November 3

What is Treatment Resistant Depression?

Treatment resistant depression (TRD) or refractory depression is a form of depression that does not respond to treatment. Unfortunately, about 10-30% of those with major depression either do not respond at all or only partially respond to antidepressant medication. Those who have TRD may also have impaired functioning, poor quality of life, suicide ideation, suicide attempts, self-injurious behavior, and relapses in depression. 

What is Treatment Resistant Depression? 

Depression can be incredibly difficult to live with and is something that millions of Americans struggle with. Depression is characterized by prolonged feelings of sadness and depressed mood. It can negatively affect the way people feel, think, and act. For depression to be diagnosed a person must present symptoms for at least two weeks and have changes in levels of functioning. Thankfully, there are treatment options that can be very effective.  

However, treatment resistant depression (TRD) or refractory depression is a form of depression that does not respond to treatment. Unfortunately, about 10-30% of those with major depression either do not respond at all or only partially respond to antidepressant medication. Those who have TRD may also have impaired functioning, poor quality of life, suicide ideation, suicide attempts, self-injurious behavior, and relapses in depression. Having this kind of depression can leave people feeling hopeless about getting better. Although, they should not despair. There are several options available, and they have shown positive results in getting TRD under control.  

How Do You Know it is Treatment Resistant Depression? 

It is not always obvious that someone might have TRD, and doctors do not always agree on the exact criteria. It may be TRD if treatment has not helped improve symptoms at all or has only partially made a difference. Even though there are no standard diagnostic criteria doctors do generally believe it is treatment resistant depression when someone has tried at least two different types of antidepressant medication without seeing any difference. Some doctors will say at least four medications, but regardless if you think you do have treatment resistant depression then you need to see your doctor to confirm it.  

There may be other explanations for why treatment hasn’t been working. It could be that someone received an incorrect diagnosis or they might have another condition along with depression that makes symptoms worse. There could be an issue with the medication itself. A person may not have taken the medication correctly, they were given the wrong dosage, or they simply haven’t been on it long enough for it to work. It does take around six to eight weeks for antidepressants to fully kick in, although those who see improvements after a few weeks have a higher chance of fully managing their depression.  

What Causes TRD? 

There seems to be a multitude of theories behind the causes of treatment resistant depression, but there is no one consensus. The causes of depression are not truly known, but it is believed to be due to low levels of neurotransmitters, such as serotonin and norepinephrine, and antidepressants are meant to raise them. Medications that treat depression may not be a one-size-fits all and an occurrence, known as Tachyphlaxis, can happen in as much as 25-30 percent of people on antidepressants. Tachyphylaxis is the medical term used to reference the body’s sudden diminish in response to successive doses of a drug, rendering it less effective. Even though the causes of TRD are not fully known, one thing is for sure though and that is that people do not exaggerate when they talk about their symptoms and it is no one’s fault if they are not able to get better.  

Anyone can suffer from depression. There are some factors that have been identified to specifically increase someone’s risk for treatment resistant depression. The first is the length of depression, as those with major depressive disorder for longer periods of time are more at risk. The severity of symptoms is another factor. Those with mild to severe depression symptoms are less likely to respond to antidepressants. Comorbid disorders, like having anxiety along with depression, can also mean being less responsive to antidepressants.   

Current Treatment Options for Treatment Resistant Depression 

Despite treatment resistant depression not responding to the traditional treatment of antidepressants, that does not mean there are no other options. There are different routes that a doctor can take to attempt to help you with refractory depression. As already discussed, a doctor will first check to be sure you have the correct diagnosis, have been using your medication correctly, and do not have any other issues that need to be treated to improve your chances of responding to treatment. After that, your doctor may consider some of the following treatments for refractory depression:  


  • Switching Antidepressants: If your current medication isn’t working then your doctor may consider switching medications for you. Typically the class of drug for depression is SSRIs or Selective Serotonin Reuptake Inhibitors (SSRIs), which specifically target serotonin levels. These include medicines, like Lexapro, Prozac, and Zoloft. Another class are SNRIs or Serotonin and Norepinephrine Reuptake Inhibitors, which are also used to effectively treat depression. These medications include Effexor, Fetzima, and Cymbalta. You may need to try another antidepressant in the same class or of a different class in order to find the right fit. 
  • Adding Medication: Another approach your doctor may try is to prescribe another medication along with the antidepressant you are currently on. This can be especially beneficial if your current medicine is partially working and it can give you the extra boost you need. First, your doctor may try combination therapy, where a second class of antidepressant is added alongside your current antidepressant. If that is not effective then your doctor may try augmentation therapy. This therapy adds a medication that does not typically treat depression, such as a mood stabilizer.   


  • Cognitive Behavioral Therapy: A popular type of talk therapy that focuses on changing thoughts and behavior to improve depression symptoms. This therapy will help teach you better life and coping skills and has been shown to effectively treat depression by improving the functioning and quality of life. 
  • Acceptance and Commitment Therapy: A form of cognitive behavioral therapy, you will learn how to engage in more positive behaviors, despite having negative feelings. The main idea is to stop avoiding and denying any inner struggles with emotions and make behavioral changes for the better. 
  • Dialectical Behavioral Therapy: Another form of therapy that branches off of cognitive behavioral therapy. This kind of therapy teaches acceptance strategies for previous experiences and problem-solving skills. It is useful for high risk or difficult to treat patients, who may be suicidal or have self-injury behaviors. 

Other Procedures: 

  • TMS: Transcranial magnetic stimulation is a non-invasive and FDA approved treatment option for treating major depression. TMS involves the use of magnetic fields to stimulate nerve cells in the brain in order to improve any symptoms associated with depression. Studies have consistently shown that TMS therapy does work for those with treatment-resistant depression and can provide long-term relief. While this therapy does require several sessions over the course of weeks, many patients start to see relief very early on. 
  • Ketamine: A medication that is traditionally used as an anesthetic by medical professionals. However, there is emerging research to show that it can be used to effectively manage depression symptoms, primarily reducing suicidal ideations, in a rapid amount of time. Racemic ketamine is generally administered as an infusion to the bloodstream, through an IV. Esketamine, which is derived from part of the ketamine molecule, has been approved by the FDA as a nasal spray under the brand name Spravato.   
  • Vagus Nerve Stimulation: This involves an implanted device sending mild electrical pulses into your body’s nervous system. An implantable vagus nerve device is also approved by the FDA to treat depression. The device is surgically implanted under the skin of the chest and is connected by a wire to a nerve in your neck, known as the vagus nerve. The electrical pulses travel along the nerve and into the mood center of the brain, which should cause a reduction in depression.  

These are some of the usual treatments that doctors will use for drug resistant depression. All of these forms of treatment should be administered and monitored by a medical practitioner for your health and safety. Some natural approaches you can take that do not involve a medical office are to sleep well, manage stress, and exercise regularly. 

Need Help With Treatment Resistant Depression? 

If you are looking for therapy services for depression or have questions, call Gemini Health today! Our highly skilled mental health professionals are experienced in treating various mental and behavioral health concerns. Gemini Health offers various therapeutic services for all clients. Call (301) 363-1063 and speak to our dedicated staff to schedule your appointment today!    


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Mount Airy, MD 21771