Bipolar disorder is a clinically challenging condition. In addition to the multiple mood states that patients can experience, the illness is frequently associated with multiple comorbid medical and psychiatric conditions. Bipolar disorder can best be understood as a family of related disorders that share core features of mood or affective variation, impulsivity, propensity toward substance abuse, and predisposition to other psychiatric conditions.1 Most patients who have bipolar disorder have a coexisting anxiety disorder.2 These include generalized anxiety disorder (GAD), social phobia, panic disorder, and PTSD.2 Anxiety disorders, by themselves or in combination with a mood disorder, are associated with an increased risk of suicide and psychosocial dysfunction.
The prevalence of comorbid bipolar and anxiety disorders (with the exception of simple phobias) is high in youths. For example, it is at least twice as high as comorbid anxiety and disruptive behavior disorders. GAD and separation anxiety are the anxiety disorders most commonly associated with bipolar disorder. In children with type I bipolar disorder, comorbid anxiety predicted greater dysfunction, manifested by earlier onset of bipolar disorder and more frequent psychiatric hospitalizations.
A comorbid anxiety disorder in bipolar patients greatly complicates the presentation, the interpretation of symptoms, and the treatment of bipolar disorder, and it negatively alters the prognosis.
Anxiety disorders comorbid with bipolar disorder
Panic disorder. In the Epidemiologic Catchment Area (ECA) study of the early 1990s, 21% of patients with bipolar disorder had comorbid panic disorder. This is a 26-fold higher incidence than in the general population.3 Panic disorder and bipolar disorder may share a special relationship with each other. A study of bipolar probands and their siblings found that panic disorder travels with bipolar disorder exclusively and rarely occurs independently of bipolar disorder.4 This unique relationship may be mediated by a genetic predisposition that resides in chromosome 18.5
Obsessive-compulsive disorder (OCD). In both the ECA study and the more recent National Comorbidity Survey, the incidence of OCD was 10-fold greater in bipolar patients than the general population.2,6 The risk of OCD is greater in family members of bipolar probands, which suggests a familial or genetic association. However, episodic obsessive-compulsive symptoms may simply be a variant of how bipolar disorder is expressed and not a true comorbidity. Either way, the relationship between bipolar disorder and OCD frequently has its origins in childhood and yields a greater burden of anxiety symptoms.
Posttraumatic stress disorder. PTSD may have a special relationship with bipolar disorder because both mania and depression may be perceived as traumatic or because events in the course of the illness may increase the risk of severe traumatic events.7 Consequently, PTSD may be over 6 times more likely to occur in bipolar patients than in the general population.2 The co-occurrence of PTSD with bipolar disorder lowers quality of life, increases rapid cycling and suicide attempts, and reduces the likelihood of remaining well.8
Social anxiety. Despite frequent grandiose or expansive behavior during mania, most patients with bipolar disorder actually suffer from social phobia—a potential contributor to dysfunction in bipolar patients.2
Comorbidity and outcomes
The combined burden of bipolar and anxiety disorders nearly always has a deleterious effect on outcomes.9 Comorbid illness is associated with marked increases in symptom burden that includes greater risk of psychosis, earlier age at onset of psychiatric symptoms, worse treatment response and more treatment resistance, impaired quality of life, increased suicidal ideation and actions, and increased substance abuse.9 Whether the poor prognosis is due to an interaction between the two conditions or to the additive burden is unknown.
Accurate diagnosis of comorbid anxiety disorder and bipolar disorder is important. The cost of care increases when a bipolar patient is treated exclusively for anxiety because of a misdiagnosis. Once a dual diagnosis has been made, effective treatment may be challenging.
Treatment of anxiety disorders
Antidepressants. Serotonergic antidepressants have shown efficacy as acute and prophylactic treatment for all anxiety disorders and are considered first-line agents.10 This is generally true whether the serotonergic effect is alone, is associated with noradrenergic reuptake inhibition, or is obtained by reuptake or monoamine oxidase inhibition.11 Non-serotonergic antidepressants (specifically bupropion) do not appear to be particularly effective.
In bipolar patients, antidepressants have the potential to induce mania, destabilize the course of illness by increasing bouts of mania and depression, and induce a chronic depressive state.11 The risk of these complications is higher if the bipolar patient receives antidepressants during periods of euthymia or over long periods.11 Use of antidepressants specifically for anxiety in bipolar patients would be expected to be associated with more complications. This may account for the observation that pharmacological treatments of comorbidities, such as anxiety disorders, in bipolar patients are generally underused, whereas psychosocial services are used more frequently by patients with coexisting anxiety disorders.12
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