May 30, 2025
Depression is a very common mental health issue, with over 8% of people struggling with it every year. While most of these people will recover from their depression within a year, others will continue to struggle. They may seek more advanced therapy treatments and up their dosage of antidepressants, but still struggle with depression.
These cases, although rare, are what’s called “treatment-resistant depression”. It is a type of depression that does not improve with the traditional methods of talk therapy and/or antidepressants.
Despite its name, there have been cutting-edge treatments that have helped people with treatment-resistant depression. These alternative therapies and medications could be the thing that turns the tide in many people’s fight against depression. Let’s dive into it.
What Is Treatment-Resistant Depression?
Treatment-resistant depression is a type of depression that does not respond to the traditional methods of talk therapy and/or antidepressants. This means that therapy modalities such as CBT and DBT don’t work, but neither do common antidepressants like Lexapro or Prozac. No matter how much the dosage is increased, the depression remains stubbornly in place.
This experience can feel disheartening, frustrating, and hopeless. It can make one feel broken and like things will never get better. Worse is when therapists “give up” on you—an unethical behavior in which they say there is no helping you. (This is completely false, as there are always other options. Even if one therapist isn’t equipped to meet your needs, they should always refer you out to someone who can.)
In recent years, research into treatment-resistant depression has been done to try and find an effective treatment. The results are optimistic: There are treatment methods for treatment-resistant depression.
What Are the Criteria for Treatment-Resistant Depression?
There is no set, agreed-upon definition for treatment-resistant depression. The most commonly used one is that of depression that is not improved by at least 2 antidepressants. The antidepressants must have been given for an adequate period of time (usually 4-6 weeks) and dosage (varies depending on the person). At this time the diagnosis of treatment-resistant depression can be given.
What Percentage of Depression Is Untreatable?
Using the above definition, Around 30% of people with Major Depressive Disorder (MDD) have treatment-resistant depression. Around 8.3% of U.S. adults have MDD. So treatment-resistant depression has a prevalency of around 2.4% in the U.S.
Do I Have Treatment-Resistant Depression?
The only way to know for sure if you have TRD is by receiving a diagnosis from a therapist or psychiatrist. However, you likely have TRD if:
- You’ve tried many different antidepressants, and none of them have many differences.
- Your depression is severe and debilitating. (If not, but it is still persistent, you might have Persistent Depressive Disorder.)
- You’ve adhered to treatment for depression very strictly, including therapy and medication, with no improvement in symptoms.
- You've prioritized self care and physical health (eating healthy, sleeping well, and getting sunlight) and still your symptoms persist.
If you answered yes to the above scenarios, then you might have TRD.
How to Treat Treatment-Resistant Depression?
Despite its name, effective treatments have been found for treatment-resistant depression. These include alternative therapies, medications, and lifestyle changes.
Remember that as with any treatment plan, the treatment discussed with your psychiatrist or therapist should be followed. Not adhering to the treatment plan can cause depression symptoms to remain, and is not a sign of treatment-resistant depression.
Alternative Therapies
There are currently 3 alternative therapies that are heavily backed by science and proven to be effective at treating resistant depression. These are:
- Transcranial Magnetic Stimulation (TMS): TMS is a non-invasive treatment that uses magnetic pulses to stimulate nerve cells in the brain, particularly in areas associated with mood regulation.
- Electroconvulsive Therapy: Electroconvulsive therapy (ECT) involves passing electric currents through the brain, triggering a controlled seizure to alleviate severe depression symptoms.
- Ketamine and Esketamine Therapy: Ketamine and its derivative, esketamine, have shown promise in rapidly reducing depressive symptoms, particularly in cases of severe depression or TRD.
Often, these alternative therapies are used in conjunction with medicines and lifestyle changes.
Alternative Medicines
When using alternative medication, most psychiatrists will prescribe them in addition to an antidepressant. Common additions are antipsychotics. Despite their name, antipsychotics are not only used to treat psychotic episodes. They are a good option for any illness that needs the regulation of dopamine. Antipsychotics used in addition to antidepressants include Aripiprazole (Abilify), Brexpiprazole (Rexulti), or Quetiapine (Seroquel XR). These are all FDA-approved.
The only FDA-approved combination drug (in which both medicines appear in the same pill) is olanzapine and fluoxetine.
Before using antipsychotics or anticonvulsants, your psychiatrist will likely try to switch you onto a different type of antidepressant. For example, although the most common type of antidepressant are SSRIs, there are many others that some find helpful, including SNRIs or monoamine oxidase (MAO) inhibitors.
Lifestyle Changes
Most therapists will encourage healthy lifestyle changes in addition to therapy and medication. Although treatment-resistant depression is unlikely to go away solely with coping skills and lifestyle changes, these behaviors can help elevate the healing effects of therapy and medication, as well as encourage long-term growth.
These lifestyle changes can include:
- Regular Exercise: Engaging in physical activity, even in small increments, can positively impact mood and overall well-being. Whether it's a leisurely walk, yoga session, or any form of exercise, movement can boost endorphins and alleviate symptoms of depression.
- Balanced Nutrition: Consuming a diet rich in fruits, vegetables, lean proteins, and whole grains can nurture the body and mind. Certain nutrients, such as omega-3 fatty acids and complex carbohydrates, are linked to improved mental health.
- Adequate Sleep: Prioritizing a consistent sleep schedule and aiming for 7-9 hours of quality sleep each night can provide essential rest and support mental resilience.
- Mindfulness and Relaxation: Practicing mindfulness, meditation, or deep-breathing exercises can help manage stress and promote a sense of calm. Engaging in activities that bring joy and relaxation can also uplift spirits.
- Social Support: Nurturing positive relationships and seeking social connections, even through support groups or therapy, can offer emotional support and a sense of belonging.
- Setting Realistic Goals: Breaking tasks into small, achievable steps and celebrating progress can instill a sense of accomplishment, boosting self-esteem and motivation.
- Limiting Substance Use: Minimizing alcohol consumption and avoiding recreational drugs is crucial, as they can exacerbate symptoms of depression.
If you think you have treatment-resistant depression, reach out for help. Proper diagnosis and treatment is paramount to your eventual recovery.
