3.3 Depressive Disorders

Depressive Disorders

Exam Tip: Always screen for a history of mania or hypomania before diagnosing a depressive disorder to rule out the bipolar spectrum.

1. Major Depressive Disorder (MDD)

MDD is a leading cause of disability worldwide. Diagnosis relies heavily on a careful clinical interview to identify symptom clusters and functional impairment.

Diagnostic Criteria (DSM-5-TR)

At least 5 of the following symptoms must have been present during the same 2-week period, representing a change from previous functioning. At least one of the symptoms must be (1) depressed mood or (2) loss of interest or pleasure (anhedonia).

Mnemonic: SIGECAPS

• Sleep changes (insomnia or hypersomnia)
• Interest loss (anhedonia)
• Guilt (worthlessness)
• Energy lack (fatigue)
• Cognition/Concentration impairment
• Appetite changes (weight loss or weight gain)
• Psychomotor agitation or retardation
• Suicidal ideation or recurrent thoughts of death

Additional criteria: symptoms cause clinically significant distress or impairment; the episode is not attributable to substance or medical condition; there is no history of manic or hypomanic episodes; the episode is not better explained by a psychotic disorder.

Specifiers

• With melancholic features: Profound anhedonia, depression worse in morning, early morning awakening, significant weight loss, excessive guilt, psychomotor retardation. Responds preferentially to ECT and TCAs.
• With psychotic features: Delusions or hallucinations, usually mood-congruent (guilt, disease, poverty). Requires combination of antidepressant plus antipsychotic, or ECT.
• With catatonic features: Motor immobility, posturing, negativism, mutism. Treat with benzodiazepine trial and ECT if unresolved.
• With atypical features: See section 4 below.
• With peripartum onset: See section 4 below.
• With seasonal pattern: Full remissions in a particular season (often spring/summer) and recurrences in fall/winter for at least 2 years. Treat with light therapy (10,000 lux for 30 min each morning).
• With anxious distress: Tension, restlessness, difficulty concentrating due to worry, fear of losing control. Associated with higher suicide risk and poorer outcomes.

2. Persistent Depressive Disorder (PDD / Dysthymia)

PDD represents a chronic, low-grade depression.

• Criteria: Depressed mood for most of the day, for more days than not, for at least 2 years (1 year for children/adolescents).
• Symptoms: While depressed, at least 2 of: poor appetite or overeating, insomnia or hypersomnia, low energy, low self-esteem, poor concentration, feelings of hopelessness.
• Timeline: During the 2-year period, the individual has never been without symptoms for more than 2 months at a time.
• Double Depression: When a patient with PDD experiences a superimposed major depressive episode, the diagnosis is PDD with intermittent major depressive episodes ("double depression").

3. Premenstrual Dysphoric Disorder (PMDD)

PMDD is a severe, debilitating extension of premenstrual syndrome (PMS).

• Criteria: In the majority of menstrual cycles, at least 5 symptoms must be present in the final week before the onset of menses, start to improve within a few days after the onset of menses, and become minimal or absent in the week postmenses.
• Symptoms: Marked affective liability, irritability/anger, depressed mood, anxiety, alongside physical symptoms (breast tenderness, bloating).
• Treatment: SSRIs (Fluoxetine, Sertraline) either continuously or during the luteal phase only.

4. Disruptive Mood Dysregulation Disorder (DMDD)

DMDD was introduced in DSM-5 to reduce overdiagnosis of pediatric bipolar disorder.

• Criteria: Severe, recurrent temper outbursts grossly out of proportion to the situation, occurring 3 or more times per week for 12 or more months. Mood between outbursts is persistently irritable or angry.
• Onset: Between ages 6 and 18; diagnosis requires onset before age 10.
• Treatment: CBT, parent training, and SSRIs for the irritable mood; stimulants if comorbid ADHD. Avoid antipsychotics as first-line due to metabolic risk in children.

5. Specifiers and Subtypes

With Atypical Features

Atypical depression presents somewhat oppositely to classic melancholic depression.

• Core Feature: Mood reactivity (mood brightens in response to positive events).
• Plus 2 or more of: Significant weight gain/hyperphagia, hypersomnia, leaden paralysis (heavy, leaden feelings in arms/legs), long-standing interpersonal rejection sensitivity.
• Historical note: MAOIs were highly effective for atypical depression, though SSRIs/SNRIs are now first-line due to the tyramine diet restriction of MAOIs.

