What are the best interventions for treatment-resistant depression?

woman in counseling

Sometimes depression doesn’t improve or alleviate despite a person trying out various treatment options.

When an individual’s depression symptoms keep getting worse or improve for a little while only to return, they may be diagnosed with treatment-resistant depression (TRP).

What is treatment-resistant depression?

Definitions can vary depending on different factors. 

But broadly, treatment-resistant depression is diagnosed when two or more treatment attempts of adequate dose and duration fail to provide expected relief (An Overview of Treatment-Resistant Depression, Verywell mind, Amy Morin, LCSW, November 2, 2020).

Treatment-resistant depression: A complex condition

The research literature has reported how complex treatment-resistant depression can be to treat. 

For instance, many patients who comply with recommended treatments experience little to no improvement in their symptoms.

Typically, a person with treatment-resistant depression may experience remission in their depressive symptoms for a while, only for the symptoms to return. 

This can happen despite the person’s compliance with treatment recommendations by their doctor or mental health professional.

Treatment attempts

Suppose you have depressive symptoms or major depressive disorder and are being treated for your condition. 

In that case, you must remember that it can take a while for medication and other forms of treatment to take effect.

It’s common for many people to not respond to the first few treatment recommendations provided by their doctor or mental health professional.

But this doesn’t mean that your condition is untreatable.


Depression can cause debilitating symptoms, including sleep deprivation, a lack of appetite (or overeating), a lack of social functioning, and a higher risk of mortality and medical co-morbidity, to name just a few.

Depression complications

Studies have shown that untreated depression can cause disability and other physical health problems.

There’s no doubt that treatment-resistant depression is a complex disease to treat.

People do everything they can to feel better, but the treatments and medications prescribed are often ineffective or only work for a while.

Studies show that around 10-15% of the population do not respond to antidepressant treatments at all (An Overview of Treatment-Resistant Depression, Verywell mind, Amy Morin, LCSW, November 2, 2020).

Furthermore, only 30-40% of people experience a partial remission of depressive symptoms after taking antidepressant medications (An Overview of Treatment-Resistant Depression, Verywell mind, Amy Morin, LCSW, November 2, 2020).

These harrowing statistics call for more research on treatment-resistant depression to improve health outcomes for affected individuals in the future.

How do you know if you have treatment-resistant depression?


Several vital indicators may warrant further investigation from a doctor or medical professional.

For instance, if a person exhibits the following symptoms, they may have treatment-resistant depression:

  • Unresponsive to standard depression treatments (or not enough of a response)
  • Short periods of improvement followed by a return in depression symptoms
  • Unresponsive to psychotherapy or medication treatments

There’s often absolute despair and hopelessness for people who cannot find relief for their depressive symptoms despite trying various treatments and medications.

Symptoms may last for months, and the individual may not experience any improvement in mood or find comfort or relief during that time.

However, it would help if you remembered to remain hopeful despite how challenging it can sometimes be.

Various treatment options are available, and medical professionals continually optimize their approach to treating patients with treatment-resistant depression.

The best interventions for treatment-resistant depression

If you’ve been receiving treatment for depression for a while and your symptoms still haven’t improved, there are various treatment options that you can try.

Typically, those with depression respond well to combination therapies such as medication and psychotherapy. However, people with treatment-resistant depression may find that they do not respond to standard treatment.

What to do if your symptoms do not improve

Perhaps you experience some improvement in your depressive symptoms (or none at all), or maybe you feel better for a while, but your symptoms return.

Speak to your doctor

men undergoing therapy

You must speak to your doctor or medical professional if you are currently receiving treatment (such as medication, psychotherapy, or both) and your depressive symptoms have not improved.

Your doctor will likely refer you to a mental health professional specializing in treating and diagnosing mental health disorders.

Treatment approaches

Once you have been referred to a mental health specialist, they will likely review your medical history to determine a proper diagnosis and treatment plan.

