Antidepressant Medications and Depressive Disorders: Study Guide

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Antidepressant Medications

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are a class of antidepressants commonly used as first-line treatment for major depressive disorder (MDD) and related conditions. They work by increasing serotonin levels in the brain.

Common SSRIs: Sertraline, Fluoxetine, Paroxetine, Citalopram, Escitalopram
Half-life: Varies by drug; Fluoxetine has a long half-life (up to several days), while Paroxetine and Sertraline are shorter.
Side Effects: Sexual dysfunction, gastrointestinal upset, insomnia, weight changes, and increased risk of QTc prolongation (notably with Citalopram).
Starting Doses: Typically low, titrated up as needed (e.g., Sertraline 25-50 mg daily).
Discontinuation Syndrome: Occurs with abrupt cessation, causing flu-like symptoms, insomnia, imbalance, sensory disturbances, and hyperarousal.
Special Considerations: Sertraline is preferred in post-stroke depression with speech difficulties. Citalopram impacts QTc interval most.

Example: Sertraline is often chosen for patients with comorbid anxiety or post-stroke depression.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs increase both serotonin and norepinephrine levels, and are used for depression, anxiety, and certain pain syndromes.

Common SNRIs: Venlafaxine, Duloxetine, Desvenlafaxine
Half-life: Generally short; Venlafaxine ~5 hours, Duloxetine ~12 hours.
Uses: Major depression, generalized anxiety disorder, neuropathic pain.
Side Effects/Cautions: Hypertension, insomnia, nausea, sexual dysfunction. Caution in patients with uncontrolled hypertension.
Starting Doses: Venlafaxine 37.5-75 mg daily; Duloxetine 30 mg daily.

Example: Duloxetine is often used for patients with depression and chronic pain.

Atypical Antidepressants and NDRI

Atypical antidepressants include medications with unique mechanisms. NDRI refers to norepinephrine-dopamine reuptake inhibitors.

Common Agents: Bupropion (NDRI), Mirtazapine, Trazodone
Uses: Bupropion for depression, smoking cessation; Mirtazapine for depression with insomnia or poor appetite.
Side Effects/Cautions: Bupropion lowers seizure threshold (avoid in seizure risk), Mirtazapine causes sedation and weight gain.
When to Add Wellbutrin (Bupropion): Often added to SSRI for residual symptoms, especially fatigue or sexual dysfunction.
Appetite/Sleep: Mirtazapine is preferred for patients needing appetite stimulation or help with sleep.

Example: Bupropion is avoided in patients with eating disorders due to increased seizure risk.

Tricyclic Antidepressants (TCAs)

TCAs are older antidepressants, now less commonly used due to side effect profile.

Common TCAs: Amitriptyline, Nortriptyline, Imipramine
Caution: Avoid in elderly, cardiac patients, and those at risk for overdose due to anticholinergic and cardiac toxicity.
Side Effects: Dry mouth, constipation, urinary retention, blurred vision, orthostatic hypotension, arrhythmias.

Example: Amitriptyline is sometimes used for neuropathic pain but rarely for depression due to risks.

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs are reserved for treatment-resistant depression due to dietary restrictions and drug interactions.

Dietary Restrictions: Avoid tyramine-rich foods to prevent hypertensive crisis.
Switching to SSRI/SNRI: Requires a washout period (usually 2 weeks) to avoid serotonin syndrome.
Fluoxetine: Due to long half-life, requires longer washout before starting MAOI.

Example: Phenelzine is a classic MAOI, rarely used today.

Serotonin Syndrome

Serotonin syndrome is a potentially life-threatening condition caused by excess serotonergic activity.

Symptoms: Agitation, confusion, hyperreflexia, fever, diaphoresis, tremor.
Causes: Combination of serotonergic drugs (SSRIs, SNRIs, MAOIs, TCAs, some analgesics).
Diagnosis: Clinical; distinguish from discontinuation syndrome (which lacks hyperthermia and neuromuscular findings).

Example: Combining SSRI and MAOI can precipitate serotonin syndrome.

