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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EMajor depression is one of the most treatable medical illnesses. There is a strong correlation between anxiety symptoms and low rates of remission in patients with major depressive disorder (MDD) [Davidson JR, et al. \u003Cem\u003EDepress Anxiety\u003C\/em\u003E 2002; Silverstone PH et al. \u003Cem\u003EInt Clin Psychopharmacol\u003C\/em\u003E 2002]. This article discusses the role of anxiety in patients with major depressive disorder at the APA annual meeting.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EAnxiety Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EMood Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EMajor depression is one of the most treatable medical illnesses. However, it is the fourth-most disabling medical condition worldwide, and it is predicted that by 2020 it will be second only to ischemic heart disease with regard to disability [National Institutes of Mental Health. How is Depression Detected and Treated? October 23, 2008; Rush AJ et al. \u003Cem\u003EClinical Controlled Trials\u003C\/em\u003E 2004]. There is a strong correlation between anxiety symptoms and low rates of remission in patients with major depressive disorder (MDD) [Davidson JR, et al. \u003Cem\u003EDepress Anxiety\u003C\/em\u003E 2002; Silverstone PH et al. \u003Cem\u003EInt Clin Psychopharmacol\u003C\/em\u003E 2002]. John Zajecka, MD, Rush University Medical Center, Chicago, IL, discussed the role of anxiety in patients with major depressive disorder at the APA annual meeting.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAnxious depression is associated with greater functional impairment, increased risk of suicide, and higher rates of treatment interruption or discontinuation [Jaffe RT et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 1993; Clayton P et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 1991; Flint AJ et al. \u003Cem\u003EAm J Geriatr Psychiatry\u003C\/em\u003E 1997]. There are a variety of anxiety symptoms that may present in MDD patients, such as phobic symptoms, panic attacks, obsessive-compulsive tendencies, somatic anxiety, and worry, although differentiating between comorbidity versus secondary anxiety remains an issue. In a study by Fava and colleagues, comorbid anxiety diagnoses were present in 50.6% of MDD patients (27% social phobia, 16.9% simple phobia, 14.5% panic disorder, 10.6% generalized anxiety disorder, 6.3% obsessive-compulsive disorder, and 5.5% agoraphobia) [Fava M et al. \u003Cem\u003ECompr Psychiatry\u003C\/em\u003E 2000]. A similar study by Zimmerman and colleagues demonstrated that 56.8% of patients with MDD (n=307) had comorbid anxiety disorders [Zimmerman M et al. \u003Cem\u003EJ Clin Psychiatry\u003C\/em\u003E 2002].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EProf. Zajecka noted that anxious depression is associated with greater morbidity and mortality rates compared with depression without anxiety. Therefore, it is important to treat both the anxiety and the depression in order to reach remission. \u201cIt can be difficult, but it should be possible for most, if not all, [MDD patients with anxious depression] to achieve remission,\u201d said Prof. Zajecka.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EDepression and anxiety disorders have been linked to abnormalities in norepinephrine (NE) signaling, serotonin (5HT) activity, corticotrophin-releasing hormone (CRH), and glucocorticoid stress response abnormalities [Ressler KJ et al. \u003Cem\u003EDepress Anxiety\u003C\/em\u003E 2000]. Audrey Tyrka, MD, PhD, Brown Medical School and Butler Hospital, Providence, RI, discussed these neurobiological pathways and how they relate to anxious depression.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003E5-HT activity may influence the amygdala region of the brain, which is associated with intense and fearful emotion, including pathological anxiety. In a study by Caspi and colleagues that investigated gene-environmental interaction, individuals who had 1 or 2 copies of the short allele of the 5-HT promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals who were homozygous for the long allele [Caspi A et al. \u003Cem\u003EScience\u003C\/em\u003E 2003]. Additionally, a pooled analysis by Hariri and colleagues found that 5-HT affects the development of a broader corticolimbic circuit and alters the functional integration of emotional information between the amygdala and medial prefrontal cortex [Hariri AR et al. \u003Cem\u003EBiol Psychiatry\u003C\/em\u003E 2006]. These results suggest that 5-HT may be a predictive biomarker of increased risk for mood disorders, such as anxious depression.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThe hypothalamic-pituitary-adrenal (HPA) axis activates the body\u0027s fight-or-flight reaction. HPA axis abnormalities, such as extreme fluctuation in glucocorticoid receptor density or negative feedback inhibition, fluctuation in basal cortisol concentrations, and increased CRH within the cerebral spinal fluid, have been implicated in anxiety and depression [Duman RS et al. \u003Cem\u003EArch Gen Psychiatry\u003C\/em\u003E 1997; Heim C et al. \u003Cem\u003EArch Gen Psychiatry\u003C\/em\u003E 2009; Risbrough VB \u0026amp; Stein MB. Horm \u003Cem\u003EBehav\u003C\/em\u003E 2006; Smoller JW et al. \u003Cem\u003EBiol Psychiatry\u003C\/em\u003E 2005]. Additionally, the HPA axis and the CRH gene may also be linked to behavioral inhibition, such as the tendency to withdraw or avoid new situations, often found in patients with anxious depression [Smoller JW et al. \u003Cem\u003EBiol Psychiatry\u003C\/em\u003E 2005; Tyrka AR et al. \u003Cem\u003EActa Psychiatr Scand\u003C\/em\u003E 2007; Tyrka AR et al. \u003Cem\u003EHorm Behav\u003C\/em\u003E 2008].