Antidepressants

Key Points

• Antidepressants require 2+ weeks to achieve peak therapeutic effect — patient education critical
• Initial improvement may appear in 1-2 weeks, but full benefit can take up to 2-3 months
• SSRIs are first-line; TCAs and MAOIs are first-generation with more serious adverse effects
• Black Box Warning: Antidepressants increase risk of suicidal ideation in children, adolescents, and young adults (≤24 years) — monitor closely in first weeks of therapy
• Serotonin syndrome: Hyperpyrexia, muscle rigidity, altered mental status, hyperreflexia — occurs when serotonergic agents are combined
• MAOIs + tyramine-containing foods → hypertensive crisis (aged cheese, cured meats, alcohol, soy sauce)
• Never discontinue antidepressants abruptly — discontinuation syndrome

Drug Class Overview

Antidepressants treat major depressive disorder (MDD) and are also used for anxiety disorders, OCD, PTSD, neuropathic pain, insomnia, and smoking cessation. Individual response varies — patients may need to try multiple agents. Some improvement can occur within 1-2 weeks, but full therapeutic effect may require 2-3 months. After symptom improvement, many clients remain on treatment for at least 6 months, with longer maintenance in high-recurrence risk groups.

Antidepressant Classes

SSRIs (Selective Serotonin Reuptake Inhibitors) — First Line

Mechanism: Block serotonin reuptake at presynaptic nerve terminal → serotonin accumulates in synapse → enhanced postsynaptic receptor activation.

Examples: Fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro).

Indications: MDD, OCD, PTSD, panic disorder, social anxiety disorder, PMDD, bulimia nervosa.

Key Side Effects: Sexual dysfunction (most common reason patients stop medication), nausea, headache, insomnia, nervousness, weight gain. Increased GI bleeding risk — use caution with NSAIDs, aspirin, and anticoagulants.

MAOI Washout:

• Most SSRIs → 2 weeks before/after MAOI
• Fluoxetine (long half-life) → 5 weeks before starting MAOI

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

Mechanism: Block reuptake of both serotonin and norepinephrine.

Examples: Venlafaxine (Effexor), duloxetine (Cymbalta).

Indications: MDD, generalized anxiety disorder, diabetic peripheral neuropathy (duloxetine), fibromyalgia.

NDRIs (Norepinephrine-Dopamine Reuptake Inhibitors)

Example: Bupropion (Wellbutrin).

Indications: MDD, seasonal affective disorder, ADHD, smoking cessation.

Critical note: Bupropion decreases seizure threshold — contraindicated in eating disorders (risk of seizure from electrolyte imbalance) and current seizure disorders.

SARIs (Serotonin Antagonist and Reuptake Inhibitors)

Example: Trazodone.

Primary Use: Most commonly prescribed off-label as a sedative/hypnotic for insomnia. Reduces arousal neurotransmitters (serotonin, dopamine, noradrenaline, histamine). Administer in the evening.

TCAs (Tricyclic Antidepressants) — Second Line

Mechanism: Block reuptake of serotonin and norepinephrine; also block muscarinic, histamine, and alpha-1 adrenergic receptors.

Examples: Amitriptyline (Elavil), nortriptyline.

Current Indications: Neuropathic pain, insomnia, migraine prophylaxis (primarily used for these now, not first-line for depression).

Adverse Effects (from receptor blockade):

Receptor Blocked	Adverse Effect
Muscarinic (anticholinergic)	Dry mouth, blurred vision, urinary retention, constipation, confusion
Histamine	Sedation, weight gain
Alpha-1 adrenergic	Orthostatic hypotension
Cardiac conduction	QTc prolongation, dysrhythmias, cardiotoxicity

Risk in Older Adults: Increased sensitivity to anticholinergic effects → confusion, falls, delirium. Start at lowest dose; monitor closely.

Overdose: Potentially fatal (especially with alcohol). For overdose: call 911 (outpatient) or rapid response (inpatient). Consult Poison Control: 1-800-222-1222.

