What medications lead to Autonomic Dysfunction?

From the Guidelines

Tricyclic antidepressants are the most notable medications that can lead to autonomic dysfunction, as they can cause orthostatic hypotension, dry mouth, constipation, urinary retention, and blurred vision, among other symptoms. According to the study published in the European Heart Journal 1, tricyclic anti-depressives, phenothiazines, antihistamines, levodopa, and MAO-inhibitors are common culprits of drug-induced autonomic failure. However, a more recent study published in the Journal of the American College of Cardiology 1 also highlights the potential of tricyclic antidepressants to exacerbate autonomic dysfunction, particularly in patients with cardiac amyloidosis.

Some key points to consider when evaluating medications that can lead to autonomic dysfunction include:

• The type of medication: tricyclic antidepressants, antihistamines, and certain antipsychotics are more likely to cause autonomic dysfunction
• The patient's underlying medical conditions: patients with cardiac amyloidosis, diabetes, or other conditions that affect the autonomic nervous system may be more susceptible to autonomic dysfunction
• The dose and duration of treatment: higher doses and longer treatment durations may increase the risk of autonomic dysfunction

It is essential to weigh the benefits and risks of medications that can lead to autonomic dysfunction and to monitor patients closely for signs and symptoms of autonomic dysfunction, such as orthostatic hypotension, dry mouth, and constipation.

In terms of management, the study published in the Journal of the American College of Cardiology 1 suggests that medications such as pregabalin, gabapentin, and duloxetine may be beneficial for neuropathic pain, while tricyclic antidepressants may have increased side effects in patients with amyloid neuropathy. Additionally, non-pharmacological interventions such as increased fluid intake, salt tablets, and compression stockings may be helpful in managing orthostatic hypotension.

From the FDA Drug Label

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

The medication that can lead to autonomic dysfunction is sertraline (PO), as it can cause autonomic instability, which is a symptom of serotonin syndrome, a potentially life-threatening condition 2.

• Autonomic instability symptoms include:
  • Tachycardia
  • Labile blood pressure
  • Dizziness
  • Diaphoresis
  • Flushing
  • Hyperthermia

From the Research

Medications Leading to Autonomic Dysfunction

• Antipsychotic medications can lead to orthostatic hypotension, a common adverse effect that may delay or prevent titration to a dose necessary to control psychotic symptoms 3.
• Antidepressant drugs, such as:
  • Selective serotonin reuptake inhibitors (limited effects on autonomic system activity and a lower impact on blood pressure) 4.
  • Serotonin-norepinephrine reuptake inhibitors (particularly venlafaxine, carry a greater risk of hypertension) 4.
  • Norepinephrine reuptake inhibitor reboxetine (considered a safe option because of its neutral effects on blood pressure) 4.
  • Dopamine-norepinephrine reuptake inhibitor bupropion (can lead to blood pressure increases, usually at high doses, but may also cause orthostatic hypotension) 4.
  • Tricyclic antidepressants (have been associated with increases in blood pressure, as well as orthostatic hypotension) 4.
  • Oral monoamine-oxidase inhibitors (less frequently skin patch formulations, have been associated with orthostatic hypotension or, conversely, with hypertensive crisis) 4.

Treatment of Orthostatic Hypotension

• Midodrine, an alpha-adrenergic agonist, is effective in the treatment of orthostatic hypotension only in those patients with significant preservation of autonomic reflexes 5.
• Fludrocortisone is a reasonable first choice for symptomatic orthostatic hypotension 3.
• Other agents, including desmopressin, may be considered in patients who do not respond favourably to a trial of fludrocortisone 3.

Management of Autonomic Dysfunction

• Nonpharmacological strategies and patient education, such as slowly rising from the supine position, are crucial first steps in the prevention and treatment of both symptomatic and asymptomatic orthostatic hypotension 3, 6.
• Pharmacological treatment is only recommended when symptomatic orthostatic hypotension persists despite proper nonpharmacological therapy and there is a compelling indication for treatment 3, 6.