FDA: some opioids can be combined with benzos

The FDA recently published an advisory on the concomitant prescription of benzodiazepines with the opioid addiction medications buprenorphine or methadone, noting that the combination of these opiates with CNS-depressants such as benzos does increase the likelihood of adverse events.  But the potential harm "usually outweighs these risks".  seehttps://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm576755.htm . They suggest a few things:

Recommendations:

Providers should:

--manage these patients carefully, educating patients about potentially serious risks (including overdose and death), trying to taper the CNS depressants to the lowest level possible, including discontinuation.

--verify the diagnosis for the CNS depressants being prescribed

--recognize that buprenorphine/methadone, referred to as MAT (medication-assisted opiate treatment), may continue indefinitely, and should be continued as long as patients are benefiting

--coordinate care with other prescribers (eg, if psychiatrist prescribing benzos, or patient is getting MAT from outside opiate treatment program)

--monitor for illicit drug use (urine/blood tox screens)

Commentary:

--this FDA alert is quite helpful. Some prescribers are very hesitant to prescribe appropriate benzos/CNS depressants to patients who need them but are on MAT. This alert puts that into perspective: we should treat the patient as an individual and evaluate their specific risks/benefits

--though there may well be an increased morbidity/mortality with concomitant use of opiates and benzos, as noted in some studies (see blog below), this risk may be overstated for a few reasons:

    --these studies in general look at benzos and opiates mostly from illicit drug purchases on the streets and are retrospective ER or mortality studies. these results may not be totally applicable to prescribed meds in a more monitored setting (eg, with illicitly-purchased drugs from the streets, who knows what the ingested dose is?, and are there other unknown drugs/substances cut into them which might themselves lead to higher mortality?). see http://www.serenityacrestreatment.com/blog/benzodiazepines-on-black-market-being-laced-with-fentanyl which documents illicit benzos being laced with fentanyl. One clear note by the FDA in supporting clinician benzo prescribing is the acknowledgement that patients otherwise might just buy them on the street, with "could result in more severe outcomes".

    ​--the underlying psychopathology leading to the use of the benzos by itself may be associated with increased morbidity/mortality. For example, panic disorder even without benzos has a substantial attributed mortality. So, the role of the benzos themselves in increasing mortality may be overstated.

--As a result of the above, the FDA is requiring that this information on combining benzos with MAT "be added to the buprenorphine and methadone drug labels along with detailed recommendations for minimizing the use of MAT drugs and benzodiazepines together"

so,​ a welcome upgrade in the FDA recommendations, which reflects the not-so-infrequent condition where patients who are opioid-dependent on MAT also have underlying psych disorders requiring benzos for adequate treatment.  This recommendation, however, does not extend to the also pretty common situation of patients who are on chronic opioid therapy for severe pain, perhaps related to a major trauma (eg, injury in Iraq, or falling off a high ladder), and need benzos as part of their overall treatment plan to maximize their function. And that seems to be the logical extension of the above FDA argument (at least to me....)

See http://gmodestmedblogs.blogspot.com/2017/03/opiates-and-benzos-assoc-with-inc.html , a blog on a retrospective observational study finding increased ER visits and hospital admissions (did not include deaths) for opiate overdoses in those on the combo of opiates and benzos.  But i would note that those patients on the opiate/benzo combination in this study had a higher incidence of all 14 of the medical conditions noted (ie, many more comorbidities than those on opiods, though the specifics of the intensity of the comorbidities was not mentioned). Depression was noted in 4.4% of the nonbenzo group but 17% in those on benzos, and they did not have information on any anxiety or bipolar disorders, which have an independent increased risk of suicide.

see http://gmodestmedblogs.blogspot.com/2017/01/increasing-deaths-from-opioids_13.html/  and http://gmodestmedblogs.blogspot.com/2017/02/opiate-prescribing-in-elderly-and.html  which note the role of fentanyl in increasing opioid deaths, including referring to many other blogs on the remarkable future addiction potential of limited opioid prescribing in adolescents and in elderly