With Peripartum Onset

• Definition: Onset of mood symptoms occurs during pregnancy or in the 4 weeks following delivery (per DSM-5-TR; clinically, postpartum depression is often diagnosed up to 12 months postpartum).
• Clinical Significance: High risk for impaired maternal-infant bonding and potential for postpartum psychosis (a psychiatric emergency requiring immediate hospitalization; characterized by delusions about the baby, hallucinations, and rapid mood swings).

6. Differential Diagnosis

MDD vs. Bipolar Depression

Misdiagnosing bipolar depression as unipolar MDD risks a manic switch when an antidepressant is prescribed. Screen every depressed patient using the MDQ or a careful lifetime history of elevated mood, decreased need for sleep, and goal-directed activity lasting ≥ 4 days.

MDD vs. Adjustment Disorder with Depressed Mood

Adjustment disorder requires symptoms within 3 months of a identifiable stressor that are out of proportion and cause significant impairment. Symptoms resolve within 6 months after the stressor ends. If the patient meets full MDD criteria, the diagnosis is MDD — not adjustment disorder.

MDD vs. Normal Grief (Bereavement)

Grief features waves of sadness with preserved self-esteem and positive memories of the deceased; MDD features pervasive anhedonia, worthlessness, and self-loathing. Grief may include hallucinations of the deceased's voice (a normal variant); MDD with psychotic features involves mood-congruent delusions of guilt or worthlessness.

7. Treatment of Depressive Disorders

Pharmacotherapy

• First-line: SSRIs (Fluoxetine, Sertraline, Escitalopram, Citalopram, Paroxetine). Efficacy takes 4-8 weeks. Start lower in elderly ("start low, go slow").
• Alternatives/Augmentation: SNRIs (Venlafaxine, Duloxetine), Bupropion (NDRI - good for fatigue, no weight gain, no sexual dysfunction; contraindicated in seizure disorders and eating disorders), Mirtazapine (good for insomnia and poor appetite).
• Augmentation strategies: Bupropion added to an SSRI for residual fatigue or sexual dysfunction; atypical antipsychotics (aripiprazole, quetiapine) for partial responders; lithium augmentation for refractory depression; thyroid hormone (T3) augmentation.
• SSRI Discontinuation Syndrome: Dizziness, nausea, sensory disturbances ("brain zaps"), anxiety, insomnia. Highest risk with paroxetine and venlafaxine (short half-lives); lowest with fluoxetine (long half-life). Taper slowly.
• Serotonin Syndrome Risk: Combining serotonergic agents (SSRIs/SNRIs with tramadol, triptans, MAOIs, linezolid) can lead to altered mental status, autonomic instability (hyperthermia, tachycardia), and neuromuscular hyperactivity (hyperreflexia, clonus). Onset is hours, unlike NMS which develops over days to weeks.
• MAOIs (Phenelzine, Tranylcypromine): Reserved for atypical or treatment-resistant depression. Require a tyramine-free diet (no aged cheeses, cured meats, fermented foods) to prevent a hypertensive crisis. Cannot be combined with SSRIs (requires 5-week washout from fluoxetine; 2 weeks from other SSRIs).

Somatic Therapies

• Electroconvulsive Therapy (ECT): The most effective treatment for severe MDD, especially with psychotic features, acute suicidality, or catatonia. Safe in pregnancy. Main side effect is transient retrograde amnesia. Unilateral electrode placement has fewer cognitive side effects than bilateral.
• Transcranial Magnetic Stimulation (TMS): Non-invasive, used for treatment-resistant depression without the cognitive side effects of ECT. No anesthesia required; common side effect is scalp discomfort.
• Ketamine / Esketamine (Spravato): Rapid-acting NMDA antagonist for treatment-resistant depression. Esketamine is intranasal, administered in a REMS-certified setting, with monitoring for 2 hours post-dose for dissociation and sedation.

Clinical Vignette: A 45-year-old male complains of feeling persistently "down in the dumps" for the past 3 years. He says he feels this way most days and also experiences low energy, poor sleep, and low self-esteem. He denies any suicidal ideation and has never felt excessively happy or energetic. Diagnosis: Persistent Depressive Disorder (Dysthymia).