Understanding Refractory Depression, also known as treatment-resistant depression (TRD) or drug-resistant depression (DRD), is a form of major depressive disorder that failed to respond to at least two antidepressant treatments.

To get a better understanding of this serious mental health condition, we'll walk you through the signs, symptoms, and treatment plan for refractory depression.

What Is Refractory Depression?

Refractory depression results from a failed response to sufficient treatment for a depressive disorder. This means that symptoms are exacerbating despite taking antidepressants or going to psychotherapy. 

What Are The Signs And Symptoms of Refractory Depression?

Pay attention to the following indicators of treatment-resistant depression:

  • Longer and worse episodes of depression
  • Lack of response to neurologic stimulants, antidepressants, and psychiatric therapies
  • Exacerbation and remission of depression symptoms
  • Anxious distress or heightened anxiety

What Causes Treatment-Resistant Depression?

A wide range of factors can cause refractory depression. When diagnosing treatment-resistant depression, psychiatrists usually watch out for these causes:

  • Chronic heart failure
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Alcohol and drug abuse and withdrawal
  • History of severe infection, e.g., HIV, infectious hepatitis, influenza, Lyme disease, tuberculosis, etc.
  • Analgesics, e.g., indomethacin, opiates, etc.
  • Antibiotics
  • Antihypertensive agents with catecholamine effects, e.g., methyldopa, propranolol, etc.
  • Antineoplastic or anticancer agents
  • Metabolic and endocrine disorders, e.g., diabetes mellitus, hypoparathyroidism. hyperthyroidism, hypothyroidism
  • Multiple sclerosis
  • Parkinson disease
  • Chronic pyelonephritis
  • Pancreatitis
  • Postpartum depression
  • Epilepsy
  • Dementia

How Is Refractory Depression Diagnosed?

There is no established set of diagnostic criteria for refractory depression. Doctors come to this diagnosis if a patient has tried at least two different types of antidepressants but did not gain improvement. They will also assess the following:

  • Was your depression diagnosed accurately?
  • Was the antidepressant given to you for a sufficient length of time? (Antidepressants need to be taken for 6-8 weeks in correct doses to see the full effect.)
  • Was the antidepressant taken at the correct dosage?
  • Was the antidepressant taken properly?
  • Is there anything else that could be causing or exacerbating your symptoms?

What Are The Risk Factors For DRD?

The following individuals have been considered by medical professionals to be susceptible to treatment-resistant depression:

  • Patients diagnosed with major depressive disorder, post-traumatic stress disorder, affective disorders, or bipolar disorder
  • Elderly men and women
  • Female adults
  • People with sleep disorders
  • Individuals experiencing chronic pain due to underlying medical conditions
  • People with addiction problems

How Do You Treat Refractory Depression?

There are several methods to treat refractory depression — from pharmacologic to psychotherapeutic. Psychiatrists will often try these methods simultaneously to see what works for the patient.

Antidepressant Medications

If you’ve taken one type of antidepressant without much success, your psychiatrist can prescribe another from a different drug class. It could be a:

  • Tricyclic antidepressant
  • Tetracycline antidepressant
  • Serotonin-norepinephrine reuptake inhibitor
  • Selective serotonin reuptake inhibitor
  • Norepinephrine and dopamine reuptake inhibitor

For some patients, a combination of two antidepressants may work better. Your doctor will assess if this approach is more suitable for your condition.

Augmentation Therapy

This involves the use of other medications and nutritional supplements with an antidepressant. Examples are:

  • Antipsychotic drugs
  • Ketamine
  • Dopamine drugs
  • Lithium
  • Thyroid hormone
  • Zinc
  • Folic acid
  • Omega-3 fatty acids
  • L-methyl folate
  • Ademetionine

Psychotherapy or Talk Therapy Sessions

Some patients do not respond well to the pharmacologic approach. Instead, they find the psychotherapeutic approach, like dialectical behavioral therapy and cognitive-behavioral therapy, more effective. It can also be combined with medication intake for a synergistic effect.

Neurological Techniques

In some cases, doctors use neurological stimulation to treat recurring depression. 

  • Vagus nerve stimulation
  • Electroconvulsive therapy (formerly called electroshock therapy and is a controversial treatment option for depressive symptoms)
  • Light therapy
  • Repetitive transcranial magnetic stimulation RTMS
  • Deep brain stimulation
  • Acupuncture

Combination Therapy Using Stimulants

The proof that the combination of stimulants with antidepressants for refractory depression is still inconclusive. But experts have begun using the following to manage the condition:

  • Adderall
  • Modafinil (Provigil)
  • Lisdexamfetamine (Vyvanse)
  • Methylphenidate (Ritalin)

Consult a Trusted Depression Psychiatrist

The success of treatment for severe depression is dependent on proper diagnosis and patient compliance to medication and/or therapy.

If you're looking for a clinical practice specializing in psychiatric disorders, reach out to us at Luminous Vitality Behavioral Health. Our experienced depression psychiatrists conduct both in-person and telehealth consultations to support you.

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