Treatment-Resistant Depression Causes and Treatment

Major depressive disorder is a mood disorder that can interfere with daily functioning if left untreated—the criteria set forth by the American Psychiatric Association to aid in correctly diagnosing the condition. For two weeks or more, a person with major depressive disorder must have symptoms like depressed mood for most of the day, losing interest in activities that were once enjoyable, weight changes, slowing of speech or movements, fatigue, feeling worthless or guilty, trouble concentrating, and thoughts of death or suicide.

Some may experience sleep disturbances, anxiety, body aches and pains, digestive problems, and irritability.

For most, treatment for major depressive disorder works. A combination of medication and psychotherapy offers excellent results for millions of Americans. There are many others, however, who continue to experience depression even after being treated.

Reports show in a twelve-month period, there are approximately 8.9 million with depression who are taking medication. Of that number, 2.8 million have treatment-resistant depression. Both conditions can be costly to personal, professional, and social aspects of a person’s life.

Treatment-Resistant Depression Causes

There is no clear answer as to why some become resistant to antidepressants and others don’t. Multiple factors play a role in development. Factors may include genetics, past trauma, current living environment, and whether or not you have other conditions, like a substance use disorder.

Other causes may include age, biological factors, underlying physical or psychological conditions, and the length of time you struggle with depression.


To be diagnosed with treatment-resistant depression, your doctor will review current and previous methods you have used to alleviate symptoms of depression. For example, ensuring you are diagnosed accurately and that you don’t have an underlying medical condition, or lifestyle situation, causing the symptoms of depression or making them worse.

Your doctor will also evaluate any antidepressants to ensure the correct dose, if taken as prescribed, and for how long. Also, is a medication prescribed in combination with other antidepressants, counseling, or other treatments?

Once a doctor gives a final diagnosis of treatment-resistant depression, treatment can begin right away.

Treatment Strategies

While treatment-resistant depression can make you feel hopeless, don’t give up. There are many strategies and emerging therapies your doctor can prescribe. If increasing doses of antidepressants or combining them with other medications is not enough, your doctor may try a combination of traditional and advanced therapies.

Modern psychiatrists have taken treatment up a level with procedures showing excellent results, like the examples below, individually and when combined:

Ketamine Treatment

Ketamine is a psychedelic drug classified as an illegal, controlled substance with a high risk for abuse when used recreationally. However, when administered in controlled doses in a clinical setting, ketamine treatment is helping those with treatment-resistant depression feel better. Ketamine-assisted therapy is a version of therapy that combines ketamine doses with psychotherapy. This process has extended the positive effects of ketamine.

Vagus Nerve Stimulation

The vagus nerve is located on each side of the neck and runs from the base of the neck to the brain stem and into the chest. The vagus nerve sends signals up the brain stem to areas in the brain that affect mood.

To stimulate the vagus nerve, doctors implant a small device in your chest with a wire attached to your vagus nerve, usually on the left side. When the device releases electrical currents, they stimulate the vagus nerve, sending signals to the brain that decrease symptoms of depression.

Behavioral Therapy

Cognitive-behavioral therapy is a common technique used to treat all forms of depression, including treatment-resistant depression. It is a form of talk therapy that changes negative thinking patterns to positive ones. It is based on the theory that what you think influences your feelings and actions. If you have negative thinking, your actions will be negative. Therefore, if you have positive thinking, your actions will be positive.

Cognitive-behavioral therapy has many sub-treatments for assisting those with depression, like trauma-focused cognitive behavioral therapy for those trying to cope with the lingering effects of trauma that may play a role in their resistance to antidepressants.

Treatment-resistant depression can lead to some people harming themselves, even if they have no intention of dying or committing suicide. Dialectical behavior therapy helps you make better decisions and create a balance between acceptance and change.

Some people may choose to misuse substances like drugs and alcohol as a coping tool to cope with treatment resistance. They soon find substance use creates more problems and worsens depression. However, there are treatments to help, like motivational enhancement therapy, which can help you gain motivation and commitment to change.

Depression is often co-occurring with substance use disorders. Treating both at the same time gives you a greater chance of recovery success for treatment-resistant depression. An assessment will help your doctor decide if you need anti-craving medication to detox, and if so, which one is the best option in combination with depression treatment.

Mindful and Holistic Therapies

Participating in wellness activities that focus on the mind, body, and spirit is referred to as practicing mindfulness for depression. Mindfulness is a holistic approach to paying attention to your thoughts, emotions, behaviors, physical and spiritual needs at the moment, without judgment.

Mindfulness-based cognitive behavioral therapy is the most common, but there are many treatments available. Some require guidance from a therapist, while others, like mindfulness-based smartphone apps, can be done at your convenience.

The goal of mindfulness is to help you regulate emotions, handle stress, reduce anxiety, and improve mood.

Holistic techniques to support mindfulness include yoga, meditation or prayer, deep breathing, and acupuncture. Others practice biofeedback, guided imagery, massage, hypnosis, and reiki. There are hundreds of ways to care for your body, mind, and spirit so you can find a depression treatment that works.

If you have tried, without success, multiple ways to improve depressive symptoms, call us today. We can determine if you have treatment-resistant depression and, if so, create a treatment plan that works. There are new methods available to help you get back to living a happy, productive life.