In this episode, I’ll discuss whether psychotropic medications other than benzodiazepines enhance respiratory depression from opioids.
Benzodiazepines are known to increase the risk of respiratory depression in patients who are taking opioids, and the FDA mandates a boxed warning to this effect in the prescribing information for both opioids and benzodiazepines. The FDA has started to study whether other psychotropic medications might have similar interactions with opioids, and they have published results of a preliminary study in healthy patients in JAMA.
Since the mechanism of respiratory depression with opioids is suppression of the normal ventilatory response to hypercapnia, the authors sought to evaluate whether combining paroxetine or quetiapine with oxycodone, compared with oxycodone alone, decreases the ventilatory response to hypercapnia. The study was a randomized, double-blind, crossover clinical trial of 25 healthy patients. The median age of the study participants was 35.
Patients were given oxycodone 10 mg on day 1 and 5 and then randomized to receive paroxetine 40 mg daily, quetiapine twice daily (with increasing daily doses from 100 mg to 400 mg), or placebo.
To evaluate the effects on ventilatory response to hypercapnia the investigators used a rebreathing methodology to assess ventilation at end-tidal carbon dioxide of 55 mm Hg, which was considered hypercapnic ventilation.
While quetiapine appeared to have no effect on the ventilatory response to hypercapnia, paroxetine significantly decreased hypercapnic ventilation on day 1 and day 5 when combined with oxycodone.
The authors concluded:
In this preliminary study involving healthy participants, paroxetine combined with oxycodone, compared with oxycodone alone, significantly decreased the ventilatory response to hypercapnia on days 1 and 5, whereas quetiapine combined with oxycodone did not cause such an effect. Additional investigation is needed to characterize the effects after longer-term treatment and to determine the clinical relevance of these findings.
This study alone will likely not lead to new FDA boxed warnings on respiratory depression with paroxetine and opioids given the small size, healthy patient population, and preliminary nature of the investigation. However the FDA is likely to devote resources to exploring this potential interaction further given the potential significance of identifying new risks to respiratory depression with psychoactive medications combined with opioids.
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