DEPRESSION AND ANXIETY 31:196–206 (2014) Review CO-OCCURRENCE OF ANXIETY AND BIPOLAR DISORDERS: CLINICAL AND THERAPEUTIC OVERVIEW Gustavo H. V´ azquez, M.D., Ph.D., 1,2∗ Ross J. Baldessarini, M.D., 1,3 and Leonardo Tondo, M.D., M.S. 1,3,4,5 Background: Anxiety commonly co-occurs with bipolar disorders (BDs), but the significance of such “co-morbidity” remains to be clarified and its optimal treatment adequately defined. Methods: We reviewed epidemiological, clinical, and treatment studies of the co-occurrence of BD and anxiety disorder through electronic searching of Pubmed/MEDLINE and EMBASE databases. Results: Nearly half of BD patients meet diagnostic criteria for an anxiety disorder at some time, and anxiety is associated with poor treatment responses, substance abuse, and disability. Reported rates of specific anxiety disorders with BD rank: panic ≥ phobias ≥ generalized anxiety ≥ posttraumatic stress ≥ obsessive-compulsive disorders. Their prevalence appears to be greater among women than men, but similar in types I and II BD. Anxiety may be more likely in depressive phases of BD, but relationships of anxiety phenomena to particular phases of BD, and their temporal distributions require clarification. Adequate treatment trials for anxiety syndromes in BD patients remain rare, and the impact on anxiety of treatments aimed at mood stabilization is not clear. Benzodiazepines are some- times given empirically; antidepressants are employed cautiously to limit risks of mood switching and emotional destabilization; lamotrigine, valproate, and second-generation antipsychotics may be useful and relatively safe. Conclusions: Anxiety symptoms and syndromes co-occur commonly in patients with BD, but “co-morbid” phenomena may be part of the BD phenotype rather than separate illnesses. Depression and Anxiety 31:196–206, 2014. C  2014 Wiley Periodicals, Inc. Key words: anxiety disorders; bipolar disorders; comorbidity; prevalence; treatment 1 International Consortium for Bipolar and Psychotic Disor- ders Research, Mailman Research Center, McLean Hospital, Belmont, Massachusetts 2 Department of Neuroscience, Palermo University, Buenos Aires, Argentina 3 Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 4 Lucio Bini Mood Disorder Centers, Cagliari, Italy 5 Lucio Bini Mood Disorder Centers, Rome, Italy Contract grant sponsor: Bruce J. Anderson Foundation. ∗ Correspondence to: Gustavo V´ azquez, Department of Neu- roscience, Palermo University, Sanchez de Bustamante 2167, 7mo “D”. CP 1425 Buenos Aires, Argentina. E-mail: gazquez@palermo.edu INTRODUCTION Bipolar disorders (BDs; types I and II), cyclothymic disorder, and proposed “bipolar spectrum” disorders with recurrent depression and relatively mild hypo- manic symptoms are episodic illnesses with high lev- els of morbidity and disability, despite use of available treatments. [1,2] Bipolar I and II disorders also carry sim- ilar, very high risks for suicide. [3] The broad range of pu- tative bipolar-like disorders occurs internationally at an estimated lifetime prevalence of up to 10% of the general population. [1,4,5] BDs of types I and II are among leading Received for publication 16 October 2013; Revised 12 January 2014; Accepted 18 January 2014 DOI 10.1002/da.22248 Published online in Wiley Online Library (wileyonlinelibrary.com). C  2014 Wiley Periodicals, Inc.