Psychiatry · Year 3 · from Psychiatry

Case 2: Treatment-Resistant Depression

Patient Demographics

  • Age: 52 years old
  • Sex: Male
  • Occupation: Accountant (currently on medical leave)

Chief Complaint

"Nothing has worked. I've tried everything and I'm still miserable."

History of Present Illness

The patient is referred to a psychiatrist by his primary care physician for treatment-resistant depression. He has a 15-year history of recurrent major depressive disorder, with the current episode lasting 18 months despite multiple medication trials. His first depressive episode occurred at age 37 following a job loss, and he has had 4 subsequent episodes. The current episode began insidiously after his divorce finalized. He describes persistent depressed mood, profound anhedonia (hasn't enjoyed anything in over a year), hypersomnia (sleeping 12-14 hours but still exhausted), significant weight gain (40 lbs), decreased concentration, and feelings of hopelessness. He reports frequent thoughts that "everyone would be better off without me" but denies active suicidal planning, stating "I'm too much of a coward to do anything." He went on medical leave 3 months ago when he could no longer function at work.

Previous Treatment Trials (Adequate dose and duration confirmed):

  1. Sertraline 200 mg x 12 weeks - minimal response
  2. Fluoxetine 60 mg x 10 weeks - no response
  3. Venlafaxine XR 225 mg x 12 weeks - partial response, discontinued due to elevated blood pressure
  4. Bupropion XL 450 mg x 8 weeks - no response
  5. Mirtazapine 45 mg x 8 weeks - weight gain without mood improvement
  6. Sertraline + Aripiprazole augmentation - partial response

Current medications: Sertraline 200 mg daily, Aripiprazole 5 mg daily

Mental Status Examination

Appearance: Overweight man appearing older than stated age, poorly groomed, dressed in rumpled clothing

Behavior: Psychomotor retardation marked, minimal eye contact, slumped posture, speaks only when spoken to

Speech: Markedly decreased rate and volume, monotone, long latencies

Mood: "Terrible, as always"

Affect: Flat, blunted, depressed

Thought Process: Impoverished, goal-directed when engaged

Thought Content: Hopelessness, helplessness, worthlessness, passive suicidal ideation without plan

Perceptions: Denies hallucinations

Cognition: Oriented x4, attention and concentration impaired, complaints of "brain fog"

Insight: Fair - understands he has depression, skeptical that anything will help

Judgment: Fair - continues to engage in treatment despite pessimism

Psychiatric Workup

Screening Tools:

  • PHQ-9: 24/27 (severe)
  • MADRS (Montgomery-Asberg Depression Rating Scale): 38 (severe)
  • Columbia-Suicide Severity Rating Scale: Passive ideation present

Laboratory Studies:

  • TSH: 2.8 mIU/L (normal)
  • Free T4: 1.2 ng/dL (normal)
  • Testosterone: 280 ng/dL (low-normal, may contribute)
  • Vitamin B12: 320 pg/mL (low-normal)
  • Folate: 8 ng/mL (normal)
  • MTHFR testing: Not previously done
  • CRP: 4.2 mg/L (elevated - inflammation)

Diagnosis

Major Depressive Disorder, Recurrent Episode, Severe without Psychotic Features, Treatment-Resistant (F33.2)

Definition of Treatment-Resistant Depression: Failure to respond to at least 2 adequate trials of antidepressants from different classes

Treatment Plan

Re-evaluate Current Regimen:

  • Continue sertraline 200 mg
  • Discontinue aripiprazole (insufficient response)

Advanced Treatment Options Discussed:

  1. Esketamine (Spravato) Nasal Spray:
  • FDA-approved for treatment-resistant depression
  • Administer in certified healthcare setting
  • REMS program enrollment required
  • Twice weekly initially, then weekly
  • Discussed dissociative side effects, monitoring requirements
  1. Electroconvulsive Therapy (ECT):
  • Highly effective for treatment-resistant depression
  • Response rates 50-70% in treatment-resistant cases
  • Right unilateral electrode placement to minimize cognitive effects
  • Discussed cognitive side effects, need for anesthesia
  • Recommended given severity and lack of response
  1. Transcranial Magnetic Stimulation (TMS):
  • Non-invasive, outpatient
  • Daily sessions for 4-6 weeks
  • Less effective than ECT but fewer side effects

Patient Decision:

  • Agreed to trial of esketamine
  • ECT reserved if esketamine insufficient

Additional Interventions:

  • Testosterone supplementation considered pending endocrinology consultation
  • Continue psychotherapy (supportive therapy currently)
  • Address sleep hygiene, encourage light physical activity

Follow-up:

  • Esketamine initiation scheduled
  • Weekly visits during acute treatment phase

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