Treatment-resistant depression (TRD)

is when a person’s depression does not adequately respond to multiple standard treatments. These standard treatments typically include antidepressant medications and psychotherapy. About one-third of people with depression may experience treatment-resistant symptoms.

Approaches to treatment for treatment-resistant depression can vary depending on the severity of the condition and individual factors. Here are some common approaches:

1. Medication adjustments: In cases of treatment-resistant depression, doctors may explore different medications or combinations of medications. They may adjust the dosage, change the medication class, or add augmentation agents to enhance the antidepressant effects.

2. Psychotherapy modifications: Different forms of psychotherapy, such as cognitive-behavioral therapy (CBT) or interpersonal therapy (IPT), may be tried. Therapists may also modify the therapeutic approach to address specific symptoms or underlying issues.

3. Electroconvulsive therapy (ECT): ECT involves administering electrical currents to the brain under general anesthesia. It is when other treatments have failed, and it has shown to be highly effective in treating severe depression. ECT may cause side effects, such as short-term memory loss.

4. Transcranial magnetic stimulation (TMS): TMS is a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain. It is when other treatments have not been successful. TMS is usually well-tolerated and has fewer side effects compared to ECT.

5. Esketamine: Esketamine is a nasal spray medication that targets the NMDA receptors in the brain. It has been approved for the treatment of treatment-resistant depression when used in combination with an oral antidepressant. Esketamine can have rapid antidepressant effects, but it also has potential side effects, such as dissociation and increases in blood pressure.

6. Vagus nerve stimulation (VNS): VNS involves the implantation of a device that stimulates the vagus nerve, which is connected to various brain regions involved in mood regulation. The device sends electrical signals to the brain, and it is typically used in cases of severe treatment-resistant depression. VNS may cause side effects such as voice changes or hoarseness.

It is important to note that the specific treatment approach for treatment-resistant depression should be determined by a qualified healthcare professional based on an individual’s unique circumstances and medical history. These treatment options may have varying success rates and potential side effects, so a thorough evaluation is crucial to determine the best course of action.

“We treat treatment resistant depression”

Risk Factor for TRD

Duration of the episode

The longer the episode of depression, the greater the atrophy in specific brain regions (eg, hippocampus); the cognitive and behavioral changes that take place during long episodes make a return to previous well-being difficult

Severity of the episode

Both ends of the depression spectrum (most severe, mildest) are hypothesized to increase the risk of poor response-severe depression is associated with biological unbalances; mild depression, with lower drug versus placebo response

Co-morbid Disorders

Comorbid disorders like anxious symptoms and full anxiety disorders (especially generalized anxiety disorder) were found to be predictors of lower rates of response and remission; personality disorders, especially avoidant and borderline, are negative prognostic factors

Biological factors

Biological factors have also been studied as possible predictors of TRD. Genetic variants within the serotonin transporter-serotonin receptors and genes involved in neurodevelopment-have been found to modulate the risk of TRD.

Combination of antidepressants

In spite of the large number of antidepressants available at the present time, they are far from ideal and all show a similar slow, and frequently, incomplete response. Thus, the need for new and better compounds is as urgent and compelling as ever. While waiting for the panacea of future antidepressants, clinicians have developed a variety of associations of several antidepressants or an antidepressant with a second different agent.

Augmentation with another drug

A combination of 2 antidepressants or augmentation with another drug, such as lithium, a thyroid hormone, or an atypical antipsychotic, can be tried. The most robust evidence is augmentation of conventional antidepressant therapy with atypical antipsychotics. Switching to another antidepressant may also help. However, there is no clear evidence to guide the choice between augmentation and switching

Psychological counseling

Psychological counseling (psychotherapy) by a psychiatrist, psychologist or other mental health professional can be very effective. For many people, psychotherapy combined with medication works best. It can help identify underlying concerns that may be adding to your depression. For example, psychotherapy can help you:

Find better ways to cope with life’s challenges

Deal with past emotional trauma

Manage relationships in a healthier way

Learn how to reduce the effects of stress in your life

Address substance use issues

Treatment options

Transcranial magnetic stimulation (TMS)


TMS is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression. TMS is typically used when other depression treatments haven’t been effective.

This treatment for depression involves delivering repetitive magnetic pulses, so it’s called repetitive TMS or rTMS.


Spravato is a prescription medicine, used along with an antidepressant taken by mouth, for treatment-resistant depression (TRD) in adults.

SPRAVATO® is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist
indicated, in conjunction with an oral antidepressant, for the treatment of:
• Treatment-resistant depression (TRD) in adults.  
• Depressive symptoms in adults with major depressive disorder (MDD) with
acute suicidal ideation or behavior.