Depression and Anxiety Comorbidity
Yes, depression very commonly comes with anxiety—approximately 85% of patients with depression experience significant anxiety symptoms, and about 90% of patients with anxiety disorders have comorbid depression. 1
Prevalence and Co-occurrence Patterns
The overlap between depression and anxiety is substantial across all populations:
In cancer survivors, 31% of patients with an anxiety disorder also meet criteria for major depressive disorder (MDD), and depression and anxiety "usually co-occur" in both cancer and non-cancer populations 1
In general practice settings, comorbid depression and anxiety disorders occur in up to 25% of patients 2
In adolescents, anxiety disorders are highly comorbid with depression, with generalized anxiety disorder with comorbid depression conveying the greatest risk for suicidal ideation and attempts 1
In patients with IBS, the prevalence of co-occurring anxiety and depressive disorders reaches 23%, with overall anxiety symptoms at 39% and depressive symptoms at 29% 1
Shared Pathophysiology
Depression and anxiety share common genetic and neurobiological mechanisms rather than one condition simply causing the other:
Genome-wide analysis of over 250,000 individuals identified shared genetic risk factors across depression, anxiety, and even conditions like IBS 1
Both conditions involve dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system 1
Reduced brain volume and altered resting brain functional connectivity patterns are implicated as shared pathophysiological mechanisms 1
Clinical Implications of Comorbidity
The presence of comorbid anxiety and depression significantly worsens clinical outcomes:
Patients with comorbid conditions experience higher rates of treatment resistance compared to either disorder alone 3, 4
The severity of symptoms increases considerably as the number of co-occurring psychological comorbidities increases 1
Comorbid patients have more protracted illness courses and less positive treatment outcomes 5
In cancer populations, reduced quality of life is mainly driven by concurrent psychological comorbidity rather than physical symptoms alone 1
Diagnostic Considerations
Both conditions must be independently assessed and diagnosed:
MDD and generalized anxiety disorder (GAD) are distinct clinical entities with specific diagnostic criteria that can coexist 6
Use standardized assessment tools: PHQ-9 for depressive symptoms and GAD-7 for anxiety symptoms (scores ≥10 suggest moderate anxiety; ≥15 indicate severe anxiety) 6
The American Academy of Pediatrics recommends assessment should include input from multiple sources including the patient, family members, and when appropriate, teachers or other caregivers 7
Treatment Approach
When both conditions are present, prioritize treating depression first with proven cognitive and/or behavioral therapies:
The American Society of Clinical Oncology recommends treating depression first, as it is typically the predominant affective, cognitive, and behavioral disruptor 1
Cognitive-behavioral therapy (CBT) and behavioral activation (BA) are first-line treatments with robust effects for both depression and anxiety that generalize across age, sex, and multiple delivery modes (in-person, app-based, virtual, telephone) 1
For adolescents with major depressive disorder, scientifically tested treatments include CBT, interpersonal therapy for adolescents (IPT-A), and/or selective serotonin reuptake inhibitors (SSRIs) 7
Pharmacological Management
SSRIs are considered first-line pharmacological treatment for comorbid anxiety and depression:
SSRIs are effective for both conditions simultaneously and are preferred due to their favorable side effect profile 6, 8, 4
For adolescents, fluoxetine is the only FDA-approved antidepressant with response rates of 47-69% compared to 33-57% for placebo; escitalopram is FDA-approved only for adolescents aged 12 years and older 7
SNRIs (serotonin-norepinephrine reuptake inhibitors) have empirical support as additional options when SSRIs are not effective or tolerated 7, 3
Pharmacotherapy is NOT recommended as first-line treatment alone—the 2023 ASCO guideline found evidence for antidepressants unconvincing, with a 2018 Cochrane review showing null findings for MDD treatment in cancer patients at 6-12 weeks 1
Common Pitfalls to Avoid
Do not delay treatment while waiting for specialty referral—primary care clinicians should provide initial management even when psychiatric services are limited 7
Do not use benzodiazepines as monotherapy for depression—they may help alleviate insomnia and anxiety but do not treat depression, and carry dependency, withdrawal, and fall risks 2
Do not ignore the comorbid condition—both the depression disorder and the specific anxiety disorder require appropriate treatment 2
Do not use low-dose tricyclic antidepressants as monotherapy in patients with established mood disorders, as these doses are insufficient for treating psychological symptoms 8
Specificity of Stress Generation
The stress generation phenomenon (where individuals create additional stressors) appears specific to depression rather than anxiety:
Multiple studies show that symptoms of depression, but not anxiety or conduct disorder, are positively correlated with generating stressful life events 1
However, the stress generation pattern is augmented when both conditions coexist—dependent stressful events are greater among depressed individuals with comorbid anxiety compared to those with depression alone 1