\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EMaurizio Fava, MD, Massachusetts General Hospital, Boston, MA, discussed pharmacotherapeutic strategies for the treatment of anxious depression. There are various pharmacological approaches for anxious depression, including monotherapy with antidepressants and augmentation with agents, such as benzodiazepines, eszopiclone, buspirone, anticonvulsants, and antipsychotics. Published studies have shown that there is no significant difference between the use of tricyclics and SSRIs for anxious depression [Tollefson GD et al. \u003Cem\u003EJ Clin Psychopharmacol\u003C\/em\u003E 1994; Marchesi C et al. \u003Cem\u003EPharmacopsychiatry\u003C\/em\u003E 1998; Versiani M et al. \u003Cem\u003EInt Clin Psychopharmacol\u003C\/em\u003E 1999; Sheehan D et al. \u003Cem\u003EPsychopharmacol Bull\u003C\/em\u003E 1992; Russell JM et al. \u003Cem\u003EDepress Anxiety\u003C\/em\u003E 2001; Moon CAL et al. \u003Cem\u003EJ Psychopharmacol\u003C\/em\u003E 1994]. To date, there is no FDA-approved indication for the use of antidepressants for the treatment of anxious depression. However, in a pooled analysis of 31 studies by Fava and colleagues, remission rates at 8 weeks in patients who were treated with venlafaxine (an SNRI) for anxious depression were significantly better than SSRI or placebo (p\u0026lt;0.001 for venlafaxine vs SSRI and placebo; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Fava M et al. 158th Annual Meeting of the American Psychiatric Association 2005].\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/21\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Pooled Analysis of Remission Rates Across 31 Studies of Venlafaxine Versus SSRIs Versus Placebo in Anxious Depression.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1455918925\u0022 data-figure-caption=\u0022Pooled Analysis of Remission Rates Across 31 Studies of Venlafaxine Versus SSRIs Versus Placebo in Anxious Depression.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/21\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/21\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/21\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11597\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003EPooled Analysis of Remission Rates Across 31 Studies of Venlafaxine Versus SSRIs Versus Placebo in Anxious Depression.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003EAnother pooled analysis by Fava and colleagues that compared eszopiclone augmentation versus placebo demonstrated improvement in HAM-D scores for patients with anxious depression (p\u0026lt;0.05; \u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) [Fava M et al. 47th Annual Meeting of the American College of Neuropsychopharmacology 2008].\u003C\/p\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/21\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Pooled Analysis of Trials Comparing Eszopiclone Added to SSRI and Placebo in Anxious Depression.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1455918925\u0022 data-figure-caption=\u0022Pooled Analysis of Trials Comparing Eszopiclone Added to SSRI and Placebo in Anxious Depression.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/21\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/21\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/9\/3\/21\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11319\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-11\u0022 class=\u0022first-child\u0022\u003EPooled Analysis of Trials Comparing Eszopiclone Added to SSRI and Placebo in Anxious Depression.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-12\u0022\u003EAlthough antidepressants are typically equally effective in anxious depression, this population tends to do poorly across the board. Patients with anxious depression do significantly worse than nonanxious MDD patients, regardless of treatment strategy [Fava M et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2008]. Anxiolytics may be indicated in nonresponders. However, side effect management is important. \u201cMonotherapies have modest effect; therefore, there is a need for novel therapies targeting this population,\u201d said Prof. Fava.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EAnother strategy for the treatment of anxious depression is cognitive behavioral therapy (CBT). Amy Farabaugh, PhD, Massachusetts General Hospital, Boston, MA, pointed out that cognition, behavior, and biochemistry are all important components of MDD and anxiety. In a study by Brown and colleagues, MDD patients with comorbid anxiety disorders tended to terminate treatment more frequently than those with depression alone [Brown C et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 1996]. This creates treatment barriers for the clinician. However, a preliminary analysis of STAR*D that evaluated CBT for anxious depression suggests that CBT is equally efficacious in patients with anxious and nonanxious depression; the rate of treatment continuation was similar for both groups [Farabaugh A et al. Manuscript in preparation].\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EAccording to Prof. Farabaugh, an important part of CBT in the patient with anxious depression is to start with small goals so that the patient is encouraged and notices progress early in the treatment. Recognizing symptoms that may lead to early treatment termination is also essential. A thorough clinical interview and careful classification of symptoms are therefore necessary. The patient\u0027s perception of how he is affected by each symptom plays a large role in CBT and should be considered and discussed.\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003EConceptualization throughout the course of therapy, such as helping the patient understand the relationship between the anxiety and depressive symptoms, is a valuable strategy in CBT. Because depression and anxiety may occur concurrently, it is helpful to consider skills and therapy that will complement both aspects of MDD. Prof. Farabaugh concluded that the integration of psychosocial and pharmacological approaches in these patients should be considered in order to establish remission. \u201cWe still have a lot to learn in terms of optimizing treatment strategies, but it does look like combining psychotherapy with pharmacotherapy may be helpful in patients with anxious depression,\u201d said Prof. Farabaugh.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2009 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/9\/3\/21.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzmk01\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmk01\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}