How does patients’ mental health influence treatment adherence and effectiveness?

Mental health: history, definitions, and current issues

Mental health is a broad and constantly evolving concept. Long reduced to the mere absence of psychiatric disease, it now encompasses much broader notions such as emotional well-being, psychological health, quality of life, or mental well-being. Historically, mental health was mainly associated with the management of psychiatric disorders. Over the past decades, however, the concept has expanded.

In 1946, the WHO already emphasized the notion of well-being, defining health as “a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity”. It was only in 2001 that the WHO clarified its definition of mental health, describing it as “a state of well-being in which every individual realizes his or her own potential, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to her or his community”. This more positive vision presents mental health not only as the absence of psychiatric disorders, but as an essential resource for a fulfilling life. In 2022, the WHO further integrated the notion of human rights into its definition by adding: “Mental health is a basic human right for all people”. Today, mental health is at the core of societal and media debates, fueling discussions around well-being, burnout, or depression.

In this article, we rely on the WHO’s 2001 definition, which distinguishes three levels of mental health:

1. Positive mental health, corresponding to a general state of well-being.
2. Reactive psychological distress, arising in response to a stressful event and potentially manifesting as anxiety, stress, sadness, irritability, or sleep disorders, without necessarily constituting a psychiatric disorder in the strict sense.
3. Psychiatric disorders, defined by a set of lasting and significant symptoms, such as mood disorders, anxiety disorders, chronic stress, psychoses, or personality disorders, which impair personal, social, or professional functioning.

In France, mental health has become a public policy priority, particularly due to the COVID-19 crisis, which exacerbated anxiety, social isolation, and depressive disorders within the population. For several years, national plans — such as the Projets territoriaux de santé mentale (PTSM) — have sought to better structure care provision, promote prevention, and reduce stigma. French public authorities have shown a growing willingness to invest in mental health, both in care and prevention, aware of the economic, social, and health challenges it represents.

Mental health affects treatment adherence and the patient care pathway

One of the first documented effects of mental health is its influence on therapeutic adherence. The WHO estimates that poor adherence drastically reduces the effectiveness of long-term treatments. For example, among patients living with HIV, depression is associated with lower adherence to antiretrovirals and higher viral load. In patients who have suffered an acute myocardial infarction, lower levels of anxiety and depression are associated with better medication adherence. More broadly, in patients with cardiovascular disease, studies show that anxiety and depressive mood reduce the ability to follow medical recommendations, whether regarding diet, physical activity, or medication intake.

Stress also plays a major role: a study conducted during the COVID-19 pandemic showed that high stress levels significantly reduced adherence to medications. Similarly, stress management programs in oncology have reduced fatigue, improved emotional well-being, and can strengthen patient engagement, leading to better treatment adherence and a greater ability to cope with side effects.

Beyond adherence, mental health also impacts care pathways, enabling better diagnosis and guiding patients toward more appropriate and optimal treatment. A study on prostate cancer screening found that men with high stress levels were 17% less likely to undergo screening, increasing the risk of late diagnosis¹Kotwal AA et al. (2013). The influence of stress, depression, and anxiety on PSA screening rates in a nationally-representative sample. Med Care.. Another study on 50,000 veterans with cancer revealed that those receiving psychological support were 35% more likely to receive optimal treatment (aligned with medical guidelines, delivered without delay, and at the right intensity)²National Cancer Institute. (2020). Study Links Mental Health Treatment to Improved Cancer Survival. https://www.cancer.gov/news-events/cancer-currents-blog/2020/lung-cancer-treating-mental-health-longer-survival. In addition, collaborative care models that integrate psychologists into medical teams help reduce unplanned hospitalizations.

All these examples demonstrate the importance of integrating psychological support for patients into care strategies — not only to improve adherence but also to optimize overall management as a true continuum of care.

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Mental health influences therapeutic response

Chronic stress and anxiety disorders profoundly alter patient physiology. They activate the hypothalamic-pituitary-adrenal axis, leading to sustained production of cortisol and adrenaline. In the long term, this fosters a pro-inflammatory state. Several meta-analyses have shown significantly higher levels of C-reactive protein (CRP, a biological marker of inflammation) and interleukin-6 (IL-6, a marker of chronic vascular inflammation) in individuals suffering from depression or anxiety³Howren MB et al. (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic Medicine.⁴Slavich GM, & Irwin, M. R. (2014). From stress to inflammation and major depressive disorder: : A Social Signal Transduction Theory of Depression. Psychological Bulletin.

