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What Is Treatment Resistance In Mental Health Illness?

In the vast landscape of mental health, treatment resistance stands as a formidable challenge, impeding the recovery journey of countless individuals. Despite significant advancements in psychiatric care, a staggering proportion of patients continue to grapple with treatment-resistant mental illnesses. 

According to statistics, approximately 1 in 25 adults in the United States grapple with a severe mental illness, including schizophrenia, bipolar disorder, or major depression. Within this demographic, treatment resistance affects a substantial 20–60% of patients. Alarmingly, many individuals remain unaware of their treatment resistance, often failing to explore alternative strategies for managing their conditions effectively. 

In this article, we delve into the intricate facets of treatment resistance in mental health disorders, shedding light on its definition, symptoms, underlying causes, and crucial coping strategies.

What is Treatment Resistance?

What Is Treatment Resistance In Mental Health Illness?

Treatment resistance refers to a phenomenon wherein individuals diagnosed with psychiatric disorders, such as Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), Bipolar Disorder, Obsessive-Compulsive Disorder (OCD), or Post-Traumatic Stress Disorder (PTSD), exhibit limited or no response to standard treatments and interventions. 

Despite receiving adequate doses of medications, psychotherapy, or a combination of both, these patients continue to experience persistent symptoms and functional impairment. The resistance may manifest as a lack of symptom improvement, recurrence of symptoms following initial relief, or inadequate response to multiple treatment attempts over time.

Symptoms of Treatment Resistance

  • Persistent and severe symptoms despite adherence to treatment regimens

  • Frequent relapses or recurrence of symptoms after periods of remission

  • Minimal improvement in overall functioning and quality of life

  • Resistance to medication adjustments or augmentation strategies

  • Heightened severity of symptoms compared to the initial presentation

  • Persistent treatment-related side effects without significant therapeutic benefits

Why treatments and medications fail?

Treatment resistance in mental health disorders is a multifaceted phenomenon influenced by a myriad of biological, psychosocial, and environmental factors. Understanding these intricacies is crucial for devising effective management strategies and promoting recovery in individuals grappling with treatment-resistant conditions.

1. Biological factors

Biological factors refer to aspects of our biology that can affect how we respond to treatment for mental health issues. These factors include things like our genes, which can influence how our bodies process medications. For example, certain genetic differences may cause some people to metabolize antidepressants or mood stabilizers differently, which can affect how well these medications work.

Additionally, imbalances in brain chemicals called neurotransmitters, like serotonin and dopamine, can disrupt our mood and emotions, making it harder for treatments to be effective. Changes in the structure and function of the brain can also impact how we respond to treatment, affecting things like how our brain cells communicate with each other.

2. Psychosocial factors

Psychosocial factors are the social and environmental aspects of our lives that can influence our mental health and how we respond to treatment. These factors include things like stress from work or relationships, traumatic experiences, and childhood hardships like abuse or neglect.

Chronic stress, or long-term exposure to stressful situations, can throw off the balance of hormones in our bodies, making it harder for us to cope with challenges and worsening our symptoms. Similarly, lacking a strong support system or not taking care of ourselves properly can also make it harder for treatments to work effectively.

3. Neuroadaptive changes

When we've been on medications or in therapy for a long time, our brains can adapt to these treatments in ways that make them less effective. This is known as neuroadaptive changes. Our brains have a remarkable ability to adapt to new situations, but this can sometimes work against us when it comes to mental health treatment.

For example, over time, our brains may become less sensitive to the effects of certain medications, requiring higher doses for the same effect. Similarly, changes in how our brain cells communicate with each other can make it harder for treatments to have the desired impact.

4. Comorbid conditions

Comorbid conditions are other medical or psychiatric issues that someone might have alongside their primary mental health diagnosis. These additional conditions can make treating mental health issues more complicated and can make it harder for treatments to be effective.

