Treatment Could Provide Relief for Comorbid Depression and Anxiety

Targeting transdiagnostic treatments  • Prioritizing prevention

On the surface, depression and anxiety may seem like polar opposite conditions. In the simplest sense, depression could be defined as an absence of energy, and this overwhelming sense of exhaustion is often accompanied by intense feelings of worthlessness and guilt, being disinterested in activities that once brought a person joy, and, for some, suicidal ideation. The uncontrollable worry characteristic of anxiety, on the other hand, often leaves people feeling jittery, tense, and irritable, as if their mind is being run by a motor that refuses to stop. 

Depression and anxiety, as outlined in the Diagnostic and Statistical Manual of Mental Disorders, also share a number of symptoms, however—including insomnia, fatigue, and difficulty concentrating—and many people who suffer from one of these disorders must also grapple with the other. 

“Comorbidity of depression and anxiety disorder is the rule, not the exemption,” wrote Sigal Zilcha-Mano (University of Haifa) in her upcoming Clinical Psychological Science article. 

A 2015 global survey by Ronald C. Kessler (Harvard Medical School) and colleagues found that 45% of people with a lifetime history of major depressive disorder (MDD) had also experienced at least one anxiety disorder and that 41% of people diagnosed with MDD in the past 12 months were also diagnosed with anxiety, Zilcha-Mano noted in her article. Additionally, current psychotherapy practices have been found to be effective for only 50% of patients across conditions, and treatment can be even less effective when patients present comorbid mental health conditions. 

Though treating one condition does not always lead to improvement in a comorbid disorder, some patients with depression and anxiety are seeing results when just one condition is targeted, Zilcha-Mano said in an interview with the Observer. 

“Targeting depression in therapy often leads to reductions not only in depressive symptoms but also in anxiety,” Zilcha-Mano said. “This insight underscores a critical point for clinical practice: Depression and anxiety are deeply interconnected, and understanding this interplay can be a powerful tool for personalizing treatment.” 

Zilcha-Mano analyzed the within-person effects of therapy focused on treating depression on comorbid anxiety through a study of 100 patients with MDD. Participants received 16 weeks of therapy focused on changing relationship patterns related to their depression, during which they continuously self-reported their levels of depression and anxiety. 

Zilcha-Mano found that patients who reported reduced depression at one appointment were likely to report reduced anxiety at their next therapy session. This effect was most pronounced for patients who reported a pretreatment increase in depression and decrease in anxiety. 

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Understanding the pretreatment relationship between each patient’s depression and anxiety could help clinicians develop personalized treatment plans, Zilcha-Mano said. For patients with the pretreatment symptom dynamic highlighted in this study, targeting depression could be enough to significantly reduce the severity of both disorders, while other patients may require additional treatment specifically for anxiety, she said. 

“This work transforms the concept of comorbidity from being seen as a source of complexity or ‘noise’ into something invaluable—a guiding factor for tailoring treatment to the unique needs of each individual,” Zilcha-Mano said. “Every patient’s journey with depression and anxiety is unique, and therapy should be tailored to reflect that in order to be most effective.” 

Studies that focus on within-person differences are essential to moving beyond one-size-fits-all approaches to treatment, she continued. 

“While between-individual studies help us understand general trends, they can miss the nuances of what happens within a single person,” Zilcha-Mano said. “Knowing that therapy is being tailored to their unique characteristics and needs can help patients feel more confident and engaged in the process, potentially leading to better outcomes.” 

Targeting transdiagnostic treatments 

There are several proposed explanations for the relationship between anxiety and depression, wrote Jaakko Tammilehto (University of Helsinki) and colleagues in their upcoming Clinical Psychological Science article.  

The helplessness–hopelessness theory suggests that depression occurs as the result of unaddressed anxiety. In this model, people are believed to become anxious due to the fear that they are unequipped to handle challenges in their lives, leading to a sense of helplessness that eventually develops into the feelings of hopelessness associated with depression. 

Current research suggests that the interplay between anxiety and depression is likely not so straightforward, however, Tammilehto and colleagues wrote. Some researchers have proposed a bidirectional model of comorbidity, in which both conditions reduce people’s motivation to approach new situations, build coping skills, and pursue their goals, contributing to a cycle of anxiety and depression. 

The transdiagnostic model, on the other hand, suggests that comorbid anxiety and depression may arise from shared risk factors, such as genetic vulnerability, adverse childhood experiences, personality traits like neuroticism, and mechanisms like rumination and emotional dysregulation that influence both conditions. 

“Rumination can intensify negative emotions and foster insecurities, creating vicious circles that may reinforce both depression and anxiety,” the researchers wrote. 

Tammilehto and colleagues evaluated these models using two advanced statistical techniques and data from four distinct cohorts. The first two cohorts consisted of patients receiving cognitive behavioral internet-based therapy (iCBT), including 6,675 patients who were treated primarily for mild to moderate depression and 6,699 patients who were treated primarily for generalized anxiety disorder. These therapies included seven or 12 iCBT lessons on a digital learning platform and weekly messaging with their online therapist. The patients reported their symptoms of anxiety and depression at the beginning, middle, and end of treatment. 

The remaining two cohorts were drawn from existing longitudinal studies of well-being in the United States and Ireland, including 3,087 American and 6,253 Irish participants. The American participants completed measures of well-being every 10 years during three waves from 1995 to 2014, while the Irish participants did so during three waves spaced 1 to 3 years apart from 2009 to 2015. 

The findings from both clinical groups and the general population showed that shared underlying factors primarily drive the co-occurrence of depression and anxiety rather than bidirectional influences between the symptoms. Furthermore, in the general population cohorts, some evidence was found that changes in depression caused changes in anxiety. 