They may:

  • Ask how you are taking your medications to check whether you are taking them as prescribed (this may include reviewing other treatments)
  • Consider any co-occurring conditions that might affect your response to treatment. For example, you may have another underlying mental health disorder, such as bipolar disorder. This condition can make depression worse, and you may require different treatment.
  • Review other factors, such as your relationships and work, etc. that may be contributing to your depression or making it worse
  • Look at how you have responded to treatment (including therapy, medications or other treatments you may have tried)
  • Assess your physical health status. Some diseases can make depression worse, such as specific heart conditions and chronic pain disorders.

In addition, your medical practitioner may suggest giving your current medication a bit more time to work, or they may increase your dose depending on other factors.

Effective therapies for treatment-resistant depression

Various therapeutic approaches may help improve your depressive symptoms. 

Fortunately, research and modern technologies have allowed mental health professionals to explore the different effects and outcomes of some therapies and treatments.

Some of the most effective treatment options for treatment-resistant depression include:

Psychological therapy

cartoon image of a brain with removed puzzle part

You may have tried various therapies in the past, such as psychotherapy or other types of talk therapy; if these haven’t helped, there are different therapy options for you to try, including:

  • Acceptance and commitment therapy (ACT) helps you to engage in positive behaviors regardless of negative thoughts and emotions. Acceptance and commitment therapy is a cognitive behavioral therapy that can benefit treatment-resistant illnesses.
  • Group psychotherapy (talk therapy) involves sharing your problems with a group of people with a similar condition; a psychotherapist usually facilitates group therapy.
  • Cognitive behavioral therapy (CBT) is a popular treatment that addresses maladaptive thoughts and behaviors that may affect an individual’s mood and ability to function. CBT helps you recognize negative thinking and behavioral patterns while teaching you healthier coping mechanisms to manage stress effectively.
  • Dialectical behavioral therapy (DBT) is effective for treating severe depression – dialectical behavior therapy is built on problem-solving techniques and acceptance strategies.

Further treatment options

Suppose medication and psychotherapy are ineffective and do not provide relief for your depressive symptoms. In that case, there are additional treatment options to explore, including:

  • Vagus nerve stimulation (VNS) – sometimes called VNS, this treatment involves using a device to stimulate the vagus nerve with electrical impulses. Studies show that implantable vagus nerve stimulators are FDA -approved to treat depression and epilepsy (Vagus nerve stimulation, Mayo Clinic).
  • Electroconvulsive therapy (ECT) – electroconvulsive therapy involves sending an electric current through your brain, which causes a brief surge of electrical brain activity (also called a seizure) as you sleep. ECT aims to alleviate some of the symptoms of specific mental health disorders.
  • Magnetic seizure therapy (MST) – sometimes called MST, magnetic seizure therapy uses rapidly alternating strong magnetic fields. Studies show that MST may have fewer cognitive side effects but similar clinical efficacy as electroconvulsive therapy (What is Magnetic Seizure Therapy? MagVenture, TMS Research).

Additional treatments

As well as the above treatment options, patients with treatment-resistant depression may benefit from additional therapies, including:

  • Mindfulness
  • Deep brain stimulation
  • Repetitive transcranial magnetic stimulation

The researchers noted that patients with major depression or treatment-resistant depression might benefit from specific lifestyle changes such as:

  • Abstaining from alcohol or drug use – some substances can worsen depression, making it much harder to treat.
  • Getting a better night’s sleep – a lack of sleep may make depression symptoms worse. Sticking to a regular sleeping pattern may help improve depressive symptoms.
  • Regular exercise – various studies have shown the positive effects of exercise on our mood and overall health. Even low-intensity activities such as walking or gardening can improve depressive symptoms.

How Tikvah Lake Recovery can help

group therapy

We specialize in treating various mental health disorders and addictions at Tikvah Lake Recovery.

Our team provides a holistic approach to treatment, meaning we treat the “whole” person and not just their symptoms. 

This approach allows us to address any co-occurring conditions an individual might have but have remained undetected and, therefore, untreated.

If you are struggling with depressive symptoms or are concerned about your mental health, speak to a specialist who can help.

Additional resources

  1. Treatment resistant-depression, Mayo Clinic 
  2. An Overview of Treatment-Resistant Depression, Verywell mind, Amy Morin, LCSW, November 02, 2020

About Adam Nesenoff

Adam Nesenoff has been working in recovery for over ten years.

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