Tramadol, gabapentinoids, and opioids

Summaries from ACP Hospitalist Weekly.

Tramadol, gabapentinoids associated with problematic opioid use in hospitalized patients, studies find

Despite being touted by some as alternatives to strong opioids, tramadol and gabapentinoids may still be associated with potentially hazardous prescriptions during and after hospitalization, according to two recent studies.

In the first study, published online by The BMJ on May 14, researchers used U.S. commercial and Medicare Advantage insurance claims data from Jan. 1, 2009, through June 30, 2018, to determine the risk of prolonged opioid use in opioid-naive patients receiving tramadol versus other short-acting opioids after elective surgery. Among the exclusion criteria were filling a prescription for opioids in the previous six months, being in treatment for opioid use disorder, and having an inpatient stay of seven days or more.

Image by Getty Images
Image by Getty Images

Risk of persistent opioid use after discharge was calculated by using three common definitions of prolonged opioid use: additional opioid use (at least one opioid fill 90 to 180 days after surgery), persistent opioid use (any span of opioid use starting in the 180 days after surgery and lasting ≥90 days), and CONsortium to Study Opioid Risks and Trends (CONSORT) definition (an opioid use episode starting in the 180 days after surgery that spans ≥90 days and includes either ≥10 opioid fills or ≥120 days' supply of opioids).

Of 444,764 patients who met the inclusion criteria and had 180 or more days of follow-up, 357,884 filled a discharge prescription for one or more opioids associated with one of 20 operations (seven common general surgery procedures, six orthopedic operations, two colorectal procedures, two urology procedures, two thoracic procedures, and minimally invasive hysterectomy). Overall, 74.9% of discharge prescriptions were for one or more short-acting opioids other than tramadol, whereas 3.0% were for tramadol alone and 1.2% were for tramadol with another short-acting opioid. The most frequently prescribed opioid was hydrocodone (53.0% of those filling a single opioid), followed by short-acting oxycodone (37.5%) and tramadol (4.0%).

Patients were followed until the end of the study period, disenrollment from insurance, or having another surgery. The unadjusted risks for additional opioid use, persistent opioid use, and meeting the CONSORT definition were 7.1% (n=31,431), 1.0% (n=4,457), and 0.5% (n=2,027), respectively. Receiving tramadol alone was associated with a 6% increase in the risk of additional opioid use compared to receiving other short-acting opioids (risk ratio with 95% CI, 1.00 to 1.13; risk difference, 0.5 percentage points; P=0.049), a 47% increase in the adjusted risk of persistent opioid use (risk ratio with 95% CI, 1.25 to 1.69; 0.5 percentage points; P<0.001), and a 41% increase in the adjusted risk of a CONSORT chronic opioid use episode (risk ratio with 95% CI, 1.08 to 1.75; 0.2 percentage points; P=0.013).

Limitations of the study include its use of claims data and the inability to ascertain the reason patients received additional opioid prescriptions, the study authors noted. In recent years, there has been a surge in use of tramadol, likely due to such perceived benefits as a favorable side-effect profile and the belief that it is safer and less addictive than other short-acting opioids, they said, adding that tramadol is a schedule IV drug, whereas hydrocodone and oxycodone are schedule II drugs.

“Although all factors related to the safety of a drug must be considered, from the standpoint of opioid dependence, the Drug Enforcement Administration and FDA should consider rescheduling tramadol to a level that better reflects its risks of prolonged use,” the authors concluded.

In the other study, researchers used medication reconciliation documents to review admissions to a medical clinical teaching unit in Canada between Dec. 17, 2013, and June 30, 2017. Of 4,103 patients admitted during the study period, 550 (13.4%) were receiving a gabapentinoid before admission, and two preadmission users were coprescribed gabapentin and pregabalin, for a total of 552 prescriptions. The study was published May 10 by the Journal of Hospital Medicine and appeared in the September issue.

Compared to nonusers, gabapentinoid users had a higher prevalence of chronic disease, and they were more likely to be coprescribed opioids (28.2% vs. 12.0%; P<0.01), benzodiazepines (24.5% vs. 14.3%; P<0.01), and nonbenzodiazepine sedative hypnotics (7.5% vs. 3.6%; P<0.01).

Overall, 10.2% of gabapentinoid users were simultaneously coprescribed both opioids and benzodiazepines, compared to 3.6% of nonusers (P<0.01). There was no significant difference in inpatient mortality between groups.

Only 94 (17%) of gabapentinoid prescriptions had an FDA-approved indication. Of these, 38 (40%) were for FDA-recommended doses, 47 (50%) were for doses below those demonstrated to be effective, and nine (10%) were for higher-than-recommended doses. New prescriptions at discharge occurred in 1.5% of patients, with the majority given for off-label indications.

Deprescribing of gabapentinoids occurred in 65 (13.1%) of 495 preadmission users who survived to discharge, and 33 (6.7%) of 495 had their dose decreased without a further plan to taper. About half of patients who had a gabapentinoid deprescribed did not have a documented justification for cessation, although commonly cited reasons included adverse drug events (ADEs), such as impaired cognition, falls, and edema, as well as the absence of a clear reason for continuation.

Limitations of the study include its single-center design and potential lack of generalizability, as well as the fact that indications for some prescriptions were omitted and inferred, the study authors said.

“The identification of gabapentinoids during hospitalization is an opportunity to reevaluate the indication for the drug, assess for effectiveness, and consider deprescribing to help reduce polypharmacy and ideally ADEs,” they concluded.