As the name suggests, treatment resistant depression is a form of depression that doesn’t respond well to “traditional” depression treatments such as psychotherapy and medication.

You can imagine how frustrating and demoralizing it can be (for both clinicians and patients) to face a mental health disorder for which nothing seems to work.

Experts have yet to determine why some forms of depression seem to be impervious to psychiatric medications and other gold-standard approaches. Nevertheless, there are plenty of alternatives available today to help people deal with this problem and its troubling symptoms.

In fact, some mental health professionals are now considering the possibility of using ketamine therapy as a viable intervention for treatment-resistant depression.

Treatment Resistant Depression: What Is It?

Treatment resistant depression, or refractory depression, is a relatively common condition that can pose serious challenges to mental health professionals.

According to a paper published in Biological Psychiatry, clinicians should consider treatment resistant depression when at least one antidepressant trial of adequate doses and duration fails to deliver any promising results.

When it comes to mood disorders, the longer you go without treatment, the more your brain will deteriorate. Eventually, you will be at an increased risk for developing a chronic form of depression. Also, with severe depression, suicide risk is another important factor that should be kept in mind.

Traditional Treatments for Depression

Over the last decades, researchers and clinicians have come up with numerous strategies and approaches for treating depressive disorder.

From a psychiatric perspective, depression (and the related symptoms) results from a chemical imbalance in the brain. In order to restore the neuro-chemical balance, psychiatrists often prescribe antidepressants like tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs).

Woman stuck in a deep depression

Another approach that clinicians use to treat severe depression is electroconvulsive therapy (ECT). This involves passing small-intensity electric currents through the brain under general anesthesia.

As for psychotherapy, many experts believe that cognitive-behavioral therapy (CBT) is ideal for treatment resistant depression. In fact, a recent study (published in the Journal of Counseling and Clinical Psychology) revealed something interesting about this type of psychotherapy. It showed that hope and emotional processing are two crucial elements through which CBT practitioners can improve the chances of recovery for people with chronic forms of depression.

Side-Effects of Medications

Even though pharmacotherapy is among the most effective interventions for treating the symptoms of depression, there is one reason why some tend to avoid this approach.

Just like any other medication, antidepressants can have some pretty unpleasant side effects. Adverse events may include anything from nausea and vomiting to irritability and a decrease in sex drive.

But despite the unpleasant side effects of antidepressants, many people just can’t get past depression without some pharmaceutical help.

Long-Term Effects of Depression Treatments

So, let’s say that, despite the side effects of antidepressants; you agree to take medication for your depression. It is at this point that you would probably start wondering about the long-term impact of your decision.

According to a 2016 study published in Patient Preference and Adherence, people who’ve taken antidepressants for extended periods report quite a few unpleasant effects. Some of the main long-term effects of antidepressant use are sexual problems and weight gain. However, it is important to highlight the fact that almost 90% of the people who participated in the study reported that antidepressants had improved their overall sense of well-being.

There are, of course, times when the positive effects of medications outweigh the costs (side effects), even if we’re thinking “long-term.”

When Depression Treatments Don’t Work

When “standard” treatments don’t work, clinicians often consider two possibilities. Either they misdiagnosed the patient, or they’re dealing with a case of treatment resistant depression.

Although the term treatment resistant might sound worrying and discouraging to many of us, it doesn’t mean that we’re out of options.

But the question is, why do some people experience this form of depression?

Why Do Some People Not Respond To Treatment

There are numerous reasons why depression doesn’t respond well to traditional treatment options.

For starters, the longer you’ve suffered from depression without seeking any form of help, the tougher it is to overcome.

There are also cases when other problems such as anxiety or personality disorders can accompany depression. Not to mention that depressive episodes can be part of a “broader” condition like bipolar disorder.

Considering all these factors, you should be able to understand why it’s not always easy to find the perfect combination of treatment options.

Approaches for Dealing With Treatment Resistant Depression

In case you’re dealing with a chronic form of depression that is proving to be a lot tougher to treat, you should know that there are some viable alternatives.

