4.1 Mood Disorders: Major Depression & Bipolar Spectrum
Key Takeaways
- Major Depressive Disorder (MDD) requires ≥5 of 9 SIGECAPS symptoms for ≥2 consecutive weeks, with at least one symptom being depressed mood or anhedonia.
- Bipolar I disorder requires at least 1 manic episode lasting ≥7 days (or any duration if hospitalization is required), whereas Bipolar II requires ≥1 hypomanic episode (≥4 days) and ≥1 major depressive episode without prior mania.
- Persistent Depressive Disorder (Dysthymia) is characterized by depressed mood for most of the day for at least 2 years in adults (1 year in children/adolescents) with no symptom-free period exceeding 2 months.
- Electroconvulsive therapy (ECT) is indicated for severe depression with psychotic features, acute suicidality, catatonia, or severe treatment resistance, with a response rate of 70% to 90%.
- Maintenance antidepressant therapy should be continued for 4–9 months after a single MDD episode, 1–3 years for recurrent episodes (≥2), and indefinitely for severe, highly recurrent, or chronic depression.
Clinical Overview & Epidemiology
Mood disorders represent a leading cause of disability worldwide. On the USMLE Step 2 CK, distinguishing unipolar depression from bipolar spectrum disorders is a critical clinical skill because inappropriate antidepressant monotherapy in bipolar illness can precipitate iatrogenic mania or rapid cycling. Mood disorders are classified based on the presence, duration, and severity of depressive, manic, or hypomanic episodes.
Diagnostic Criteria for Major Depressive Disorder (MDD)
To meet DSM-5 diagnostic criteria for Major Depressive Disorder, a patient must experience ≥5 of the 9 SIGECAPS symptoms during the same 2-week period, representing a clear change from previous functioning. At least one of the symptoms must be depressed mood or anhedonia (loss of interest or pleasure).
- S — Sleep disturbances (insomnia or hypersomnia)
- I — Interest loss (anhedonia)
- G — Guilt or feelings of worthlessness
- E — Energy reduction or fatigue
- C — Concentration impairment or indecisiveness
- A — Appetite or weight changes (increase or decrease of >5% in a month)
- P — Psychomotor agitation or retardation (observable by others)
- S — Suicidal ideation, recurrent thoughts of death, or suicide attempts
Symptoms must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning and must not be attributable to the physiological effects of a substance or another medical condition (e.g., hypothyroidism).
Diagnostic & Screening Algorithm for Mood Disorders
Diagnostic Flowchart for Depressed or Elevated Mood:
1. Assess duration and symptom core:
- Depressed mood/anhedonia + ≥5 total SIGECAPS symptoms for ≥2 weeks -> Evaluate for Major Depressive Disorder.
- Depressed mood for ≥2 years (never asymptomatic >2 months) + ≥2 symptoms -> Persistent Depressive Disorder (Dysthymia).
2. Screen for manic or hypomanic episodes:
- ≥1 manic episode (≥7 days or requiring hospitalization, causing severe impairment) -> Bipolar I Disorder.
- ≥1 hypomanic episode (≥4 days, no marked impairment, no psychosis) AND ≥1 MDD episode -> Bipolar II Disorder.
- Fluctuating hypomanic and depressive symptoms for ≥2 years without meeting full MDE or manic criteria -> Cyclothymic Disorder.
3. Rule out secondary etiologies:
- Medical conditions (e.g., hypothyroidism, Cushing syndrome, stroke, pancreatic carcinoma).
- Substance/medication-induced (e.g., beta-blockers, corticosteroids, interferon-alpha, alcohol/cocaine withdrawal).
Differential Diagnosis of Mood Spectrum Disorders
Accurate diagnosis hinges on identifying symptom duration, severity, and history of elevated mood.
| Disorder | Episode Duration | Core Clinical Criteria | Distinguishing Feature | First-Line Management |
|---|---|---|---|---|
| Major Depressive Disorder (MDD) | ≥2 consecutive weeks | ≥5 of 9 SIGECAPS symptoms (must include depressed mood or anhedonia) | Functional decline without manic/hypomanic history | SSRI/SNRI + Psychotherapy (CBT) |
| Persistent Depressive Disorder (Dysthymia) | ≥2 years (adults) / ≥1 year (kids) | Chronic depressed mood + ≥2 secondary depressive symptoms | No symptom-free interval >2 months | SSRI/SNRI + Psychotherapy |
| Bipolar I Disorder | Manic: ≥7 days (or any if hospitalized) | ≥1 manic episode (DIG FAST criteria) ± major depressive episodes | Mania induces severe social/occupational ruin or psychosis | Lithium, Valproate, or SGAs (e.g., Quetiapine) |
| Bipolar II Disorder | Hypomanic: ≥4 days; MDE: ≥14 days | ≥1 hypomanic episode AND ≥1 major depressive episode | Never has full manic episode or psychosis during hypomania | Quetiapine, Lurasidone, Lithium |
| Cyclothymic Disorder | ≥2 years chronic fluctuation | Hypomanic & depressive periods that do not meet full episode criteria | Mild chronic mood instability without full MDE or mania | Mood stabilizers (Valproate, Lithium) / CBT |
The DIG FAST mnemonic identifies manic and hypomanic symptoms: Distractibility, Indiscretion/impulsivity, Grandiosity, Flight of ideas/racing thoughts, Activity increase (goal-directed), Sleep requirement decrease (e.g., feeling rested after 2 hours), and Talkativeness (pressured speech).
