Is Trazodone associated with polydipsia?

Trazodone and Polydipsia: Association and Management

Trazodone can cause hyponatremia and polydipsia as a side effect through its mechanism of inappropriate antidiuretic hormone secretion (SIADH). This is documented in the FDA drug label and supported by clinical evidence.

Mechanism and Evidence

Trazodone's association with polydipsia and hyponatremia is clearly established in the FDA drug label:

• The FDA label explicitly states that "hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including Trazodone Hydrochloride Tablets" 1
• This hyponatremia "appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)" 1
• Signs and symptoms include "headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness" 1
• More severe cases can present with "hallucination, syncope, seizure, coma, respiratory arrest, and death" 1

Risk Factors

Certain patient populations are at increased risk for developing trazodone-induced hyponatremia:

• Elderly patients 1
• Patients taking diuretics 1
• Volume-depleted patients 1
• Patients with psychiatric disorders, particularly schizophrenia and bipolar disorder 2, 3

Clinical Presentation

Polydipsia associated with trazodone may present as:

• Excessive thirst and water consumption
• Polyuria (excessive urination)
• Dilute urine with low osmolality 4
• Symptoms of hyponatremia as sodium levels drop 1

Management Approach

When trazodone-induced polydipsia is suspected:

1. Monitor sodium levels - Check serum sodium in patients on trazodone who report increased thirst or show signs of hyponatremia

2. Assess severity - For symptomatic hyponatremia, discontinue trazodone and institute appropriate medical intervention 1

3. Consider alternative medications for insomnia:

   • First-line: Cognitive Behavioral Therapy for Insomnia (CBT-I) 5
   • Second-line: FDA-approved medications like zolpidem, eszopiclone, or zaleplon 5
   • Alternative sedating antidepressants: doxepin, mirtazapine, or amitriptyline 5

4. For patients who must continue trazodone:

   • Limit fluid intake to reasonable amounts
   • Monitor sodium levels regularly
   • Consider dose reduction
   • Add sodium chloride supplementation in severe cases 2

Prevention

To prevent polydipsia and hyponatremia in patients taking trazodone:

• Start with low doses (25 mg at bedtime) and titrate slowly 5
• Do not exceed 100 mg for insomnia treatment 5
• Monitor sodium levels periodically, especially in high-risk patients
• Educate patients about symptoms of hyponatremia and when to seek medical attention

Clinical Pearls

• Trazodone is commonly prescribed off-label for insomnia despite limited evidence for efficacy at low doses (50 mg) 5
• The American Academy of Sleep Medicine suggests that clinicians not use trazodone for sleep onset or maintenance insomnia 5
• When discontinuing trazodone, taper gradually rather than stopping abruptly to avoid discontinuation syndrome 1
• In cases of psychogenic polydipsia with psychiatric comorbidities, addressing the underlying psychiatric condition is essential 6, 3

Clinicians should maintain a high index of suspicion for hyponatremia in any patient on trazodone who presents with neurological symptoms, confusion, or reports excessive thirst.