For example, someone with depression might also struggle with substance abuse, which can interfere with their ability to stick to their treatment plan and can worsen their symptoms. Similarly, having a chronic medical condition like diabetes or heart disease can impact how our bodies respond to certain medications and therapies.

5. Treatment adherence

Treatment adherence refers to how well someone follows their treatment plan, including taking medications as prescribed and attending therapy sessions regularly. Poor treatment adherence can significantly impact the effectiveness of mental health treatments and can contribute to treatment resistance.

There are many reasons why someone might have trouble sticking to their treatment plan, including side effects from medications, stigma around mental illness, financial difficulties, or simply forgetting to take their medications. Finding ways to address these barriers and support individuals in adhering to their treatment plan is crucial for improving outcomes for those with treatment-resistant mental illnesses.

Medication Strategies

1. Augmentation therapy

Augmentation therapy is like adding a boost to your existing treatment plan by introducing a second medication. This extra medication can help improve the effectiveness of your current treatment or target specific symptoms that haven't improved with your current medications. 

For example, if someone is struggling with depression and their antidepressant isn't fully doing the job, their doctor might suggest adding another type of medication like an antipsychotic or a mood stabilizer to help alleviate their symptoms.

2. Switching medications

Sometimes, if the medication you're currently taking isn't working well for you or is causing too many side effects, your doctor might recommend switching to a different medication. This could mean trying a different type of antidepressant or adjusting the dosage of your current medication. By switching medications, you might find a treatment that works better for you and helps improve your symptoms.

3. Combination therapy

Combination therapy means using more than one medication at the same time to treat your condition. By combining different medications that work in different ways, you might be able to target your symptoms more effectively and improve your overall treatment response. For example, your doctor might suggest combining two different antidepressants or adding an extra medication like an antipsychotic or a mood stabilizer to your current treatment plan.

4. Targeted pharmacogenetic testing

Pharmacogenetic testing is a fancy way of saying that your doctor can use information about your genes to help determine which medications might work best for you. By analyzing your genetic makeup, your doctor can get a better idea of how your body processes medications and whether you might be more likely to have side effects from certain drugs. This can help your doctor choose the right medications for you and improve the chances of finding a treatment that works well and doesn't cause unwanted side effects.


1. Mindfulness-Based Therapies

Mindfulness-based interventions, such as Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy (MBCT), emphasize present-moment awareness, acceptance, and nonjudgmental observation of thoughts and emotions. These approaches can enhance emotional regulation, reduce rumination, and cultivate resilience in individuals with treatment-resistant depression, anxiety, or trauma-related disorders.

2. Acceptance and Commitment Therapy (ACT)

ACT integrates mindfulness techniques with acceptance and value-based behavioral strategies to promote psychological flexibility and meaningful engagement in life. By fostering acceptance of difficult thoughts and emotions and encouraging actions aligned with personal values, ACT can empower individuals to navigate treatment-resistant conditions with greater resilience and purpose.

3. Dialectical Behavior Therapy (DBT)

DBT combines cognitive-behavioral techniques with mindfulness practices to address emotion dysregulation, interpersonal difficulties, and impulsive behaviors. Targeting distress tolerance, emotion regulation, interpersonal effectiveness, and mindfulness skills, DBT can offer valuable tools for individuals with borderline personality disorder, mood disorders, or PTSD.

4. Eye Movement Desensitization and Reprocessing (EMDR)

EMDR is a specialized psychotherapeutic approach designed to alleviate symptoms of trauma and PTSD by facilitating adaptive processing of distressing memories. Through guided eye movements or other bilateral stimulation techniques, EMDR can help individuals reprocess traumatic experiences, reduce emotional arousal, and foster resolution of treatment-resistant symptoms.

Other Treatment Options

Transcranial Magnetic Stimulation (TMS)

TMS is a non-invasive brain stimulation technique that uses magnetic pulses to modulate neuronal activity in targeted brain regions implicated in mood regulation. Approved for treatment-resistant depression, TMS has shown promising results in reducing depressive symptoms, enhancing neuroplasticity, and restoring functional connectivity in treatment-resistant cases.

