Amitriptyline for depression

Generic Name

Amitriptyline

Brand Names

Elavil

Tryptanol

Laroxyl

Endep

Vanatrip

Widely available in generic formulations

Drug Class

Tricyclic antidepressant (TCA)

Monoamine reuptake inhibitor

Antidepressant with sedative properties

Mechanism of Action

Amitriptyline functions by inhibiting the neuronal reuptake of serotonin and norepinephrine at the synaptic cleft in the central nervous system

By increasing the concentration of these neurotransmitters in the brain, it enhances mood and emotional stability

Additionally, it has strong antagonistic properties at muscarinic (anticholinergic), histamine H1, and alpha-1 adrenergic receptors, which contribute to its side effect profile including sedation, dry mouth, and orthostatic hypotension

Its ability to modulate monoaminergic neurotransmission supports its use in major depressive disorder and other affective syndromes

Indications in Psychiatry

Major Depressive Disorder (MDD)

Effective for moderate to severe endogenous depression

Particularly useful in depression with melancholic features, early morning awakening, weight loss, and psychomotor retardation

Depressive Symptoms Associated with Anxiety

Treats depression with significant anxiety, tension, or insomnia

Dysthymia (Persistent Depressive Disorder)

May be used when SSRIs are ineffective or poorly tolerated

Bipolar Depression (Adjunctive)

Can be used with mood stabilizers in select cases, though TCAs may precipitate mania in bipolar disorder

Psychotic Depression (Adjunctive)

Used in combination with antipsychotics under supervision

Off-label or Investigational Psychiatric Uses

Obsessive-compulsive disorder (less commonly now due to SSRIs)

Panic disorder

Post-traumatic stress disorder

Borderline personality disorder (affective instability)

Dosing and Administration for Depression

Adults (initial dosing)

Typical starting dose: 25–50 mg per day at bedtime or in divided doses

May be increased by 25–50 mg every few days based on response and tolerability

Usual maintenance dose: 75–150 mg/day in single or divided doses

Maximum dose: up to 300 mg/day in hospitalized patients

Elderly Patients

Initial dose: 10–25 mg at bedtime

Maintenance dose rarely exceeds 75 mg/day due to increased sensitivity to adverse effects

Adolescents (where appropriate)

Starting dose: 10–25 mg/day

Titrated cautiously under psychiatric supervision

Administration Notes

Administer with or without food

Due to sedative properties, once-daily dosing at bedtime is preferred

Takes 2–4 weeks to show significant antidepressant effect

Taper dose gradually when discontinuing to avoid withdrawal symptoms

Pharmacokinetics

Oral bioavailability: ~50% due to first-pass hepatic metabolism

Peak plasma levels in 2–12 hours

Half-life: 10–28 hours

Metabolized in the liver by CYP2D6 to active metabolite nortriptyline

Excreted in urine as metabolites

Contraindications

Recent myocardial infarction

Cardiac conduction disorders such as bundle branch block or arrhythmia

Hypersensitivity to amitriptyline or other TCAs

Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days

Severe liver disease

Untreated narrow-angle glaucoma

Urinary retention

Precautions

History of seizures – lowers seizure threshold

Elderly – increased risk of falls, cognitive impairment, and anticholinergic toxicity

Suicidal ideation – caution due to increased risk of overdose and toxicity

History of bipolar disorder – may induce manic episodes

Cardiac disease – ECG monitoring recommended

Avoid abrupt withdrawal to prevent cholinergic rebound

Adverse Effects

Very Common

Dry mouth

Drowsiness

Constipation

Dizziness

Weight gain

Increased appetite

Blurred vision

Sedation

Orthostatic hypotension

Common

Urinary retention

Sweating

Tachycardia

Headache

Nausea

Photosensitivity

Serious and Rare

Cardiac arrhythmias including prolonged QT interval

Heart block

Mania or hypomania

Hepatotoxicity

Bone marrow suppression

Serotonin syndrome (if combined with serotonergic agents)

Neuroleptic malignant syndrome

SIADH and hyponatremia

Withdrawal syndrome if discontinued abruptly

Toxicity in Overdose

High risk in overdose situations

Severe anticholinergic effects, arrhythmias, seizures, respiratory depression, coma, and death

Requires urgent medical intervention and supportive measures

ECG changes (QRS widening, heart block) may appear early

Withdrawal Symptoms

Nausea

Malaise

Headache

Sleep disturbance

Anxiety and irritability

Flu-like symptoms

Use in Pregnancy

Generally avoided unless benefit outweighs risk

Not associated with major congenital malformations, but use near term may cause neonatal withdrawal or toxicity

Monitor neonate for sedation, hypotonia, respiratory distress

Use in Lactation

Excreted into breast milk in small amounts

Generally considered compatible with breastfeeding

Monitor infants for excessive sedation or feeding difficulties

Use in Special Populations

Elderly

Start low and go slow

High risk of orthostatic hypotension, cognitive impairment, and delirium

Avoid polypharmacy involving other anticholinergic agents

Hepatic Impairment

Use lower doses and monitor liver function

Hepatic metabolism may be reduced

Renal Impairment

Dose adjustment usually not required

Caution if associated with uremia or comorbid cardiac issues

Drug Interactions

MAOIs

Absolute contraindication due to risk of hypertensive crisis or serotonin syndrome

SSRIs (fluoxetine, paroxetine, sertraline)

Increase amitriptyline plasma levels via CYP2D6 inhibition

Risk of serotonin syndrome and toxicity

CYP2D6 Inhibitors (quinidine, terbinafine, bupropion)

May increase plasma levels and toxicity of amitriptyline

Alcohol

Increased CNS depression and sedation

Opioids and Benzodiazepines

Additive CNS effects – increased risk of drowsiness and respiratory depression

QT-Prolonging Agents (macrolides, antipsychotics, fluoroquinolones)

Increased risk of torsades de pointes

Monitor ECG if combined

Clonidine and Guanethidine

Reduced antihypertensive effect

Anticholinergics (e.g. atropine, oxybutynin)

Increased anticholinergic burden

Risk of delirium and urinary retention in elderly

Monitoring Parameters

Suicidal ideation and behavior (especially early in therapy)

Mood improvement and affective symptoms

Vital signs – especially blood pressure and heart rate

Weight and appetite

ECG in patients with cardiac disease

Anticholinergic symptoms – constipation, confusion, urinary retention

Liver function tests in prolonged treatment or hepatic disease

Formulations

Tablets: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg

Oral liquid formulations may be available

Store at room temperature and protect from moisture

Patient Counseling Points

Take the medication exactly as prescribed

Sedation is common – take it at bedtime

Do not drink alcohol during treatment

May take 2 to 4 weeks before mood improvement is noticeable

Do not stop the medication suddenly – consult your provider before any dose change

Avoid operating machinery until you know how the drug affects you

Report any chest pain, palpitations, suicidal thoughts, or mood changes

Dry mouth, dizziness, and constipation are common but manageable side effects

Stand slowly from sitting or lying positions to avoid dizziness

Inform your doctor about all other medications you are taking to avoid interactions