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Updated: May 23, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
The clinical management of bipolar disorder complexity using a stratified model
Gin S Malhi1, Danielle M Bargh, Emma Cashman
1CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, Sydney, New South Wales, Australia. gin.malhi@sydney.edu.au
Objective:
To provide practical and clinically meaningful treatment recommendations that amalgamate clinical and research considerations for several common, and as yet understudied, bipolar disorder complex presentations, within the framework of a proposed stratified model.
Methods:
A comprehensive search of the literature was undertaken using electronic database search engines (Medline, PubMed, Web of Science) using key words (e.g., bipolar disorder, anxiety, rapid cycling, and subsyndromal). All relevant randomised controlled trials were examined, in addition to review papers, meta-analyses, and book chapters known to the authors. The findings formed the basis of the treatment recommendations within this paper.
Results:
In light of the many broad presentations of bipolar disorder, a stratified model of bipolar disorder complexity was developed to facilitate consideration of the myriad of complexities that can occur during the longitudinal course of illness and the appropriate selection of treatment. Evidence-based treatment recommendations are provided for the following bipolar disorder presentations: bipolar II disorder, subsyndromal symptoms, mixed states, rapid cycling, comorbid anxiety, comorbid substance abuse, and for the following special populations: young, elderly, and bipolar disorder around the time of pregnancy and birth. In addition, some key strategies for countering treatment non-response and alternative medication recommendations are provided.
Conclusions:
Treatment recommendations for the more challenging presentations of bipolar disorder have historically received less attention, despite their prevalence. This review acknowledges the weaknesses in the current evidence base on which treatment recommendations are generally formulated, and additionally emphasises the need for high-quality research in this area. The stratified model provides a means for conceptualizing the complexity of many bipolar disorder presentations and considering their management.
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