What are the Symptoms, Causes, and Treatment of Treatment-Resistant Depression?

Sometimes depression does not get any better, despite all the treatments. TRD (Treatment-resistant depression’) is a term used if a person with depression do not respond at all or up to the expectation to at least 2 different antidepressant medications.

TRD is a condition where a person has not responded to multiple treatments for depression.

It is characterized by persistent depressive symptoms that do not improve with standard treatments such as:

  • Medication
  • Talk therapy
  • Other lifestyle changes.

TRD is a complex condition that can have a significant impact on the quality of life of a person.

The causes of TRD are not fully understood but may be related to any of the following:

  • Genetics
  • Brain chemistry
  • Co-occurring disorders
  • Environmental factors.

Treatment options for TRD include medication, talk therapy, lifestyle changes, brain stimulation, and clinical trials. It is important to seek help from a mental health professional if you have symptoms of TRD, as specialized care can make a significant difference in managing the condition.

When a person has tried all these treatment options and still struggles with depressive symptoms, it may be a sign of treatment-resistant depression. Let us try to learn more on the symptoms, causes, and treatments of TRD.


The symptoms of TRD are similar to those of depression. However, TRD is characterized by the fact that these symptoms persist even after multiple attempts at treatment.

Some of the common symptoms of TRD include:

  • Persistent sadness or hopelessness
  • Loss of interest in all activities that one used to enjoy earlier
  • Difficulty concentrating or making decisions
  • Changes in appetite or sleep patterns
  • Fatigue and lack of energy
  • Feelings of guilt or worthlessness
  • Thoughts of suicide or self-harm.

If you experience these symptoms and have not responded to standard treatments for depression, you may have TRD.

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The causes of TRD are not fully understood. However, some factors may contribute to this condition including:

1. Genetics

Some people may have a genetic predisposition to depression, making them more likely to develop TRD.

2. Brain chemistry

Depression is believed to be caused by an imbalance in brain chemicals called neurotransmitters. When these chemicals are not functioning properly, it can lead to depression. Some people may have an imbalance that is not responsive to traditional treatments.

3. Co-occurring disorders

If a person has other mental health conditions, such as anxiety, substance abuse, or post-traumatic stress disorder (PTSD), it can make depression more difficult to treat.

4. Environmental factors

Traumatic life events, chronic stress, and other environmental factors can contribute to depression and make it harder to treat.


There are several treatment options available for TRD. Your doctor may recommend one or more of these treatments based on your specific symptoms and medical history.

Some of the treatments for TRD include:

1. Medication

Your doctor may prescribe different medications or adjust your current medication to see if it can alleviate your symptoms. Often, a combination of different medicines may be more effective. Your doctor may also try alternative therapies, such as ketamine or electroconvulsive therapy (ECT), to treat TRD.

2. Talk therapy

Different types of talk therapy, such as cognitive-behavioural therapy (CBT) and interpersonal therapy, can help you understand the root causes of your depression and develop coping strategies.

3. Lifestyle changes

Lifestyle changes, such as regular exercise, a healthy diet, and getting enough sleep, can help alleviate depression symptoms.

4. Brain stimulation

Brain stimulation therapies, such as transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS), are non-invasive treatments that can help alleviate symptoms of TRD.

5. Clinical trials

There are ongoing clinical trials for new treatments for TRD, such as psilocybin therapy and deep brain stimulation (DBS).

It is important to note that not all treatments for TRD are effective for everyone. Your doctor may need to try different approaches to find the treatment that works best for you.


In conclusion, treatment-resistant depression is a complex condition that requires specialized care. If you have symptoms of TRD, it is important to seek help from a mental health professional. Ultimately, depression counselling will help you to minimise the impact of your condition on your daily life.

Your doctor can work with you to develop a treatment plan that is tailored to your specific needs. While it may take time to find the right treatment for TRD, there are several options available that can help alleviate symptoms and improve your quality of life.