Introduction
Elavil (amitriptyline hydrochloride) is a tricyclic antidepressant (TCA) that has been in clinical use since the 1960s. Originally developed and approved for the treatment of depression, it has since gained widespread off-label use for various chronic pain conditions, migraine prophylaxis, and other neurological disorders. Despite the development of newer antidepressant classes, Elavil remains a clinically relevant medication due to its efficacy and cost-effectiveness.
Mechanism of Action
Amitriptyline exerts its therapeutic effects primarily through inhibition of serotonin and norepinephrine reuptake in the central nervous system, thereby increasing the concentration of these neurotransmitters in the synaptic cleft. Additionally, it demonstrates significant antagonism at muscarinic acetylcholine, histamine H₁, and α₁-adrenergic receptors, which accounts for many of its side effects. The analgesic effects in chronic pain conditions are thought to involve enhancement of descending inhibitory pain pathways in the central nervous system.
Indications
FDA-approved indications:
- Major depressive disorder
Common off-label uses:
- Neuropathic pain (diabetic neuropathy, postherpetic neuralgia)
- Migraine prophylaxis
- Tension-type headache prophylaxis
- Fibromyalgia
- Nocturnal enuresis in children (>6 years)
- Irritable bowel syndrome
Dosage and Administration
Depression:- Initial dose: 25-75 mg daily as a single dose at bedtime
- May increase by 25-50 mg every 3-7 days
- Maintenance dose: 50-150 mg daily
- Maximum dose: 300 mg daily
- Initial dose: 10-25 mg at bedtime
- Titrate gradually to 25-100 mg daily
- Geriatric patients: Start with 10 mg at bedtime
- Hepatic impairment: Use lower doses and titrate slowly
- Renal impairment: Use caution; consider lower doses
- Pediatrics: Not recommended for depression under age 12
Pharmacokinetics
- Absorption: Well absorbed from GI tract; extensive first-pass metabolism
- Distribution: Widely distributed throughout body; protein binding ~95%
- Metabolism: Extensive hepatic metabolism via CYP2D6, CYP2C19, and CYP3A4
- Elimination: Half-life: 10-28 hours; primarily renal excretion
- Active metabolite: Nortriptyline
Contraindications
- Hypersensitivity to amitriptyline or other TCAs
- Acute recovery phase after myocardial infarction
- Concomitant use with MAOIs (allow 14-day washout period)
- Uncontrolled narrow-angle glaucoma
- Severe urinary retention
Warnings and Precautions
- Black Box Warning: Increased risk of suicidal thinking and behavior in children, adolescents, and young adults
- Cardiovascular effects: May prolong QT interval; use caution in patients with cardiac disease
- Seizures: May lower seizure threshold
- Elderly patients: Increased risk of falls, cognitive impairment, and anticholinergic effects
- Pregnancy: Category C; use only if potential benefit justifies potential risk
- Withdrawal: Abrupt discontinuation may cause withdrawal symptoms
Drug Interactions
- MAOIs: Risk of serotonin syndrome and hypertensive crisis
- CNS depressants: Additive sedation with alcohol, benzodiazepines, opioids
- Anticholinergics: Enhanced anticholinergic effects
- SSRIs/SNRIs: Increased risk of serotonin syndrome
- CYP2D6 inhibitors: May significantly increase amitriptyline levels (e.g., fluoxetine, paroxetine)
- Antihypertensives: May reduce effects of guanethidine and similar agents
- Sympathomimetics: Enhanced pressor effects
Adverse Effects
Common (>10%):- Sedation/drowsiness
- Dry mouth
- Constipation
- Blurred vision
- Weight gain
- Orthostatic hypotension
- QT prolongation and arrhythmias
- Suicidal ideation (particularly in young adults)
- Seizures
- Neuroleptic malignant syndrome
- Hepatitis
- Blood dyscrasias
- Serotonin syndrome
Monitoring Parameters
- Baseline: ECG (if cardiac risk factors), liver function tests, renal function, weight
- Therapeutic drug monitoring: Therapeutic range 100-250 ng/mL (combined amitriptyline + nortriptyline)
- Mental status: Regular assessment for depression worsening or suicidal ideation
- Cardiac: Monitor for orthostatic hypotension, tachycardia
- Metabolic: Weight, blood glucose
- Adherence and effectiveness: PHQ-9 for depression, pain scales for analgesic use
Patient Education
- Take at bedtime to minimize daytime sedation
- Do not abruptly discontinue medication
- Avoid alcohol and other CNS depressants
- Rise slowly from sitting/lying position to prevent dizziness
- Use sugar-free gum or candy for dry mouth
- Report any thoughts of self-harm or worsening depression
- May take 2-4 weeks to experience full antidepressant effect
- Use effective contraception; notify provider if pregnancy is planned or suspected
- Avoid activities requiring alertness until effects are known
References
1. FDA Prescribing Information: Elavil (amitriptyline hydrochloride) 2. American Psychiatric Association. (2010). Practice Guideline for the Treatment of Patients with Major Depressive Disorder 3. Finnerup NB, et al. (2015). Pharmacotherapy for neuropathic pain in adults: systematic review and meta-analysis. Lancet Neurology 4. Rao SC, et al. (2018). Tricyclic antidepressants for migraine prevention: a systematic review and meta-analysis. Cephalalgia 5. Glassman AH, et al. (1993). Cardiovascular effects of tricyclic antidepressants. Annual Review of Medicine 6. Joint Formulary Committee. (2023). British National Formulary 7. Micromedex Solutions: Amitriptyline Drug Monograph 8. Lexicomp Online: Amitriptyline Hydrochloride Monograph