Anxious distress in people with major depressive episodes: a cross-sectional analysis of clinical correlates.

OBJECTIVE: Most people with major depressive episodes meet the criteria for the anxious distress (AD) specifier defined by DSM-5 as the presence of symptoms such as feelings of tension, restlessness, difficulty concentrating, and fear that something awful may happen. This cross-sectional study was aimed at identifying clinical correlates of AD in people with unipolar or bipolar depression. METHODS: Inpatients with a current major depressive episode were included. Data on socio-demographic and clinical variables were collected. The SCID-5 was used to diagnose depressive episodes and relevant specifiers. The Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were used to assess the severity of depressive and manic (mixed) symptoms, respectively. Multiple logistic regression analyses were carried out to identify clinical correlates of AD. RESULTS: We included 206 people (mean age: 48.4 ± 18.6 yrs.; males: 38.8%) admitted for a major depressive episode (155 with major depressive disorder and 51 with bipolar disorder). Around two-thirds of the sample (N = 137; 66.5%) had AD. Multiple logistic regression models showed that AD was associated with mixed features, higher YMRS scores, psychotic features, and a diagnosis of major depressive disorder (p < 0.05). CONCLUSION: Despite some limitations, including the cross-sectional design and the inpatient setting, our study shows that AD is likely to be associated with mixed and psychotic features, as well as with unipolar depression. The identification of these clinical domains may help clinicians to better contextualize AD in the context of major depressive episodes.

Neural correlates of anxious distress in depression: A neuroimaging study of reactivity to emotional faces and resting-state functional connectivity.

BACKGROUND: Comorbid anxiety disorders and anxious distress are highly prevalent in major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. However, little is known about the neurobiological correlates of anxious distress in MDD. METHODS: We probed the relation between the DSM-5 ADS and task-related reactivity to emotional faces, as well as resting-state functional connectivity patterns of intrinsic salience and basal ganglia networks in unmedicated MDD patients with (MDD/ADS+, N = 24) and without ADS (MDD/ADS-, N = 48) and healthy controls (HC, N = 59). Both categorical and dimensional measures of ADS were investigated. RESULTS: MDD/ADS+ patients had higher left amygdala responses to emotional faces compared to MDD/ADS- patients (p = .015)-part of a larger striato-limbic cluster. MDD/ADS+ did not differ from MDD/ADS- or controls in resting-state functional connectivity of the salience or basal ganglia networks. CONCLUSIONS: Current findings suggest that amygdala and striato-limbic hyperactivity to emotional faces may be a neurobiological hallmark specific to MDD with anxious distress, relative to MDD without anxious distress. This may provide preliminary indications of the underlying mechanisms of anxious distress in depression, and underline the importance to account for heterogeneity in depression research.

The relationship between depression with anxious distress DSM-5 specifier and mixed depression: a network analysis.

INTRODUCTION: Epidemiological, clinical, and treatment response characteristics of major depression with anxious distress (ADS) are quite similar to those of mixed depression, but no study investigated the symptom interplay of these conditions. OBJECTIVE: To analyze the correlations among symptom criteria for major depression with ADS and for mixed depression using a network analysis. METHODS: Two hundred and forty-one outpatients with major depression were consecutively recruited. DSM-5 criteria for major depression with ADS or with mixed features (MF) and Koukopoulos' criteria for mixed depression (MXD) were assessed using a structured clinical interview. RESULTS: A total of 58.9% of patients met DSM-5 criteria for major depression with ADS, 48.5% for MXD, and 2.5% for major depression with MF, so that the symptoms of this specifier were excluded from the network analysis. The most frequent symptoms were difficulty concentrating due to worries (57.7%), feeling keyed up or on edge (51%) (major depression with ADS), and psychic agitation or inner tension (51%) (MXD). Psychic agitation or inner tension had a central position in the network and bridged MXD to major depression with ADS through feeling keyed up or on edge. CONCLUSIONS: Criteria for major depression with ADS and for MXD are partially overlapping, with psychic agitation or inner tension and feeling keyed up or on edge that feature in both conditions and are difficult to distinguish in clinical practice. The clarification of the relationship between these two psychopathological conditions could bring important implications for diagnosis, prognosis, and treatment of depressive episodes.

