Comorbidity in Bipolar Disorder

The Complexity of Diagnosis and Treatment

By Doron Sagman, MD and Mauricio Tohen, MD | March 23, 2009

Dr Sagman is staff psychiatrist, Toronto East General Hospital, Toronto, and associate vice-president, clinical research, Eli Lilly Canada Inc, and Dr Tohen is Distinguished Lilly Scholar for Neurosciences, Lilly Research Laboratories, Indianapolis. The authors report that they have no other conflicts of interest concerning the subject matter of this article.

In This Special Report:

Schizophrenia With Obsessive-Compulsive Disorder, by Alexandra Bottas, MD

Psychiatric Comorbidity in Persons With Dementia, by Denis Shub, MD and Mark E. Kunik, MD, MPH

Diagnosing Comorbid Psychiatric Conditions, by Johnny L. Matson, PhD and Daniene Neal

Development of a Dual Disorders Program, by Mark D. Green, MD

Comorbidity in Bipolar Disorder, by Doron Sagman, MD and Mauricio Tohen, MD

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(Drug information on 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.^7,8Recent studies suggest that rates of anxiety in bipolar depression tend to exceed those in the general population.^1,9,10In 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.”^14,15Mixed states tend to have an early onset and are associated with other risks including suicide and substance abuse.¹⁶

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by john gergen | September 12, 2011 3:26 PM EDT

There are those of us who feel that the biological linage of bipolar disorders, particularly bipolar II and bipolar NOs with ADHD is very strong when an early onset (by age 21) is present. In support of this is the recognition that many of the positive or unusual features of the genetic basis of ADHD also occur in many bipolar patients. To begin with ADHD is a highly genetic disorder whose biological traits are equally present in both sexes and which from a trait point of view is essentially dominant in a traditional sense. About half of individuals with trait evidences actually become clinically cases of ADHD but confirmation of trait presence emerges in their offspring. Among common trait issues are an all-or-none memory, a strong push towards leadership or or its alternative (essentially social withdrawal.. a so-called leader or loner position, think Bill Clinton for instance), a hyperfocus in areas of interest with a push towards goal completion, an ability to think outside the box with creativity (think Steve Jobs for instance). Energy like other areas is usually bimodal, either high of low. The presence of bipolarity seems to push traited individuals into difficult to treat situations. Personality disorders such as borderline syndromes are not uncommon along with a propensity to develop anxiety difficulties and post-traumatic stress problems (presumably a function of altered fragments of overly embedded memories). One further argument around ADHD traits are whether on the whole they have a positive social value in cultures such as our which emphasizes the individual over the group and values creativity.
John Gergen, MD

by Bennie Bennie | July 08, 2010 12:39 PM EDT

When this writer read the following two papers it seemed that in principle the mystery of bipolar disorder was solved. It still seems that way:

The primacy of mania: A reconsideration of mood disorders

Athanasios Koukopoulos a,*, S. Nassir Ghaemi b

a Centro Lucio Bini, 42, Via Crescenzio, 00193 Rome, Italy

b Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Boston, MA, USA

Received 6 March 2008; received in revised form 7 July 2008; accepted 13 July 2008

Available online 11 September 2008

Biological Sensitivity to Context

Bruce J. Ellis1 and W. Thomas Boyce2

1John and Doris Norton School of Family and Consumer Science, University of Arizona, and 2College for

Interdisciplinary Studies and Faculty of Medicine, University of British Columbia