What is it?
Major depressive disorder is a medical condition characterized by persistent changes in mood, cognition, and physical functioning that significantly impair daily life. In 2025, about 20 million U.S. adults (7.4%) had an episode of major depression (SAMHSA, 2026). It is also one of the most commonly misdiagnosed psychiatric conditions.
Depression is not sadness. Sadness is a normal emotional response to loss. Depression is a sustained alteration in brain function that affects how a person thinks, feels, sleeps, eats, and relates to others. The distinction is clinically important because many conditions mimic depression, and treating the wrong diagnosis with antidepressants often fails. Thyroid dysfunction, sleep apnea, vitamin deficiencies, medication side effects, and undiagnosed ADHD can all produce depressive symptoms that will not respond to standard antidepressant therapy.
Clinical presentation
The textbook presentation includes persistent low mood, loss of interest, changes in appetite and sleep, fatigue, difficulty concentrating, and feelings of worthlessness. In practice, adult depression frequently presents differently.
Many adults describe persistent irritability rather than sadness. Others experience primarily physical symptoms: chronic pain, gastrointestinal complaints, or unexplained fatigue. Executive dysfunction (difficulty with decision-making, organization, and follow-through) is common and often misattributed to laziness or ADHD. Depression in men is particularly underrecognized; men are more likely to present with anger, risk-taking, or substance use.
Older adults may present with cognitive complaints that suggest early dementia rather than depression. This overlap, sometimes called pseudodementia, requires careful neuropsychiatric evaluation to distinguish from neurodegenerative conditions.
Evaluation
Depression rarely exists in isolation. Approximately 60% of adults with depression also meet criteria for an anxiety disorder (Kessler et al., 2015). Studies that follow people with depression for 10 to 20 years find that roughly 1 in 12 to 1 in 4 are later diagnosed with bipolar disorder (Ratheesh et al., 2017). Undiagnosed ADHD underlies a significant subset of treatment-resistant depression.
Medical conditions frequently produce depressive symptoms. Overt hypothyroidism is found in about 1% to 4% of people with mood disorders, and milder thyroid underactivity is more common (Hage and Azar, 2012). Obstructive sleep apnea, chronic pain, autoimmune conditions, and traumatic brain injury all carry elevated rates. Medication-induced depression is more common than most clinicians appreciate.
Treatment-resistant depression, defined as failure to respond to two or more adequate antidepressant trials, affects roughly one-third of patients. In our experience, many of these cases are not truly treatment-resistant; they are treatment failures caused by an incomplete or inaccurate diagnosis.
Treatment
Treatment begins with a comprehensive 60-minute evaluation. We complete a thorough differential diagnosis considering medical, neurological, and psychiatric causes before prescribing. We favor conservative, evidence-based pharmacotherapy: a single agent at the lowest effective dose, titrated based on response.
For patients on complex multi-medication regimens, we evaluate whether each medication is necessary and may recommend deprescribing where appropriate. We coordinate with therapists, particularly those offering CBT or behavioral activation. We do not prescribe benzodiazepines.
Finding the cause of depression
Most practices prescribe an antidepressant, titrate, switch if it fails, add a second agent. Our approach begins with the question most practices skip: why is this patient depressed? A patient whose depression is driven by undiagnosed ADHD needs a stimulant, not another SSRI. A patient with unrecognized bipolar depression needs a mood stabilizer.
Two of our three physicians completed neuropsychiatry fellowships at Stanford, which means we evaluate the neurological and medical dimensions of depressive presentations that general psychiatry may miss. For patients labeled treatment-resistant, we go back to the diagnostic question, because correcting the diagnosis changes the trajectory.
Frequently asked questions
What makes your approach to depression different?
We spend 60 minutes on initial evaluations because accurate diagnosis requires it. Before prescribing, we rule out medical causes, check for comorbid conditions like ADHD or bipolar disorder, and review your complete treatment history. Many patients referred for treatment-resistant depression turn out to have been treated for the wrong diagnosis.
What is treatment-resistant depression?
Typically defined as depression that has not improved after two or more adequate antidepressant trials. However, many cases labeled treatment-resistant are actually diagnostic failures: an incomplete evaluation that misses bipolar disorder, ADHD, or a medical cause of depression leads to treatment that cannot work.
Can depression be caused by a medical condition?
Yes. Thyroid disorders, sleep apnea, vitamin deficiencies, chronic pain, autoimmune conditions, and certain medications can produce symptoms indistinguishable from major depression. This is one reason our evaluation considers medical and neurological factors.
Do you prescribe antidepressants?
Yes, when clinically appropriate and after a thorough diagnostic evaluation. We are conservative prescribers who start with a single medication at the lowest effective dose and actively evaluate whether patients on multiple medications can safely reduce their regimen.
Requesting a depression evaluation
Your first appointment is a 60-minute evaluation by secure video, and it reviews your complete treatment history before anything new is prescribed. The plan that follows may include medication, recommendations for psychotherapy, or further medical workup such as labs.
This information is for educational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations. Always consult a qualified physician before making medication or treatment decisions. Content reviewed by physicians at Bay Area Neuropsychiatry who are board-certified by the American Board of Psychiatry and Neurology.