Validity of the DSM-5 anxious distress specifier for major depressive disorder.

BACKGROUND: DSM-5 introduced the anxious distress specifier in recognition of the clinical significance of anxiety in depressed patients. Recent studies that supported the validity of the specifier did not use measures that were designed to assess the criteria of the specifier but instead approximated the DSM-5 criteria from scales that were part of an existing data base. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined the validity of the specifier diagnosed with a semistructured interview. METHODS: Two hundred sixty patients with a principal diagnosis of major depressive disorder were evaluated with semistructured diagnostic interviews. The patients were rated on clinician rating scales of depression, anxiety and irritability, and completed self-report measures. RESULTS: Approximately three-quarters of the depressed patients met the criteria for the anxious distress specifier. Patients with anxious distress had a higher frequency of anxiety disorders, particularly panic disorder and generalized anxiety disorder, as well as higher scores on measures of anxiety, depression, and anger. The patients meeting the anxious distress subtype reported higher rates of drug use disorders, poorer functioning during the week before the evaluation, and poorer coping ability compared to the patients who did not meet the anxious distress specifier. Moreover, anxious distress was associated with poorer functioning and coping after controlling for the presence of an anxiety disorder. CONCLUSIONS: The results of the present study indicate that anxious distress is common in depressed patients and support the validity of the DSM-5 anxious distress specifier.

Clinical and socio-demographic correlates of anxious distress in Asian outpatients with major depressive disorder.

BACKGROUND: Anxious distress in major depressive disorder (MDD) is common and associated with poor outcomes and management difficulties. AIMS: This post hoc analysis aimed to examine the socio-demographic and clinical correlates of anxiety distress in Asian outpatients with MDD. METHODS: Instead of two out of five specifiers defined by the Diagnostic and Statistical Manual Version-5, anxious distress defined in this study was operationalized as the presence of at least two out of four proxy items drawn from the 90-item Symptom Checklist, Revised (SCL-90-R). Other measures included the Montgomery-Asberg Depression Rating Scale (MADRS), the Fatigue Severity Scale, the Sheehan Disability Scale and the Multidimensional Scale of Perceived Social Support. RESULTS: The data of 496 patients with MDD were included. Anxious distress was found in 371 participants (74.8%). The binary logistic regression analysis found that anxious distress was independently and significantly correlated with working status, higher MADRS scores, severe insomnia and functional impairment. CONCLUSIONS: Three-fourths of Asian patients with MDD in tertiary care settings may have DSM-5 anxious distress of at least moderate distress. Its prevalence may vary among working groups. The specifier was associated with greater depressive symptom severity, severe insomnia and functional impairment.

Clinical correlates of anxious depression in youth from the Texas Youth Depression and Suicide Research Network (TX-YDSRN).

BACKGROUND: Anxious depression is a prevalent subtype of depression associated with adverse outcomes such as higher depression severity and higher rates of suicidality. This study leveraged a state-wide research registry of depressed and/or suicidal youth to compare the prevalence, clinical correlates, and symptom patterns of those with versus without anxious depression. METHODS: We included baseline data from 797 participants (ages 8-20) with a diagnosis of a depressive disorder. A score on the Generalized Anxiety Disorder Scale (GAD-7) ≥ 10 was used to define individuals with and without anxious depression. A structured battery was used to capture psychiatric diagnostic status, depression/anxiety severity, suicide risk, history of trauma, functioning, and resilience. RESULTS: The prevalence of anxious depression among youth with depressive disorders was 59.5 % (n = 474). Youth with anxious depression had greater depression severity and anxiety symptoms, higher suicidality, and a higher prevalence of comorbid anxiety disorders than those without. Youth with anxious depression had greater impairment in functioning defined as worse pain interference, pain severity, fatigue, and social relationships compared to those without anxious depression. Youth with anxious depression also reported higher rates of depressive symptoms such as irritable mood, feelings of guilt, and psychomotor agitation compared to those without anxious depression. CONCLUSION: Anxious depression is associated with worse depression severity, higher suicidality, and lower functioning. Longitudinal work is needed to examine long-term courses of anxious depression to explore its stability as a diagnostic subcategory.

