Why Do I Feel Empty? Treatment Resistant Depression FAQs

Have you attempted several different treatments for depression yet still ask yourself why do I feel empty? These feelings of emptiness and despair can be overwhelming and confusing, and you may have what is known as treatment resistant depression, or TRD.
 
For those struggling with TRD, this emotional void can feel extremely isolating. Let's answer some common questions about TRD, explore why some people experience this persistent sense of emptiness, and discuss effective treatment options that may help restore hope and well-being.

What Is Major Depressive Disorder

First let’s talk about MDD, or Major Depressive Disorder, which typically is the first diagnosis you would receive. This serious mental health condition affects millions of people around the world.
 
Typically, the symptoms include persistent feelings of sadness, and/or hopelessness, and a loss of interest in previously-enjoyable activities  People with MDD often experience physical symptoms such as changes in sleep issues, loss of appetite (or increase), and a drop in energy levels.
 
To be diagnosed with MDD, these symptoms typically must last for at least two weeks and significantly impact a person’s daily life, relationships, or ability to function. MDD can vary in severity, with some individuals responding well to standard treatments like therapy and medication, while others may develop treatment-resistant depression (TRD).

What Causes Depression?

To be honest, we don’t always know the specific reasons why depression occurs. Depression is a complex mental health condition with no single cause. Instead, it typically arises from a combination of biological, psychological, and environmental factors. Some common contributors include:

Biological Factors

• Brain Chemistry: Imbalances in neurotransmitters like serotonin, dopamine, and norepinephrine can affect mood regulation.
• Hormonal Changes: Hormone fluctuations, such as those occurring during pregnancy, menopause, or due to thyroid issues, can contribute to depression.
• Genetics: Individuals with a family history of depression may have a higher risk of developing the condition.

 
Psychological Factors

• Personality Traits: People with low self-esteem, perfectionism, or a tendency to ruminate may be more vulnerable.
• Unresolved Trauma: Past emotional or physical trauma can increase the risk of developing depression.

 
Environmental Factors

• Chronic Stress: Prolonged exposure to stressful situations, such as financial struggles, work pressure, or relationship conflicts, can trigger depression.
• Life Events: Major life changes — including the loss of a loved one, divorce, or job loss — are common triggers.
• Childhood Experiences: Adverse childhood experiences, such as neglect or abuse, can increase the risk.

 
Medical Conditions

• Chronic Illness: Conditions such as diabetes, heart disease, and chronic pain can contribute to depressive symptoms.
• Medication Side Effects: Certain drugs, including some blood pressure medications or hormonal treatments, may cause or worsen depression.

 
Lifestyle Factors

• Poor Sleep: Lack of restful sleep is closely linked to mood disorders.
• Substance Abuse: Alcohol, drugs, or certain medications can contribute to or exacerbate depressive symptoms. Of course, as an addiction psychiatrist, I often find that substance use disorders develop because a person is suffering from depression and drugs or alcohol are used to self-medicate.
• Nutritional Deficiencies: Deficiencies in key nutrients, such as vitamin D, omega-3 fatty acids, and B vitamins, have been linked to depression.

 
Social Isolation

• Limited social support or feelings of loneliness can increase the risk of developing depression.

 
Because depression can stem from multiple factors, effective treatment often requires a depression doctor to try a combination of therapies tailored to an individual's unique circumstances.

What Is Treatment Resistant Depression?

TRD is a form of major depressive disorder (MDD) that does not respond adequately to at least two different antidepressant treatments, taken at the appropriate dose and duration. Individuals with TRD may experience ongoing symptoms such as:

• Persistent sadness
• Fatigue
• Lack of motivation
• Emotional numbness

 These feelings persist despite trying multiple treatment approaches. Because TRD can be challenging to manage, it often requires a combination of therapies, specialized treatments, and expert care.

How Is TRD Treated?

In this blog, the first in a series regarding TRD, we will briefly describe the various treatment resistant depression treatment options. As we dive further into the subject our next blogs will take a deeper dive into specific treatments, specifically some of the latest alternative treatments for people with TRD or depression in general.
 
But first, let’s take a quick look at the many different options psychiatrists can utilize to help patients with TRD. Keep in mind, that in many cases, it’s best to use a combination approach that includes multiple treatment options.

