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 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(Drug information on 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(Drug information on 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(Drug information on valproate), carbamazepine(Drug information on carbamazepine), lamotrigine(Drug information on lamotrigine), topiramate(Drug information on topiramate), gabapentin(Drug information on gabapentin), and pregabalin(Drug information on 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(Drug information on risperidone), and quetiapine(Drug information on 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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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