Long-Term Effects of Treatment-Resistant Depression

While depression is often treatable with therapy, medication, or lifestyle changes, for millions of people, symptoms do not respond adequately to standard treatments. This condition, known as treatment-resistant depression (TRD), is one of the most complex and to treat in mental health care today, and according to the National Institutes of Health, it can have significant and long-lasting consequences beyond mood symptoms. TRD can affect nearly every aspect of a person’s life, including physical health, cognitive function, and relationships.

Understanding Treatment-Resistant Depression

Treatment-resistant depression typically refers to depression that does not significantly improve after at least two antidepressant treatments. While many people with depression eventually find relief, individuals with TRD often try various therapies without seeing a sustained improvement in their symptoms, which causes feelings of extreme hopelessness and frustration, as well as many negative effects on health and well-being.

Physical Health

One of the most overlooked aspects of depression is its impact on physical health. When depression becomes chronic and resistant to treatment, these effects will only be more significant.

Some physical issues caused or made worse by TRD include:

• Inflammation and physiological stress
• Higher risks of cardiovascular and cerebrovascular diseases, including heart attacks and strokes
• Increased risk of thyroid disorders, chronic pain conditions, and digestive problems
• Issues with hormone and immune function caused by the persistent stress response associated with long-term depression, which can increase the risk of illnesses such as diabetes and heart disease
• Chronic pain, such as headaches, back pain, or body aches that do not resolve easily, causing an unpleasant cycle where pain worsens depression, and depression exacerbates the perception of pain

Over time, the combination of these physical and mental symptoms will make recovery from TRD even more challenging.

Cognitive and Functional Impairment

These cognitive impairments can persist even during periods when mood symptoms appear somewhat improved. Over time, this decline may significantly limit independence and productivity.

Negative cognitive effects associated with TRD include:

• Memory lapses, slowed processing speed, and difficulty concentrating
• Trouble making decisions, even for simple daily tasks
• Trouble remaining productive at work or reduced performance
• Increased feelings of frustration, confusion, or brain fog

Reduced Quality of Life

One of the most difficult long-term effects of TRD is the significant effect it has on overall quality of life. Depression, especially TRD, can make it very difficult for those living with it to experience any happiness or pleasure at all.

Those with TRD may experience a reduced quality of life for the following reasons:

• An inability to maintain a daily routine or manage household responsibilities
• A loss of desire to engage in hobbies and activities once enjoyed

• A decline in social relationships, as loved ones struggle to understand why symptoms persist and those with TRD experience feelings of guilt, shame, and isolation
• Financial strain due to an inability to maintain steady employment

Neurobiological Changes

Long-term untreated or poorly managed TRD is also linked to changes in brain biology. TRD is associated with reduced levels of brain-derived neurotrophic factor (BDNF), a protein that supports brain plasticity, neural growth, and healthy connections between brain cells.

This means that lower BDNF levels can impair the brain’s ability to adapt and reorganize, potentially contributing to persistent symptoms and cognitive struggles. This neurobiological component is evidence that TRD is not the result of poor willpower or motivation to get better – these complex changes in brain function require comprehensive, science-based treatment approaches.

The Importance of Early and Comprehensive Care

Early treatment for TRD is crucial to prevent symptoms from worsening and improving quality of life. Because those with TRD struggle to find relief with standard treatment, specialized, innovative therapies are often necessary to see a reduction in symptoms. Esketamine therapy is a groundbreaking treatment and one of the only FDA-approved therapies that has shown in multiple studies to provide fast and effective relief from treatment-resistant depression.

This self-administered FDA-approved nasal spray may improve symptoms for those with TRD even after the first session. It also helps combat long-term damage caused by TRD by repairing the damaged connections in the brain and reducing harmful effects.

SPRAVATO® at LiveWell Counseling

LiveWell Counseling now offers esketamine therapy with SPRAVATO®, the first and only FDA-approved nasal spray for adults with treatment-resistant depression. In our comfortable, calming lounge, clients can now self-administer the SPRAVATO® (esketamine) nasal spray under the supervision of our board-certified psychiatrists and nurses.

To learn more, please call (201) 848-5800 or visit SPRAVATO®. This innovative treatment is covered by most insurance providers.