Steer Clear of Driving While Taking Prescribed Opioids?

Damian McNamara

December 17, 2018

Higher-dose opioids impair driving performance to a minor degree, but patients still need to be advised of this risk so they can decide whether to steer clear of driving while taking these medications.

In a study of healthy volunteers, investigators at Oslo University Hospital in Norway found that high-dose buprenorphine caused slight impairment on highway driving compared to placebo. In contrast, low-dose buprenorphine and both high- and low-dose methadone did not significantly impair driving skills.

"Patients should be informed about the possible risk of driving impairment when initiating treatment with these medications. Even though mild impairing effects were seen on the group level, large individual differences were observed, and 4 out of 22 participants terminated the driving due to sleepiness," principal investigator Maren Cecilie Strand, MD, told Medscape Medical News.

The study was published online December 4 in the British Journal of Clinical Pharmacology.

Some Opioids Riskier Than Others?

The Centers for Disease Control and Prevention estimates that 42,000 Americans died in 2016 from an opioid overdose, including overdoses related to prescription opioids.

Driving under the influence of opioids also is risky. For example, a review article reported that 17 of 25 opioid studies found statistically significant links between use of opioids and road traffic accidents.

In other research, the average odds ratio for experiencing a serious injury or death in an accident increased by a factor 2 to 10 for people driving under the influence of medicinal opioids, the European Monitoring Center for Drugs and Drug Addiction reported.

The risk was comparable to driving with a blood alcohol concentration of 0.5 – 0.8 mg/mL.

Even with this previous research, studies of the acute effects of buprenorphine or methadone using real roadway tests "are still lacking," the investigators note. An unanswered question is whether the link between these agents and motor vehicle accidents is stronger for some opioids than others.

To address these limitations in the literature, the investigators conducted a study involving 11 men and 11 women (mean age, 36 years). These healthy volunteers were opioid-naive, had had a valid driving license for at least 4 years, drove at least 5000 km (about 3100 miles) per year on average, and were good sleepers.

The researchers compared the acute effects of two single analgesic doses of methadone (5 and 10 mg oral) and buprenorphine (0.2 and 0.4 mg sublingual) vs placebo in a five-way, double-blind, randomized, placebo-controlled, double-dummy, crossover study. There was a washout period of at least 10 days between test days.

The researchers instructed the participants to drive in a steady lateral position in the right lane of a portion of a highway. Participants maintained a constant speed of 95 km/hr (60 mph) for each test in normal traffic conditions.

Left of Center Lane

A specially instrumented vehicle measured the primary outcome — "weaving," or standard deviation of lateral position (SDLP) — in centimeters. A licensed driving instructor accompanied the volunteers during each driving test.

The instructor terminated the driving test if it was deemed necessary, Strand noted.

"The participants are also instructed to indicate whether they do feel fit to drive or not and to terminate the driving at any point if not feeling suitable to drive safely," she added.

An on-road driving test to measure drug effects on driving has been used for more than 30 years and in approximately 100 studies, she said. "The actual on-road driving test is very sensitive to drug impairing effects," she noted.

Each participant underwent testing for reaction time to a visual stimulus, divided attention, processing speed, reaction time under sensory stress, and other cognitive and psychomotor assessments.

The participants also completed portions of the Norwegian Clinical Test of Impairment, a measure used by physicians who work with the police in Norway to assess people suspected of driving under the influence of drugs. In addition, the volunteers rated their feelings on a 16-item mood scale and completed the Karolinska Sleepiness Scale.

Compared to placebo, high-dose buprenorphine 0.4 mg significantly increased SDLP.

Analysis of variance showed no significant main effects of treatment on SDLP or standard deviation of speed, but there was a significant effect on mean lateral position (MLP).

MLP measures whether participants followed instructions to drive in the center of their lane. This outcome was lower with low-dose buprenorphine relative to placebo and differed significantly across the treatments, the researchers note.

After taking an opioid, participants tended to drive slightly to the left of the center of their lane.

Impaired Performance

The lower doses of buprenorphine and methadone affected some parameters during cognitive and psychomotor testing, including a postural balance test, the Divided Attention Test (DAT), and the Psychomotor Vigilance Task (PVT).

