When Depression and Anxiety Overlap: Understanding MDD with Comorbid Anxiety

By Natalie Blaum, Ph.D., MagVenture A/S

Major Depressive Disorder (MDD) and anxiety are often discussed as separate mental health conditions. In clinical practice, however, they frequently overlap.

Many people living with depression also experience significant anxiety symptoms, such as persistent worry, tension, restlessness or difficulty relaxing. When significant anxiety symptoms occur alongside depression, this is sometimes referred to as anxious depression or MDD with comorbid anxiety symptoms.¹

When depression and anxiety overlap

Depression is one of the most common mental health conditions worldwide. The World Health Organization estimates that approximately 332 million people globally are living with depression.²
Depression is prevalent across both Europe and the United States. In Europe, a large population-based study spanning 30 countries estimated that 6.5% of the population experienced clinically relevant depressive symptoms in 2018–2020, although prevalence varied considerably between countries.³ In the United States, an estimated 21.0 million adults, or 8.3% of the adult population, experienced at least one major depressive episode in 2021.⁴

For a substantial proportion of people with MDD, depression is accompanied by significant symptoms of anxiety.

In the large STAR*D study of 1,450 people with MDD, approximately 46% met the study criteria for anxious depression.¹ A 2023 review noted that studies have reported prevalence estimates of anxious depression ranging from 50% to 75% among patients with MDD.⁵

Importantly, having anxiety symptoms alongside MDD does not necessarily mean that a person has a separate anxiety disorder such as Generalized Anxiety Disorder (GAD). Anxiety symptoms can occur at different levels and in different forms within depression itself.⁵

The neurobiology of MDD with comorbid anxiety

Depression and anxiety involve complex and partly overlapping brain systems involved in emotional and cognitive processing. Research has implicated interconnected brain regions involved in processes such as salience detection, cognitive control and the integration of emotional and bodily information, including the insula and prefrontal regions.^6,7 However, the precise neurobiology of MDD with comorbid anxiety is still being investigated.

Recent neuroimaging research suggests that MDD with comorbid anxiety may be associated with differences in structural brain connectivity compared with MDD without comorbid anxiety.⁸ In a large 2026 diffusion-MRI study, researchers compared 781 people with MDD, including 249 with and 532 without a comorbid anxiety disorder, with 906 healthy controls.⁸

Individuals with MDD without a comorbid anxiety disorder showed decreased structural connectivity within an identified network compared with healthy controls. In contrast, individuals with MDD and a comorbid anxiety disorder showed increased structural connectivity within a spatially overlapping network. Regions involved included the insula as well as frontal and temporal areas. Higher anxiety severity was also associated with greater structural connectivity across the overall sample.⁸

These findings add to our understanding of the heterogeneity of MDD and suggest that MDD with a comorbid anxiety disorder may be associated with different patterns of structural brain connectivity than MDD without a comorbid anxiety disorder.⁸ However, further research is needed to understand how these differences relate to symptoms, treatment response and clinical outcomes.

Treating MDD with comorbid anxiety

In the European Union, MagVenture TMS Therapy® is CE marked for the treatment of Major Depressive Disorder in adult patients who have failed to receive satisfactory improvement from two prior antidepressant medications, at or above the minimal effective dose and duration in the current episode.⁹

For individuals who respond to treatment for MDD and who have symptoms of comorbid anxiety, the clinical benefit may also include improvement of anxiety symptoms.⁹

The CE-marked indication remains the treatment of Major Depressive Disorder. This does not represent a separate indication for an anxiety disorder.⁹

We still have a lot to learn

MDD with comorbid anxiety symptoms is a common and clinically important presentation of depression. For many people with MDD, anxiety symptoms form a significant part of their experience.^1,5 Continued research into its neurobiology and treatment may help improve our understanding of how best to support this substantial patient population.

References:

1. Fava M, Alpert JE, Carmin CN, et al. Clinical correlates and symptom patterns of anxious depression among patients with major depressive disorder in STAR*D. Psychological Medicine. 2004;34(7):1299–1308. doi:10.1017/S0033291704002612
2. World Health Organization. Depressive disorder (depression). WHO. Updated August 29, 2025.
3. Arias-de la Torre J, Vilagut G, Ronaldson A, et al. Prevalence and variability of depressive symptoms in Europe: update using representative data from the second and third waves of the European Health Interview Survey (EHIS-2 and EHIS-3). The Lancet Public Health. 2023;8(11):e889–e898. doi:10.1016/S2468-2667(23)00220-7
4. Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: Results from the 2021 National Survey on Drug Use and Health. Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration; 2022. HHS Publication No. PEP22-07-01-005.
5. Hopwood M. Anxiety symptoms in patients with Major Depressive Disorder: commentary on prevalence and clinical implications. Neurology and Therapy. 2023;12(Suppl 1):5–12. doi:10.1007/s40120-023-00469-6
6. Menon V, Uddin LQ. Saliency, switching, attention and control: a network model of insula function. Brain Structure and Function. 2010;214:655–667. doi:10.1007/s00429-010-0262-0
7. Uddin LQ. Salience processing and insular cortical function and dysfunction. Nature Reviews Neuroscience. 2015;16:55–61. doi:10.1038/nrn3857
8. Gruber M, Schulte J, Mauritz M, et al. Network-based analysis of differential white matter connectivity in major depressive disorder with and without comorbid anxiety. Neuropsychopharmacology. 2026;51:916–925. doi:10.1038/s41386-025-02312-y
9. MagVenture A/S. CE Markings: EU CE marked for the treatment of Major Depressive Disorder. Current MagVenture CE-mark information.