BYLINE: João L. de Quevedo, MD, PhD | Professor, director of the UTHealth Houston Center for Interventional Psychiatry, and director of the Treatment-Resistant Depression Program with the Department of Psychiatry and Behavioral Sciences at McGovern Medical School at UTHealth Houston.
Welcome to “Ask the Expert,” a UTHealth Houston newsroom series where our leading physicians examine pressing health challenges. In this edition, we address depression and what to do if depression becomes treatment resistant.
May is Mental Health Awareness Month. It’s a time to reduce the stigma around mental health, educate the public, and share resources for those who need support.
Among the conditions we seek to raise awareness about is depression, which affects 5.7% of adults globally according to the World Health Organization. A depression diagnosis can be challenging, but many levels of depression are treatable.
What is depression?
Depression, also known as major depressive disorder, is a common but serious medical condition that affects how a person feels, thinks, and functions. It goes beyond normal sadness or temporary emotional reactions to life’s challenges.
Depression involves changes in brain chemistry, neural circuits, and stress-response systems, which can lead to persistent symptoms that interfere with daily life, relationships, and overall well-being. Importantly, depression is a treatable condition, and effective therapies are available.
What are the symptoms of depression?
Depression can present differently from person to person, but the most common symptoms include:
Persistent sadness, low mood, or feelings of emptinessLoss of interest or pleasure in activities once enjoyedChanges in sleep (insomnia or sleeping too much)Changes in appetite or weightFatigue or low energyDifficulty concentrating, thinking, or making decisionsFeelings of worthlessness, guilt, or hopelessnessSlowed movements or restlessnessThoughts of death or suicide
To be diagnosed, symptoms typically need to be present most of the day, nearly every day, for at least two weeks and cause significant impairment in functioning. If suicidal thoughts are present, immediate medical attention is essential.
Who is most likely to be affected by depression?
Depression can affect anyone, regardless of age, gender, or background. However, certain factors increase depression risk:
Family history of depression or other mental health conditionsChronic medical illnesses, such as cardiovascular disease, cancer, or neurological disordersStressful life events, including trauma, loss, or major transitionsSubstance use, including alcohol or drugsHormonal changes, such as during pregnancy or postpartumPrevious episodes of depression
Depression is more commonly diagnosed in women, but men may be underdiagnosed and present differently, sometimes with irritability or substance use.
What is treatment-resistant depression?
Depression is defined as treatment-resistant if it hasn’t improved after someone tries at least two different at adequate doses and duration. While this can feel discouraging, it is more common than many people realize. It reflects the complexity of depression, not a personal failure.
Depression is not a one-size-fits-all condition. It involves multiple brain circuits, neurotransmitters, and biological pathways. As a result, a treatment that works well for one person may not work for another.
Why don’t some treatments work?
There are several reasons why depression may not respond to initial treatments:
The underlying biology of depression varies from person to personCoexisting conditions such as anxiety, trauma, or physical illnesses may complicate treatmentMedications may not have been optimized in dose or durationLife stressors and environmental factors can play a significant role
Understanding these factors is essential to developing a more effective, personalized treatment plan.
What are the next steps?
When depression does not improve, the approach should shift from repeating the same strategies to exploring new, evidence-based options. These may include:
Adjusting or combining medicationsIncorporating structured psychotherapiesAddressing sleep, lifestyle, and medical contributors
For many individuals, however, the most meaningful improvements come from newer, targeted treatments—including ketamine and esketamine, transcranial magnetic stimulation, and electroconvulsive therapy—that work in different ways than traditional antidepressants.
A message of hope
One of the most important things to understand about treatment-resistant depression is that it is still treatable. The field of psychiatry is rapidly evolving, with new therapies offering hope to patients who previously had limited options.
If you are struggling with depression that has not improved, do not give up. The right treatment approach may not have been found yet, but with today’s advances, there are more paths to recovery than ever before.
João L. de Quevedo, MD, PhD | Professor, director of the UTHealth Houston Center for Interventional Psychiatry, and director of the Treatment-Resistant Depression Program with the Department of Psychiatry and Behavioral Sciences at McGovern Medical School at UTHealth Houston. All quotes should be attributed to him.
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