multi class comparison

Antidepressant Classes: SSRI vs SNRI vs TCA vs MAOI — Efficacy, Safety Profile, Critical Interactions

All four classes treat depression effectively, but their safety profiles are drastically different. Picking the wrong answer on overdose lethality, dietary restrictions, or first-line status costs you NCLEX points — and in practice, costs lives. The exam loves asking which class requires food restrictions and which kills in overdose.

Comparison

Side-by-side4 compared
Comparevs
Dimension
SSRIs
SNRIs
TCAs
MAOIs
Class & mechanism
  • Selective serotonin reuptake inhibition
  • Block serotonin + norepinephrine reuptake
  • Block 5-HT/NE reuptake + anticholinergic
  • Inhibit monoamine oxidase → ↑ monoamines
Indications
  • First-line depression & anxiety
  • Depression
  • Neuropathic pain
  • Depression
  • Neuropathic pain
  • Refractory / atypical depression
Onset
  • Full effect in 4–6 weeks
  • Full effect in 4–6 weeks
  • Full effect in 4–6 weeks
  • Full effect in 4–6 weeks
Key assessment
  • Assess suicide risk, especially early
  • Assess suicide risk, especially early
  • Monitor BP — may ↑ blood pressure
  • Assess suicide risk, especially early
  • Orthostatic BP; anticholinergic effects
  • Assess suicide risk, especially early
  • Review diet & meds before starting
Monitoring
  • No routine drug levels
  • No routine drug levels
  • ECG at baseline (cardiotoxic)
  • No routine drug levels
Adverse effects
  • GI upset
  • Sexual dysfunction
  • GI upset
  • Dose-related ↑ blood pressure
  • Anticholinergic effects
  • Orthostatic hypotension
  • Orthostatic hypotension
  • Insomnia, agitation
Black box & toxicity
  • Suicidality risk in patients <25 (black box)
  • Safest class in overdose
  • Suicidality risk in patients <25 (black box)
  • Suicidality risk in patients <25 (black box)
  • Cardiotoxic — wide QRS, lethal overdose
  • Suicidality risk in patients <25 (black box)
Contraindications & interactions
  • Risk of serotonin syndrome with serotonergic drugs
  • Risk of serotonin syndrome with serotonergic drugs
  • Risk of serotonin syndrome with serotonergic drugs
  • Risk of serotonin syndrome with serotonergic drugs
  • Tyramine foods → hypertensive crisis
Patient teaching
  • Do not stop abruptly (discontinuation syndrome)
  • Do not stop abruptly (discontinuation syndrome)
  • Do not stop abruptly (discontinuation syndrome)
  • Do not stop abruptly (discontinuation syndrome)
  • Avoid aged cheese, cured meats, wine
Class & mechanism

SSRIs

  • Selective serotonin reuptake inhibition

SNRIs

  • Block serotonin + norepinephrine reuptake
Indications

SSRIs

  • First-line depression & anxiety

SNRIs

  • Depression
  • Neuropathic pain
Onset

SSRIs

  • Full effect in 4–6 weeks

SNRIs

  • Full effect in 4–6 weeks
Key assessment

SSRIs

  • Assess suicide risk, especially early

SNRIs

  • Assess suicide risk, especially early
  • Monitor BP — may ↑ blood pressure
Monitoring

SSRIs

  • No routine drug levels

SNRIs

  • No routine drug levels
Adverse effects

SSRIs

  • GI upset
  • Sexual dysfunction

SNRIs

  • GI upset
  • Dose-related ↑ blood pressure
Black box & toxicity

SSRIs

  • Suicidality risk in patients <25 (black box)
  • Safest class in overdose

SNRIs

  • Suicidality risk in patients <25 (black box)
Contraindications & interactions

SSRIs

  • Risk of serotonin syndrome with serotonergic drugs

SNRIs

  • Risk of serotonin syndrome with serotonergic drugs
Patient teaching

SSRIs

  • Do not stop abruptly (discontinuation syndrome)

SNRIs

  • Do not stop abruptly (discontinuation syndrome)

marks the fact that sets a column apart.

Clinical Pearl

SSRIs = safest first-line. TCAs = cardiac death in overdose. MAOIs = no aged cheese or you spike the BP.

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