Respiratory Depressant Medications in This List
Among the medications listed, clonazepam (Klonopin) is the only clear respiratory depressant, while quetiapine (Seroquel) carries a secondary risk of respiratory depression particularly in vulnerable patients. 1, 2
Primary Respiratory Depressant
Clonazepam (Klonopin) 2 mg twice daily
Clonazepam is a benzodiazepine that causes respiratory depression and should be used with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, sleep apnea). 2
All benzodiazepines, including clonazepam, cause respiratory depression through their action on GABA-A receptors, which directly suppress respiratory drive. 1, 3
The FDA drug label explicitly warns that clonazepam "may cause respiratory depression" and requires careful monitoring in patients with any respiratory compromise. 2
When combined with opioids, benzodiazepines significantly worsen respiratory depression through synergistic effects at different CNS receptor sites—benzodiazepines at GABA-A sites and opioids at mu receptors. 2
Population-based observational studies confirm that benzodiazepine-related negative respiratory outcomes are a significant clinical concern. 3
Secondary Respiratory Risk
Quetiapine (Seroquel) 100 mg
Quetiapine's most common side effects include somnolence and sedation, which can indirectly compromise respiratory function, particularly in elderly or medically compromised patients. 4
While not classified as a direct respiratory depressant like benzodiazepines, the sedative properties of quetiapine may contribute to hypoventilation in at-risk populations. 4
Non-Respiratory Depressants
Levetiracetam (Keppra) 750 mg IV every 12 hours
Levetiracetam has no evidence of respiratory depression and appears to be the best tolerated among newer antiepileptic drugs with no unique respiratory toxicities. 5
No respiratory depression is listed among the adverse effects of levetiracetam in clinical guidelines or research. 1, 5
Oxcarbazepine (Trileptal) 1,200 mg
Oxcarbazepine is not associated with respiratory depression. 1, 5
The primary concerns with oxcarbazepine are hyponatremia and CNS effects such as sedation, but not direct respiratory suppression. 5
Fluoxetine (Prozac) 80 mg daily
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) with no respiratory depressant effects. 1
SSRIs do not act on respiratory centers and are not classified as respiratory depressants in any clinical guidelines. 1
Critical Clinical Considerations
The 2 mg twice daily dose of clonazepam in this regimen is substantial and carries significant respiratory risk, particularly if:
The patient has any underlying pulmonary disease (COPD, sleep apnea, restrictive lung disease). 2
The patient is receiving concurrent opioid therapy, which creates potentially fatal additive respiratory depression. 2
The patient is elderly, as older adults are 7-18 times more likely to be prescribed benzodiazepines and are significantly more sensitive to their respiratory effects. 6
The patient has hepatic or renal dysfunction, which prolongs benzodiazepine elimination and increases toxicity risk. 6
Common pitfall to avoid: Do not overlook the cumulative sedative burden when multiple CNS-active medications are prescribed together. The combination of clonazepam with quetiapine increases overall sedation and may compound respiratory risk beyond what either agent would cause alone. 1, 2