Clinical News & Knowledge: Bipolar Disorder
August 1, 2007
Psychiatric Times.
No. 5
Antipsychotics in the Treatment of Comorbid Anxiety in Bipolar Disorder
Keming Gao, MD, PhD
Dr Gao is assistant professor in the Department of Psychiatry at Case Western Reserve University School of Medicine and University Hospitals Case Medical Center in Cleveland. He reports that he receives grant support and/or honoraria from AstraZeneca, GlaxoSmithKline, and Abbott Laboratories; and he is on the speakers' bureau for AstraZeneca.
IS USE OF ANTIPSYCHOTICS FOR ANXIETY JUSTIFIED?
Good quality data for antipsychotics in the treatment of anxiety disorder are limited to trifluoperazine. It is the only antipsychotic that has been approved by the FDA for the short-term treatment of primary GAD. At present, the use of other antipsychotics in primary or comorbid anxiety disorder should be considered off-label.
Although adjunctive atypical antipsychotics appeared to be useful in refractory OCD or chronic PTSD, and monotherapy appeared useful in bipolar depression with anxiety symptoms, the results were confounded by small sample sizes or lack of systematic assessment of the nature of anxiety. Therefore, caution should be followed in the use of these agents for primary or comorbid anxiety symptoms/disorders.
Anxiety is a very complicated phenomenon. So far, there is no single agent that can be used effectively and safely by all patients. A systemic consideration of the risks and benefits of antidepressants, antipsychotics, benzodiazepines, and other agents should be carried out before the initiation of treatment.
SPECIAL CONSIDERATIONS
Since there are no efficacy data supporting the use of any agent in the treatment of comorbid anxiety disorder in patients with bipolar disorder, attention should be paid to the potential adverse effects. For antidepressants, in addition to the common adverse effects experienced by patients who are not bipolar, patients with bipolar disorder may experience treatment-related mania/hypomania. To minimize this risk, adequate treatment with a mood stabilizer is essential when an antidepressant is indicated. Benzodiazepine use in patients with bipolar disorder and a history of substance use disorder, especially current substance use disorder, should be carefully documented and monitored because of the abuse/dependence potential of benzodiazepines. Using an agent with a long half-life may minimize the risk of abuse or withdrawal.
Although antipsychotics do not pose a risk for mania/hypomania or abuse/ dependence with bipolar disorder, the burden of potential adverse effects cannot be ignored. The lower prevalence of atypical antipsychotic-induced extrapyramidal symptoms (EPS) compared with typical agents has led clinicians to prioritize their use, but atypical antipsychotic-induced EPS do occur in the treatment of schizophrenia or acute mania. More important, there is evidence, although inconsistent, that bipolar disorder is a risk factor for EPS. Similarly, metabolic abnormalities have been reported in patients with schizophrenia who are treated with typical or atypical antipsychotics. Therefore, patients treated with antipsychotics should be closely monitored for metabolic syndrome and movement disorders regardless of the drug classes.
CONCLUSION
There is no pharmacological study designed for a cohort of patients with bipolar disorder and a specific comorbid anxiety disorder. Low-dose trifluoperazine was well tolerated and superior to placebo in the short-term treatment of primary GAD.27 Adjunctive therapy with an atypical antipsychotic (risperidone, olanzapine, or quetiapine) was superior to placebo in the treatment of refractory OCD or chronic PTSD, but these studies were confounded by small sample sizes.
The preliminary data on olanzapine and quetiapine in reducing anxiety symptoms in patients with bipolar depression suggest that this class of agents may have promise for the treatment of comorbid anxiety disorders with bipolar disorder. There exists an urgent need for large randomized controlled trials of the various atypical antipsychotic agents in patients who have bipolar disorder and comorbid specific anxiety disorders, especially in those with substance use disorder.
- Hirschfeld RM, Weisler RH, Raines SR, Macfadden W; for the BOLDER Study Group. Quetiapine in the treatment of anxiety in patients with bipolar I or II depression: a secondary analysis from a randomized, double-blind, placebo-controlled study. J Clin Psychiatry.2006;67:355-362.
- Mendels J, Krajewski TF, Huffer V, et al. Effective short-term treatment of generalized anxiety disorder with trifluoperazine. J Clin Psychiatry. 1986;47:170-174.
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