Spaulding Clinical and FDA research dangers of drug-opioid combinations

Spaulding Clinical, a Phase I clinical service provider, announced that it had worked with the US Food and Drug Administration (FDA) to organize clinical trials to help address the opioid crisis​. The trial was set up to evaluate whether two common psychotropic drugs would further decrease ventilation when combined with an opioid, when compared to an opioid alone.

The two compounds that were tested were paroxetine and quetiapine. The former is an antidepressant of the selective serotonin reuptake inhibitor class, and the latter is an antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder.

As both treatments are commonly prescribed, the FDA and Spaulding Clinical were seeking to determine whether the use of such treatments alongside opioids could require boxed warnings.

Benzodiazepine and opioids

Currently, there are boxed warnings for both benzodiazepine and opioid products regarding increased risk of respiratory depression with simultaneous use. Opioids can decrease ventilatory response to hypercapnia, or excessive carbon dioxide in the bloodstream, which can cause severe respiratory depression or death.

In order to counter opioid overdose deaths, the FDA has encouraged the development of a greater number of products formulated against abuse and also rescue treatments, such as naloxone spray​.

The clinical trial to determine risk factors of drug-opioid combinations is another method to try to reduce the number of deaths from opioid overdose. The findings of the study saw Spaulding Clinical identify that paroxetine posed a similar risk to those of benzodiazepines when used in combination with opioids.

Respiratory depression 

Spaulding Clinical principal investigator, Jan Matousek, said: “While quetiapine combined with oxycodone did not cause this effect, this preliminary study conducted at Spaulding Clinical from January to May 2021 demonstrated that paroxetine combined with oxycodone, versus oxycodone with a placebo, did cause a greater risk of respiratory depression. ​

"Further testing is therefore essential to determine if common therapies increase the risk of respiratory depression when combined with opioids​.”

According to the company, further investigation is also needed to assess whether the clinical results hold long-term effects, and to determine the clinical relevance of the findings.

In details published in an academic paper​, the researchers outlined that the study had been completed with 25 participants, in a randomized, double-blind, crossover clinical trial. The paper also stated that the FDA had a particular interest in whether other drugs that might be used in place of benzodiazepines may have similar effects in respiratory depression.