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World J Biol Psychiatry. 2018 Feb;19(1):2-58. doi: 10.1080/15622975.2017.1384850. Epub 2017 Nov 3.

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Acute and long-term treatment of mixed states in bipolar disorder.

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a Institute of Neuroscience , Newcastle University , Newcastle upon Tyne , UK.
b Paracelsus Medical University , Nuremberg , Germany.
c Zentrum für Psychiatrie Weinsberg , Klinikum am Weissenhof , Weinsberg , Germany.
d Bipolar Disorders Programme, Institute of Neuroscience , Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM , Barcelona , Catalonia , Spain.
e Department of Psychiatry , University of Oxford, Warneford Hospital , Oxford , UK.
f Dept. of Psychiatry , University of Texas Health Science Center , San Antonio , TX , USA.
g Psychiatric Research Unit, Psychiatry , Aalborg University Hospital , Aalborg , Denmark.
h Clinical Department of Medicine , Aalborg University , Aalborg , Denmark.
i Department of Psychiatry , Hospital Ste. Marguerite , Marseille , France.
j Department of Psychiatry , University of British Columbia , Vancouver , BC , Canada.
k Department for Therapy of Mental Disorders , Moscow Research Institute of Psychiatry , Moscow , Russia.
l Department of Psychiatry and Psychotherapy , Ludwigs-Maximilian University , Munich , Germany.
m Department of Psychiatry and Psychotherapy , Medical University of Vienna , Vienna , Austria.



Although clinically highly relevant, the recognition and treatment of bipolar mixed states has played only an underpart in recent guidelines. This WFSBP guideline has been developed to supply a systematic overview of all scientific evidence pertaining to the acute and long-term treatment of bipolar mixed states in adults.


Material used for these guidelines is based on a systematic literature search using various data bases. Their scientific rigour was categorised into six levels of evidence (A-F), and different grades of recommendation to ensure practicability were assigned. We examined data pertaining to the acute treatment of manic and depressive symptoms in bipolar mixed patients, as well as data pertaining to the prevention of mixed recurrences after an index episode of any type, or recurrence of any type after a mixed index episode.


Manic symptoms in bipolar mixed states appeared responsive to treatment with several atypical antipsychotics, the best evidence resting with olanzapine. For depressive symptoms, addition of ziprasidone to treatment as usual may be beneficial; however, the evidence base is much more limited than for the treatment of manic symptoms. Besides olanzapine and quetiapine, valproate and lithium should also be considered for recurrence prevention.


The concept of mixed states changed over time, and recently became much more comprehensive with the release of DSM-5. As a consequence, studies in bipolar mixed patients targeted slightly different bipolar subpopulations. In addition, trial designs in acute and maintenance treatment also advanced in recent years in response to regulatory demands.


Current treatment recommendations are still based on limited evidence, and there is a clear demand for confirmative studies adopting the DSM-5 specifier with mixed features concept.


Mixed states; acute treatment; antidepressants; antipsychotics; bipolar disorder; electroconvulsive therapy; guidelines; maintenance treatment; mood stabiliser; pharmacotherapy

[Indexed for MEDLINE]

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