Characteristics of attentional bias in adolescents with major depressive disorders: differentiating the impact of anxious distress specifier.

Background: No consistent conclusion has been reached regarding the attentional bias characteristics of adolescents with major depressive disorders (MDD), and unexamined co-occurring anxiety distress may contribute to this inconsistency. Methods: We enrolled 50 MDD adolescents with anxiety distress, 47 MDD adolescents without anxiety distress and 48 healthy adolescents. We measured attentional bias using a point-probe paradigm during a negative-neutral emotional face task. Reaction time, correct response rate and attentional bias value were measured. Results: MDD adolescents did not show a negative attentional bias; MDD adolescents with anxiety distress exhibited longer reaction time for negative and neutral stimuli, lower correct response rate for negative stimuli. Hamilton Anxiety Scale scores were positively correlated with reaction time, negatively correlated with correct response rate, and not significantly correlated with attentional bias value. Limitations: The cross-sectional design hinders causal attribution, and positive emotional faces were not included in our paradigm. Conclusion: Negative attentional bias is not a stable cognitive trait in adolescents with MDD, and avoidance or difficulty in disengaging attention from negative emotional stimuli may be the attentional bias characteristic of MDD adolescents with anxiety distress.

The Potential Role of Aripiprazole Augmentation for Major Depressive Disorder with Anxious Distress in Naturalistic Treatment Setting.

Objective: : This study tried to observe clinical benefit of aripiprazole augmentation (ARPA) treatment for major depressive disorder with anxious distress (MDDA) in routine practice. Methods: : Retrospective chart review (n = 41) was conducted for clinical benefit of ARPA in patients with MDDA in routine practice. The primary endpoint was the mean change of Hamilton Anxiety Rating scale (HAMA) total scores from baseline to the endpoint. Additional secondary endpoints were also retrieved. Results: : The changes of primary endpoint HAMA (t = 5.731, -4.6, p = 0.001), and secondary endpoints including Hamilton Depression Rating scale (HAMD, t = 4.284, -3.4, p ＜ 0.001), Clinical Global Impression-Clinical Benefit (CGI-CB, -0.9, t = 1.821, p = 0.026), and Clinical Global Impression Score-Severity (CGI-S, t = 3.556, -0.4, p ＜ 0.001) scores were also significantly improved during the study. No significant adverse events were observed. Conclusion: : This study has shown additional benefit of ARPA treatment for MDDA patients in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.

High-definition transcranial direct current stimulation (HD-tDCS) in major depressive disorder with anxious distress-a study protocol for a double-blinded randomized sham-controlled trial.

BACKGROUND: Comorbid anxiety disorders and anxious distress are highly prevalent among individuals with major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. Few studies have evaluated the therapeutic effects of High-definition transcranial direct current stimulation (HD-tDCS) on depressive and anxiety symptoms among MDD patients with ADS. The current randomized controlled trial aims to assess the efficacy of HD-tDCS as an augmentation therapy with antidepressants compared to sham-control in subjects of MDD with ADS. METHODS: MDD patients with ADS will be recruited and randomly assigned to the active HD-tDCS or sham HD-tDCS group. In both groups, patients will receive the active or sham intervention in addition to their pre-existing antidepressant therapy, for 2 weeks with 5 sessions per week, each lasting 30 min. The primary outcome measures will be the change of depressive symptoms, clinical response, and the remission rate as measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before and after the intervention and at the 2nd and 6th week after the completed intervention. Secondary outcome measures include anxiety symptoms, cognitive symptoms, disability assessment, and adverse effects. DISCUSSION: The HD-tDCS applied in this trial may have treatment effects on MDD with ADS and have minimal side effects. TRIAL REGISTRATION: The trial protocol is registered with www.chictr.org.cn under protocol registration number ChiCTR2300071726. Registered 23 May 2023.

Hematochezia caused by tandospirone in a patient with major depressive disorder and anxious distress: a case report.

