Cited by 139Treatment of Major DepressionAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesPsychological Treatments and Disorders

The DOI matches its Crossref record; 83 of the 85 references it cites were found in a registry or an index; 2 of the 78 sources its claims cite were checked for support.

Patients with anxious depression: overview of prevalence, pathophysiology and impact on course and treatment outcome

Open access

Abstract

PURPOSE OF REVIEW: Major depressive disorder with a comorbid anxiety disorder or with significant anxiety symptoms (here called anxious depression) is common and has been associated with poor clinical course trajectories. However, various dichotomous as well as dimensional definitions have been used to label anxious depression and it remains unclear to which extent these result in inconsistent findings. This review provides an overview of recent literature on the impact of anxiety in depressed patients on clinical course trajectories, treatment outcomes, and underlying neurobiological dysregulations. RECENT FINDINGS: Anxious depression seems associated with poorer clinical course trajectories and treatment nonresponse as compared with 'pure' depression, regardless of which definition is used. Recent studies have attempted to determine specific efficacy of novel pharmacological treatments for anxious depressed patients, but have not been conclusive because of the insufficient number of studies and differences in definitions and assessment of anxious depression. Neurobiology studies suggest that anxious depression is associated with increased immune dysregulation, more cortical thinning, and corticolimbic dysfunctions as compared with 'pure' depression. SUMMARY: Anxious depression appears to be a common and clinically relevant subtype of depression as it predicts poorer course trajectories. As populations with anxious depression may benefit from specific treatment regimens, further research is necessary to better delineate its definition and neurobiology. The relatively new Diagnostic and Statistical Manual of Mental Disorders-5 anxious distress specifier is a welcome development and should be further investigated and compared against other anxiety constructs.

Overview

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Written from the paper’s full text.

TL;DR

Anxious depression—defined variably as MDD with a comorbid anxiety disorder, elevated anxiety symptoms, or DSM-5 anxious distress—is common and associated with poorer clinical course and treatment outcomes. Recent evidence suggests a distinct neurobiological profile involving immune dysregulation, cortical thinning, and altered corticolimbic connectivity, but definitional heterogeneity limits conclusions.

Key findings

  • Prevalence is high across definitions: 42–78% of depressed patients have cooccurring anxiety; in lifetime MDD, 46% had at least one lifetime anxiety disorder, and in 12-month MDD, 52% had lifetime anxiety disorders and 42% had 12-month anxiety disorders. Dimensional studies found 53% of 2876 STAR*D MDD patients and 70% of 375 Chinese MDD patients had anxious depression; DSM-5 anxious distress prevalence ranged from 54 to 78%.
  • Anxious depression is associated with poorer course trajectories: greater depression chronicity and severity, higher suicide risk, lower quality of life, impaired social/occupational dysfunction, higher readmission rates, and lower remission rates. The DSM-5 anxious distress specifier outperformed DSM-4-based anxiety disorder comorbidity in predicting subsequent chronicity, longer time to remission, and greater functional disability.
  • Treatment findings are mixed: traditional antidepressants may be less effective for maintaining response/remission and may cause more side effects in anxious depression. Novel agents show inconsistent results; single-infusion ketamine was more effective in anxious than nonanxious depression, and vilazodone was more effective in 708 anxious versus 155 nonanxious patients, but evidence remains insufficient to establish specific efficacy.
  • Neurobiological studies suggest increased immune dysregulation (e.g., higher monocyte counts, higher innate cytokine production capacity), HPA-axis dysregulation, more cortical thinning in orbitofrontal/anterior cingulate cortex, insula, and temporal lobes, and increased corticolimbic functional connectivity compared with nonanxious MDD.

Methods

  • Narrative review of recent literature on anxious depression, covering prevalence, clinical course trajectories, treatment outcomes, and underlying neurobiological dysregulations.
  • Synthesizes large epidemiological and clinical studies and pharmacological trials, including a 74,045-adult 24-country study, STAR*D (n=2876), a European multicenter study (n=1346), and various randomized/post hoc treatment studies.
  • Main analysis is qualitative synthesis, with attention to whether findings depend on the definition or assessment method used for anxious depression; no meta-analysis or systematic search strategy is described.

Limitations

  • The paper states that various dichotomous and dimensional definitions and assessment instruments are used, no uniform definition has been established, and different definitions do not necessarily capture the same patients (e.g., DSM-5 anxious distress specifier poorly overlapped with DSM-4-based anxiety disorders, Cohen κ = 0.09).
  • The paper states that treatment studies are scarce, often use post hoc analyses with limited sample sizes, and not all directly compare anxious with nonanxious depression, so current evidence is insufficient to establish whether novel pharmacological treatments are specifically beneficial.
  • The paper states that neuroimaging and biological studies are limited and use various definitions; evident from the text, the review also lacks a described systematic search or risk-of-bias assessment and excludes bipolar depression and DSM-4 mixed anxious-depressive disorder.

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Integrity signals

Registry

Crossref · 10.1097/yco.0000000000000376

Cites

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  • It may state two separate claims as one. 31
  • Probably not a substantial claim. 4
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Metadata

Authors
Gaspersz, R., Nawijn, L., Lamers, F., & Penninx, B. W. J. H.
Affiliations
Amsterdam Neuroscience (NL)
Corresponding author
Gaspersz, Roxanne
Venue
Current Opinion in Psychiatry
Published
2018-01
Volume
31
Issue
1
Pages
17-25
ISSN
0951-7367 (ISSN-L)
OpenAlex
W2767830383
Cited by
139
References
85
Citations by year
2026: 11 · 2025: 14 · 2024: 25 · 2023: 19 · 2022: 15 · 2021: 21 · 2020: 12 · 2019: 16 · 2018: 6
FWCI
1.18
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Current Opinion in Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
Funders
European Commission
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
  • Social Sciences › Psychology › Clinical Psychology › Psychological Treatments and Disorders
Keywords
anxious depression, major depressive disorder, anxiety comorbidity, treatment non-response, neurobiology of depression, immune dysregulation, cortical thinning
MeSH terms
Antidepressive Agents, Anxiety, Anxiety Disorders, Depressive Disorder, Major, Major Depressive Disorder, Humans, Anti-Anxiety Agents, Comorbidity, Prevalence, Treatment Outcome, Disease Progression, Diagnostic and Statistical Manual of Mental Disorders

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