Ketamine Infusion Therapy

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a rapid-acting and effective intervention for treatment-resistant depression. Administered via intravenous infusion or nasal spray, ketamine can induce rapid antidepressant effects, potentially providing relief for individuals who have not responded to traditional medications or psychotherapy.

Electroconvulsive Therapy (ECT)

ECT is a well-established treatment for severe and treatment-resistant psychiatric conditions, including depression, bipolar disorder, and certain psychotic disorders. By inducing controlled seizures through electrical stimulation, ECT can modulate neurotransmitter activity, restore neurocognitive functioning, and alleviate symptoms in refractory cases.

Vagus Nerve Stimulation (VNS)

VNS involves the implantation of a device that delivers electrical impulses to the vagus nerve, a key regulator of autonomic nervous system activity and mood modulation. Approved for treatment-resistant depression and epilepsy, VNS has demonstrated efficacy in reducing depressive symptoms, enhancing neuroplasticity, and improving quality of life in select individuals.

Additional Coping Strategies

1. Grounding techniques

5-4-3-2-1 technique: Engage your senses by noticing and describing

  • 5 things you can see around you

  • 4 things you can touch or feel

  • 3 things you can hear

  • 2 things you can smell

  • 1 thing you can taste

Deep breathing: Take slow, deep breaths, focusing on inhaling and exhaling fully. You can count to four as you inhale, hold for a moment, and then exhale slowly. Repeat this several times to help calm your mind and body.

2. Distraction strategies

Engage in a hobby: Spend time doing something you enjoy, such as reading, listening to music, gardening, cooking, or crafting. Immersing yourself in a favorite activity can provide a welcome distraction and promote relaxation.

Watch a funny video: Take a break and watch a funny video or comedy show. Laughter releases endorphins, which are natural mood-boosting chemicals, and can help alleviate stress and tension.

3. Self-care practices

Take a warm bath or shower: Allow yourself to relax and unwind by taking a soothing bath or shower. You can add calming essential oils, such as lavender or chamomile, to enhance relaxation.

Practice mindful eating: Pay attention to the taste, texture, and aroma of your food as you eat. Focus on nourishing your body and savor each bite mindfully, without distractions.

4. Social connection

Reach out to a friend: Connect with a friend or loved one for a chat, whether in person, over the phone, or through video call. Sharing your thoughts and feelings with someone supportive can provide comfort and perspective.

Join an online support group: Participate in online support groups or forums where you can connect with others who may be going through similar experiences. Sharing and receiving support from peers can reduce feelings of isolation and provide validation.

5. Nature and outdoor time

Take a walk outside: Spend some time outdoors, even if it's just for a short walk around your neighborhood or a nearby park. Fresh air and natural surroundings can have a calming effect on your mind and mood.

Practice grounding in nature: Take off your shoes and feel the grass beneath your feet, or sit under a tree and observe the sights and sounds of nature around you. Connecting with the earth can help you feel more grounded and centered.


In conclusion, dealing with treatment resistance in mental health disorders is a complex challenge that requires a deep understanding of its causes, symptoms, and how to manage it. By recognizing these complexities and taking a comprehensive approach to care, people can move forward in their recovery journey with strength, optimism, and a sense of control. By working together, conducting research, and providing support, we can work towards reducing the impact of treatment resistance and creating environments that promote mental health and overall well-being for everyone.

More From Josh

About Josh Brar: 

Author - Josh Brar

Hello, I'm Josh Brar. My journey includes over 15 years in the pharmaceutical industry, which took an unexpected path in my 40s due to my struggle with treatment-resistant depression. Leveraging my pharmaceutical background, I gained extensive knowledge about mental disorders. Despite exploring numerous treatments, the challenge of finding relatable information and community support was significant. This inspired me to establish this platform, with the aspiration of it being a helpful resource for others on similar paths.


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