Why Some Depressions Don’t Respond to Medication and What That Means for Treatment Resistant Depression and TMS

For many people, starting antidepressant medication is the first step offered when depression begins to interfere with daily life. For some, medication provides meaningful relief. For others, it helps a little but not enough. And for a significant number of people, symptoms persist despite trying multiple medications at appropriate doses and durations. This experience can be confusing, discouraging, and often misunderstood.

When depression does not improve with medication alone, it is often described as treatment resistant depression, a term that reflects the biology of the condition rather than any failure on the part of the individual. Understanding why this happens is an important step toward exploring additional options, including treatment resistant depression and TMS, in a way that feels informed and grounded rather than intimidating.

Depression Is Not a Single Condition

One reason depression can be difficult to treat is that it is not a single, uniform illness. Depression can look similar on the surface but arise from different underlying brain processes. While medications primarily work by influencing neurotransmitters such as serotonin, norepinephrine, and dopamine, not all depressive symptoms are driven by chemical imbalance alone.

Research increasingly shows that depression also involves changes in how certain brain networks function, particularly those involved in mood regulation, motivation, attention, and emotional processing. In some individuals, these networks do not respond fully to medications that target neurotransmitters, even when those medications are carefully selected and adjusted.

This helps explain why two people with similar symptoms may have very different responses to the same treatment.

What “Treatment Resistant Depression” Really Means

The term treatment resistant depression can sound discouraging, but clinically it has a specific and neutral meaning. It typically refers to depression that has not responded adequately to at least two different antidepressant trials that were taken correctly and for a sufficient period of time.

It does not mean that nothing will work. It does not mean symptoms are permanent. And it does not reflect a lack of effort or commitment on the part of the patient. Instead, it signals that a different therapeutic approach may be needed, one that works through a different mechanism than medication alone.

Recognizing treatment resistance is often a turning point in care, opening the door to more individualized and targeted options.

Why Medications Sometimes Fall Short

There are several reasons depression may not respond fully to medication:

• The primary drivers of symptoms may be related to brain circuit activity rather than neurotransmitter levels

• Side effects may limit the ability to reach an effective dose

• Co-occurring conditions such as anxiety, trauma, or chronic stress may complicate response

• Genetic differences can affect how medications are metabolized and processed

• Longstanding depression may involve entrenched neural patterns that are less responsive to medication alone

None of these factors mean that improvement is out of reach. They simply suggest that a different tool may be more appropriate.

How TMS Fits Into the Conversation

Transcranial Magnetic Stimulation, commonly referred to as TMS, is often introduced when depression has not responded to traditional treatments. Unlike medication, TMS does not work systemically throughout the body. Instead, it uses targeted magnetic stimulation to engage specific areas of the brain involved in mood regulation.

For individuals navigating treatment resistant depression and TMS, this distinction matters. TMS focuses on brain networks that may not be adequately reached by medication. It is a non-invasive, outpatient treatment that does not require sedation and does not involve medication changes during the course of treatment.

From a clinical perspective, TMS represents a shift from chemical modulation to circuit-based care. This shift reflects a broader evolution in how depression is understood and treated.

Normalizing the Need for Additional Options

It is common for people to feel discouraged or even ashamed when medications do not work as expected. Many internalize the idea that they should simply “try harder” or that something is uniquely wrong with them. In reality, non-response to medication is well documented in psychiatric care and increasingly recognized as part of the natural diversity of depressive disorders.

Exploring treatment resistant depression and TMS is not about giving up on previous treatments. It is about building on what has already been learned and using that information to guide next steps.

At Goodwin Health Café, conversations around advanced treatment options are approached with care, education, and respect for each individual’s experience. The goal is not to rush decisions, but to help people understand why certain treatments may or may not be effective for them.

A Broader View of Healing

Depression treatment is rarely linear. Many people move through different phases of care as their understanding of their condition deepens. Medication, therapy, lifestyle support, and neuromodulation can all play meaningful roles at different points.

Learning that depression has not responded to medication can feel like a setback, but it can also be a moment of clarity. It often leads to more personalized care, more precise interventions, and a better alignment between treatment and brain function.

When treatment resistant depression and TMS are discussed in an educational, grounded way, they become less about last resorts and more about appropriate next steps.

Moving Forward With Information and Support

If you or someone you care about has experienced limited relief from antidepressants, know that this experience is more common than many people realize. It does not mean progress has stalled. It means the treatment plan may need to evolve.

Understanding why some depressions do not respond to medication is the first step toward making informed decisions about what comes next. For many, learning about treatment resistant depression and TMS provides reassurance that there are additional options rooted in science, compassion, and ongoing research.

To learn more about mental health care approaches and services, visit

Goodwin Health Café at https://www.goodwinhealthcafe.com/

5625 N. Wall St. Suite 100

Spokane, WA 99205