Comorbidity in Bipolar Disorder
The Complexity of Diagnosis and Treatment

The central tenet of clinical comorbidity, the occurrence of 2 syndromes in the same patient, presupposes that they are distinct categorical entities. By this definition, 2 or more coexisting syndromes do not negate one another, nor paradoxically does this coexistence negate the potential for one to influence the course, outcome, and treatment response of the other. Isolating a syndrome by characterizing it through a unique pathogenic process allows for diagnostic fidelity even while acknowledging overlapping phenotypes.

Bipolar disorder (BPD) is highly prevalent and heterogeneous. Its increasing complexity is often caused by the presence of comorbid conditions, which have become the rule rather than the exception. Lifetime prevalence of psychiatric comorbidity has been reported in community and clinical studies. Most (95%) of the respondents with BPD in the National Comorbidity Survey met criteria for 3 or more lifetime psychiatric disorders.¹ In a Stanley Foundation Bipolar Treatment Outcome Network study of almost 300 patients, 65% met DSM-IV criteria for at least 1 comorbid Axis I disorder.²

Analogous to models in medicine (eg, cardiovascular disease), BPD incorporates psychiatric and medical comorbidities (Table) whose simultaneous treatment is equally pressing to the core mood disturbance.³ Checks and balances must be used to address the distressing comorbid condition (eg, anxiety) whose treatment with an SSRI or serotonin norepinephrine reuptake inhibitor (SNRI) may catalyze a round of mood cycling in an otherwise stable patient; a greater degree of protection via mood stabilizers may be warranted in such an individual to reduce this possibility.

Overall, the presence of comorbidities in BPD has negative prognostic implications for psychological health and for medical well-being and longevity.^4-6 The most common comorbid conditions are reviewed below to help guide the clinician through this diagnostic maze and associated treatment considerations.

Anxiety

The well-established relationship between anxiety symptoms and major depressive disorder usually forges a more complicated course, something that is equally, if not more, characteristic of bipolar depression.^7,8 Recent studies suggest that rates of anxiety in bipolar depression tend to exceed those in the general population.^1,9,10 In the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), lifetime prevalence for a comorbid anxiety disorder reached 51.2% while rates for a current anxiety disorder reached 30.5%; comorbid anxiety tended to be more common in patients with bipolar I disorder compared with bipolar II.¹¹

Anxiety may be interwoven into the fabric of syndromic bipolarity, may occur alongside it as a comorbid condition, and may occur in subsyndromal bipolar states as well.¹² Patients with BPD are at higher risk for many other anxiety subtypes, including generalized anxiety disorder, simple phobia, social phobia, obsessive-compulsive disorder, posttraumatic stress disorder, and panic disorder.^1,2 Of these, panic disorder appears to have the highest risk of comorbidity. Panic disorder also tends to cosegregate with BPD in families with high rates of BPD.¹³ Panic disorder and anxiety tend to be particularly manifest in bipolar mixed states, which echoes Emil Kraepelin’s description of mixed states as “anxious mania” or “excited depression” whereby the “mood is anxiously despairing.”^14,15 Mixed states tend to have an early onset and are associated with other risks including suicide and substance abuse.¹⁶