Background: Major depressive disorder (MDD) with anxious distress is a relatively common condition that is often associated with a poor treatment response. In order to enhance the effectiveness of MDD treatment, 5-HT1A agonists like tandospirone are often prescribed in conjunction with antidepressants. While it is known that antidepressants can increase the risk of bleeding, whether tandospirone poses a similar risk remains uncertain. Case presentation: We presented the case of a 55-year-old Chinese woman diagnosed with MDD and anxious distress. After receiving various types of antidepressants, she experienced hematochezia following the administration of tandospirone, sertraline, and agomelatine. The occurrence of hematochezia ceased after tandospirone was discontinued. The patient was subsequently discharged with a treatment regime consisting of sertraline and agomelatine. During the 1-month follow-up, she reported no hematochezia. Conclusion: Tandospirone may potentially increase the risk of hematochezia in patients with MDD and anxious distress.

An exploratory study of the gut microbiota in major depression with anxious distress.

OBJECTIVES: To explore differences in the diversity and composition of the gut microbiome between major depressive disorder (MDD) with and without anxious distress. METHODS: The study comprised 117 participants (79 female, 36 male, 2 other, mean age 38.2 ± 13.4 years) with a current major depressive episode (MDE) with (n = 63) and without (n = 54) the anxious distress specifier. A clinical psychologist administered the structured clinical interview for the DSM-5-RV to confirm a diagnosis of depression. Participants provided stool samples which were immediately frozen and stored at -80 °C. These samples were analysed using the Illumina 16S Metagenomics sequencing protocol in which the sequencing primers target the V3 and V4 regions of the 16S rRNA gene. Participants also completed mental health questionnaires to assess severity of depression (BDI-II), generalized anxiety (GAD-7), and stress (PSS). RESULTS: There were no significant group differences in α-diversity (Shannon's diversity Index; Simpson Index), richness (ACE; Chao1), (Pielou's) evenness, or beta diversity (Bray-Curtis dissimilarity index and weighted UniFrac distance) of gut bacteria. Significant group differences in the relative abundance of gut microbiota however were observed at each taxonomical level, including across 15 genera and 18 species. LIMITATIONS: This was an exploratory study that needs to be replicated across larger samples and compared with a healthy control group. CONCLUSIONS: The research contributes to knowledge of the depressive gut microbial profile unique to the anxious distress subtype of MDD.

Are anxious and mixed depression two sides of the same coin? Similarities and differences in patients with bipolar I, II and unipolar disorders.

BACKGROUND: Diagnostic criteria are not always useful to discriminate major depression with anxious distress (ADS-D; Diagnostic and Statistical Manual for Mental Disorders, version-5 [DSM-5] criteria) from mixed depression (Koukopoulos' criteria; KMX-D). So, clinicians need alternative tools to improve their diagnostic ability and to choose the most appropriate treatment. The aim of the present study is to identify socio-demographic and clinical features that discriminate patients with ADS-D from those with KMX-D. METHODS: Two hundred and forty-one consecutive outpatients with unipolar (51%) and bipolar (49%) disorder, fulfilling DSM-5 criteria for a current major depressive episode (MDE) and with a 21-item Hamilton Depression Rating Scale score ≥ 14, were recruited and treated in a prospective observational study. RESULTS: Ten percent of patients met criteria for KMX-D, 22% ADS-D, and 37% for both. Irritable premorbid temperament, mixed depression polarity at onset, mixed depression recurrence, and a high number of mania symptoms at intake were typical features of patients with KMX-D. Depressive polarity at onset, a low number of mania symptoms at intake, and generalized anxiety disorder comorbidity were typical features of patients with ADS-D. Multinomial logistic regression confirmed that higher rate of irritable temperament and higher Young Mania Rating Scale total score differentiated patients with KMX-D from patients with pure MDE. CONCLUSION: Our findings suggest some clinical features that could help differentiate between ADS-D and KMX-D in patients meeting both conditions and to select the appropriate treatment. However, the small sample size may have limited the power to detect differences between the groups. Further research is needed to confirm the results of present study.

