Effectiveness of placebo interventions for patients with nonspecific low back pain: a systematic review and meta-analysis.

ABSTRACT: Little is known about the effectiveness of placebo interventions in patients with nonspecific low back pain (LBP). This systematic review assessed the magnitude of the effects of placebo interventions as compared to no intervention in randomized controlled trials (RCTs) including patients with LBP. Embase, MEDLINE (Ovid), and Cochrane CENTRAL databases were searched from inception to December 5, 2019. Randomized controlled trials comparing placebo intervention vs no intervention in adult patients with nonspecific LBP were included. Pain intensity, physical functioning, and health-related quality of life measured at short-term, medium-term, and long-term follow-up were the outcomes of this review. Twenty-one randomized controlled trials were included; one concerning acute LBP and one subacute LBP, whereas 19 studies reported on chronic LBP. In chronic LBP, placebo interventions were more effective than no intervention at short-term follow-up for pain intensity (standardized mean difference = -0.37, 95% confidence interval [CI] = -0.55 to -0.18, moderate-quality evidence), physical functioning (standardized mean difference -0.19, 95% CI = -0.39-0.01, moderate-quality evidence), and physical quality of life (mean difference = -2.71, 95% CI = -4.71-0.71, high-quality evidence), respectively. These effects were not significant at medium-term follow-up, and no data were available at long-term follow-up. These results show placebo interventions are more effective than no intervention at short-term follow-up in patients with chronic LBP. However, the magnitude of the effects is probably not clinically relevant (approximately 8 points on a 0-100 pain scale). Future research should identify effect modifiers and causal mechanisms explaining the short-term effects of placebo interventions in patients with chronic LBP.

Paracetamol for low back pain: the state of the research field.

INTRODUCTION: Paracetamol is one of the most frequently used analgesics for people with low back pain, but despite its frequent use there is still debate regarding its efficacy and safety for this indication. AREAS COVERED: We describe the origin of paracetamol and its proposed mechanisms of action. We focus in on low back pain and describe the evidence it has on the efficacy of paracetamol (taken by patients orally) and current insights on its side-effects. When searching for relevant publications we focused mainly on recent Cochrane reviews and published RCTs. We found that there is increasing evidence that shows paracetamol is not more effective than placebo in patients with acute low back pain. Concerning patients with subacute and chronic back pain, the evidence for or against the efficacy of paracetamol vs placebo is lacking and would need more research. EXPERT OPINION: We argue that we still need better evidence on the efficacy of paracetamol for acute and chronic back pain. Until that evidence becomes available paracetamol should still be considered as an option for patients with back pain. However, we suggest that a strategy focusing on non-pharmacological management as the first treatment option in low back pain may be equally effective with less side effects.

Inferential reproduction analysis demonstrated that "paracetamol for acute low back pain" trial conclusions were reproducible.

OBJECTIVES: The aim of this study was to reanalyze and reinterpret data obtained in Paracetamol in Acute Low Back Pain (PACE), the first large randomized controlled trial evaluating the efficacy of paracetamol in acute low back pain, to assess the inferential reproducibility of the original conclusions. STUDY DESIGN AND SETTING: Mixed effects models were used to reanalyze pain intensity (primary outcome; 11-point Numeric Rating Scale) and physical functioning, health-related quality of life, sleep quality, and time until recovery (as secondary outcomes), according to the intention-to-treat principle. The original authors of the PACE study were not involved in the development of the methods for this reanalysis. RESULTS: The reproduction analyses indicated no effect of treatment on pain intensity and confidence intervals excluded clinically worthwhile effects (adjusted main effect for regular paracetamol vs. placebo 0.00 [-0.02, 0.01; P = 0.85]; adjusted main effect for paracetamol as-needed vs. placebo 0.00 [-0.02, 0.01; P = 0.92]). Similar results were obtained for all secondary outcomes. CONCLUSION: This study indicates that the conclusions of the PACE trial are inferentially reproducible, even when using a different analytical approach. This reinforces the notion that the management of acute low back pain should focus on providing patients advice and reassurance without the addition of paracetamol.

Paracetamol is ineffective for acute low back pain even for patients who comply with treatment: complier average causal effect analysis of a randomized controlled trial.

In 2014, the Paracetamol for Acute Low Back Pain (PACE) trial demonstrated that paracetamol had no effect compared with placebo in acute low back pain (LBP). However, noncompliance was a potential limitation of this trial. The aim of this study was to investigate the efficacy of paracetamol in acute LBP among compliers. Using individual participant data from the PACE trial (ACTN12609000966291), complier average causal effect (CACE), intention-to-treat, and per protocol estimates were calculated for pain intensity (primary), disability, global rating of symptom change, and function (all secondary) after 2 weeks of follow-up. Compliance was defined as intake of an average of at least 4 of the prescribed 6 tablets of regular paracetamol per day (2660 mg in total) during the first 2 weeks after enrolment. Exploratory analyses using alternative time points and definitions of compliance were conducted. Mean between-group differences in pain intensity on a 0 to 10 scale using the primary time point and definition of compliance were not clinically relevant (propensity-weighted CACE 0.07 [-0.37 to 0.50] P = 0.76; joint modelling CACE 0.23 [-0.16 to 0.62] P = 0.24; intention-to-treat 0.11 [-0.20 to 0.42] P = 0.49; per protocol 0.29 [-0.07 to 0.65] P = 0.12); results for secondary outcomes and for exploratory analyses were similar. Paracetamol is ineffective for acute LBP even for patients who comply with treatment. This reinforces the notion that management of acute LBP should focus on providing patients advice and reassurance without the addition of paracetamol.

Guideline recommendations on the pharmacological management of non-specific low back pain in primary care - is there a need to change?

INTRODUCTION: Analgesic drugs are often prescribed to patients with non-specific low back pain (NSLBP). Recommendations for non-invasive pharmacological management of NSLBP from recent clinical practice guidelines were compared with each other and with the best available evidence on drug efficacy. Areas covered: Recommendations concerning opioids, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, antidepressants, anticonvulsants and muscle relaxants from national primary care guidelines published within the last 3 years were included in this review. For each pharmacological treatment, the most recent systematic review was included as the best available evidence on drug efficacy and common adverse effects were summarized. Expert opinion: Although differences exist between guidelines, publications are universally moving away from pharmacotherapy due to the limited efficacy and the risk of adverse effects. NSAIDs have replaced paracetamol as the first choice analgesics for NSLBP in many guidelines. Opioids are generally considered to be a last resort, but opioid prescriptions have been increasing over recent years. Upcoming guideline updates should explicitly shift their focus from pain to function and from pharmacotherapy to non-pharmacological treatments; patient education is important to make sure NSLBP patients accept these changes. To improve the quality of NSLBP care, the evidence-practice gap should be closed through guideline implementation strategies.