At the beginning and across treatment, depression and anxiety were found to vary together among patients receiving iCBT, with treatment targeting one condition reducing symptoms of both disorders. As patients progressed through treatment, however, the relationship between their symptoms of anxiety and depression began to look more similar to that of the general population. In line with this, from the middle to the end of treatment, changes in patients’ levels of depression increasingly appeared to cause changes in their anxiety. 

“Overall, this large-scale study suggests that the interplay between depression and anxiety is primarily driven by shared transdiagnostic processes alongside the causal primacy of depression,” Tammilehto and colleagues wrote. “Over the course of treatment, the primary causal relationship between depression and anxiety may change to align with the primary dynamic observed in the general population.” 

These findings also suggest that iCBT may address similar underlying dynamics of depression and anxiety regardless of which disorder the intervention is intended to treat. CBT’s emphasis on changing dysfunctional thought patterns, self-acceptance, and behavioral activation, along with spontaneous recovery, are all potential contributors to this effect, Tammilehto and colleagues wrote. 

Prioritizing prevention 

According to recent modeling studies, the current treatment options for depression have the potential to reduce the prevalence of depression in the global population by up to one third, wrote Pim Cuijpers (Vrije Universiteit Amsterdam) in his 2024 Current Directions in Psychological Science article. These models promise relief for some of the 280 million people diagnosed with depression worldwide, but the ongoing increase in treatment uptake has yet to make a dent in the prevalence of depression. 

In order to meaningfully reduce the number of people living with this condition, which is currently responsible for 6% of years lived with a disability worldwide, researchers need to develop more effective programs for preventing the onset of depression in the first place, Cuijpers explained.

“If we really want to make progress in preventing depressive disorders, we need policymakers, funders, and researchers to take the problem seriously and make sufficient resources available for research,” wrote Cuijpers. Given that subclinical depression may cause anxiety, as Tammilehto and colleagues found, prevention could also help reduce the prevalence of comorbid depression and anxiety.

Prevention programs can be delivered at three levels, each with their own tradeoffs, Cuijpers explained in his article. Universal programs are aimed at an entire population, typically in educational, professional, and healthcare settings, regardless of individuals’ risk of developing depression. Universal prevention interventions are often low cost and have a low level of stigma associated with them because they can be delivered as part of existing programs related to health education, workplace well-being, and postpartum care. 

Unfortunately, it can be difficult to prove the effectiveness of universal interventions because doing so would require a very large participant pool, and each participant would need to complete multiple expensive, time-consuming diagnostic interviews, Cuijpers wrote. Given that 1.7% of the general population is expected to experience depression each year, a trial would need to include over 60,000 participants to have enough statistical power to detect even a small reduction in the onset of depression, he explained. 

Studies of selective prevention interventions can also require large participant groups, but these programs have a greater potential to prevent depression because they are aimed at people who have a high risk of developing the disorder. These include people who have recently experienced a traumatic event, the children of depressed parents, nursing home residents, caregivers for people with chronic illnesses, and people with a history of childhood abuse. Selective prevention programs also have a relatively low level of stigma associated with them because they often take the form of support groups for people with a shared identity rather than a shared diagnosis.  

In a 2021 meta-analysis, Cuijpers and colleagues found that people who participated in selective prevention programs aimed at the children of depressed parents, caregivers for patients with dementia, and people with physical health conditions were 21% less likely to develop depression than people with similar life challenges who did not participate. That said, some people choose to participate in support groups because they are already depressed, which can complicate studies on the preventative potential of these programs, Cuijpers noted. 

Finally, indicated prevention programs offer interventions to people with subclinical symptoms of depression. These interventions can also be highly effective—in the same meta-analysis, Cuijpers and colleagues found that participants were 19% less likely to develop depression—but people are often reluctant to engage with them because of the stigma associated with mental healthcare. In the Netherlands, for example, most people with subclinical depression were able to access a free support group until 2012, but just 1% of people who qualified chose to participate in the group, Cuijpers noted in his article. 

More research is needed on how to increase participation in selective and indicated prevention programs if these interventions are going to meaningfully reduce the prevalence of depression, Cuijpers wrote. People with subclinical depression may be more willing to attend online support groups or to participate in indirect interventions that target related but less stigmatized challenges, such as insomnia, perfectionism, and stress, he added. It’s also important for researchers to explore how to prevent depression at the structural level through reducing economic inequality, increasing access to high-quality housing, and providing resources and social support for disadvantaged groups. 

Although comorbid depression and anxiety can feel insurmountable to those in the thick of it, the work of researchers like Cuijpers, Tammilehto, and Zilcha-Mano offers patients the possibility of a more peaceful future. 

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References 

Cuijpers, P. (2024). Preventing the onset of depressive disorders: State of the art and future directions. Current Directions in Psychological Science, (0)0. https://doi.org/10.1177/09637214241297667 

Lind, M., Ture, S., McAdams, D. P., & Cowan, H. R. (2024). Narrative identity, traits, and trajectories of depression and well-being: A 9-year longitudinal study. Psychological Science, 35(12), 1325–1339. https://doi.org/10.1177/09567976241296512  

Tammilehto, J. (In Press) Temporal dynamics between depression and anxiety symptoms during internet-based therapy and in the general population. Clinical Psychological Science. 

Zilcha-Mano, S. (2024) Is targeting depression sufficient to alleviate anxiety comorbidity? Exploring between-individual heterogeneity in within-individual processes. Clinical Psychological Science.