In this review, 17 RCTs were included that evaluated the effectiveness of pharmacological interventions for non-specific chronic low back pain.
The effectiveness of the different pharmacological interventions
No studies were found for muscle relaxants. In this review we found low quality evidence for effects on pain intensity for NSAIDs and opioids, and a small effect on function for opioids compared to placebo on the short term (<3 months) for patients with chronic low back pain. No effects were found for the use of antidepressants compared to placebo on any of the primary outcomes. NSAIDS and opioids seem to be associated with more adverse effects compared with placebo.
Despite the fact that the RoB of the studies was generally low, many studies showed flaws regarding concealment of treatment allocation, compliance, and drop-out rates. We feel the quality of future RCTs in the field of low back pain regarding these issues could be improved to reduce bias in future systematic reviews and overviews.
In three of the four studies assessing NSAIDs for chronic LBP and five of the eight studies on opioids, a so called “flare design” was used, in which patients who were already responding well to NSAIDs or opioids were only included when they showed a large worsening in LBP complaints during a wash-out period. This may have caused favourable results of the investigated NSAIDs and opioids, expressed in an overestimation of the effects and an underestimation of the adverse effects due to the selection of the study population, and certainly decreases the external validity for daily practice. It is uncertain if the results also apply to other patients with low back pain (who have not yet received NSAIDs or opioids for their LBP episode).
In the studies presented in this review adverse effects were reported, although we would like to emphasize the need for a complete and better report of adverse effects in clinical trials. Clearly, smaller randomised trials are unlikely to detect rare adverse events. Better reporting of adverse events in larger trials or prospective cohort sties is required.
According to the authors of the studies on NSAIDs, most adverse effects, including abdominal pain, diarrhea, edema, dry mouth, rash, dizziness, headache, and tiredness, were considered to be mild to moderately severe. However, the sample sizes of most of the studies were relatively small, and therefore no clear conclusion can be drawn from these studies regarding the risks of gastrointestinal and other adverse effects of NSAIDs. The statistical pooling of all adverse effects of NSAIDs compared to placebo for acute LBP indeed showed an increased RR, indicating the additional risk of using NSAIDs.
For antidepressants adverse effects, such as dry mouth, constipation, tachycardia, sedation, orthostatic hypotension, and tremor, were commonly reported, but no serious adverse effects were documented. However, the trials were also very small and not designed to evaluate adverse effects.
For opioids adverse effects were reported extensively and seemed to occur more in the opioid group compared to placebo, although here as well the numbers are small.
Overall it is difficult to draw firm conclusions regarding the risks for adverse effects of NSAIDs, antidepressants and opioids. Prospective studies with larger sample sizes are necessary to evaluate the incidence of both minor and major adverse effects.
Strengths and limitations
Several biases can be introduced in systematic reviews by literature search and selection procedure. We might have missed relevant unpublished trials, which are more likely to be small studies without positive results, leading to publication bias. Screening references of identified trials and systematic reviews may result in an over representation of positive studies in the review, because trials with a positive result are more likely to be referred to in other publications, leasing to reference bias. Studies not published in English, Dutch or German were not included in this review. It is not clear whether a language restriction is associated with bias [30
Another important limitation was the poor reporting of co-interventions, especially in the studies regarding NSAIDs and antidepressants, which hampered the study of the potential bias caused by this issue.
Implications for research
To conclude, we identified 17 RCTs that evaluated pharmacological treatment effects for patients with chronic non-specific LBP. Most of the studies included in this review had a low RoB, although there were methodological weaknesses, especially regarding concealment of allocation, compliance, and drop-out rates. There is a need for future high-quality RCTs with special emphasis on these subjects.
Implications for practice
NSAIDs and opioids might be useful for short-term pain relief in patients with chronic LBP, who responded with an exacerbation of their symptoms after stopping their medication. However, possible adverse effects should be weighed in deciding which medication to prescribe.