Contraindications: Recent myocardial infarction, cardiac dysrhythmia, angle-closure glaucoma, children <12 years.

TCA Cardiac Risk

TCAs prolong the QTc interval → risk of life-threatening dysrhythmias (torsades de pointes). Use with extreme caution in patients with electrolyte abnormalities or bradycardia.

MAOIs (Monoamine Oxidase Inhibitors) — Rarely Used / Last Resort

Mechanism: Inhibit monoamine oxidase enzyme → prevents breakdown of serotonin, norepinephrine, and dopamine → elevated levels of all three.

Examples: Phenelzine, tranylcypromine.

Critical Danger: Hypertensive crisis when combined with tyramine-containing foods or stimulant/sympathomimetic drugs. Severe blood pressure elevation (often >180/120 mm Hg) with end-organ injury is a medical emergency.

Tyramine-Restricted Foods (avoid completely while taking MAOIs):

• Aged cheeses (cheddar, blue cheese, brie)
• Cured or smoked meats (salami, pepperoni)
• Alcoholic beverages (especially beer, red wine)
• Soy sauce, miso, teriyaki
• Fermented or pickled foods

Drug Interactions: MAOIs are contraindicated with ALL other antidepressants, stimulants, and sympathomimetic agents.

Critical Safety Warnings

Serotonin Syndrome

Occurs when multiple serotonergic agents are combined (SSRIs + MAOIs, tramadol, triptans, linezolid) or serotonergic doses are rapidly escalated. Typical onset is within 24 hours. Signs: hyperpyrexia, muscle rigidity, hyperreflexia, diaphoresis, altered mental status, tremor. Immediate treatment includes stopping serotonergic agents and hospital-level supportive care (including IV fluids); severe cases may require cyproheptadine.

Suicidal Ideation — Black Box Warning

All antidepressants carry FDA Black Box Warning for increased suicidal ideation in patients ≤24 years. Monitor most closely during first weeks of therapy and after dose changes. Establish safety contract; assess for access to lethal means.

Nursing Assessment and Interventions

Before Starting:

• Assess baseline mood, suicidal ideation (Columbia Suicide Severity Rating Scale), current medications for interactions
• Teach patient that effect requires 2–6 weeks — do not stop prematurely
• For MAOIs: complete dietary restrictions teaching before first dose

Ongoing Monitoring:

• Suicidal ideation — especially first weeks of therapy in patients ≤24 years
• Monitor QTc interval for TCAs (baseline ECG)
• Older adults on TCAs: fall risk, anticholinergic burden, confusion
• Report serotonin syndrome symptoms immediately

Patient Education:

• Do not stop suddenly — taper under provider guidance to prevent discontinuation syndrome (flu-like symptoms, dizziness, irritability)
• Avoid alcohol (increases CNS depression, increases overdose risk)
• SSRIs: take with food to reduce nausea; avoid concurrent NSAIDs/aspirin without provider guidance
• MAOIs: strict tyramine diet restriction for entire course of therapy plus 2 weeks after discontinuation

Related Concepts

• psychopharmacology — Broader psychiatric medication overview including antipsychotics and mood stabilizers
• depression — Pathophysiology and nursing care for depressive disorders
• substance-use-disorders — Alcohol interactions and contraindications with antidepressants
• self-harm-and-suicide — Risk assessment for patients starting antidepressant therapy
• anxiolytics — Concurrent anxiety treatment often paired with antidepressants
• analgesics — TCAs used as adjuvant analgesics for neuropathic pain

Self-Check

1. A patient on fluoxetine is prescribed a MAOI for refractory depression. What is the minimum washout period, and why?
2. What are the classic signs of serotonin syndrome, and which drug combination commonly causes it?
3. A patient taking amitriptyline reports dry mouth, difficulty urinating, and constipation. What receptor blockade explains these symptoms?