Antipsychotics. Second-line pharmacotherapy for anxiety becomes first line in bipolar patients with anxiety disorder. Specifically, studies of atypical antipsychotics such as quetiapine(Drug information on quetiapine) have shown that these agents reduce anxiety in social anxiety disorder and GAD.13 Although the patients recruited for these studies did not have a mood disorder, quetiapine monotherapy (300 to 600 mg/d) significantly reduced anxiety and depressive symptoms in patients with bipolar disorder.14 Quetiapine may be of questionable benefit in patients with PTSD. While open-label, uncontrolled studies support use of this agent for PTSD, there were more early discontinuations with quetiapine than with prazosin and, thus, long-term benefit was lost.15,16
At doses below 4 mg/d, risperidone(Drug information on risperidone) does not appear to be helpful for the treatment of anxiety symptoms in patients with bipolar disorder.17 Augmentation of mood stabilizer treatment with risperidone was also ineffective.18
The olanzapine(Drug information on olanzapine)/fluoxetine combination is approved for the treatment of bipolar depression. It may be useful in the treatment of comorbid anxiety as well. However, olanzapine alone has minimal effect.19
Anticonvulsants. There are no randomized controlled trials that examine the use of anticonvulsants for the anxiety component in bipolar patients. However, anticonvulsants appear to have a small effect in reducing anxiety. In a small open-label study, more than 40% of patients with GAD (without mood disturbance) saw at least a 50% improvement in symptoms with valproate(Drug information on valproate).20 Similarly, modest benefit was seen in a group of patients with PTSD who received divalproex in an open-label study.21 Unfortunately, when the effect size is small in open-label studies, it suggests that results of blinded studies are likely to be negative.
Alternative agents. Gabapentin(Drug information on gabapentin) has been shown to be effective for social phobia in a randomized placebo-controlled trial.22 This effect on anxiety is probably what underlies the early reports of gabapentin efficacy in bipolar disorder. The related anticonvulsant, pregabalin(Drug information on pregabalin), is also useful in social phobia and GAD at higher doses (approximately 600 mg/d).23 These agents have not been studied in bipolar patients with anxiety but are probably safe to use in this patient population.
Benzodiazepines are clearly effective in many different types of anxiety disorders. However, their use is problematic, and these agents must be prescribed cautiously.
Nonpharmacological approaches. Psychotherapy may be the treatment of choice for patients with anxiety disorders in general. For example, CBT is as effective as medications in the acute management of panic disorder. Unlike medications, the effect lasts long after treatment has ended.24 However, there are no randomized controlled trials for psychotherapy in bipolar patients who have comorbid anxiety. Nonetheless, therapies such as CBT and relaxation training may be useful in bipolar patients.25
Summary
Anxiety disorders are commonly comorbid with bipolar disorder and are responsible for much of the morbidity associated with this condition. Treatment of anxiety can be a challenge, since the mainstay of treatment—serotonergic antidepressants—may adversely affect the course of bipolar disorder. Although other agents are available, there is a dearth of information on the outcomes of anxiety treatment for bipolar patients.
Clinicians generally must apply the results of studies performed in patients who have anxiety disorders without mood disturbance to their bipolar patients. This is a reasonable practice, although it is far from ideal. The field needs more high-quality research studies to define the best practice options in treating patients with comorbid anxiety and bipolar disorders.
