Antidepressant Medications

Antidepressants: Intro & Classes - Mood Boosters 101

• Function: Elevate mood; treat depression, anxiety, OCD, pain.
• Mechanism Basis: Monoamine hypothesis - targets serotonin (5-HT), norepinephrine (NE), dopamine (DA) deficiencies.
• Key Classes:
  • SSRIs (Selective Serotonin Reuptake Inhibitors)
  • SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
  • TCAs (Tricyclic Antidepressants)
  • MAOIs (Monoamine Oxidase Inhibitors)
  • Atypical Antidepressants
• Therapeutic Lag: Full effect in 2-4 weeks.

⭐ Most antidepressants achieve therapeutic effects by blocking reuptake or inhibiting metabolism of monoamines.

SSRIs - Happy Pills Parade

• Mechanism: Selective Serotonin Reuptake Inhibitors; ↑ synaptic serotonin.
• Drugs (📌 "Effective SSRIs Can Prove Fun"):
  • Escitalopram, Sertraline, Citalopram, Paroxetine, Fluoxetine, Fluvoxamine.
• Indications: Depression, Anxiety disorders (GAD, Panic, Social anxiety), OCD, PTSD, Bulimia nervosa (Fluoxetine).
• Side Effects: GI upset (nausea, diarrhea), sexual dysfunction (↓ libido, anorgasmia), headache, insomnia/sedation. Weight gain (Paroxetine). Hyponatremia (SIADH).
• Serotonin Syndrome: ⚠️ With MAOIs, triptans. Triad: cognitive (agitation, confusion), autonomic (fever, tachycardia), neuromuscular (myoclonus, hyperreflexia, tremor).

⭐ Fluoxetine has the longest half-life (4-6 days for parent drug, 4-16 days for norfluoxetine metabolite), making it suitable for patients with poor compliance but also requiring a longer washout period (5 weeks) before starting MAOIs. Paroxetine has the shortest half-life and is most associated with discontinuation syndrome and weight gain.

• Discontinuation Syndrome: (📌 FINISH: Flu-like, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal) - esp. Paroxetine, Venlafaxine (SNRI).

SNRIs & TCAs - Dual Action & Old Gold

• SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
  • Action: Inhibit 5-HT & NE reuptake.
  • Drugs: Venlafaxine (dose-dependent ↑BP, discontinuation syndrome), Duloxetine (neuropathic pain, hepatotoxicity risk).
  • SEs: SSRI-like + NE effects (↑BP, ↑HR).
• TCAs (Tricyclic Antidepressants)
  • Action: Inhibit 5-HT & NE reuptake; block M1, H1, α1 receptors.
  • Drugs: Amitriptyline, Nortriptyline, Imipramine. Clomipramine (OCD).
  • SEs: Anticholinergic (📌 "Can't see, can't pee, can't spit, can't shit"), sedation, weight gain, orthostatic hypotension.
  • ⚠️ Cardiotoxicity: QRS prolongation; lethal in overdose. ECG monitoring.

⭐ TCA overdose is life-threatening due to cardiotoxicity (Na+ channel blockade); management includes sodium bicarbonate.

MAOIs & Atypicals - Unique Mood Menders

• MAOIs (Monoamine Oxidase Inhibitors)
  • Irreversible: Phenelzine, Tranylcypromine. Reversible (RIMA): Moclobemide.
  • ⚠️ "Cheese reaction": Hypertensive crisis with tyramine (aged cheese, wine).
  • ⚠️ Serotonin Syndrome risk with SSRIs/TCAs; 2-week washout (5 weeks for fluoxetine).
• Atypical Antidepressants
  • Bupropion: NDRI. For depression, smoking cessation. Lowers seizure threshold. No sexual dysfunction.
  • Mirtazapine: $\alpha_2$ antagonist. Sedating, ↑weight. Good for depression + insomnia.
  • Trazodone: SARI. For insomnia (low dose). Risk of priapism ⚠️.
  • Agomelatine: MT1/MT2 agonist, 5-HT2C antagonist. Monitor LFTs.

⭐ MAOIs: "Cheese reaction" (hypertensive crisis) with tyramine-rich foods is a critical interaction to remember for exams.

Clinical Pearls & Pitfalls - Smart Prescribing

• Switching Antidepressants:

• ⚠️ Serotonin Syndrome: Triad: mental status Δ, autonomic hyperactivity, neuromuscular abnormalities. Immediately stop agent(s); supportive care; consider cyproheptadine.
• ⚠️ Antidepressant Discontinuation Syndrome: (📌 FINISH: Flu-like, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal). Prevent with gradual taper over 2-4 weeks or longer. Fluoxetine less prone.
• Special Populations:
  • Pregnancy: Sertraline often preferred; avoid Paroxetine (cardiac risk).
  • Elderly: Start low, go slow. SSRIs (e.g., Citalopram, Sertraline) preferred; TCAs high risk.

⭐ MAOIs + SSRI/SNRI/TCA combination is contraindicated due to high risk of Serotonin Syndrome; requires adequate washout period (2 wks, or 5 wks for fluoxetine).

High‑Yield Points - ⚡ Biggest Takeaways

• SSRIs (e.g., Fluoxetine) are first-line for depression and anxiety; main side effect: sexual dysfunction.
• TCAs (e.g., Amitriptyline) cause anticholinergic effects and cardiotoxicity in overdose.
• MAOIs (e.g., Phenelzine) require a tyramine-free diet to prevent hypertensive crisis.
• SNRIs (e.g., Venlafaxine, Duloxetine) are effective for depression and neuropathic pain.
• Bupropion is unique: no sexual dysfunction, aids smoking cessation, contraindicated in seizure disorders.
• Serotonin syndrome is a risk with combined serotonergic agents; presents with hyperthermia, rigidity, and myoclonus.
• Mirtazapine causes sedation and weight gain; useful for patients with insomnia and poor appetite.