Is the DSM-5 Anxious Distress Specifier Interview a valid measure of anxiety in patients with generalized anxiety disorder: A comparison to the Hamilton Anxiety Scale.

DSM-5 includes criteria for an anxious distress specifier for major depressive disorder, and measures have been developed to assess these criteria. The validity of measures of the severity of anxious distress has been established in depressed patients. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined whether a severity measure of anxious distress was as valid as the Hamilton Anxiety Scale (HAMA) as a measure of the severity of anxiety in patients with generalized anxiety disorder (GAD). Eighty-five patients with GAD were interviewed by trained raters who administered the DSM-5 Anxious Distress Specifier Interview (DADSI), HAMA, and Hamilton Depression Rating Scale (HAMD). The patients completed self-report measures of depression, anxiety, and irritability. The DADSI and HAMA were significantly correlated (r  0.52, p < .001). Both the DADSI and HAMA were more highly correlated with measures of anxiety than with measures of the other symptom domains. The HAMD was significantly more highly correlated with the HAMA than with the DADSI. Both measures were significantly correlated with measures of positive mental health, functioning, life satisfaction, and general well-being. Both measures were sensitive to change in response to treatment. Both the DADSI and HAMA were valid measures of anxiety severity in patients with GAD, though the HAMA was more highly confounded with the HAMD than the DADSI. The DADSI is briefer than the HAMA, and thus may be more practical to use in research studies as well as clinical practice.

A comparison of the dimensionality of the Hamilton Rating Scale for anxiety and the DSM-5 Anxious-Distress Specifier Interview.

The Hamilton Rating Scale for Anxiety (HAM-A) is one of the most widely used measures for assessing anxiety in research settings. However, it has been criticized for its inclusion of items that assess depressive symptoms. The DSM-5 Anxious Distress Specifier Interview (DADSI), developed as one assessment tool for measuring anxiety among depressed patients, demonstrates similar validity when compared with the HAM-A. However, its underlying factor structure has never been explored. The goal of the current study, therefore, was to compare the underlying factor structures of the HAM-A and the DADSI among clinically depressed (n = 576) and non-depressed (n = 146) patient samples. While two- and three-factor structures of the HAM-A fit similarly well among patients with a current major depressive episode, the three-factor structure-with anxiety and depressive symptoms forming separate factors-fit best among patients without a current major depressive episode. The DADSI was best represented by a single-factor model in both groups. The DADSI showed stronger associations with anxiety and somatic symptoms than with depressive symptoms of the HAM-A. These findings add to the characterization of the DADSI, and further highlight an important consideration for the use of HAM-A as a measure of anxiety in outcome studies.

Association between anxious distress in a major depressive episode and bipolarity.

PURPOSE: Mixed features in a major depressive episode (MDE) predict bipolar disorder (BD). The mixed features specifier included in the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) could be restrictive because it excludes the symptoms common to both mania/hypomania and depression, including psychomotor agitation. On the other hand, an anxious distress (ANXD) specifier has also been introduced in the DSM-5, and psychomotor agitation has been defined as a severity of ANXD. In this study, we retrospectively investigated the association between presence of ANXD in an MDE and bipolarity. PATIENTS AND METHODS: The subjects were patients admitted with an MDE to the Department of Psychiatry at Tokyo Women's Medical University Hospital from December 2014 to March 2016. Eligible patients were older than 20 years of age and met the DSM-5 criteria for major depressive disorder or BD. All data were extracted from medical records. The subjects were grouped according to whether they did or did not have ANXD. The demographics and clinical features of these groups were compared. Severity of illness was evaluated according to the Hamilton Rating Scale for Depression (HRSD) score on admission. RESULTS: ANXD was present in 31 and absent in 33 of 64 patients with MDE. The HRSD score was significantly higher in the group with ANXD than in the group without ANXD (P=0.0041). Mixed features (P=0.0050) and suicide attempts (P=0.0206) were significantly more common in the group with ANXD than in the group without ANXD. CONCLUSION: We found that the presence of ANXD in an MDE was associated with greater severity and more mixed features and suicide attempts. It is important to evaluate a patient with an MDE for ANXD so that a diagnosis of mixed depression is not missed. More studies in larger samples are needed to investigate further the association between ANXD in MDE and bipolarity.

