First-line for MDD and anxiety disorders; require 4-6 weeks for clinical response; black box warning for suicidality in patients < 25.
NE/DA reuptake inhibitor; no sexual dysfunction, promotes weight loss and smoking cessation; contraindicated in bulimia and seizures.
Narrow therapeutic index (0.6-1.2 mEq/L); monitor BUN/Cr, thyroid (causes hypothyroidism), and ECG; Ebstein anomaly teratogenicity.
Clozapine (agranulocytosis monitoring); Olanzapine (severe metabolic syndrome); Risperidone (hyperprolactinemia & gynecomastia).
Antidepressant Classes & Receptor Mechanics
| Class & Prototype | Mechanism of Action | Unique Board High-Yield Features |
|---|---|---|
| SSRIs (Sertraline, Fluoxetine) | Blocks 5-HT reuptake transporter (SERT) | First-line depression/anxiety; sexual dysfunction, GI upset, SIADH in elderly; Fluoxetine has longest half-life |
| SNRIs (Venlafaxine, Duloxetine) | Blocks SERT and NET (norepinephrine transporter) | Dual action; Venlafaxine causes dose-dependent diastolic hypertension; Duloxetine also treats diabetic peripheral neuropathy and fibromyalgia |
| NDRI (Bupropion) | Blocks NET and DAT (dopamine transporter) | No sexual dysfunction, no weight gain; lowers seizure threshold; strictly contraindicated in anorexia/bulimia |
| NaSSA (Mirtazapine) | Antagonist at central α2, 5-HT2, 5-HT3, and H1 receptors | Causes significant sedation and appetite stimulation/weight gain; excellent for depressed elderly with insomnia and anorexia |
| TCAs (Amitriptyline, Nortriptyline) | Blocks SERT, NET, α1, H1, and muscarinic receptors | Fatal in overdose (the 3 Cs: Convulsions, Coma, Cardiotoxicity via sodium channel blockade; treat with Sodium Bicarbonate) |
| MAOIs (Phenelzine, Tranylcypromine) | Inhibits MAO-A and MAO-B enzymes | Tyramine-rich foods (aged cheeses, red wine) provoke fatal Hypertensive Crisis; requires 2-week washout before starting SSRIs |
Extrapyramidal Symptoms (EPS) & Movement Disorders Timeline
EPS occurs predominantly with high-potency first-generation antipsychotics (Haloperidol, Fluphenazine) due to D2 receptor blockade in the nigrostriatal pathway:
Sustained painful muscle contractions (torticollis, oculogyric crisis, laryngeal spasm). Treatment: IV/IM Benztropine (anticholinergic) or Diphenhydramine.
Subjective internal restlessness, inability to sit still, pacing. Frequently misdiagnosed as worsening anxiety. Treatment: Propranolol, Lorazepam, or dose reduction.
Bradykinesia, cogwheel rigidity, masked facies, resting tremor. Treatment: Benztropine or Amantadine.
Choreoathetoid movements of face, tongue, and extremities due to D2 receptor upregulation. Often irreversible. Treatment: Switch to Clozapine; VMAT2 inhibitors (Valbenazine, Deutetrabenazine).
- Acute Dystonic Reactions: Severe acute torticollis exhibits pronounced spasm of the sternocleidomastoid (SCM) and trapezius muscles. Pharmacologic treatment with benztropine must precede any manual therapy.
- Parkinsonian Rigidity: Cogwheel rigidity induces restricted rib excursion and thoracic inlet tightness. Gentle articulatory techniques and rib raising restore thoracic compliance.
- Autonomic Balancing: Suboccipital release and cranial base decompression aid in dampening the physical symptoms of psychotropic-induced akathisia.
- TCA overdose presents with the '3 Cs': Coma, Convulsions, and Cardiotoxicity (QRS widening > 100 ms and ventricular arrhythmias); immediately administer IV Sodium Bicarbonate to alkalinize serum and displace drug from cardiac sodium channels.
- Patients on MAOIs who ingest tyramine-rich foods (aged cheeses, cured meats, draught beer) experience massive catecholamine surge leading to lethal Hypertensive Crisis.
- Clozapine carries an absolute requirement for weekly absolute neutrophil count (ANC) monitoring; discontinue drug immediately if ANC drops below 1,000 / μL.