Depressive Disorders: Diagnosis and Management

Major Depressive Disorder (MDD) vs Persistent Depressive Disorder (PDD)

Both are mood disorders, but differ in duration and severity.

MDD: At least 2 weeks of depressed mood or anhedonia plus 5 or more symptoms (DSM criteria).
PDD (Dysthymia): Chronic depressed mood for at least 2 years, with fewer symptoms than MDD.
DSM Criteria for MDD: Depressed mood, anhedonia, weight/appetite change, sleep disturbance, psychomotor changes, fatigue, guilt/worthlessness, poor concentration, suicidal ideation.

Example: A patient with 3 years of low mood and poor concentration meets criteria for PDD.

MDD vs Mourning vs Complicated Grief vs PDD

It is important to distinguish normal grief from depressive disorders.

Mourning: Normal response to loss, typically resolves over time.
Complicated Grief: Prolonged, intense grief interfering with functioning.
PDD: Chronic, less severe depression.

Example: Persistent sadness and functional impairment months after a loss may indicate complicated grief or MDD.

Best Psychotherapy for MDD

Psychotherapy is a key component of treatment for depression.

Cognitive Behavioral Therapy (CBT): Most evidence-based for MDD.
Interpersonal Therapy (IPT): Also effective, especially for grief-related depression.

Example: CBT helps patients identify and change negative thought patterns.

Special Populations: SSRIs

Choice of SSRI may depend on patient characteristics.

OCD/Anxiety: Sertraline, Fluoxetine, Paroxetine are preferred.
Pregnancy: Sertraline is considered safest.
Elderly: Sertraline, Escitalopram (lower anticholinergic burden).
Children: Fluoxetine is FDA-approved.

Example: Sertraline is often used in pregnant women with depression.

When to Avoid Certain Medications

Some antidepressants are contraindicated in specific populations.

Liver Disease: Avoid drugs with extensive hepatic metabolism.
Post-Cardiac Surgery: Avoid TCAs due to arrhythmia risk.
Seizure Risk: Avoid Bupropion.
Overdose Concern: Avoid TCAs and MAOIs.

Example: TCAs are not recommended for elderly patients due to anticholinergic effects.

PHQ-9 and Treatment Initiation

The PHQ-9 is a validated screening tool for depression severity and guides treatment decisions.

Scoring: 0-27; higher scores indicate more severe depression.
Initiate Treatment: Moderate to severe scores (≥10) warrant consideration of pharmacotherapy and/or psychotherapy.

Example: A PHQ-9 score of 15 suggests moderate depression; treatment should be initiated.

Treatment Strategies and Adjuncts

Switching and Augmentation

If a patient fails to respond to an SSRI, alternative strategies are considered.

Switching: Try another SSRI, SNRI, or atypical antidepressant.
Augmentation: Add non-antidepressant adjuncts such as atypical antipsychotics (e.g., Aripiprazole), lithium, or thyroid hormone.

Example: If SSRI and SNRI fail, consider adding Aripiprazole as adjunct.

Summary Table: Antidepressant Classes

The following table summarizes key properties of major antidepressant classes.

Class	Examples	Key Side Effects	Special Considerations
SSRI	Sertraline, Fluoxetine, Citalopram	Sexual dysfunction, GI upset, QTc prolongation	Safe in pregnancy (Sertraline), long half-life (Fluoxetine)
SNRI	Venlafaxine, Duloxetine	Hypertension, insomnia	Useful for pain syndromes
NDRI	Bupropion	Insomnia, seizure risk	Avoid in eating disorders, good for fatigue
Atypical	Mirtazapine, Trazodone	Weight gain, sedation	Good for insomnia/appetite
TCA	Amitriptyline, Nortriptyline	Anticholinergic, cardiac toxicity	Avoid in elderly, overdose risk
MAOI	Phenelzine, Tranylcypromine	Hypertensive crisis	Dietary restrictions, drug interactions

Key Equations and Diagnostic Criteria

DSM-5 Criteria for MDD:

PHQ-9 Scoring:

Additional info: Academic context and examples have been added to clarify medication uses, diagnostic criteria, and treatment strategies.