Amitriptyline
Saroten · Amitriptylin Abcur · Amitriptylin Orifarm
A tricyclic antidepressant that is rarely used for depression in contemporary practice — its role today is neuropathic pain and prophylaxis for migraine and chronic tension-type headache, at doses well below the antidepressant range. The effect on pain occurs already at 10–50 mg and depends on noradrenergic and sodium-channel-mediated modulation, not on antidepressant action. What limits treatment is anticholinergic side effects, and what makes the drug dangerous is cardiotoxicity in overdose.
Overdose is life-threatening through sodium channel blockade: widened QRS, right-axis deviation, seizures, and ventricular arrhythmias. QRS above 100 ms warns of seizures and above 160 ms of ventricular arrhythmia — treat with intravenous sodium bicarbonate until the QRS narrows. Even a few grams can be fatal.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Neuropathic pain | 10 mg at night, increase by 10 mg per week | usual maintenance 25–50 mg, occasionally 75 mg |
| Migraine prophylaxis and chronic tension-type headache | 10–25 mg at night, slow titration | usually 25–50 mg, evaluate after 2–3 months |
| Depression | 25–75 mg at night, titrate to response | rarely first-line today, specialist indication |
| Elderly | 10 mg at night, very slow titration | anticholinergic burden, fall risk, and confusion |
| Discontinuation | dose reduction in steps over at least 4 weeks | abrupt discontinuation causes nausea, headache, and sleep disturbance |
No established dose adjustment — amitriptyline is excreted mainly as metabolites. In severe renal failure cautious titration and lowest effective dose are nonetheless recommended.
Reduce dose and titrate slowly in impaired hepatic function. In severe hepatic failure the drug should be avoided; metabolism is entirely hepatic.
Not recommended for depression under 18 years. An approved indication exists for nocturnal enuresis from 6 years of age when an organic cause has been excluded and other treatment, including desmopressin, has not been effective — the dose is specified in the summary of product characteristics by age, in the order of 10–20 mg at 6–10 years and 25–50 mg from 11 years, with treatment duration no more than three months. An ECG should be obtained before starting to exclude long QT syndrome, and prescribing should be by a physician experienced in the condition.
Avoid after recent myocardial infarction, conduction defects, prolonged QT interval, untreated angle-closure glaucoma, and urinary retention due to prostatic enlargement. Use particular caution in the elderly, where anticholinergic burden causes confusion and falls, and in patients at risk of suicide — the lethal dose is close to the therapeutic dose and the prescribed quantity should be limited.
Pharmacokinetics
- BIOAVAIL.
- 30–60 %
- t½
- approximately 25 hours (9–36 hours)
- ACTIVE METABOLITE
- Nortriptyline
- PROTEIN BINDING
- approximately 95 %
- METABOLISM
- CYP2C19 and CYP2D6, also CYP3A4
- EXCRETION
- Renal, as metabolites
- ONSET
- 1–2 weeks for pain, 2–4 weeks for depression