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Do I Have Treatment-Resistant Depression? Signs and Symptoms of TRD 

8 min read

Many individuals with depression experience improvement after using medications and therapies to manage their symptoms. However, for some, standard treatments provide little to no relief, they are often struggling with a condition known as treatment-resistant depression (TRD). If this description resonates with your experience, you might be wondering if you have TRD.

What Is Treatment-Resistant Depression?

Treatment-resistant depression (TRD) is a challenging subtype of major depressive disorder (MDD) where standard antidepressant therapies fail to alleviate symptoms adequately. Typically, TRD is diagnosed when at least two different first-line antidepressants, such as SSRIs (selective serotonin reuptake inhibitors) or SNRIs (serotonin and norepinephrine reuptake inhibitors), are prescribed at sufficient dosages and durations without success during a depressive episode. 

What makes treatment-resistant depression different is that it doesn’t go away easily with standard treatments, even if they’ve worked before. This type of depression can stick around, causing ongoing symptoms and possibly coming back after feeling better. Dealing with treatment-resistant depression can be tough because the first things tried often don’t help enough. But there are different ways to manage it, like trying different antidepressants, adding therapy like talking to a counselor, or considering treatments like magnetic therapy or shock therapy. 

If you think you might have treatment-resistant depression because your symptoms aren’t getting better with treatment, it’s important to talk openly with your healthcare provider. Together, you can look into other options and find a way to improve your mental health and well-being. Even though it’s challenging, many people find relief with the right treatment that fits their needs.

How Common Is Treatment-Resistant Depression?

Treatment-resistant depression (TRD) is not uncommon among individuals diagnosed with major depressive disorder (MDD). Roughly 30% of people diagnosed with MDD and who have tried medications for depression may experience treatment-resistant depression. To put this into perspective: 

  • Globally, depression affects an estimated 5% of adults.
  • Major depressive disorder (MDD) is one of the most prevalent mental health conditions, impacting between 5% to 17% of people at some stage in their lives.

Given these statistics, many people with depression feel better with standard treatments like medications and therapy. But some people still have symptoms even after trying these treatments. This is called treatment-resistant depression. It shows why we need more research and different ways to treat this tough condition.

What Are the Signs and Symptoms of Treatment-Resistant Depression?

People with treatment-resistant depression (TRD) experience symptoms similar to those with major depressive disorder (MDD), including persistent feelings of sadness, changes in sleep and appetite, and a loss of interest in activities. However, TRD stands out because these symptoms tend to be more severe and can last longer compared to other forms of depression. Here are some key signs and symptoms of treatment-resistant depression:

Severe Symptoms
Treatment-resistant depression often presents with more intense feelings of sadness, hopelessness, and despair compared to non-resistant depression. These emotions can be overwhelming and persistent.

Prolonged Depressive Episodes
Unlike typical depression, which may have episodic periods of low mood, individuals with treatment-resistant depression may experience prolonged episodes that endure for weeks, months, or even years.

A hallmark of treatment-resistant depression is anhedonia, where individuals lose interest in activities they once found enjoyable. This profound lack of pleasure can significantly impact daily life and relationships.

Higher Frequency of Depressive Episodes
People with treatment-resistant depression often have a history of multiple depressive episodes throughout their lives, which may contribute to the resistance to treatment.

Anxiety disorders frequently co-occur with treatment-resistant depression, intensifying overall distress and complicating treatment strategies.

Suicidal Thoughts or Behaviors
Individuals with treatment-resistant depression are at an increased risk of experiencing suicidal thoughts or engaging in self-harm behaviors. This risk underscores the critical need for vigilant monitoring and intervention by healthcare professionals. 

Persistent Depressive Mood
Despite efforts with medications, therapy, or other interventions, the depressive mood in treatment-resistant depression persists, affecting emotional well-being and daily functioning. 

Physical Symptoms
Alongside emotional distress, treatment-resistant depression can manifest in physical symptoms such as chronic fatigue, disruptions in sleep patterns (insomnia or hypersomnia), changes in appetite leading to weight loss or gain, and various unexplained aches or pains.

Who Is at Risk for Treatment-Resistant Depression?

Several factors contribute to the increased risk of developing treatment-resistant depression (TRD). Understanding these risk factors can help identify individuals who may benefit from more intensive or alternative treatment approaches:

Early Onset of Depression
If depression first manifests at a younger age, it may indicate a more chronic and persistent course of the illness. Early-onset depression has been associated with a higher likelihood of treatment resistance, possibly due to longer exposure to the condition and its effects on brain function and development.