Psychopharmacology & Somatic Interventions
Antidepressant Classes & Adverse Effect Profiles
- Selective Serotonin Reuptake Inhibitors (SSRIs) (e.g., Escitalopram, Fluoxetine, Sertraline): First-line for MDD and anxiety disorders. Common side effects include sexual dysfunction, gastrointestinal distress, weight changes, and emotional blunting. Fluoxetine has the longest half-life (~1–2 weeks for active metabolite norfluoxetine).
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) (e.g., Venlafaxine, Duloxetine): First-line alternative, especially in patients with comorbid neuropathic pain or fibromyalgia. Venlafaxine can cause dose-dependent hypertension due to noradrenergic stimulation.
- Atypical Antidepressants:
- Bupropion: Norepinephrine-dopamine reuptake inhibitor. Does not cause sexual dysfunction or weight gain. Contraindicated in patients with bulimia nervosa, anorexia nervosa, or seizure disorders due to a lowered seizure threshold.
- Mirtazapine: Alpha-2 antagonist and 5-HT2/5-HT3 receptor antagonist. Promotes sedation and weight gain/appetite stimulation, making it ideal for elderly patients with depression, severe insomnia, and cachexia.
- Tricyclic Antidepressants (TCAs) (e.g., Amitriptyline, Nortriptyline): Inhibits 5-HT and NE reuptake; blocks H1, alpha-1, and muscarinic receptors. Toxic in overdose due to the 3 Cs: Cardiotoxicity (wide QRS complex, arrhythmias due to fast sodium channel blockade), Convulsions (seizures), and Coma. Treatment for TCA-induced sodium channel blockade is intravenous sodium bicarbonate.
- Monoamine Oxidase Inhibitors (MAOIs) (e.g., Phenelzine, Tranylcypromine, Selegiline): Reserved for refractory depression. Risk of hypertensive crisis when combined with tyramine-rich foods (aged cheeses, wine, cured meats) due to uninhibited accumulation of sympathomimetic amines.
Mood Stabilizers in Bipolar Disorder
- Lithium: Reduces suicide risk in bipolar disorder. Excreted renally. Toxicity presents with coarse tremor, ataxia, confusion, and emesis. Chronic side effects include nephrogenic diabetes insipidus, hypothyroidism, epstein anomaly (if taken in 1st trimester of pregnancy), and tubulointerstitial nephritis. Mandatory lab monitoring: TSH, BUN/Creatinine, serum lithium levels, and calcium.
- Valproic Acid / Divalproex: Preferred for rapid cycling bipolar disorder (>4 episodes/year). Side effects include hepatotoxicity, pancreatitis, thrombocytopenia, and neural tube defects (spina bifida).
- Lamotrigine: Effective for bipolar depression maintenance. Requires slow titration due to risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Somatic Therapies: Electroconvulsive Therapy (ECT)
ECT is the most rapidly effective treatment for major depression, with a response rate exceeding 80%. Absolute indications include:
- Severe depression with psychotic features
- Acute suicidality requiring rapid response
- Depression causing severe catatonia or refusal to eat/drink leading to dehydration
- Treatment-resistant depression failing multiple drug trials
- Pregnancy where pharmacotherapy is contraindicated
The primary adverse effect is transient retrograde and anterograde amnesia, which typically resolves within a few months.
Treatment Duration & Maintenance Guidelines
- Single MDD Episode: Continue antidepressant therapy for 4 to 9 months at the dose that achieved remission (continuation phase).
- Recurrent MDD (≥2 episodes), severe episodes (suicide attempt), or chronic duration (≥2 years): Maintain antidepressant therapy for 1 to 3 years or indefinitely.
- Discontinuation of SSRIs/SNRIs (especially Paroxetine or Venlafaxine) requires gradual tapering over weeks to prevent SSRI discontinuation syndrome (flu-like symptoms, electric-shock sensations, dizziness, anxiety).
A 34-year-old woman presents to the clinic reporting a 3-month history of persistent depressed mood, loss of interest in her hobbies, difficulty sleeping, early morning awakening, a 6-kg weight loss, and feelings of worthlessness. She has no prior psychiatric history and no medical conditions. Physical examination and laboratory studies, including thyroid-stimulating hormone, are normal. What is the most appropriate first-line pharmacotherapy?
A 28-year-old man with a history of Bipolar I disorder is brought to the emergency department because of confusion, dysarthria, severe ataxia, and a coarse hand tremor. His family reports he recently started taking an over-the-counter anti-inflammatory drug for knee pain. Serum drug levels reveal a concentration of 2.1 mEq/L (therapeutic range: 0.6–1.2 mEq/L). Toxicity from which medication is responsible for this presentation?
A 22-year-old college student is brought to the emergency department by his roommate after spending $15,000 on high-risk stock options over 3 days. He has not slept in 5 days but reports feeling 'more energetic than ever.' He speaks rapidly, jumping from topic to topic, and claims he was chosen by God to revolutionize global trading. He has no prior medical history. What is the most likely diagnosis?