In contrast, the higher doses of each agent impaired performance on almost every cognitive test.

High-dose buprenorphine, for example, significantly prolonged reaction time on multiple measures and affected the number of lapses on the PVT, tracking on the Critical Tracking Task, and the number of control losses on the DAT.

High-dose buprenorphine was also associated with a decrease in the number of hits on the DAT, fewer correct responses on the Digital Symbol Substitution Test (DSST), and poorer results on the postural balance test.

Similarly, high-dose methadone significantly increased the number of lapses and control losses on the PVT and reaction time on the Vienna Test System–Determination Test. High-dose buprenorphine also decreased the number of hits on the DAT and was associated with poorer performance on postural balance testing and processing speed, as measured on the Useful Field of View Test.

Nausea, vomiting, dizziness, and tiredness/sleepiness were the most frequently reported opioid side effects.

The researchers also found that reaction times, control losses, false alarms, postural balance, and correct responses on the DSST varied on the basis of elapsed time since participants took the opioid.

In some instances, "opioid effects were more pronounced at 6 hours post administration as compared to 2 hours," they note. "This suggests that impairments levels may increase with increasing time on task due to tiredness. Participants indeed felt less alert and sleepier during the final part of the test schedule."

Evidence for Legal Limits

Four of the participants asked six times to stop their driving test prematurely. In each instance, they told the driving instructor that they were too sleepy to continue. Test cessation occurred after taking buprenorphine or morphine.

"This indicates large inter-individual variations in driving performance of patients who receive opioid treatment, some of whom might be impaired whilst most are not," the researchers note.

"Individual differences in impairment levels might be associated to individual differences in drug concentrations, drug sensitivity and the presence of side effects that may affect driving," they add.

In addition, some participants were unable to complete neurocognitive tests because of side effects. These data were considered missing and were not included in the analysis.

"When initiating treatment with these opioids, the patient should be informed about the potential impairing effects on driving," said Strand, noting that higher doses caused more impairment and more sleepiness.

When opioids are used repeatedly over time, some tolerance to the drug's effects will develop, she added.

"Our study only addresses the question whether these drugs have impairing effects on driving after single-dose intake, in other words, similar to the situation when initiating treatment with these drugs. We cannot state anything about the risk over time based on our findings," she said.

The researchers plan a follow-up study to assess the correlation between drug concentrations in the blood and the effect size.

"These results can be used as scientific evidence for legal limits. In Norway, we already have implemented legal limits for driving under the influence of several nonalcohol drugs. Studies like ours add new insights on the degree of impairment relevant to safe driving," she said.

A Challenge for Clinicians

Commenting on the findings for Medscape Medical News was William Maixner, DDS, PhD, president of the American Pain Society, professor of anesthesiology, and director of the Center for Translational Pain Medicine at Duke University Medical Center in Durham, North Carolina.

"Patients driving while taking opioids can be a difficult situation for a physician to consider," said Maixner.

The variables involved include individual patient tolerance and physiology, dosing, type of opioid prescribed, and symptoms a patient might experience, Maixner explained. "The red flag is drowsiness. If a patient says the medication makes [them] drowsy, they should not drive."

Also commenting on the findings, Ameet Nagpal, MD, associate professor in the Department of Anesthesiology and medical director of UT Health San Antonio Pain Consultants in Texas, said the study is a "welcome addition to the literature."

Driving while using prescription opioids is a relevant topic, and "the results of any study must be interpreted with caution," Nagpal, who is also associate program director of the UT Health San Antonio Pain Medicine Fellowship, told Medscape Medical News.

"For example, while the findings in this article did not rise to the level of what the authors describe as clinical significance using a statistical measure, I think it's clearly significant that 18% of the subjects felt uncomfortable with driving after ingesting the single dose of opioid due to sleepiness," he added.

Nagpal also pointed out that the administered doses were higher than the usual starting dose in most practices.

"I would be interested to see how these results would differ in chronic opioid users," he added.

The study was sponsored by the Norwegian Ministry of Transport and Communications. Dr Strand, Dr Maixner, and Dr Nagpal have disclosed no relevant financial relationships.

Br J Clin Pharmacol. Published online December 4, 2018. Abstract

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