Duloxetine and Lorazepam Combination: Safety Assessment
Direct Answer
Yes, it is safe for a patient to be on duloxetine and lorazepam concurrently—the FDA drug label explicitly states that lorazepam does not affect duloxetine pharmacokinetics, and no contraindication exists for this combination. 1
Pharmacokinetic Evidence
The combination has been specifically studied and found to be safe from a drug interaction perspective:
- Under steady-state conditions (duloxetine 60 mg every 12 hours and lorazepam 2 mg every 12 hours), the pharmacokinetics of duloxetine were not affected by co-administration. 1
- Duloxetine is metabolized primarily by CYP1A2 and CYP2D6 enzymes, while benzodiazepines like lorazepam undergo glucuronidation, making clinically significant metabolic interactions unlikely. 1, 2
- Duloxetine is a moderate inhibitor of CYP2D6 but does not inhibit the pathways relevant to lorazepam metabolism. 1, 3
Pharmacodynamic Considerations
While no pharmacokinetic interaction exists, there are important pharmacodynamic effects to monitor:
- Duloxetine may enhance the effects of benzodiazepines through additive CNS depression. 4
- Both medications can cause sedation, dizziness, and somnolence, which may be additive when used together. 2, 5, 6
- The combination does not carry the same severe risks as seen with olanzapine plus benzodiazepines (where fatalities have been reported with high-dose combinations). 7
Clinical Monitoring Algorithm
When prescribing this combination, monitor for:
- Excessive sedation or somnolence, particularly during the first 2-4 weeks of concurrent therapy 5, 6
- Fall risk, especially in elderly patients (≥65 years) who are more susceptible to CNS depressant effects 8
- Cognitive impairment or psychomotor slowing that could affect driving or operating machinery 4
- Respiratory depression in patients with underlying pulmonary disease, though this risk is lower than with opioid combinations 8
Important Clinical Context
The CDC guidelines note that benzodiazepines should generally be used cautiously and for short durations, particularly when combined with other CNS-active medications. 8 However, this does not constitute a contraindication to the duloxetine-lorazepam combination specifically.
For chronic pain management, duloxetine is recommended as a first-line agent for conditions like diabetic neuropathy, fibromyalgia, and chronic low back pain, while benzodiazepines are not recommended for chronic pain. 8 If the lorazepam is being used for anxiety rather than pain, this combination may be appropriate during acute phases of treatment.
Common Pitfalls to Avoid
- Do not abruptly discontinue either medication, as duloxetine is associated with discontinuation syndrome and benzodiazepines carry withdrawal risks. 2, 5
- Avoid combining duloxetine with potent CYP1A2 inhibitors (like fluvoxamine or ciprofloxacin), which can increase duloxetine levels 6-fold—this is a separate concern from the lorazepam interaction. 1, 3
- Do not use duloxetine with MAOIs due to risk of serotonin syndrome—allow at least 14 days between discontinuing an MAOI and starting duloxetine. 1
- Use caution in patients with hepatic impairment or severe renal impairment, as duloxetine clearance is significantly reduced in these populations. 3, 4
Dosing Considerations
- The optimal therapeutic dose of duloxetine is 60 mg once daily, which has been shown effective for depression, anxiety, and pain conditions. 6
- Higher doses (up to 120 mg daily) may be used but do not consistently provide additional benefit and increase adverse effects. 5, 6
- Lorazepam should be used at the lowest effective dose for the shortest duration necessary, particularly in elderly patients. 8