What is Treatment-Resistant Depression?

February 3, 2024

3 min read

Treatment-resistant depression is a major depressive disorder that happens when a person with lingering depression symptoms does not respond to treatment of at least two different first-line anti-depressants.

What is treatment-resistant depression?

Treatment-resistant depression is a form of major depressive disorder that fails to respond to the standard depression treatments involving taking an anti-depressant or going to psychotherapy.

What causes treatment-resistant depression?

Even though the exact causes of treatment-resistant depression are not known, there can be several contributing factors.

Genetic factors: Genetic variations can affect how the body breaks down or responds to anti-depressants.
Metabolic disorder: Some people who do not respond to the standard depression treatments often have nutritional deficiencies like low folate on the cerebrospinal fluid (the fluid around the brain or spinal cord).
An incorrect diagnosis: People who do not respond to standard depression treatment may not have a major depressive disorder. They may have other mental conditions like bipolar disorder with similar depressive symptoms.
Chronic stress: Chronic stress can alter the functions of the (hypothalamic- pituitary- adrenal) HPA axis, worsening depression.

Symptoms of treatment-resistant depression

Here are some of the symptoms of TRD:

Anxiety disorder
Anhedonia (A reduced ability to experience pleasure)
A higher number of depressive episodes
Short moments of improvement followed by symptoms of depression
Suicidal behavior or ideation

Risks of treatment-resistant depression

You are more at risk of developing TRD if:

Your onset of depression began at an earlier age.
Your depressive episodes last longer.
You have frequent and recurrent depressive episodes.
You have severe depression.
You have substance use disorder with addictions.
You lead a sedentary lifestyle.
You are older.

People with the following diseases may have an increased risk of TRD.

Heart disease
Thyroid disease
Autoimmune disease
Cerebrovascular disease

Some medications that can cause TRD are:

Recreational drugs
Supplements and herbal preparations
Over-the-counter medicines
Prescription drugs

Life issues like stress, poverty, unresolved grief or loss, and family problems can increase the risk of treatment-resistant depression.

Diagnosis of treatment-resistant depression

Your healthcare provider shall prescribe depression medicines like Mirtazapine, Bupropion, SSRIs, and SNRIs for your depression.

Where the depression symptoms do not get better after the use of at least two anti-depressants, they may refer you to a psychiatrist.

The psychiatrist will assess your physical and mental health history, including:

Reviewing your medications, including prescriptions, over-the-counter drugs, herbal supplements, and nonmedical drugs.
Assessing physical conditions like chronic pain and thyroid disease that worsens depression.
Assessing issues, like substance abuse and other addiction problems.
Reviewing previous experiences with psychotherapy and whether it has helped manage depression.
Considering whether other mental health conditions, like bipolar disorder, more accurately describe the condition.

Based on the assessment, your provider will diagnose treatment-resistant depression to find the best possible treatment.

Treatment of treatment-resistant depression

Your psychiatrist may use several strategies to treat TRD.To start, they may,

Increase the dose of your current anti-depressant or ask you to continue the medication for a prolonged period.
Add a different class of anti-depressant to your current treatment.
Refer you to a psychologist for psychotherapy.
Consider pharmacogenetic testing.

Your psychiatrist may recommend a combination of medications and treatments like:

Antipsychotic medicines: They treat TRD by affecting the levels of serotonin and norepinephrine.
Ketamine: A drug used for hard-to-treat depressive symptoms.
Repetitive transcranial magnetic stimulation (rTMS): The procedure uses magnets to stimulate the brain’s nerve cells for controlling depressive symptoms
Electroconvulsive therapy(ECT): A procedure where a mild electric current is passed through the brain, causing brief seizures that reverses major depressive symptoms.
Vagus nerve stimulation (VNS): The treatment stimulates the vagus nerve with electrical stimulation to improve depression symptoms.