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NERVOUS SYSTEM › PSYCHOANALEPTICS › PSYCHOLEPTICS AND PSYCHOANALEPTICS IN COMBINATION › Antidepressants in combination with psycholeptics
amitriptyline and psycholeptics
N06CA01
Forms & Strengths
- Oral tablets: 10 mg, 25 mg, 50 mg (amitriptyline alone)
- Oral solution: 10 mg/mL amitriptyline
- Combination tablets: amitriptyline 10 mg + perphenazine 2 mg (psycholeptic)
Adult Dosing
- Depression: start 25 mg PO at bedtime; titrate by 25‑50 mg weekly to 150‑300 mg/day divided or qHS
- Chronic pain/migraine prophylaxis: 25‑75 mg PO qHS, may increase to 150 mg/day
- Combination with psycholeptic (e.g., perphenazine): amitriptyline 25‑75 mg + perphenazine 2‑4 mg qHS; total amitriptyline not to exceed 300 mg/day
Pediatric Dosing
- Enuresis (age > 5 y): 0.5‑1 mg/kg PO at bedtime, max 25 mg/day
- Depression: not recommended; limited data, use specialist guidance
Indications
- Major depressive disorder","Neuropathic pain (e.g., diabetic peripheral neuropathy)
- Chronic tension‑type headache and migraine prophylaxis
- Nocturnal enuresis in children
- Adjunctive treatment of depressive episodes with psychotic features (amitriptyline + psycholeptic)
Mechanism of Action
- Inhibits neuronal reuptake of norepinephrine and serotonin, increasing synaptic concentrations
- Blocks muscarinic cholinergic, histamine H1, and α1‑adrenergic receptors (anticholinergic, sedative, orthostatic effects)
- Psycholeptic component antagonizes dopamine D2 receptors, adding antipsychotic effect
Contraindications
- Recent myocardial infarction or unstable angina
- Conduction abnormalities (e.g., second‑ or third‑degree AV block) without pacemaker
- Severe coronary artery disease or arrhythmias
- Glaucoma (narrow‑angle)
- Severe urinary retention or prostatic hypertrophy
- Pheochromocytoma
- Concurrent MAO‑inhibitor use or within 14 days of discontinuation
- Known hypersensitivity to tricyclics or psycholeptics
Adverse Reactions
- Dry mouth, blurred vision, constipation (anticholinergic)
- Sedation, drowsiness, weight gain
- Orthostatic hypotension, dizziness
- Cardiac toxicity: tachyarrhythmias, QRS widening, sudden death
- Seizures (dose‑related)
- Photosensitivity, rash
- Sexual dysfunction, ejaculation disorders
Drug Interactions
- MAO inhibitors – risk of hypertensive crisis or serotonin syndrome
- Selective serotonin reuptake inhibitors, tramadol, linezolid – serotonin syndrome risk
- CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine) – increase amitriptyline levels
- CYP2D6 inducers (carbamazepine, rifampin) – decrease efficacy
- Other CNS depressants, alcohol, antihistamines – additive sedation
- Drugs that prolong QT/QRS (e.g., class IA antiarrhythmics) – increase cardiac risk
- Anticholinergic drugs – enhanced anticholinergic side effects
- Sympathomimetics (e.g., epinephrine) – may exacerbate hypertension
Curated Content: Needs Vetting Before Put to Clinical Use