What are common autonomic side effects of Tricyclic Antidepressants (TCAs)?

From the Guidelines

Tricyclic antidepressants (TCAs) commonly cause autonomic side effects, particularly anticholinergic effects, which include dry mouth, blurred vision, constipation, urinary retention, and tachycardia, due to their blockage of muscarinic acetylcholine receptors throughout the body. These side effects are a significant concern in the management of patients on TCAs, especially in older adults who are more susceptible to adverse drug reactions 1. The severity of anticholinergic effects varies among different TCAs, with tertiary amines like amitriptyline and imipramine typically causing more pronounced effects than secondary amines like nortriptyline and desipramine 1.

Some key points to consider when managing patients on TCAs include:

• Starting with lower doses, especially in older patients, to minimize the risk of adverse reactions 1
• Monitoring for signs of anticholinergic toxicity, such as dry mouth, blurred vision, and urinary retention 1
• Considering alternative treatments, such as switching to a TCA with fewer anticholinergic properties or changing to a different class of antidepressant, for patients experiencing significant side effects 1
• Being cautious when prescribing TCAs to patients with a history of cardiovascular disease, as they may be at increased risk of sudden cardiac death, particularly at doses above 100 mg/day 1

It is essential to weigh the benefits of TCAs against their potential risks and to carefully monitor patients for signs of adverse reactions, particularly in vulnerable populations such as older adults 1. Overall, the management of autonomic side effects in patients on TCAs requires a careful and individualized approach, taking into account the specific needs and risks of each patient.

From the FDA Drug Label

In patients with angle-closure glaucoma, even average doses may precipitate an attack. Patients with cardiovascular disorders should be watched closely Tricyclic antidepressant drugs, including amitriptyline hydrochloride, particularly when given in high doses, have been reported to produce arrhythmias, sinus tachycardia, and prolongation of the conduction time. Myocardial infarction and stroke have been reported with drugs of this class Amitriptyline may enhance the response to alcohol and the effects of barbiturates and other CNS depressants In patients who may use alcohol excessively, it should be borne in mind that the potentiation may increase the danger inherent in any suicide attempt or overdosage. Delirium has been reported with concurrent administration of amitriptyline and disulfiram Other signs of overdose may include: impaired myocardial contractility, confusion, disturbed concentration, transient visual hallucinations, dilated pupils, disorders of ocular motility, agitation, hyperactive reflexes polyradiculoneuropathy, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia

Common autonomic side effects of Tricyclic Antidepressants (TCAs) include:

• Cardiovascular effects: arrhythmias, sinus tachycardia, prolongation of the conduction time, myocardial infarction, and stroke
• Anticholinergic effects: dry mouth, blurred vision, constipation, and urinary retention
• Orthostatic hypotension: dizziness, lightheadedness, and fainting
• Sweating: hyperpyrexia and diaphoresis
• Pupillary dilation: mydriasis

2, 3, and 3

From the Research

Autonomic Side Effects of Tricyclic Antidepressants (TCAs)

• Orthostatic hypotension is a common autonomic side effect of TCAs, as observed in studies 4, 5, 6, 7, 8
• This side effect is more pronounced in patients with pre-existing cardiac disease 5, 6
• Orthostatic hypotension can lead to injuries from falls, particularly in elderly depressed patients 5, 8
• Other autonomic side effects of TCAs include:
  • Prolonged conduction and cardiac complications in overdose 6
  • First-degree atrioventricular block and prolonged QTc interval 7
  • Sedation, insomnia, and impaired sleep, which can contribute to falls 8
  • Impaired postural reflexes and increased reaction times, which can also contribute to falls 8
  • Cardiac rhythm and conduction disorders, which can increase the risk of falls 8
• The correlation between antidepressant serum levels and adverse effects, including orthostatic hypotension, has been observed in some studies 4, 7