🧠 What is Depression?

• Major depression – severe, long-lasting low mood
• Chronic depression – milder but lasts for years
• Atypical depression – mood can briefly lift with positive events
• Bipolar depression – low mood that alternates with high (manic) phases
• Seasonal depression – linked to changes in seasons (e.g., winter)

😔 Symptoms of Depression

• Persistent sadness, anxiety, or feeling empty
• Loss of enjoyment in activities you used to love (called anhedonia)
• Feelings of worthlessness, guilt, or hopelessness
• Constant tiredness and low energy
• Memory problems, difficulty concentrating or making decisions
• Restlessness, irritability
• Sleep problems (too much or too little)
• Changes in appetite or weight
• Unexplained physical pain (especially stomach problems)
• Thoughts of suicide or death
• Low self-esteem (e.g., constantly criticizing yourself)

🔬 What Causes Depression? (Brain Chemistry)

💊 Classes of Antidepressants

1. MAO Inhibitors (MAOIs / RIMAs)

• Moclobemide – a safer, reversible MAO-A blocker. Good for elderly patients or those with heart disease. Does not have the harsh side effects of older antidepressants.

• "Cheese reaction" – eating foods rich in tyramine (aged cheese, wine, cured meats) while on MAOIs can cause a sudden, dangerous spike in blood pressure (hypertensive crisis)
• Should NOT be combined with: cough medicines, pain killers like pethidine, or other antidepressants

2. Tricyclic Antidepressants (TCAs)

• In normal people: cause drowsiness, clumsiness, light-headedness
• In depressed patients: after 2–3 weeks, mood gradually improves; patients become more talkative and re-engaged with life
• Sleep: reduce nighttime waking
• Body (ANS): cause dry mouth, blurred vision, constipation, difficulty urinating

• Can cause fast heart rate (tachycardia)
• Can cause a drop in blood pressure when standing (postural hypotension)
• Dangerous in overdose — can cause fatal heart rhythm problems

• Imipramine → converted in the body to Desipramine
• Amitriptyline → converted to Nortriptyline
• Amoxapine → works faster than most (4–7 days vs 2–3 weeks)
• Doxepin → used for pain and itching too

• Dry mouth, blurred vision (muscarinic block)
• Sedation (histamine block)
• Dizziness (alpha block)
• Sexual problems (serotonin block)

• Stomach washout (gastric lavage)
• IV fluids, breathing support
• Bicarbonate for acid imbalance
• Diazepam for seizures
• Propranolol/lidocaine for heart rhythm problems

3. SSRIs — Selective Serotonin Reuptake Inhibitors ✅ (Most commonly used today)

• No sedation
• Don't affect thinking or coordination
• Safe for elderly patients (no blood pressure drop)
• Safe in overdose (no heart rhythm problems)
• No dry mouth, constipation, etc.

• Nausea, vomiting (especially at the start — improves with time)
• Diarrhea/loose stools
• Teeth grinding (bruxism)
• Vivid strange dreams
• Emotional blunting (feeling "flat")

• Fluoxetine (Prozac) – approved for children 7+ for depression and OCD; only use in children if therapy alone fails
• Fluvoxamine – used mainly for OCD and anxiety disorders; more nausea than others
• Paroxetine – short-acting; more GI side effects, sexual problems, and agitation
• Citalopram / Escitalopram – most selective for serotonin, fewest drug interactions

4. SNRIs — Serotonin & Noradrenaline Reuptake Inhibitors

• Venlafaxine – no sedation, no dry mouth, no blood pressure drop. Good for depression and anxiety
• Duloxetine – mildly sedating; also approved for nerve pain (diabetic neuropathy)

5. Atypical Antidepressants

• Trazodone – first atypical antidepressant; mainly blocks serotonin 5-HT2 and alpha-1 receptors; often used for sleep
• Mianserin – does NOT block reuptake; instead increases norepinephrine release by blocking presynaptic alpha-2 receptors
• Mirtazapine – boosts both norepinephrine and serotonin by blocking alpha-2 receptors; also very sedating (useful for insomnia + depression)
• Bupropion – blocks dopamine and norepinephrine reuptake; energizing rather than sedating; approved for smoking cessation
• Amoxapine – also blocks dopamine D2 receptors (unique among antidepressants)

🏥 Uses of Antidepressants Beyond Depression

🔑 Key Takeaways

1. SSRIs are the first-choice antidepressants today — safer, fewer side effects
2. TCAs work well but have more side effects — dangerous in overdose
3. MAOIs require strict diet restrictions (no aged cheese, cured meats, etc.)
4. Antidepressants take 2–3 weeks to start working — patience is essential
5. Never stop antidepressants suddenly — taper gradually under doctor supervision
6. Antidepressants are NOT addictive — but stopping abruptly can cause withdrawal symptoms