The use of acetaminophen for acute low-back pain was no more effective than placebo, with similar times to recovery regardless of whether the drug was taken regularly or as needed, a large randomized trial found.

Among patients who took acetaminophen on a regular schedule, median time to recovery was 17 days (95% CI 14-19) compared with 16 days (95% CI 14-20) for patients receiving placebo, for a hazard ratio of 0.99 (95% CI 0.87-1.14), according to Christopher M. Williams, PhD, of the University of Sydney in Australia, and colleagues.

And patients who took the drug as needed also had a median time to recovery of 17 days (95% CI 15-20), for an HR versus placebo of 1.05 (95% CI 0.92-1.19), the investigators reported online in The Lancet.

“Guidelines for acute low-back pain universally recommend paracetamol [acetaminophen in the U.S.] as the first-line analgesic,” Williams and colleagues observed, but noted that there is little evidence to support this recommendation.

They previously published a systematic review that found no benefit, but the included trials were small and methodologically flawed.

To address this evidence gap, they enrolled 1,643 patients from 235 centers in Australia in a trial known as Paracetamol for Low-Back Pain (PACE), randomizing them to a regular-treatment group, who were instructed to take the drug three times per day for a daily dosage of 3,990 mg; an as-needed group, who could use a maximum of 4,000 mg per day; or to placebo.

The medication could be taken for up to 4 weeks or until recovery, and naproxen was permitted as rescue medication.

Recovery was defined as beginning on the first day when pain scores were 0 or 1 and persisting for at least a week.

Participants’ mean age was 45, and slightly more than half were men.

Mean pain intensity score at baseline was 6.3 on a scale of 1 to 10, and duration since pain onset was 10 days.

Disability was measured on a scale of 0 to 24, with higher scores reflecting more disability, and function on a scale of 0 to 10, with higher scores representing better functioning.

At baseline, the average disability score was 12.7, and function score was 3.6.

During the first week of treatment, mean pain intensities were 3.7 for the regular-treatment group, 3.8 in the as-needed group, and 3.6 in the placebo group. Scores in the second week were 2.6 for both active treatment groups and 2.5 for the placebo group, and by the fourth week, scores were 1.7, 1.8, and 1.7, respectively.

Mean disability scores for the regular-treatment, as-needed, and placebo groups during week one were 7.7, 8, and 8.3, falling to 3.2, 3.5, and 3.3 by week four. By 3 months, disability scores were 2.4, 2.6, and 2.4, respectively.

Function scores during week one were 6.2, 6.1, and 6.2, increasing to 8.7 for all groups by 3 months.

By 3 months, sustained recovery was reported by 85% of patients receiving the regular treatment, by 83% of those using the medication on an as-needed basis, and by 84% of those given placebo.

Similar results also were seen for other secondary endpoints such as sleep quality and physical and mental scores on the Short Form 12 quality of life instrument.

Across the three groups, 19% experienced one or more adverse events, with no between-group differences. The use of rescue medication was minimal and again had no between-group differences.

Adherence to treatment also was similar in the three groups. Patients in the regular treatment group took a median of four tablets per day (out of the recommended six), for median dosages of 3,500 mg per day during the first week and 2,800 mg per day during the second week.

In the as-needed group, median dosages in the first and second week were 1,000 and 500 mg per day.

The researchers noted that patients’ recovery was more rapid in PACE than in other reported cohorts, which they suggested may be explained by provision of “good-quality advice and reassurance, a feature that is often absent from usual care.”

“While we cannot disregard the possibility of a placebo effect in PACE leading to improved recovery, the provision of advice and reassurance of the favorable prognosis might be the more important factor in management of acute low-back pain than drug therapy,” Williams and colleagues wrote.

“Our results convey the need to reconsider the universal endorsement of paracetamol in clinical practice guidelines as first-line care for low-back pain,” they observed.

“This study adds to what we’ve known for a while: everything works for low-back pain — ice, heat, exercises, ibuprofen, Tylenol — but nothing works that well,” said Matthew Pirotte, MD, of the department of emergency medicine at Loyola University Chicago-Stritch School of Medicine, who wasn’t involved in the trial.

“I usually use episodes of low-back pain as a chance to counsel patients about weight loss and exercise, both of which usually decrease the frequency of episodes of low-back pain,” Pirotte told MedPage Today in an email.

In a comment accompanying the study, Bart W. Koes, PhD, and Wendy T. Enthoven, PhD, of Erasmus Medical Center in Rotterdam, posed the question as to whether guidelines should now be changed to reflect the lack of benefit seen with acetaminophen in this trial.

“Although the findings from this high-quality trial are clear, the content of guidelines should not be changed on the basis of a single trial; more robust and consistent evidence, including verification of the results in other populations, is needed,” Koes and Enthoven stated.

Limitations of the trial included the imperfect adherence to treatment and the possibility that some patients may have taken drugs other than the specified rescue medication.