Depression is something that many people deal with and there can be many factors that can cause or worsen depressive symptoms. While there are many medications and therapies that can help to relieve depression when addressed with a professional, sometimes depression can be difficult to treat with traditional therapies and medications. This type of depression is referred to as treatment-resistant depression. 

While treatment-resistant depression can be more difficult to treat, it is not impossible. In this article we’ll discuss some FDA approved therapies for treatment-resistant depression as well as other ways to manage treatment-resistant depression (TRD). 

What is treatment-resistant depression?

As in the name TRD is depression that is treatment-resistant or resistant to the traditional forms of psychotherapy or psychopharmaceuticals. Typically someone who is suffering from major depressive disorder is considered to have treatment-resistant depression if their symptoms are not relieved after trials with two different antidepressant medications.

Treatment-resistant depression can add to already overwhelming feelings of hopelessness or despair and many patients who struggle with this disorder can feel like they are out of options due to the inaccessible and often expensive nature of psychiatric services. However there are many new therapeutic treatments and ways to manage treatment-resistant depression. 

Alternative FDA-approved treatments for treatment-resistant depression

While there continues to be research done regarding treatment-resistant depression and cases vary from patient to patient, there are many newer therapies that psychiatrists and other health professionals are starting to prescribe or recommend to patients who suffer from treatment-resistant depression or severe treatment-resistant depression. 

A few new therapies and medications with hope for treatment-resistant depression include:

• Transcranial magnetic stimulation therapy
• Spravato (esketamine) nasal spray
• Psychedelic Mushrooms

Transcranial magnetic stimulation therapy 

One of the most common forms of therapy for treatment-resistant depression, repetitive transcranial magnetic stimulation therapy (rTMS) is a noninvasive therapy that uses magnetic fields to stimulate nerve cells in the brain. 

Repetitive transcranial magnetic stimulation has been researched for over 20 years as an alternative treatment for depression. It has been an FDA approved treatment for treatment-resistant depression since 2008 and is often the first option given to patients who have not seen any improvement with antidepressant medications. 

Repetitive transcranial magnetic stimulation involves multiple 40 minute sessions that take place over the course of a few weeks. During these appointments a trained healthcare provider monitors the patient undergoing the treatment. rTMS allows the patient to remain awake and alert during the treatment and since it is considered outpatient care, patients can drive themselves to and from appointments. 

rTMS has been shown to be effective as a stand-alone treatment and in conjunction with antidepressant medications. Further research into the addition of psychotherapy is currently being done in this area of treatment. 

Spravato (esketamine) nasal spray

While many antidepressant medications can take weeks to take effect or relieve depression symptoms, esketamine is incredibly fast acting, taking effect in a couple of hours. 

Esketamine was approved in 2019 by the FDA for treatment of TRD with the requirement that treatment is monitored by a health professional. Like rTMS, esketamine therapy is an outpatient program meaning patients have to go to the doctor’s office in order to receive treatment. Unlike rTMS, patients are not allowed to drive home until one day after their treatment, as the effects of esketamine can have some lasting effects. 

Research has suggested that long-term untreated depression can cause brain damage and increase risk for dementia. However, esketamine therapy may counteract some of these harmful effects. Studies indicate that esketamine reverses the damage that chronic stress causes on brain cells and prevents the neurotoxic effect of depression on the brain. 

What are the side effects of esketamine therapy?

When people see the word ketamine, many may think of drugs such as opiates or cocaine which have extremely addictive and damaging qualities to them. Ketamine is not as addictive as many may believe, however it should be monitored by a trained professional as people can have a wide variety of reactions to this drug. 

The most common side effects of esketamine therapy includes:

• Nausea
• Drowsiness
• Increased blood pressure
• Feeling drunk
• Headache
  

More dramatic or intense side effects can include hallucinations or dissociation/depersonalization (feeling disconnected from yourself or reality). These side effects are not extremely common and tend to peak at 40 minutes and wear off within two hours of treatment. 

Psychedelic mushrooms (magic mushrooms)

Another emerging form of treatment in psychiatry and psychiatric medication is that of psychedelic mushrooms or magic mushrooms. 

While research continues to be done on the potential of magic mushrooms, completed research has shown that the compound, psilocybin, found in psychedelic mushrooms, has relieved many symptoms of major depressive disorder. 

The use of magic mushrooms for treating major depressive disorder and treatment resistant depression was approved by the FDA in December of 2021. 

While scientists at the forefront of these studies stress that more research needs to be done to understand how best to use magic mushrooms for psychiatric treatments, they state that the emerging research has shown hope for the future of depression treatment. 

Continued management of treatment-resistant depression

Consistency is key for mental health care.

No matter what form of therapy you are able to pursue, the most important factor in recovering is consistency. Making sure that you continue to take prescribed medications and attend some form of therapy is key in managing symptoms even after they improve. 

Other forms of self-care can include incorporating healthy food into your diet and making sure you spend time outside at least once a day. Exercise can also be extremely beneficial in improving some symptoms of depression. Some healthcare professionals may even prescribe physical activity along with pharmacological treatments. 

If you or someone you know is in crisis or in need of immediate support, some options for help include:

• 24/7 National Suicide Prevention Hotline (800-273-8255)
• Text “HOME” to the Crisis Textline at 741-741
• For anyone outside of the USA go to Befrienders Worldwide to find a helpline in your country.