Frequent and Recurring Depressive Episodes
People who experience depression with frequent relapses or recurrent episodes are more vulnerable to developing treatment-resistant depression. Each episode of depression can potentially alter brain chemistry and increase the risk of future episodes that are harder to treat.

Longer Duration of Depressive Episodes
Individuals whose depressive episodes persist for extended periods despite treatment efforts are at heightened risk for developing treatment-resistant depression. Prolonged episodes may indicate underlying biological or psychological factors that complicate treatment response.

Severity of Depression
Severe depression, characterized by intense symptoms such as profound sadness, hopelessness, and impaired functioning, poses a significant challenge in treatment. The severity of symptoms may necessitate more aggressive treatment strategies, and failure to respond adequately can lead to the designation of treatment-resistant depression.

Older Age
While depression can affect individuals of all ages, older adults may face unique challenges. Age-related factors such as coexisting medical conditions, cognitive decline, or reduced tolerance to medications can impact treatment outcomes. Additionally, older adults may have experienced longer durations of untreated or undertreated depression, contributing to treatment resistance.

How Is Treatment-Resistant Depression Treated?

Treatment-resistant depression (TRD) can be challenging to manage, but there are several strategies and treatments available to help alleviate symptoms and improve quality of life. Here’s an overview of how TRD is typically treated:  

Adjusting Current Treatment 

Adjusting your current treatment for treatment-resistant depression (TRD) often begins with giving your current antidepressant more time to work effectively. Sometimes, antidepressants require several weeks to reach their full therapeutic effect, so patience is essential during this phase. If initial improvement is observed but not sufficient, your psychiatrist may opt to increase the dosage of your current antidepressant. This adjustment aims to enhance its effectiveness in alleviating depressive symptoms. By gradually increasing the dosage under medical supervision, potential benefits can be maximized while carefully monitoring for any adverse effects. 

Combining Different Antidepressants

When a single antidepressant does not adequately alleviate symptoms of TRD, combining different classes of antidepressants becomes a viable strategy. For instance, combining a selective serotonin reuptake inhibitor (SSRI) with a serotonin-norepinephrine reuptake inhibitor (SNRI) targets multiple neurotransmitters involved in mood regulation. This dual-action approach can enhance antidepressant effects by addressing different aspects of depression, such as mood, energy levels, and motivation. By tailoring medication combinations to individual responses and tolerances, psychiatrists strive to optimize treatment outcomes and provide relief from persistent depressive symptoms.


Psychotherapy plays a crucial role in the treatment of TRD by addressing underlying psychological factors that contribute to depression. Engaging in regular sessions with a psychologist or therapist allows individuals to explore and understand their thoughts, emotions, and behaviors in a supportive environment. Cognitive-behavioral therapy (CBT), for example, helps individuals identify and change negative thought patterns and behaviors that perpetuate depressive symptoms. Similarly, interpersonal therapy (IPT) focuses on improving relationships and social interactions, which may be strained or affected by depression. The therapeutic relationship and the specific approach used can vary, so finding a therapist with whom you feel comfortable and who offers an effective therapy style is key to achieving lasting improvements in mood and overall well-being. 

Alternative Treatments 

Alternative treatments for individuals with treatment-resistant depression (TRD) who do not respond to conventional therapies present valuable options for managing severe and persistent depressive symptoms. One such alternative is Spravato (esketamine) nasal spray, a derivative of ketamine that acts rapidly to alleviate depression symptoms by targeting glutamate receptors in the brain. Administered under medical supervision, Spravato nasal spray treatment offers relief within hours of use, making it particularly beneficial for those with acute and treatment-resistant depression episodes. Despite its efficacy, Spravato nasal spray treatment requires careful monitoring due to potential side effects such as sedation and dissociation. Its FDA approval represents a significant advancement in TRD treatment, offering hope to individuals who have not found relief with other medications or therapies.  

Dealing with Treatment-Resistant Depression

Finding effective treatment for treatment-resistant depression often requires patience and a willingness to explore different options. It typically involves collaborating closely with your healthcare provider to identify the approach that suits you best. Monitoring your symptoms and making adjustments to treatment plans as necessary are crucial steps in achieving relief and improving your quality of life. If you’re struggling with treatment-resistant depression and seeking professional support, consider reaching out to Marpa Minds, a dedicated Spravato treatment clinic based in Westchester County NY. We specialize in providing comprehensive care and support tailored to individual needs. To start your journey towards relief, contact Marpa Minds today at 1-877-88-MARPA.