Can Thorazine (chlorpromazine) cause hyponatremia?

Can Thorazine (Chlorpromazine) Cause Hyponatremia?

Yes, Thorazine (chlorpromazine) can cause hyponatremia through the syndrome of inappropriate antidiuretic hormone secretion (SIADH), though this is an uncommon adverse effect.

Mechanism and Evidence

Chlorpromazine is documented as one of several psychotropic medications capable of inducing hyponatremia via SIADH 1. The mechanism involves inappropriate secretion of antidiuretic hormone, leading to impaired free water excretion and dilutional hyponatremia 1.

Clinical Characteristics

Timing of Onset

• Hyponatremia associated with psychotropic medications typically develops within the first 2 weeks of treatment, with the highest risk during this initial period 2
• The median time to onset for psychotropic-induced hyponatremia is approximately 7 days following first dose or dose increase 3

Symptom Presentation

• Patients may present with headaches, blurry vision, weakness, cramps, vomiting 1
• More severe manifestations include confusion, agitation, lethargy, seizures, or coma that can lead to death 2, 1
• Approximately 57% of psychotropic-induced hyponatremia cases present symptomatically, with 19% showing severe symptoms 3

High-Risk Patient Populations

Primary Risk Factors

• Advanced age: Each 10-year increment in age doubles the risk of drug-induced hyponatremia 4
• Female gender: Women, particularly elderly women, face substantially elevated risk 4, 3
• Low body weight: Each 5 kg decrease in body mass increases risk by approximately 30% 4

Highest Risk Subgroup

• Female patients aged ≥65 years using concomitant hyponatremia-inducing drugs represent the population subgroup with the highest risk 3

Critical Drug Interactions

The risk of hyponatremia increases 16-42 times when chlorpromazine is combined with other potentially hyponatremia-inducing medications 3, including:

• Diuretics (thiazides, loop diuretics, spironolactone) 5, 3
• ACE inhibitors and angiotensin II receptor blockers 3
• Proton pump inhibitors 3
• Other psychotropics (carbamazepine, SSRIs, SNRIs) 5, 3

Monitoring Recommendations

Initial Monitoring

• Check serum sodium and electrolytes within the first 2 weeks of initiating chlorpromazine, as this is the highest-risk period 2
• Monitor more frequently (within 3-7 days) in elderly patients, those with low body mass, or those on concomitant hyponatremia-inducing drugs 4, 5

Ongoing Surveillance

• Any change in mental status or clinical course should prompt immediate sodium level assessment 2
• Be particularly vigilant during acute illness with vomiting, diarrhea, or decreased oral intake 6

Management Approach

When Hyponatremia Develops

• Discontinue chlorpromazine if hyponatremia is identified, as the condition is typically reversible after stopping the causative medication 1
• Assess for concurrent polydipsia, which occurs in 6-17% of psychiatric inpatients and can compound the problem 1
• Evaluate for other contributing medications and consider discontinuation or dose reduction 5

Common Pitfalls

• Overlooking chlorpromazine as a cause when evaluating new-onset confusion or altered mental status in psychiatric patients 2
• Failing to recognize drug combinations that synergistically increase hyponatremia risk, particularly when prescribing combination preparations 5
• Assuming dose-dependency: The development of hyponatremia is not related to the dosage of the psychotropic medication 2
• Inadequate monitoring in high-risk populations, particularly elderly women on multiple medications 4, 3