What Is Treatment-Resistant Depression and How Can It Be Managed?

What you need to know

• Treatment-resistant depression (TRD) refers to major depression that does not respond adequately to at least two different antidepressant treatments.
• TRD affects 20-40% of patients with major depression and is associated with higher rates of hospitalization, suicide, and mortality.
• Management of TRD may involve optimizing current treatment, switching medications, combining therapies, or using other approaches like psychotherapy or brain stimulation techniques.

Understanding treatment-resistant depression

Depression is a common mental health condition that can significantly impact a person’s quality of life. While many people with depression respond well to initial treatments, a substantial portion continue to struggle with symptoms despite trying multiple therapies. This scenario is known as treatment-resistant depression (TRD).

What is treatment-resistant depression?

Treatment-resistant depression refers to cases of major depression that do not show adequate improvement after at least two different antidepressant treatments given at proper doses for sufficient time. Specifically, TRD is typically defined as a lack of significant clinical response (less than 50% reduction in symptoms) to two or more antidepressant medications from the same or different classes.

It’s important to note that what may appear to be treatment resistance could sometimes be due to other factors, such as:

• Incorrect diagnosis
• Inadequate treatment regimen
• Presence of other mental health conditions (e.g., anxiety disorders, eating disorders)
• Personality disorders
• Substance abuse or addiction
• Post-traumatic stress disorder (PTSD)
• Poor adherence to prescribed treatments
• Undiagnosed medical conditions
• Ongoing chronic stress

Healthcare providers will typically rule out these possibilities before concluding that a patient has true treatment-resistant depression.

How common is treatment-resistant depression?

Research indicates that approximately 20-40% of patients with a major depressive episode do not show a significant clinical response to their first antidepressant treatment. Furthermore, even among those who do show improvement, about half continue to have residual symptoms that negatively affect their functioning and increase the risk of relapse.

Only about 20-40% of patients achieve remission (defined as at least a 70% reduction in symptom severity or very low scores on depression rating scales) with their first depression treatment. Even when remission is achieved, there is often still a long journey to full recovery and return to previous levels of occupational and social functioning.

The impact of treatment-resistant depression

Treatment-resistant depression can have significant consequences for those affected:

Health complications

TRD is associated with higher rates of other health problems, including:

• High blood pressure
• Diabetes
• Heart failure

Increased healthcare utilization

Compared to depression that responds to treatment, TRD is linked to:

• Double the rate of hospitalizations
• 36% longer hospital stays

Suicide risk

The rate of suicide attempts is seven times higher in people with TRD compared to those with treatment-responsive depression.

Mortality

TRD is associated with higher overall mortality rates:

• 29-35% higher all-cause mortality compared to non-resistant depression
• Mortality risk similar to non-depressed individuals who are 13 years older

Functional impairment

People with TRD often experience ongoing difficulties with:

• Work performance and employment status
• Social relationships
• Daily activities and self-care

Approaches to managing treatment-resistant depression

While TRD can be challenging to treat, there are several strategies that healthcare providers may use to help improve symptoms and functioning:

Optimizing current treatment

This involves ensuring the current medication is being taken at the optimal dose for an adequate duration. Sometimes, what appears to be treatment resistance is actually under-treatment.

Watchful waiting

In some cases, it may take longer than expected for a treatment to show its full effects. Providers may recommend continuing the current treatment for a bit longer while closely monitoring for signs of improvement.

Reviewing past responses

If a patient has responded well to a particular medication in the past, it may be worth trying that treatment again, even if it’s not the most recent one used.

Switching medications

Changing to a different antidepressant, either within the same class or to a different class of medications, can sometimes lead to better results.

Combination treatment

This approach involves using two different antidepressants together, which may have complementary effects.

Augmentation strategies

“Add-on” or augmentation treatments involve adding a non-antidepressant medication to the current antidepressant regimen. Examples might include mood stabilizers, antipsychotics, or thyroid hormones.

Brain stimulation techniques

Several forms of brain stimulation may be considered for TRD:

• Electroconvulsive therapy (ECT): This involves applying electrical currents to the brain to trigger a brief seizure, which can rapidly improve severe depression symptoms.
• Transcranial magnetic stimulation (TMS): This non-invasive technique uses magnetic fields to stimulate specific areas of the brain involved in mood regulation.
• Vagus nerve stimulation: This involves implanting a device that sends electrical impulses to the vagus nerve, which has connections to brain regions involved in mood regulation.

Other approaches

Additional strategies that may be helpful include:

• Phototherapy (light therapy): Especially useful for depression with a seasonal pattern.
• Psychotherapy: Various forms of talk therapy, such as cognitive-behavioral therapy (CBT) or interpersonal therapy, can be beneficial alongside medication.
• Neurosurgery: In extremely severe and persistent cases, certain neurosurgical procedures might be considered as a last resort.

The importance of comprehensive care

It’s crucial to remember that managing treatment-resistant depression often requires a multifaceted approach. While medications play an important role, other factors such as lifestyle modifications, stress management, social support, and addressing any co-existing health conditions are also vital components of a comprehensive treatment plan.

Patients and their families should work closely with their healthcare providers to develop a personalized treatment strategy. This may involve collaborating with multiple specialists, including psychiatrists, psychologists, and other mental health professionals.

Conclusions

• Treatment-resistant depression is a significant challenge in mental health care, affecting a substantial portion of people with major depression.
• TRD can have severe consequences on health, functioning, and mortality if not adequately addressed.
• While TRD is difficult to treat, there are multiple strategies available, from medication adjustments to brain stimulation techniques.
• A comprehensive, individualized approach to care is essential for managing TRD effectively.