Medication Strategies

1. Switching Antidepressants
If one type of antidepressant doesn’t work, switching to another class of medications (e.g., from SSRIs to SNRIs) may be beneficial.
 
2. Combination Therapy
Using two different classes of antidepressants together can sometimes provide better results.

Augmentation Therapy

This entails adding non-antidepressant medications to enhance the effects of current treatment. Options may include:

• Atypical antipsychotics (e.g., aripiprazole, quetiapine)
• Mood stabilizers (e.g., lithium)
• Stimulants (e.g., methylphenidate)
• Thyroid hormones in some cases
• Ketamine or Esketamine (Spravato)
• Dopamine agonists (e.g. Pramipexole)

Ketamine for treatment resistant depression (often administered via IV infusion) and esketamine (a nasal spray) have shown rapid improvement in depressive symptoms, particularly in individuals with TRD. We will explore ketamine and specifically esketamine further on during our series about TRD. Pramipexole alone or in combination with other drugs, such as ketamine, is another subject we will explore more deeply in future blogs.

Psychedelic-Assisted Therapy

Emerging research supports the use of psilocybin (magic mushrooms) in controlled, therapeutic settings for some forms of TRD. Again, this will be a subject we will explore psilocybin for treatment resistant depression more deeply in a future blog.

Therapy and Non-Medication Treatment

​1. Psychotherapy (Talk Therapy)
Cognitive Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), and Acceptance and Commitment Therapy (ACT) may offer support when combined with other treatments. Again, as an experienced depression psychiatrist, I strongly recommend adding some type of talk therapy to any treatment plan.
 
2. Transcranial Magnetic Stimulation (TMS)
This is a non-invasive treatment where we use magnetic fields to stimulate the nerve cells in the brain. TMS has been found to be effective for some patients who haven’t responded to traditional medications.
 
3. Electroconvulsive Therapy (ECT)
ECT can be highly effective for severe TRD, particularly when other treatments have failed. Modern ECT is safer and involves controlled electrical currents under anesthesia.
 
4. Vagus Nerve Stimulation (VNS)
A device implanted in the chest sends electrical impulses to the vagus nerve, which can help regulate mood.
 
5. Deep Brain Stimulation (DBS)
Typically used for neurological conditions like Parkinson’s, DBS is now being explored for severe cases of TRD.

Lifestyle and Complementary Therapies

1. Exercise & Physical Activity
I know it can be tough for people with depression to get outside and get moving, but regular exercise has been shown to improve mood and overall mental well-being. I highly recommend trying to get outside and walking for at least 20 minutes per day. Sunshine, fresh air and a change of scene might not be a miracle cure, but they certainly can help improve your mood.
 
2. Mindfulness & Meditation
Practices such as mindfulness, meditation, yoga, or tai chi may reduce depressive symptoms.
 
3. Nutritional Support
Omega-3 fatty acids, vitamin D, and certain amino acids may provide additional support.
 
4. Light Therapy
This is especially effective for individuals with seasonal affective disorder (SAD) but can also benefit TRD patients.

Emerging & Experimental Treatments

1. Neurofeedback
This therapy trains individuals to regulate brainwave patterns.
 
2. Digital Therapeutics
App-based programs designed to support mental health may provide adjunctive benefits.
 
3. Biomarker Testing
Genetic testing may help identify which medications are most likely to be effective for an individual.

Support Networks & Community

Joining support groups or participating in peer support programs can help individuals manage feelings of isolation and frustration. If you are religious, I also find that spirituality and fellowship can help lessen the impact of depression and help you feel less alone and isolated.

Please Seek Help Today!

As a psychiatrist for depression, I understand how frustrating it can be to have treatment resistant depression. Many with TRD feel very hopeless, but generally, we can always find some type of treatment option that works, even if we need to veer away from some traditional therapies. If you are struggling with TRD and wondering “Why do I feel empty” despite several attempts at treatment, please contact me today and let’s find a new approach that can help you rebuild your life and mental health.
 
Whether you need a psychiatrist for TRD or perhaps a psychiatrist for bipolar disorder, anxiety, borderline personality disorder or another mental health condition, I work as a local psychiatrist for patients in Thousand Oaks, Westlake Village and surrounding areas. Don’t give up hope, together we can find a treatment plan that helps you live a better and happier life.