What is anxious depression? Overlap and agreement between different definitions.

Anxiety is common in depressed patients. However, a problem with the research on the significance of anxiety in depressed patients is that anxiety has been characterized in different ways. Little research has examined the concordance and overlap between the various definitions of anxious depression. With research on the DSM-5 anxious distress specifier just beginning, it will be important to understand how defining anxious depression according to DSM-5 agrees with previously studied definitions. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we examined the association between the DSM-5 anxious distress specifier and 6 other approaches towards defining anxious depression. Three hundred thirty-one patients with a principal diagnosis of major depressive disorder were evaluated with semi-structured diagnostic interviews. The mean number of anxious depression definitions met was 4.7 (SD = 2.1). Only 4.2% (n = 14) of the 331 patients did not meet any anxious depression definition, and 28.1% (n = 93) met all 7 definitions. The level of agreement between the definitions was significant, albeit modest (median kappa = .28). The modest association between the different definitions of anxious depression suggests that the results based on one approach towards subtyping may not generalize to the DSM-5 anxious distress specifier. It therefore cannot be assumed that the DSM-5 anxious distress specifier is valid just because other definitions of anxious depression have been shown to be valid.

Is there a relationship between depression with anxious distress DSM-5 specifier and bipolarity? A multicenter cohort study on patients with unipolar, bipolar I and II disorders.

BACKGROUND: To estimate the prevalence of DSM-5 anxious distress specifier (ADS) in depressed patients with major depressive disorder (MDD) or bipolar I or II disorder (BD), and to compare socio-demographic and clinical characteristics, and response to naturalistic short-term treatment between ADS and non-ADS group. METHODS: 241 outpatients with a major depressive episode (MDE) were consecutively recruited. Outcome were remission (HDRS21 total score < 7), response (≥50% reduction of baseline HDRS21) and improvement (CGI-i score ≤ 2) after 12 weeks of treatment sustained for 4 weeks. RESULTS: ADS was more frequent in BD than in MDD (respectively, 66.9% and 51.2%, χ2 = 6.1, p = 0.013). Compared with those non-ADS, patients with ADS had more severe depressive (respectively, HDRS21 total score 20.0 ±â€¯4.4 and 18.6 ±â€¯3.9, t-test = 2.67, p = 0.008) and mania symptoms (respectively, Y-MRS total score 2.2 ±â€¯2.9 and 1.3 ±â€¯2.3, M-W-test = 2.86; p = 0.004) at intake, a higher rate of BD family history (respectively, 35.2% and 22.2%, Χ2-test 10.4, p = 0.004) and more previous hypomanic episodes (respectively, (median (range) 0 (0-20) and 0 (0-15), MW-test = 2.39 p = 0.017). In the MDD group, patients with ADS had higher scores on hyperthymic temperament and mania symptoms (Y-MRS total score (median (range) 2.2 (0-26) and 0 (0-11), respectively, M-W test 2.071, p = 0.038). ADS and no-ADS patients did not significantly differ on outcome measures. LIMITATIONS: The observational nature of the study and the absence of blinding in outcome assessment. CONCLUSIONS: ADS is the most common DSM-5 specifier for MDE, is more frequent in BD and need a personalized treatment with moderate use of antidepressants, mostly tricyclic.

Anxious distress in depressed outpatients: Prevalence, comorbidity, and incremental validity.