Switching Medicines

If you’re under psychiatric treatment, but you’re still feeling “down in the dumps,” the first thing your doctor will try is to change medicines.

Finding the right treatment is a matter of trial and error. There are, in actual fact, only a few cases where the clinician gets it right the first time. And that’s not because they’re inexperienced or ill-prepared, but because there’s no way of telling which of the neuro-chemicals in your brain are affected by depression.

Adding a New Medicine

Another strategy that psychiatrists use whenever they’re dealing with a case of treatment resistant depression is adding a new medicine.

Depending on how you respond to the initial treatment, your clinician can choose to eliminate a drug or add a new one to the intervention plan.

Approved Treatment Alternatives

Among the few approved alternatives for depression are CBD oils and CBD-based products. cbd stands for cannabidiol, a cannabinoid that can be found in both marijuana and agricultural hemp.

A recent study published in CNS & Neurological Disorders, revealed that cannabidiol has both anti-anxiety and antidepressant effects.

Since cbd is a non-psychoactive compound, you don’t have to worry about getting “high.” Plus, there’s little to no side effects associated with the use of cannabidiol.

Another notable alternative treatment coming into prominence is transcranial magnetic stimulation. TMS is a non-invasive procedure where magnetic waves from a small emitter are used to stimulate cells in the frontal areas of the brain.

TMS is also helpful for having very limited side effects. As an alternative to standard medications or more substantial procedures like electro-convulsive therapy, TMS can be much easier to work into a treatment plan.

Ketamine Nasal Spray for Depression

Ketamine Spray Molecule

Ketamine, a substance that is generally used for starting and maintaining anesthesia, has recently been approved as a safe treatment for chronic forms of depression.

A 2016 study published in the American Journal of Psychiatry, revealed that intravenous ketamine could be a viable solution for treatment resistant depression.

Recently, experts have developed a ketamine nasal spray which has shown promising results for people who haven’t yet found the right treatment for their depression.

Living With Treatment-Resistant Depression

We can all imagine how difficult it is to live with a chronic form of depression. The lack of motivation and “grim” perspective which is specific to this condition, coupled with the frustration of not finding the right treatment, can easily make you give up all hope.

But no matter how “resilient” your depression might seem, there’s always a viable alternative. You just need to be patient and brave enough to keep looking for it.


  1. M. Fava, “Diagnosis and definition of treatment-resistant depression,” Biological Psychiatry, vol. 53, no. 8, pp. 649-659, 2003.
  2. A. Abel, A. M. Hayes, W. Henley and W. Kuyken, “Sudden gains in cognitive–behavior therapy for treatment-resistant depression: Processes of change,” Journal of Consulting and Clinical Psychology, vol. 84, no. 8, pp. 726-737, 2016.
  3. C. Cartwright, K. Gibson, J. Read, O. Cowan and T. Dehar, “Long-term antidepressant use: patient perspectives of benefits and adverse effects,” Patient Preference and Adherence, vol. 10, 2016.
  4. S. de Mello, R. de Oliveira, D. S. Coutinho, S. Machado, O. Arias-Carrión, J. A. Crippa, A. W. Zuardi, A. E. Nardi and A. C. Silva, “Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa,” CNS & Neurological Disorders, vol. 13, no. 6, pp. 953-960, 2014.
  5.  J. B. Singh, M. Fedgchin and a. others, “A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression,” The American Journal of Psychiatry, vol. 173, no. 8, pp. 816-826, 2016.
author avatar
Angel Rivera
I am a Bilingual (Spanish) Psychiatrist with a mixture of strong clinical skills including Emergency Psychiatry, Consultation Liaison, Forensic Psychiatry, Telepsychiatry and Geriatric Psychiatry training in treatment of the elderly. I have training in EMR records thus very comfortable in working with computers. I served the difficult to treat patients in challenging environments in outpatient and inpatient settings

Similar Posts

Leave a Reply