Treatment-Resistant Depression: What to Know About the Symptoms and Treatment Options

Depression can affect various aspects of life, modifying how a person thinks, feels, works, and interacts with others. While traditional depression treatments can bring a change in many patients, others continue to struggle despite trying multiple medications or therapeutic approaches. When depression symptoms remain despite adequate treatment, it may be a sign of treatment-resistant depression (TRD).

For individuals who have tried different treatments without experiencing meaningful relief, Treatment-Resistant Depression could be a major issue. However, that doesn’t mean there is no cure. Advances in mental healthcare have introduced additional treatment options, including Spravato treatment for depression, that may offer another route forward for eligible patients.

What Is Treatment-Resistant Depression?

Treatment-resistant depression is generally used to describe major depressive disorder that has not responded adequately to at least two different antidepressant treatments given at appropriate doses and for an adequate duration.

People respond differently to different antidepressants. Some patients may not see much improvement, while others may notice little or no change in their symptoms.

Treatment-resistant depression does not mean someone is incapable of recovering. Instead, it suggests that their current treatment approach may need to be reassessed or expanded.

A mental health professional can evaluate previous treatments, review symptoms, and determine whether other treatment strategies may be appropriate.

Common Signs and Symptoms of Treatment-Resistant Depression

Treatment-resistant depression can involve many of the same symptoms associated with major depressive disorder. The difference is that these symptoms continue despite trying multiple appropriate treatment approaches.

Here are some of the common signs:

1. Ongoing Feelings of Sadness or Hopelessness

People may experience ongoing sadness, emptiness, or hopelessness that interferes with everyday life. These feelings may continue even after starting or changing antidepressant medications.

2. Feeling uninterested in Everyday Activities

Activities that once brought joy and excitement may no longer feel enjoyable. They may lose interest in hobbies, social gatherings, and other activities.

3. Ongoing Fatigue and Low Energy

Depression can make even simple daily responsibilities feel overwhelming. Ongoing exhaustion may interfere with work, responsibilities, and personal relationships.

4. Difficulty in Concentrating

Treatment-resistant depression (TRD) may affect many things such as memory, focus, decision-making, and mental clarity. Some individuals describe feeling mentally exhausted or struggling to complete tasks that were once easy and manageable.

5.  Changes in Appetite

Depression may change eating habits, leading to a reduction in appetite or increased cravings.

6. Alterations in Sleep Patterns

Sleep disturbances are common symptoms of depression. Some individuals experience insomnia, while others sleep excessively but still feel tired throughout the day.

7. Feelings of Inferiority or Guilt

People may experience persistent self-criticism, guilt, or feelings of inadequacy. These thoughts can become particularly difficult when previous treatments have not provided sufficient relief.

If depression symptoms include thoughts of suicide or self-harm, immediate support is important. In the United States, individuals can call or text 988 for the Suicide & Crisis Lifeline.

Why Does Depression Become Treatment-Resistant?

There is no single explanation for why some individuals do not respond adequately to traditional depression treatments.

Numerous factors may contribute, including:

• Biological differences: Brain chemistry, genetics, and other biological factors may affect how someone responds to antidepressants.
• Coexisting mental health conditions: Anxiety disorders, post-traumatic stress disorder, and other conditions may complicate depression treatment.
• Medical conditions: Certain physical health conditions can contribute to symptoms that resemble or worsen depression.
• Medication-related factors: Dosage, treatment duration, medication interactions, etc., can affect treatment response.
• Lifestyle and environmental stressors: Chronic stress, trauma, sleep disturbances, and difficult life circumstances may influence depression symptoms.

Sometimes, what appears to be treatment-resistant depression may involve an underlying condition that has not yet been identified. A comprehensive psychiatric evaluation can help to choose the right treatment path.

Treatment Options for Treatment-Resistant Depression

Although traditional antidepressants remain an important part of depression treatment, individuals who do not respond adequately may benefit from trying additional approaches.

Treatment options depend on an individual’s medical history, previous treatment experiences, and also his personal needs.

1. Medication Adjustments

A psychiatrist may recommend adjusting an existing antidepressant, changing medications, or combining medications when clinically appropriate.

Some individuals benefit from augmentation approaches, which involve adding another medication to an existing antidepressant regimen to improve treatment response.

