Amitriptyline Side Effects
Amitriptyline commonly causes anticholinergic side effects including somnolence, dry mouth, blurred vision, constipation, and weight gain, as well as potential cardiac effects such as prolonged QTc interval on ECG. 1
Common Side Effects
Amitriptyline, a tricyclic antidepressant (TCA), is associated with numerous side effects that can impact patient quality of life and medication adherence. The most frequently reported side effects include:
Anticholinergic Effects
- Dry mouth
- Blurred vision
- Constipation
- Urinary retention
- Tachycardia
Central Nervous System Effects
- Somnolence/sedation (particularly prominent)
- Dizziness
- Cognitive impairment (especially in elderly)
- Confusion
- Headache
Other Common Effects
- Weight gain
- Sexual dysfunction
- Fatigue
- Orthostatic hypotension
- Sweating
Serious Side Effects
Several potentially serious adverse effects require monitoring and may affect morbidity and mortality:
Cardiovascular Effects
- Prolonged QTc interval on ECG 1
- Arrhythmias
- Sinus tachycardia
- Myocardial infarction and stroke have been reported 2
- Hypertension (even in young patients without concomitant medications) 3
Psychiatric/Neurological Effects
- Increased risk of suicidal thoughts and behaviors, particularly in children, adolescents, and young adults 2
- Seizures
- Delirium (especially when combined with other substances like alcohol or disulfiram) 2
- Potential for abuse (though uncommon) 4
Other Serious Effects
- Angle-closure glaucoma exacerbation
- Hyperpyrexia (when combined with anticholinergic agents or neuroleptics) 2
- Paralytic ileus (when combined with anticholinergic drugs) 2
Special Population Considerations
Elderly Patients
Elderly patients are particularly sensitive to anticholinergic side effects, including:
- Cognitive impairment
- Psychomotor slowing
- Confusion
- Sedation
- Delirium
- Increased fall risk 2
Pregnancy and Breastfeeding
- Crosses the placenta and is excreted in breast milk
- Some reports of adverse events in infants whose mothers took amitriptyline during pregnancy
- Potential teratogenic effects in animal studies at high doses 2
Drug Interactions
Amitriptyline has significant potential for drug interactions:
- May block antihypertensive effects of guanethidine
- Potentiates effects of alcohol and other CNS depressants
- Interactions with SSRIs that inhibit P450 2D6 (fluoxetine, paroxetine, sertraline)
- Contraindicated with MAO inhibitors
- Increased plasma levels when used with cimetidine 2
Clinical Management of Side Effects
To minimize side effects:
- Start with low doses (10-25 mg at bedtime)
- Titrate slowly (increments every 3-7 days)
- Monitor for adverse effects, especially cardiac effects
- Consider alternative TCAs with better side effect profiles (e.g., nortriptyline) for certain patients 1
Efficacy vs. Side Effect Profile
Despite its side effect burden, amitriptyline remains an effective treatment for various conditions:
- Neuropathic pain conditions 5, 6
- Migraine prevention 1
- Fibromyalgia 6
- Cyclic vomiting syndrome 1
- Depression
However, only about 38% of patients with neuropathic pain or fibromyalgia achieve satisfactory pain relief with amitriptyline, while 64% experience at least one adverse event 6.
Important Monitoring Considerations
- ECG monitoring for patients with cardiovascular risk factors
- Blood pressure monitoring regardless of dose 3
- Monitor for emergence of suicidality, especially during initial treatment or dose changes
- In overdose situations, cardiac monitoring is essential due to risk of dysrhythmias 2
Side effects may not necessarily diminish with continued treatment as commonly believed; long-term users may continue to experience anticholinergic side effects with similar severity ratings as new users 7.