Psychiatry · Year 2 · from Psychiatry
Case 3: Treatment-Resistant Depression
Patient Presentation
Demographics: 42-year-old female
Chief Complaint: "Nothing works for my depression. I've tried everything."
History of Present Illness: A 42-year-old woman with a 15-year history of recurrent major depressive disorder is referred to a tertiary mood disorders clinic for treatment-resistant depression. Her first episode occurred at age 27 postpartum. She has had 5 major depressive episodes, with her current episode lasting 18 months. She has failed adequate trials (8+ weeks at therapeutic doses) of sertraline 200 mg, fluoxetine 60 mg, venlafaxine 225 mg, and duloxetine 120 mg. Bupropion 450 mg was partially helpful but caused a seizure at higher doses. Augmentation with aripiprazole caused intolerable akathisia; lithium augmentation produced modest benefit but was discontinued due to tremor. She currently rates her depression as 7/10 in severity. She has passive suicidal ideation but strong protective factors (two children). She is currently on venlafaxine 225 mg with lithium 600 mg daily. She expresses hopelessness about ever improving.
Mental Status Examination:
- Appearance: Well-groomed, appears fatigued
- Behavior: Psychomotor slowing
- Speech: Normal rate and volume but low energy
- Mood: "Hopeless"
- Affect: Constricted, tearful at times
- Thought content: Passive SI, pervasive hopelessness, no psychotic symptoms
- Insight: Good
- Judgment: Fair - continues to work and care for children despite symptoms
Workup:
- PHQ-9: Score 18 (moderately severe)
- TSH: 2.1 mIU/L (normal)
- Lithium level: 0.6 mEq/L (therapeutic)
- Review of records confirms adequate doses and durations of previous trials
Diagnosis: Major Depressive Disorder, recurrent, severe, treatment-resistant (failed 4 adequate antidepressant trials)
Treatment:
- Discussed treatment options for TRD including:
- Esketamine nasal spray (Spravato) - FDA-approved for TRD
- Electroconvulsive therapy (ECT) - most effective treatment
- Transcranial magnetic stimulation (TMS)
- Additional augmentation strategies
- Patient elected to try esketamine given concerns about ECT cognitive effects
- Initiated esketamine in certified treatment center, twice weekly initially
- Continued venlafaxine 225 mg as background antidepressant
- Tapered and discontinued lithium given limited benefit and side effects
- By week 4 of esketamine: significant improvement, PHQ-9 decreased to 10
- Transitioned to once-weekly, then every-other-week maintenance
- Added cognitive behavioral therapy once mood improved sufficiently
- Discussed ECT as option if esketamine response wanes
Clinical Pearl: Treatment-resistant depression (TRD) is defined as failure of at least 2 adequate antidepressant trials. Before concluding treatment resistance, ensure trials were truly adequate (therapeutic dose, sufficient duration of 8-12 weeks). ECT remains the most effective treatment for severe, treatment-resistant depression with response rates exceeding 70%. Esketamine provides a newer option with rapid onset but requires in-office administration and monitoring. The STAR*D trial demonstrated that response rates decrease with each successive medication trial.
Clinical Image
Image Description: PET scan comparing brain metabolic activity in a healthy control versus a patient with major depressive disorder, demonstrating decreased prefrontal cortex activity and altered limbic system function characteristic of depression.
Attribution: Image from Wikimedia Commons - PET scan depression comparison. Creative Commons Attribution-ShareAlike license.
Image Source: https://commons.wikimedia.org/wiki/Category:Depression_(mood) - Search for "PET scan depression" or "brain imaging depression"