Does Lorazepam Affect the Dexamethasone Suppression Test?
Yes, lorazepam can cause false-negative results on the dexamethasone suppression test (DST), particularly when used at high doses, by potentially suppressing cortisol levels and interfering with the test's ability to detect hypercortisolism.
Mechanism of Interference
Benzodiazepines, including lorazepam, can interfere with the hypothalamic-pituitary-adrenal (HPA) axis and alter cortisol suppression patterns. The research evidence specifically identifies benzodiazepines at high dosages as a cause of false-negative DST results 1. This means that patients with true Cushing's syndrome or autonomous cortisol secretion might appear to suppress normally on the DST when taking lorazepam, leading to a missed diagnosis.
Clinical Implications
When to Avoid or Discontinue Lorazepam
- Ideally discontinue lorazepam before DST testing to avoid false-negative results that could mask hypercortisolism
- The duration of discontinuation needed is not well-established in guidelines, but given lorazepam's relatively short half-life (10-20 hours), a washout period of at least 3-5 days would be prudent
- If discontinuation is not feasible due to severe anxiety or other psychiatric conditions, document the concurrent use and interpret results with caution
Interpreting DST Results in Patients on Lorazepam
When a patient cannot safely discontinue lorazepam:
- Consider alternative screening tests first: Late-night salivary cortisol or 24-hour urinary free cortisol (UFC) may be less affected by benzodiazepine use 2, 3
- If DST shows normal suppression but clinical suspicion remains high, repeat testing after lorazepam discontinuation or use complementary tests
- Document lorazepam use (dose and timing) when ordering the DST so the interpreting physician is aware of potential interference
Practical Testing Algorithm
For patients requiring Cushing's syndrome screening:
If patient is on lorazepam and can safely discontinue:
- Taper and discontinue lorazepam over 5-7 days (to avoid withdrawal)
- Wait 3-5 days after last dose
- Proceed with standard DST (1-mg overnight or 48-hour low-dose)
If patient cannot discontinue lorazepam:
If results are discordant or equivocal:
- Perform additional testing with dexamethasone-CRH test or midnight serum cortisol 2
- Consider endocrinology referral for complex cases
Important Caveats
Dose-Dependent Effect
The interference appears to be dose-dependent, with high doses of benzodiazepines more likely to cause false-negative results 1. Low-dose lorazepam (e.g., 0.5-1 mg daily) may have minimal impact, but this has not been rigorously studied.
Other Interfering Factors
Remember that multiple factors can affect DST results 4, 1, 5:
- False-positives: Stress, weight loss, alcohol withdrawal, medications that increase dexamethasone metabolism (phenytoin, phenobarbital, rifampin, carbamazepine)
- False-negatives: Liver disease, indomethacin, possibly methadone and ketoconazole, in addition to benzodiazepines
Pseudo-Cushing States
Psychiatric conditions (depression, anxiety, OCD) can themselves cause HPA axis activation and abnormal DST results 2. This creates a clinical dilemma: the patient may be on lorazepam for anxiety, which itself can cause pseudo-Cushing's syndrome. In these cases, the 48-hour low-dose DST or dexamethasone-CRH test may better distinguish true Cushing's from pseudo-Cushing's 2, 6.
Bottom Line for Clinical Practice
Do not perform a DST in patients currently taking lorazepam if you can avoid it. If screening for hypercortisolism is necessary and lorazepam cannot be discontinued, use late-night salivary cortisol or 24-hour UFC instead. If a DST must be performed while the patient is on lorazepam, interpret normal suppression with extreme caution and consider confirmatory testing with alternative methods, especially if clinical suspicion remains high.