Amitriptyline Side Effects
Amitriptyline has numerous side effects including anticholinergic effects (dry mouth, constipation, urinary retention), cardiovascular effects (orthostatic hypotension, arrhythmias), neurological effects (sedation, dizziness), and others that require careful monitoring, especially in older adults or those with pre-existing conditions. 1
Common Side Effects
Anticholinergic Effects
- Dry mouth, blurred vision, constipation, and urinary retention are common anticholinergic side effects 1
- These effects can be particularly problematic in older adults and may limit tolerability 2
- Increased intraocular pressure and mydriasis may occur, requiring caution in patients with glaucoma 1
Neurological and CNS Effects
- Sedation, drowsiness, dizziness, and fatigue are frequently reported 1
- Headache, weakness, and nightmares may occur 1
- More severe effects can include confusion, tremors, ataxia, and incoordination 1
- Rarely, seizures, hallucinations, and delusions may occur 1
Cardiovascular Effects
- Orthostatic hypotension is the most common serious cardiovascular side effect 3
- Tachycardia and palpitations are frequently reported 1
- ECG changes including prolongation of conduction time may occur 1
- Serious but rare effects include myocardial infarction and stroke 1
- Patients with pre-existing bundle-branch disease are at risk for heart block 3
Gastrointestinal Effects
- Nausea, epigastric distress, vomiting, and anorexia 1
- Rarely, hepatitis with altered liver function and jaundice 1
Special Considerations
Use in Specific Populations
- Tricyclic antidepressants are potentially inappropriate for older adults (≥65 years) due to anticholinergic effects 4
- Not recommended for patients under 12 years of age 1
- Should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 1
- Excreted into breast milk; consider discontinuing nursing or the medication 1
Drug Interactions
- May enhance response to alcohol and effects of barbiturates and other CNS depressants 1
- May block antihypertensive action of guanethidine or similar compounds 1
- Delirium has been reported with concurrent administration of amitriptyline and disulfiram 1
- Interferes with radionuclide imaging using MIBG and must be stopped at least 10 days prior to such procedures 4
Serious Adverse Effects
Psychiatric Effects
- Risk of suicidality, especially during initial treatment or dose changes 1
- May precipitate mania or hypomania, particularly in patients with bipolar disorder 1
- Withdrawal symptoms can occur after abrupt cessation of prolonged administration 1
Overdose Toxicity
- Tricyclic antidepressants are among the most common causes of drug poisoning 5
- Overdose can cause severe cardiac effects, coma, convulsions, and respiratory depression 5
- Treatment of overdose is essentially supportive 5
Dosing and Monitoring Considerations
Starting and Titration
- When used for neuropathic pain or IBS, should be started at a low dose (e.g., 10 mg daily) 4
- Gradually titrate to effective dose (typically 25-100 mg daily for pain conditions) 4
- For migraine prevention, doses of 30-150 mg per day are recommended 4
Long-term Side Effects
- Contrary to common belief, many side effects (particularly anticholinergic) do not necessarily abate with continued treatment 6
- Regular monitoring for adverse effects is necessary even in long-term users 6
Comparison with Other Antidepressants
- Tricyclic antidepressants have higher withdrawal rates compared to SSRIs in older adults 2
- Side effects of dry mouth, drowsiness, dizziness, and lethargy are more common with TCAs than with SSRIs 2
- Despite better tolerability of SSRIs, a significant minority of older people still experience nausea, vomiting, dizziness, and drowsiness with these medications 2