# Clinical Cases: Mood Disorders ## Case 1: Major Depressive Disorder with Melancholic Features ### Patient Presentation **Demographics:** 58-year-old male **Chief Complaint:** "I wake up every morning feeling like there's a heavy weight on my chest. I can't feel anything anymore." **History of Present Illness:** A 58-year-old retired accountant presents to his primary care physician with his wife, who is concerned about significant changes over the past 2 months. The patient reports waking at 3-4 AM daily, unable to return to sleep, with mood at its worst in the early morning hours. He describes a complete inability to experience pleasure - even visits from his grandchildren, which previously brought him great joy, now "mean nothing." He has lost 18 pounds due to complete loss of appetite; his wife reports he "pushes food around his plate." He moves and speaks slowly, sometimes sitting motionless for hours. He ruminates constantly about past business decisions, convinced he is a "failure" who "ruined the family." He denies active suicidal ideation but admits to passive wishes that he "wouldn't wake up tomorrow." No previous psychiatric history. His father completed suicide at age 62. **Physical Examination:** - Vital signs within normal limits - General: Thin, elderly-appearing male with psychomotor retardation - Neurological: Grossly intact **Mental Status Examination:** - Appearance: Disheveled, unshaven, appears older than stated age - Behavior: Marked psychomotor retardation, minimal spontaneous movement - Speech: Low volume, slow rate, prolonged latency - Mood: "Hollow... empty" - Affect: Blunted, unreactive even to positive topics - Thought content: Excessive guilt, worthlessness, passive death wishes - Cognition: Intact but effortful **Workup:** - **PHQ-9:** Score 26 (severe depression) - **TSH:** 4.2 mIU/L (normal) - **Vitamin B12:** 380 pg/mL (normal) - **CBC, CMP:** Within normal limits - **Testosterone level:** 180 ng/dL (low - may contribute to symptoms) **Diagnosis:** Major Depressive Disorder, single episode, severe, with melancholic features **Treatment:** - Given severity, melancholic features, and family history of suicide, started on venlafaxine XR 75 mg daily (SNRI chosen for melancholic subtype) - Discussed ECT as potential treatment given severity and melancholic features; patient prefers medication trial first - Weekly monitoring with PHQ-9 and safety assessment - Increased venlafaxine to 150 mg at week 2, then 225 mg at week 4 - Sleep hygiene education; trazodone 50 mg at bedtime for insomnia - Referral for cognitive behavioral therapy once medication takes effect - Discussed testosterone replacement with primary care - At 6-week follow-up: significant improvement, PHQ-9 decreased to 12 - Continuation phase treatment planned for at least 9 months **Clinical Pearl:** Melancholic features (profound anhedonia, depression worse in morning, early morning awakening, marked psychomotor changes, excessive guilt) may predict better response to SNRIs or TCAs compared to SSRIs. Family history of completed suicide significantly elevates patient risk and should prompt thorough safety assessment. The presence of melancholic features is also a predictor of good response to ECT if medication fails. --- ## Case 2: Bipolar I Disorder - Bipolar Depression ### Patient Presentation **Demographics:** 29-year-old female **Chief Complaint:** "I've been in bed for three weeks. I can barely move." **History of Present Illness:** A 29-year-old woman with known bipolar I disorder (diagnosed at age 22 after a manic episode requiring hospitalization) presents to her outpatient psychiatrist with worsening depression. She has been in a depressive episode for 6 weeks with hypersomnia (sleeping 14-16 hours daily), hyperphagia with 12-pound weight gain, profound fatigue described as "leaden paralysis" where her limbs feel "too heavy to lift," and rejection sensitivity that has caused her to isolate from friends. She stopped going to her job as a graphic designer 3 weeks ago. She denies suicidal ideation. Her current medications include lithium 900 mg daily, which has successfully prevented manic episodes for the past 4 years. Her most recent lithium level was 0.8 mEq/L. She asks about adding an antidepressant because "they helped my friend." **Mental Status Examination:** - Appearance: Overweight female, casually dressed, fatigued appearance - Behavior: Psychomotor slowing, speaks with effort - Speech: Slow rate, low volume - Mood: "Exhausted... empty" - Affect: Constricted, mood-congruent - Thought content: Hopelessness about recovery, no SI/HI - Insight: Good - understands this is bipolar depression **Workup:** - **Lithium level:** 0.78 mEq/L (therapeutic) - **TSH:** 6.8 mIU/L (mildly elevated - lithium-induced) - **Creatinine:** 0.9 mg/dL (normal) - **PHQ-9:** Score 21 (severe depression) **Diagnosis:** Bipolar I Disorder, current episode depressed, severe **Treatment:** - Discussed the risks of antidepressant-induced mania/mood switching in bipolar disorder - Added quetiapine XR 50 mg at bedtime, titrated to 300 mg over 2 weeks (FDA-approved for bipolar depression) - Continued lithium at current dose - Started levothyroxine 25 mcg for subclinical hypothyroidism - Discussed importance of sleep regulation and social rhythm stability - Referral for interpersonal and social rhythm therapy (IPSRT) - Antidepressants avoided as monotherapy; if needed, bupropion would be safer option combined with mood stabilizer - At 4-week follow-up: moderate improvement, tolerating quetiapine well - Monitored for metabolic side effects with weight and glucose **Clinical Pearl:** Bipolar depression differs from unipolar depression in treatment approach. Antidepressants carry risk of inducing mania or rapid cycling and should generally be avoided or used only with a mood stabilizer. First-line treatments for bipolar depression include quetiapine, lurasidone, lamotrigine, and the olanzapine-fluoxetine combination. Atypical features (hypersomnia, hyperphagia, leaden paralysis, rejection sensitivity) are more common in bipolar than unipolar depression and may suggest bipolarity in an undiagnosed patient. --- ## 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 ![PET scan showing brain activity in depression](case_01_image.jpg) **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"