ANXIOUS–BIPOLAR COMORBIDITY: Diagnostic and Treatment Challenges

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… [The] problem with categorical models is that those who use them come to believe in them. Instead of realising that a categorical diagnosis is both provisional and hypothetical, the true believer reifies it.
GOLDBERG30

The term comorbidity indicates the presence of more than one disorder in a person in a given period of time.83 Therefore, in defining comorbidity rates, it is important to specify the period under investigation (i.e., current, lifetime, 1-year comorbidity). If it is not specified, comorbidity usually refers to a lifetime period, and this is the case in this article.

In psychiatric research, the advent of standardized operational criteria for the definition of discrete mental disorders and the introduction of diagnostic structured inteviews have prompted numerous studies on the frequency, nature, and implications of comorbidity.18, 83 The magnitude of comorbidity between anxiety and mood disorders, identified in community studies,56 demonstrates that the associations first observed in clinical settings could not be attributed merely to bias arising from an overrepresentation of comorbid cases in treatment settings.

In discussing anxious–bipolar comorbidity, this article focuses on panic-agoraphobic (PD), social phobic (SP), and obsessive-compulsive disorders (OCD). Excluded from this discussion is generalized anxiety disorder, for which there exists increasing evidence of a shared common diathesis with unipolar major depression.20, 40 Frequent comorbidity among PD, SP, OCD, and mood disorders has been widely reported in clinical18, 53, 54 and epidemiologic studies.42, 47, 68 Much of this research, however, has been essentially limited to the co-occurrence of anxiety disorders and unipolar depression. This narrow viewpoint is being increasingly challenged, and the available evidence strongly suggests that comorbidity between anxiety and mood disorders—conventionally conceived as the relationship between anxiety and depression—extends into the domain of bipolar spectrum disorders.62

Section snippets

EXTENT OF ANXIETY–BIPOLAR SPECTRUM COMORBIDITY

The occurrence of bipolar features in patients with anxiety disorders is counterintuitive, but evidence for such a relationship has come from both epidemiologic and clinical studies. In the National Comorbidity Survey, the reported risk of comorbid PD and SP is higher in bipolar disorder (odds ratios of 11.0 versus 4.6) compared to unipolar disorder (odds ratios of 7.0 versus 3.6). Chen and Dilsaver,23 analyzing the epidemiologic catchment area (ECA) database, reported lifetime rates of OCD

IMPACT OF ANXIOUS–BIPOLAR COMORBIDITY ON COURSE

It follows that the bipolar-unipolar distinction in affective comorbidity has relevant clinical implications as far as other concomitant disorders, clinical features, and course of anxiety disorders are concerned. In the aforementioned study on 342 OCD patients,61 the authors observed that when OCD was associated with bipolar disorder, there proved also to be an increased lifetime and intraepisode comorbidity with PD-agoraphobia. Moreover, bipolar OCD patients evidenced more frequently than

BIPOLAR II AND EPISODIC OBSESSIVE-COMPULSIVE DISORDER

The authors published a study of 135 OCD patients with an illness duration of at least 10 years divided on the basis of course: episodic (27.4%) versus continuous (72.6%). Multivariate stepwise discriminant analysis on clinical and familial characteristics revealed a positive correlation between episodic course, family history for mood disorders, lifetime comorbidity for panic and bipolar II disorders, late age at onset, and negative correlation with generalized anxiety disorder. These data are

FAMILIAL-GENETIC IMPLICATIONS OF BIPOLAR II–PANIC COMORBIDITY

In a more practical vein, multiple comorbidity and consequent symptomatologic instability appear as the most relevant clinical implications of anxious–bipolar presentations. Many patients receive diagnoses of borderline, narcissistic, or histrionic personality disorders, which may rob them of the opportunity to receive adequate pharmacologic treatment. Increased risk of mixed states,73 suicidal behavior, and alcohol and drug abuse60 are other important prognostic possibilities. Further

TEMPORAL RELATIONSHIPS BETWEEN ANXIETY DISORDERS AND HYPOMANIA

Available data on temporal relationships between anxiety and mood disorders are currently limited almost exclusively to major depression, and there does not seem to be a consistent pattern. In some studies, depression was found to be more likely to precede anxiety disorders,19, 25, 70 whereas other investigators reported the opposite tendency.76 The latter is in accordance with the hypothesis that depression, at least in some cases, may be secondary to anxiety disorders. The complexity of the

ATYPICAL DEPRESSION, INTERPERSONAL SENSITIVITY, CYCLOTHYMIA, AND BORDERLINE PERSONALITY

In exploring the putative temperamental foundations of comorbidity between anxiety and mood disorders, atypical depression represents an intriguing challenge. The rubric atypical depression defines a large subset of depressive states, in which mood and anxiety disorders are commonly coexisting, characterized by reactive mood; a pattern of stable interpersonal sensitivity (exaggerated vulnerability to feeling hurt by criticism or rejection); and reverse vegetative symptoms, such as increased

TREATMENT CONSIDERATIONS

Although comorbidity between bipolar and anxiety disorders reported in this article is partly due to the fact that centers specializing in these illnesses are referred the most difficult patients in this realm, there remains the challenge of how best to treat them in the long-term. Anxiety disorders are usually treated with antidepressants, which, not infrequently, trigger hypomanic or mixed states in patients with bipolar diathesis.36, 48, 66, 80, 82 Some antimanic agents, such as classic

CONCLUSIONS

Although the relationship between anxiety and mood disorders has been conventionally limited to unipolar depression, clinical observations have revealed complex associations between anxiety and bipolar disorders. The frequent coexistence of anxiety and bipolar disorders (mainly bipolar II) has also been reported in epidemiologic samples12 and primary care settings,52 indicating that clinical referral bias is unlikely to be the main explanation for this phenomenon.

Symptomatologic instability,

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    Address reprint requests to Giulio Perugi, MD, Institute of Psychiatry, Via Roma 67, 56100, Pisa, Italy, e-mail: [email protected]

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