Amitriptyline Side Effects
Amitriptyline has numerous significant side effects including anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision), cardiovascular effects (orthostatic hypotension, tachycardia, arrhythmias, QT prolongation), and CNS effects (sedation, dizziness, confusion), which must be carefully monitored, especially in elderly patients. 1
Common Side Effects
Anticholinergic Effects
- Dry mouth (very common)
- Constipation
- Urinary retention
- Blurred vision and disturbance of accommodation
- Increased ocular pressure
- Mydriasis (pupil dilation)
Cardiovascular Effects
- Orthostatic hypotension
- Tachycardia
- Nonspecific ECG changes
- Changes in AV conduction
- Heart block
- Arrhythmias
- Hypertension (rare but documented) 2
- QT interval prolongation 3
Central Nervous System Effects
- Drowsiness/sedation (very common)
- Dizziness
- Headache
- Fatigue
- Weakness
- Tremors
- Confusion
- Disorientation
- Anxiety
- Insomnia
- Nightmares
Gastrointestinal Effects
- Nausea
- Epigastric distress
- Vomiting
- Anorexia
- Peculiar taste
- Rarely hepatitis with altered liver function and jaundice 1
Endocrine and Metabolic Effects
- Weight gain
- Changes in blood sugar levels (both elevation and lowering)
- Sexual dysfunction
- Decreased libido or impotence
- Testicular swelling and gynecomastia in males
- Breast enlargement and galactorrhea in females 1
Serious Adverse Effects
Neurological
- Seizures
- Peripheral neuropathy
- Extrapyramidal symptoms
- Tardive dyskinesia
- Ataxia 1
Psychiatric
- Hallucinations
- Delusions
- Confusional states
- Mania or hypomania (particularly after cessation of therapy) 1
Hematologic
- Bone marrow depression
- Agranulocytosis
- Leukopenia
- Thrombocytopenia
- Eosinophilia 1
Severe Reactions
- Serotonin syndrome (very rare, especially when combined with other serotonergic medications)
- Neuroleptic malignant syndrome-like reactions (very rare)
- Paralytic ileus
- Hyperpyrexia 1
Dosing and Risk Factors
Dosing Considerations
- Starting doses should be low (10-25 mg at bedtime) and gradually titrated
- For pain management: typically 25-100 mg/day 3, 4
- For migraine prevention: 25-150 mg/day 3
- For cyclic vomiting syndrome: 75-150 mg or 1-1.5 mg/kg at bedtime 3
Risk Factors for Adverse Effects
- Advanced age (elderly patients are more susceptible)
- Cardiovascular disease
- History of seizures
- Prostatic hypertrophy
- Narrow-angle glaucoma
- Hepatic or renal impairment
- Concomitant use of other medications with anticholinergic properties
Monitoring and Management
Monitoring Recommendations
- Baseline ECG recommended before starting treatment, especially in patients with cardiovascular risk factors or those over 65 years 4
- Regular blood pressure monitoring regardless of dose 2
- Periodic assessment of anticholinergic side effects
- Monitor for changes in mood or behavior
- Consider monitoring blood levels in patients on higher doses
Withdrawal Considerations
- Abrupt cessation after prolonged use may cause withdrawal symptoms:
- Nausea
- Headache
- Malaise
- Irritability
- Restlessness
- Sleep disturbances
- Gradual dose reduction is recommended when discontinuing 1
Clinical Pearls
- Side effects are often dose-dependent; lower doses used for pain management (25-50 mg) may cause fewer side effects than higher doses used for depression (75-150 mg) 5
- Nighttime dosing can help minimize daytime sedation
- Anticholinergic side effects (dry mouth, sedation) are commonly reported even at low doses used for pain control 5
- Nortriptyline may have fewer anticholinergic side effects than amitriptyline and may be better tolerated in some patients 3
- The risk of QT prolongation requires careful monitoring, especially with higher doses or in patients with cardiac risk factors 3
- Despite side effects, amitriptyline remains an effective treatment for various pain conditions, with good to moderate response in up to two-thirds of patients with neuropathic pain 5