Treatment-Resistant Depression: Why Standard Medications Aren’t Always Enough
- Moe | Scarlet Plus
- Sep 29
- 4 min read
Depression is one of the most common mental health conditions, affecting millions worldwide. For many, antidepressant medications combined with therapy provide relief. But for some, these treatments don’t work—or don’t work well enough. This condition is called treatment-resistant depression (TRD).
At Adelson Behavioral & Mental Health, we frequently meet patients who say:
“I’ve tried several antidepressants, but I still feel stuck.”
“My doctor keeps adjusting doses, but my mood doesn’t improve.”
“I thought treatment meant I’d feel better, but nothing seems to work.”
This blog explains what treatment-resistant depression is, why standard medications may fall short, and what advanced treatment options can help.
On this page:
What Is Treatment-Resistant Depression?
Treatment-resistant depression occurs when a person doesn’t respond to at least two different antidepressant trials, taken at the right dose and duration.
According to the National Institute of Mental Health (NIMH):
About 30% of people with depression fall into the TRD category.
TRD doesn’t mean “untreatable”—it simply means different strategies are needed.
Why Some Depression Doesn’t Respond to Medication
There are many reasons why standard antidepressants don’t always work:
Biological Differences
Brain chemistry varies widely. Antidepressants that target serotonin may not address other neurotransmitters involved in a patient’s depression, like glutamate or dopamine.
Co-Occurring Conditions
Anxiety, trauma, substance use, or medical conditions (like thyroid disorders) may complicate treatment.
Undiagnosed Bipolar Disorder
Sometimes what looks like major depression is actually part of the bipolar spectrum, requiring a very different treatment approach.
Genetic Factors
Genes influence how the body metabolizes medications. Genetic testing can sometimes guide medication choices.
Medication Non-Adherence
Side effects, cost, or lack of motivation may prevent consistent use of antidepressants.
The Mayo Clinic notes that TRD is complex and requires a customized approach.
Signs That Depression May Be Treatment-Resistant
Minimal improvement after multiple medications
Worsening symptoms despite treatment
Persistent fatigue, hopelessness, or lack of motivation
Functional impairments in work, school, or relationships
The Emotional Toll of TRD
Living with TRD can feel especially discouraging:
Patients may feel hopeless after failed treatments.
They may blame themselves, believing they’re “not trying hard enough.”
Friends and family may not understand why progress seems slow.
At Adelson Behavioral & Mental Health, we remind patients: TRD isn’t a personal failure—it’s a medical condition that requires a different strategy.
Advanced Treatment Options for TRD
Fortunately, several innovative treatments are now available:
1. Medication Adjustments
Augmenting antidepressants with mood stabilizers or antipsychotics
Switching medication classes (SSRIs, SNRIs, atypical antidepressants)
Using combination therapy
2. Psychotherapy
Cognitive Behavioral Therapy (CBT) – Effective when combined with medication.
Acceptance and Commitment Therapy (ACT) – Helps patients live meaningfully despite symptoms.
Trauma-Informed Therapy – Addresses underlying trauma that may fuel depression.
3. Brain Stimulation Therapies
Transcranial Magnetic Stimulation (TMS): Non-invasive magnetic pulses stimulate underactive brain areas (Cleveland Clinic).
Electroconvulsive Therapy (ECT): For severe, life-threatening depression; highly effective.
Vagus Nerve Stimulation (VNS): Implanted device stimulating mood regulation.
4. Esketamine (Sparavato)
An FDA-approved nasal spray, esketamine targets the glutamate system and works within hours to reduce depressive symptoms, especially for patients at risk of suicide.
5. Lifestyle and Complementary Approaches
Exercise programs to boost serotonin and endorphins
Sleep regulation strategies
Mind-body practices like meditation, yoga, and breathing techniques
Daily Coping Strategies
For patients navigating TRD, everyday strategies make a difference:
Structured Routines – Provide predictability and reduce overwhelm.
Support Networks – Family, friends, or support groups prevent isolation.
Journaling – Helps track triggers, medication effects, and mood patterns.
Nutrition and Exercise – Improve brain health and resilience.
The Harvard Medical School highlights exercise as a powerful complement to medical care.
When to Seek Immediate Help
If depression leads to thoughts of self-harm or suicide, immediate support is essential. In the U.S., call 988 (Suicide & Crisis Lifeline) for 24/7 help.
How Adelson Behavioral & Mental Health Supports TRD Patients
At Adelson Behavioral & Mental Health – Maryland & Washington, D.C., we provide:
Comprehensive evaluations to identify hidden factors behind TRD.
Advanced treatment options, including medication management, therapy, and TMS referrals.
Sparavato therapy for rapid relief when needed.
Collaborative care, ensuring all aspects of a patient’s health are addressed.
Compassionate, personalized support for every step of recovery.
Our mission is to help patients move beyond trial-and-error care and access treatments that truly work.
Conclusion
Treatment-resistant depression is challenging, but it is not hopeless. When standard medications don’t work, advanced therapies—from TMS to Sparavato—offer new possibilities for healing.
At Adelson Behavioral & Mental Health, we help patients find the strategies that finally bring relief. Because everyone deserves the chance to move beyond depression and live a fulfilling life.
References
National Institute of Mental Health – Depression
Cleveland Clinic – TMS Therapy
Harvard Health Publishing – Exercise for Depression
Take the First Step with Adelson Behavioral & Mental Health
Beginning your journey toward better mental health is a courageous move, and finding the best psychiatrist is a crucial part of that process.
If you're looking for a psychiatrist in Arlington, TX | Dallas, TX | Fort-Worth, TX, Mansfield, TX, Adelson Behavioral & Mental Health is ready to help. We offer personalized and empathetic care tailored to your unique needs.
