Medicine, Aristotle University, Thessaloniki, Greece; Department of Psychiatry, University of British Columbia, Mood Disorders Centre of Excellence, Djavad Mowafaghian Centre for Brain Health, Canada; Paracelsus Medical University, Salzburg, Austria; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; The Royal Institute of Mental Health Research, Department of Psychiatry, University of Ottawa, Ottawa, Canada; Department of Psychiatry and Psychotherapy, Medical University Vienna, MUV, AKH, Vienna, Austria; Psychiatric Department Ludwig Maximilians University, Munich, Germany.
Hans Jurgen
HJ
Moeller
D000328:Adult; D000465:Algorithms; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy*; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D017408:Guidelines as Topic / Q000592:standards*; D006801:Humans; D015201:Meta-Analysis as Topic; D011600:Psychopharmacology / Q000379:methods* / Q000592:standards*
D014150:Antipsychotic Agents
anticonvulsants; antidepressants; antipsychotics; bipolar depression; bipolar disorder; clinical trials; evidence-based guidelines; lithium; mania; mood stabilizers; treatment