This chronic inflammation is associated with increased pain, fatigue, sleep disorders, and a subjective worsening of physical symptoms. Among coronary patients, elevated CRP levels are linked to a higher risk of cardiovascular complications.

These biological imbalances can directly impair the effectiveness of medical treatments. For example, in lung cancer patients undergoing immunotherapy, severe psychological distress has been associated with lower response rates, faster tumor progression, and progression-free survival reduced by half. Targeted interventions, such as stress management programs, have proven effective in lowering cortisol levels and improving biological responses in cancer patients.

This is more than a correlation: precise biological mechanisms explain these effects. Stress fosters sustained elevation of norepinephrine — a stress hormone — which can directly stimulate tumor growth. In mice, this hormone promotes angiogenesis (formation of new blood vessels feeding the tumor) and can even reactivate dormant cancer cells, contributing to metastatic spread. Specific molecular pathways have been identified, including β2-adrenergic receptor activation and the cAMP-PKA signaling pathway, which promote cancer progression⁵Cole SW et al. (2015). Sympathetic nervous system regulation of the tumor microenvironment. Nature Reviews Cancer.. In other words, psychological stress not only weakens patients but directly acts on tumor mechanisms at the cellular level.

Reactive psychological distress also indirectly affects treatment effectiveness by promoting the onset or worsening of comorbidities such as obesity. These, in turn, can impair therapeutic response by inducing chronic inflammation and contributing to resistance to certain chemotherapies.

The specific case of depression

Depression is a psychiatric disorder in its own right, requiring tailored medical management. It affects up to 40% of patients with chronic illnesses such as cancer or cardiovascular diseases and leads to lasting symptoms — fatigue, cognitive disorders, loss of interest — that complicate care management⁶INSERM. (2019). Depression. [in French] https://www.inserm.fr/dossier/depression/. Its impact on health is often more significant than that of other chronic diseases such as asthma or diabetes. It also substantially increases suicide risk: according to the WHO, more than 60% of suicides worldwide are linked to major depressive disorder⁷World Health Organization (2022). Suicide worldwide in 2021: global health estimates. https://www.who.int/publications/i/item/9789240069953. For this reason, depression is treated separately here, although it is often the avoidable outcome of reactive psychological distress.

Depression is a major factor in non-adherence: a meta-analysis showed that depressed patients are about three times more likely not to follow their treatment properly⁸DiMatteo MR et al. (2000). Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Archives of Internal Medicine.. Among diabetic patients, depression increases the risk of non-adherence or treatment abandonment by 76%⁹Gonzalez JS et al. (2008). Depression and diabetes treatment nonadherence: a meta-analysis. Diabetes Care.. This lower adherence worsens prognosis, particularly in oncology, where depression is associated with a 25% to 39% increase in mortality¹⁰Pinquart M et al. (2010). Depression and cancer mortality: a meta-analysis. Psychol Med..

Despite this concerning data, depression is still insufficiently addressed in care pathways. However, collaborative care models that combine medical follow-up with psychological support have proven effective in improving treatment adherence and clinical outcomes, particularly in chronic diseases such as diabetes or cardiovascular conditions. These approaches have led to improvements in clinical indicators, such as better glycemic control in diabetic patients.

Since mental health influences treatment effectiveness through its impact on adherence and therapeutic response, the pharmaceutical industry must consider its potential levers of action. We recommend a comprehensive approach to mental health built around three main areas: data generation (integration of indicators in clinical trials, research on biological mechanisms and at-risk populations, etc.), evolution of care models (support for integrated care including psychological support, training professionals to detect psychological distress, etc.), and development of patient solutions (coaching, apps, monitoring, “beyond the pill” initiatives, etc.).

Alcimed can support you in exploring these opportunities and implementing innovative approaches at the interface of mental health and therapeutic impact. Don’t hesitate to contact our team!

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About the author, 

Fanny, Consultant in Alcimed’s Healthcare team in France