A qualified healthcare professional should always supervise medication changes.

2. Psychotherapy

One commonly used approach is cognitive behavioral therapy (CBT). It helps individuals recognize unhelpful thought patterns and develop better coping strategies.

Other therapeutic approaches may include:

• Interpersonal therapy (IPT)
• Dialectical behavior therapy (DBT), when appropriate
• Mindfulness-based cognitive therapy
• Trauma-informed psychotherapy

3. Transcranial Magnetic Stimulation (TMS)

Transcranial magnetic stimulation uses magnetic pulses to stimulate specific brain areas involved in affect regulation. It is a non-invasive treatment.

Treatment generally involves multiple sessions over a few weeks. TMS may be recommended for patients with depression who have not experienced adequate improvement with antidepressant medications.

4. Electroconvulsive Therapy (ECT)

ECT is a treatment option for certain severe or treatment-resistant depression cases. It involves delivering controlled electrical stimulation to the brain while the patient is under general anesthesia.

It may be considered when depression is particularly severe, when a rapid response is needed, or when other treatments have been unsuccessful.

5. Spravato (Esketamine) Treatment

One treatment-resistant depression treatment that has attracted attention in recent years is Spravato (esketamine).

Spravato is an FDA-approved prescription nasal spray used for certain adults with depression. It is approved for:

• Treatment-resistant depression in adults, either as a standalone treatment or along with an oral antidepressant.
• Depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior, in conjunction with an oral antidepressant.

Spravato works differently from traditionally used antidepressants. It acts on the brain’s glutamate system by blocking NMDA receptors, influencing pathways involved in brain signaling and possibly supporting changes in neural connections.

This different mechanism of action makes Spravato an important option for eligible individuals who have not experienced adequate improvement with conventional antidepressant treatments.

What Happens During Spravato Treatment?

Spravato is given as a nasal spray in a certified healthcare setting under medical supervision.

A typical treatment session involves:

1. Pre-treatment assessment: A medical practitioner reviews the patient’s health, medications, and vital signs.
2. Medicine administration: The nasal spray is self-administered under supervision by a healthcare professional.
3. Post-treatment monitoring: Staff monitor patients for at least two hours for potential side effects, including sedation, dissociation, and changes in blood pressure.
4. Discharge assessment: The healthcare team determines when the patient is ready to leave.

Patients should arrange transportation home because they must not drive or operate machinery until the following day after a good night’s sleep.

Spravato is not appropriate for everyone. A psychiatric provider can determine whether it’s a suitable option based on individual circumstances.

How Do You Know If It’s Time to Explore a Different Depression Treatment?

It may be time to change your depression treatment plan if:

• You have tried two or more antidepressants without meaningful improvement.
• Your depression symptoms continue to impede daily activities.
• You experience only partial relief from your current medication.
• You continue to struggle with sleep, motivation, concentration, or mental well-being.
• Medication side effects make it hard to continue treatment.
• Your depression symptoms have returned despite previous improvement.

Rather than assuming that nothing will work, try discussing your treatment history and ongoing symptoms with a psychiatrist.

A different medication, psychotherapy approach, or advanced depression treatment may offer additional possibilities.

Can Treatment-Resistant Depression Improve?

Yes. Treatment-resistant depression can improve, even when previous treatment attempts have been unsuccessful.

Finding an effective approach may take time and involve reassessing the diagnosis, investigating alternative medications, incorporating psychotherapy, or considering treatments such as TMS, ECT, or Spravato.

No universal treatment plan works for everyone. The goal is to identify an approach which addresses an individual’s symptoms, medical needs, and treatment history.

Keep in mind that progress may look different for each person. Improvements in sleep, energy, concentration, motivation, and daily functioning can all be meaningful parts of recovery.

Finding New Possibilities for Depression Treatment

Living with depression that does not respond to traditional treatment can feel discouraging. However, unsuccessful treatment attempts do not mean that other options are unavailable.

With advances in psychiatric care, individuals now have access to additional treatment approaches designed to address depression in different ways.

Spravato is one option that may be appropriate for adults with treatment-resistant depression. Through a comprehensive psychiatric evaluation at the Spravato Treatment Center, patients can learn whether this treatment or another approach corresponds with their individual needs. Contact our experts at Torii Wellness Center to determine whether Spravato is right for you.