The goals of this study were to estimate the prevalence of the DSM-5 anxious distress specifier (AD) among depressed outpatients, to examine associations of AD with comorbid diagnoses, and to test the incremental validity of AD over comorbidity in predicting functional impairment and severity of anxiety and depression symptoms. The sample was 237 outpatients diagnosed with major depressive disorder (MDD) or persistent depressive disorder (PDD), with and without AD, using the Anxiety and Related Disorders Interview Schedule for DSM-5. Outpatients also completed self-report questionnaires assessing functional impairment and anxiety, stress, and depression symptom severity. Two-by-two contingency tables were used to examine the associations of AD with comorbidity. Two-thirds (66.2%) of outpatients were assigned AD, with similar rates among those with MDD and PDD. Outpatients with AD were significantly more likely than those without AD to have a comorbid GAD diagnosis (OR = 2.47). Hierarchical multiple regressions were used to test the incremental validity of AD in predicting functional impairment and symptom outcomes beyond comorbid disorders. Controlling for comorbid disorders, AD was significantly associated with more severe functional impairment, autonomic arousal, stress, panic, generalized anxiety, and depression. The strongest incremental association were observed between AD and autonomic arousal (f2 = 0.12-0.18) and generalized anxiety (f2 = 0.17). These findings add to a growing literature that AD is common among outpatients and associated with important clinical outcomes, suggesting that AD should be routinely assessed in patients with mood disorders.

Anxious distress predicts subsequent treatment outcome and side effects in depressed patients starting antidepressant treatment.

Evidence has shown that the DSM-5 anxious distress specifier captures a clinically valid construct that predicts a worse clinical course. Although of importance for treatment planning and monitoring, however, the specifier's ability to predict treatment outcome is unknown. This is the first study to examine the ability of the DSM-5 anxious distress specifier to predict treatment response and side effects in depressed patients who recently initiated antidepressant treatment. Patients were from the Netherlands Study of Depression and Anxiety, an ongoing longitudinal cohort study. Baseline, 1-year and 2-year follow-up data were used from 149 patients (18-65 years) with current Major Depressive Disorder (MDD) who recently started adequately dosed antidepressant medication. Five self-report items were used to construct the DSM-5 anxious distress specifier. Treatment outcomes were depression severity after 1 year and 2 years, remission of MDD after 2 years and antidepressant side effects during treatment. For comparison, analyses were repeated for comorbid DSM-IV-based anxiety disorders as a predictor. In depressed patients who received antidepressant treatment, the anxious distress specifier (prevalence = 59.1%) significantly predicted higher severity (1 year: B = 1.94, P = 0.001; 2 years: B = 1.63, P = 0.001), lower remission rates (OR = 0.44, P = 0.0496) and greater frequency of side effects (≥4 vs. 0: OR = 2.74, P = 0.061). In contrast, the presence of comorbid anxiety disorders did not predict these treatment outcomes. The anxious distress specifier significantly predicts poorer treatment outcomes as shown by higher depression severity, lower remission rates, and greater frequency of antidepressant side effects in patients with MDD on adequate antidepressant treatment. Therefore, this simple 5-item specifier is of potential great clinical usefulness for treatment planning and monitoring in depressed patients.

Measuring anxiety in depressed patients: A comparison of the Hamilton anxiety rating scale and the DSM-5 Anxious Distress Specifier Interview.

DSM-5 included criteria for an anxious distress specifier for major depressive disorder (MDD). In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we examined whether a measure of the specifier, the DSM-5 Anxious Distress Specifier Interview (DADSI), was as valid as the Hamilton Anxiety Scale (HAMA) as a measure of the severity of anxiety in depressed patients. Two hundred three psychiatric patients with MDD were interviewed by trained diagnostic raters who administered the Structured Clinical Interview for DSM-IV (SCID) supplemented with questions to rate the DADSI, HAMA, and Hamilton Depression Rating Scale (HAMD). The patients completed self-report measures of depression, anxiety, and irritability. Sensitivity to change was examined in 30 patients. The DADSI and HAMA were significantly correlated (r = 0.60, p < 0.001). Both the DADSI and HAMA were more highly correlated with measures of anxiety than with measures of the other symptom domains. The HAMD was significantly more highly correlated with the HAMA than with the DADSI. For each anxiety disorder, patients with the disorder scored significantly higher on both the DADSI and HAMA than did patients with no current anxiety disorder. A large effect size of treatment was found for both measures (DADSI: d = 1.48; HAMA: d = 1.37). Both the DADSI and HAMA were valid measures of anxiety severity in depressed patients, though the HAMA was more highly confounded with measures of depression than the DADSI. The DADSI is briefer than the HAMA, and may be more feasible to use in clinical practice.