Comorbidity of Bipolar and Panic Disorders and Its Consequences
By Dean F. MacKinnon, MD |
March 1, 2007
Dr MacKinnon is associate professor in the department
of psychiatry at Johns Hopkins University
School of Medicine. He reports that he
has no conflicts of interest concerning the subject
matter of this article.
Evidence for the model
Glucocorticoids and related neurohormones, as well as monoaminergic neurotransmitters, have both direct and indirect effects on neuronal plasticity—some positive, some negative. For example, cortisol is known to inhibit the growth of new neurons in the hippocampus in humans41 and, based on animal studies,42 presumably in the amygdala as well. High cortisol tone, whether a primary deficit, a secondary result of the stress response, or externally induced by prednisone(Drug information on prednisone), may thus result in deficient cellular substrate in the amygdala (and possibly in the hippocampus) with which to form and revise conditioned responses. Factors that diminish available serotonin (such as low-functioning alleles of SERT) also diminish the salutary effects of brain-derived neurotrophic factor,43 again impinging on plasticity and emotional conditioning.
Treatment of panic disorder and bipolar disorder
In clinical settings, mania and depression are generally more pressing clinical problems than panic and thus more likely to receive therapeutic attention44; however, patients suffer severely from panic attacks. Treatment of panic disorder using conventional methods is perilous in the context of bipolar disorder. In patients with bipolar disorder, it appears that antidepressants commonly used to prevent panic attacks may exacerbate cycling.45 On the other hand, drugs used to relieve anxiety when panic occurs (eg, benzodiazepines) may become abused or foster dependency in a population of patients whose mood disorder puts them at high risk for chemical dependency.46 Although there is a role for these treatments, they must be used with caution. One possible solution would be using medications proved effective for both disorders independently. However, the only antimanic agent with reported efficacy in controlling panic is divalproex.47
Since there are no placebo-controlled trials of treatment for panic attacks with bipolar disorder,48 it is prudent to make mood stabilization the first priority. There is reason to hope that one can address both problems with 1 treatment. If the root of both problems is a deficit in emotional conditioning, as described in the model, the same neurotrophic factors most useful in treating bipolar disorder, such as lithium(Drug information on lithium),49 may have benefit in treating panic disorder in the context of bipolar disorder. At least one study has found that anxiety comorbidity increases the likelihood of bipolar response to lithium relative to anticonvulsants,50 while in another, panic comorbidity was a robust predictor of bipolar response to lamotrigine(Drug information on lamotrigine).51
When patients who are acutely manic or depressed demand treatment for ongoing panic attacks, it is reasonable to offer lithium or other antimanic agents supplemented by benzodiazepines as needed to suppress attacks when they emerge. Because of the risk of habituation, it is prudent to replace benzodiazepines with definitive treatment of panic attacks if they persist after the mood is stabilized.
Thinking beyond pharmacology, if one is open to the idea that the distress from panic and bipolar disorders is often caused as much by their residual, conditioned effects as by their acute symptoms, then one will keep in focus the goal of improving a patient's global functioning through rehabilitative, or reconditioning, therapies while optimizing the pharmacological regimen.
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