Treating Nonspecific Anxiety and Anxiety Disorders in Patients With Bipolar Disorder: A Review

Objective: To review the evidence for treating anxiety in patients with bipolar disorder.

Data Sources: A literature search from 1950 to week 1 of August 2009 was conducted via OVID and the National Institutes of Health’s clinical trials online databases. Search terms included anxiety, anxiety disorders, bipolar disorder, panic disorder, generalized anxiety disorder, social phobia, social anxiety, obsessive compulsive disorder, specific phobia, posttraumatic stress disorder, and treatment. Reference lists of identified articles were also searched.

Study Selection: Fourteen treatment studies that included patients with bipolar disorder with either a syndrome-defined anxiety disorder or nonspecific anxiety were selected.

Data Extraction: Sample size, bipolar disorder subtype, comorbid anxiety disorders, baseline anxiety, treatment interventions, and outcome measurements were extracted.

Results: The majority of studies focus on treating anxiety disorders and nonspecific anxiety occurring during bipolar mood episodes. Studies of syndrome-defined anxiety disorders reveal that risperidone monotherapy did not separate from placebo and that olanzapine was superior to lamotrigine when used to augment lithium treatment. A study using open-label divalproex sodium and an uncontrolled study of group cognitive-behavioral therapy both suggest some benefit from these treatments in patients with bipolar disorder with panic disorder.

Studies of nonspecific anxiety reveal some benefit for divalproex, quetiapine, olanzapine, and olanzapine-fluoxetine combination. Weaker evidence supports the use of Mindfulness-Based Cognitive Therapy, and observational studies suggest potential efficacy for gabapentin and valproate.

Conclusions: Nonspecific anxiety symptoms occurring during a mood episode improve with treatment of the mood disturbance, though divalproex may be the mood stabilizer of choice for anxious patients with bipolar disorder. Given their reduced risk for manic induction and episode cycling, psychotherapy, benzodiazepines, and certain atypical antipsychotics are recommended for treatment of anxiety disorders present in patients with bipolar disorder not currently experiencing an acute mood episode.

J Clin Psychiatry

Submitted: November 4, 2009; accepted January 11, 2010.

Online ahead of print: November 16, 2010 (doi:10.4088/JCP.09r05815gre).

Corresponding author: Jeffrey J. Rakofsky, MD, Department of Psychiatry and Behavioral Sciences, Mood and Anxiety Disorders Program/Bipolar Disorders Clinic, Emory University, 1256 Briarcliff Rd, 3rd Floor, Atlanta, GA 30306 (Jrakofs@emory.edu).