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Comorbidity in Bipolar Disorder: Page 2 of 5

Comorbidity in Bipolar Disorder: Page 2 of 5

In general, anxiety tends to predict an earlier age at onset of BPD and results in a more complicated and severe disease course.2,11,17

Aside from an early onset, the parallels to bipolar mixed states include an increased incidence of suicide, psychotic features, substance abuse, panic comorbidity, and poor response to lithium.17 Anxiety and substance abuse are the most frequent lifetime comorbid disorders in BPD and the presence of comorbid anxiety further increases the likelihood of substance abuse.2,18,19 Rates of alcohol dependency can be up to 2-fold higher in patients with anxiety.11 The risk of suicide is increased in patients with bipolar depression and comorbid anxiety and/or substance abuse.20 Overall, the presence of anxiety in patients with BPD tends to amplify or intensify core bipolar symptoms or to aggravate other comorbid conditions. The course of the illness and response to treatment are also adversely affected.

Treatment approaches

There are relatively few studies and no randomized controlled trials that isolate pharmacological treatment strategies in bipolar patients with comorbid anxiety.21 Traditional bipolar treatments (such as lithium) tend to be less effective when anxiety coexists: combination therapy is often necessary in this setting.10 Anticonvulsants, including valproate, carbamazepine, lamotrigine, topiramate, gabapentin, and pregabalin, have been studied in anxiety conditions; there is limited controlled evidence to support the use of these agents in comorbid anxiety.22

The efficacy of antidepressant agents, including the SSRIs and SNRIs, has been extensively demonstrated in anxiety conditions. These agents are often used to manage anxiety conditions when comorbid with BPD.21 Although controversial, the use of these agents is widespread in bipolar depression and its associated comorbidities; rapid switching of moods may be more prominent in the face of early-onset bipolarity, anxiety comorbidity, and antidepressant activation.23

Therefore, the challenge in treating BPD comorbidities is to avoid exacerbating other elements within the comorbid symptom complex—especially the core mood disturbance.

Second-generation antipsychotic agents, including olanzapine, risperidone, and quetiapine, have shown direct or adjunctive benefits in the treatment of anxiety conditions; their additional role as mood stabilizers, with a relatively protective effect against bipolar mood switching, may be advantageous for the patient with comorbidities.22,24 The clinician’s task is to treat the comorbid anxiety condition (along with its heightened attendant risks) while first insulating the patient against further destabilization of the primary mood disorder.

Substance use disorder

As noted, the added burden of substance use disorder (SUD) to comorbid anxiety in BPD substantially raises the risk profile of the disorder while complicating treatment options. Comorbid SUD was found to exist in 61% of patients with bipolar I disorder and in 48% of bipolar II patients in the Epidemiologic Catchment Area. These rates are much higher than the rate of 10% to 20%, respectively, in patients without the SUD comorbidity and the highest rate within any psychiatric disorder.25

Reflecting findings from other studies, the most common SUD appears to be alcohol abuse and dependence.26,27 Research from the Stanley Foundation Bipolar Network found that the lifetime prevalence rate of alcohol abuse or dependence was 49% for bipolar men and 29% for bipolar women. Women with BPD seemed to be at higher risk for alcoholism than women in the general population.28,29 Whereas alcoholism in bipolar men may have more of a genetic influence, in women the risk may be more of an acquired burden related to depressive illness.29 Depressive symptoms are especially common in female bipolar patients with comorbid alcohol abuse.30


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