Case 2: Lan Chen - Depression

Depressive Disorders: Description

Conditions with symptoms of depression impairing ability to function

Depressive Disorders: Types

Major depressive disorder (MDD)

Premenstrual dysphoric disorder (PMDD)

Disruptive mood dysregulation disorder (DMDD)

Persistent depressive diosrder (Dysthymia)

MDD

Episodic mood disorder

• Depressed mood + anhedonia ≥ 2 weeks

Atypical Features: Mood reactivity

• Mood brightening in response to positive events

Psychotic Features: Congruent with mood

Seasonal Pattern: Episodes only in winter

PMDD

Affective + somatic symptoms during luteal phase

Resolve with menstruation

DMDD

Extreme irritability + recurrent anger outbursts

> 3/weeks for > 12 months

Dysthymia

Chronic depression ≥ 2 years

MDD: Description

Episodic mood disorder with depressed mood + anhedonia ≥ 2 weeks

MDD: Epidemiology

Risk factors…

• Poor sleep hygiene

  • Sleep apnea → Intermittent cerebral hypoxia

• Alcohol use

• Childhood trauma

• Family history

• Women

MDD: Etiology

Biological

Psychological

Comorbidities

MDD: Biological Etiology

NT + hormone dysregulation

Genetics: Increased risk with 1º relatives with depression

MDD: Psychological Etiology

Increased stress/trauma

• Stress-Diathesis Model: Combination of predisposition (diathesis) + external stressors = Mental/physical disorder development

Behavioural factors

• Learned helplessness

MDD: Comorbidities Etiology

Neurodegenerative diseases

Chronic inflammatory disease

Psychiatric disorders

MDD: Pathophysiology

Monoamine hypothesis

HPA axis dysfunction

Cognitive model

MDD Pathophysiology: Monoamine Hypothesis

Monoamine NT deficiency (serotonin + tryptophan (precursor), norepinephrine, dopamine) = Impaired mood circuit regulation = Depressive symptoms

MDD Pathophysiology: HPA Axis Dysfunction

1. Stress = Activate HPA axis

• Increase CRH (hypothalamus) → Increase ACTH (anterior pituitary) → Increase cortisol (adrenal cortex)

• Negative feedback = Inhibit hypothalamus + anterior pituitary

2. Chronic stress = Decrease glucocorticoid receptors in hypothalamus + anterior pituitary (resistance) = No negative feedback from glucocorticoids (cortisol)

3. Continued CRH release = Cause…

• Hippocampal damage = Mood dysregulation + cognitive dysfunction

• Neuroinflammation

• Frontolimbic disconnection

MDD Pathophysiology: Cognitive Model

Repeated negative experiences = Learned helplessness = Negative view of self (internal), world (external environment), and future (uncontrollable hopelessness)

MDD: Clinical Presentation

MSIGECAPS

• M: Mood changes

  • Depressed mood

  • Irritability

• S: Sleep disturbances

  • Insomnia

  • Hypersomnia

• I: Interest

  • Anhedonia: Lack of interest in enjoyable activities

• G: Guilt

  • Feelings of guilt, worthlessness, hopelessness

• E: Energy

  • Low energy

  • Fatigue

• C: Concentration (Pseudodementia)

  • Difficulty concentrating

  • Decreased cognition

  • Difficulty making decisions

• A: Appetite

  • Changes in appetite/weight

• P: Psychomotor

  • Agitation

  • Retardation

• S: Suicide

  • Ideation/thoughts

MDD: Diagnostic Criteria

DSM-5

• A-C: Episode

• A-E: MDD

Criteria:

• A: 5+ MSIGECAPS for ≥ 2 weeks

  • ≥ 1 must be depressed mood or anhedonia

• B: Cause…

  • Distress

  • Impaired function in work/school

• C: Not caused by substances/organic disease

• D: Not caused by schizoaffective/psychotic disorder

• E: No mania/hypomania episodes

MDD: Screening

Pt health questionnaire-2 (PHQ-2)

• Assess depressed mood + anhedonia

Suicide risk

MDD: Investigations

Physical exam

Lab tests

• TFTs

• Serum + urine toxicology

• HIV testing

Neuroimaging

Cognitive testing

Polysomnography: Not routine

• Sleep study assessing sleep hygiene

• R/O sleep disturbances

MDD: Treatment/Management

Nonpharmacological

Pharmacological

MDD Management: Nonpharmacological

Lifestyle modifications

• Sleep hygiene

• Decrease substance use

• Stress reduction + mindfulness

• Increase social support

• Regular exercise

• Improve nutrition

Psychotherapy

• CBT:

  • Mild: First-line

  • Moderate-Severe: Combine with antidepressants

MDD Management: Pharmacological

Antidepressants

• ≥ 4 weeks for effects

Antidepressants

Selective serotonin reuptake inhibitors (SSRIs)

Serotonin norepinephrine reuptake inhibitors (SNRIs)

Atypical

Tricyclic antidepressants (TCAs)

Monoamine oxidase inhibitors (MAOIs)

Antidepressants: SSRIs

Ex: Fluoxetine, sertraline, citalopram

MOA: Inhibit serotonin reuptake

Indications: First-line

Adverse Effects:

• Headache

• GI symptoms

• Activating effects

  • Agitation

  • Anxiety

  • Insomnia

• Sexual dysfunction

• SIADH

• Serotonin syndrome (SS)

  • Neuromuscular excitability → Hyperthermia, autonomic dysfunction, altered mental status

Antidepressants: SNRIs

Ex: Venlafazine, duloxetine

MOA: Inhibit serotonin + norepinephrine reuptake

Indications: Second-line

Adverse Effects:

• Increase BP

• Increase cholesterol + TAG

• Sleep disturbances

• SS

Antidepressants: Atypical

Bupropion

Mirtazapine

Atypical Antidepressant: Bupropion

MOA: Decrease dopamine + norepinephrine reuptake

Indications:

• Seasonal depression

• Weight concerns + sexual dysfunction

Adverse Effects:

• Tachycardia + palpitations

• Weight loss

• Decrease seizure threshold

  • NOT for ED pt

• SS

Atypical Antidepressant: Mirtazapine

MOA:

• A2-adrenergic antagonist = Increase serotonin + norepinephrine release

• 5-HT1/3 receptor antagonist = Increase serotonin effects on 5-HT1

• H1 antagonists

Indications: Underweight + insomnia

Adverse Effects:

• Increase appetite + weight

• Sedation

• Increase cholesterol + TAG

• SS

Antidepressants: TCAs

Ex: Amitryptyline, nortriptyline

MOA: Inhibit serotonin + norepinephrine reuptake

Indications: Third/fourth-line

Adverse Effects:

• Orthostatic hypotension

• Cardiotoxicity

  • Tachycardia

  • Arrhythmias

  • Prolonged QT interval → Torsades de pointes

  • Wide QRS

• Anticholinergic symptoms

  • Confusion + hallucinations

  • Constipation

  • Urinary retention

  • Dry skin

• SS

Antidepressants: MAOIs

Ex: Selegiline, phenelzine

MOA: Inhibit MAO = Decrease epinephrine, norepinephrine, serotonin, dopamine breakdown

• Selegiline: Selective MAO-B inhibition = Decrease dopamine breakdown

Indications: Atypical MDD

Adverse Effects:

• Sexual dysfunction

• Orthostatic hypotension

• Weight gain

• + Tyramine = HTN crisis

• SS

MDD: Complications

SI

Cognitive deficits

• Increased with severity

• Decreased executive function, memory, attention, learning

CVD