Paracetamol: an oldie repurposed

14. September 2015
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In recent years, there have been a lot of warnings against the use of paracetamol: the painkiller can cause all sorts of diseases. Recent studies no longer suggest using this old favourite for joint and back pain and instead have set their eye on new applications.

The painkiller paracetamol has been on the WHO list of essential drugs since 1977. Considering that the group of non-opioid analgesics is quite small, an understandable idea. For several years, there has been evidence that paracetamol is not as harmless as long assumed. Increasingly, there have been studies that even deny the pain medication’s efficacy in certain diseases. In July 2014, the PACE study [paywall] (Paracetamol for Low-Back Pain Study) showed that the popular analgesic failed to relieve low back pain. A meta-analysis published early this year by Christopher Maher’s working group at the George Institute for Global Health in Sydney looked at the efficacy of paracetamol for acute low back pain. The result: paracetamol (PCM) neither reduces the intensity of pain (mean difference -0.5, 95-percent confidence interval -2.9 to 1.9) nor diminished the pain-related disability (0.4, -1.7 to 2.5); it also did not improve the quality of life (0.4, -0.9 to 1.7).

Maher’s working group evaluated ten high-quality, randomised and placebo-controlled trials with 3,541 patients and evaluated the efficacy of paracetamol for back pain. The pain intensity improved with PCM by 3.7 points (5.5 to 1.9) and the disability decreased by 2.9 points from (4.9 to 0.9). If the researchers had used the analogue numerical pain scale (1 to 10) commonly used in Germany, this would be a respectable success. But they were using a scale from 1 to 100. The difference from the placebo is therefore not significant. In the studies, it was almost four times more likely to result in an increase in liver enzymes (risk ratio 3.8; 1.9 to 7.4), which is why paracetamol should never be used without hesitation.

PCM does not speed recovery

Christopher Williams [paywall] from the George Institute examined the recovery time for back pain when treated with paracetamol. The 1,652 patients were divided into three groups. One group was given the analgesic three times a day, the second received it only in acute cases, and the third group received placebos. In the treatment group, the patients were free of symptoms after 17 days; in the placebo group after 16 days. “Our results suggest that regular or dosage as needed of paracetamol does not affect recovery time for lower back pain compared to placebo,” the authors said.

Questionable effect on osteoarthritis, too

Results of a study by Dougados et al. show no effect of paracetamol in patients with osteoarthritis (OA) of the knee. A total of 779 patients were randomized to receive six weeks of treatment with 4 grams of paracetamol or placebo daily. The primary endpoint was a 30 percent decrease in overall pain intensity in the knee. After six weeks, the analgesic effect of the paracetamol was not significantly different from placebo. Even the study’s authors admit that a study of nearly 800 patients was not sufficiently broad enough to conclude that paracetamol is completely ineffective in joint pain.

Risk to the foetus?

It has been a frequent subject of discussion whether paracetamol presents a risk to male foetuses and could promote cryptorchidism. A recent study by van den Driesche sees a risk to the future fertility of unborn male children. The analgesic is said to affect foetal testosterone levels. The Information page of the German Pharmacovigilance and Advisory Centre on Embryonal Toxicology still sees no increased risk for embryos: “According to current knowledge, paracetamol does not increase the risk of malformations. (…) This is also true for the recently alleged relationship between taking paracetamol at the end of the first trimester or early in the second and the occurrence of cryptorchidism. The results in question are contradictory, based on small sample sizes in studies with problematic methodology, and cannot be plausibly explained.”

Paracetamol makes the psyche feel good

Regardless of possible risks during pregnancy, paracetamol has effects in an entirely different area: “Taking paracetamol appears to have more far-reaching consequences than previously thought. Because the drug apparently does not just dull the pain, but also one’s feelings,” says Geoffrey Durso summarising the result of his investigation [paywall]. 82 subjects were shown pictures that were neutral, pleasant, or those which aroused strong emotions. Cute kittens, cows grazing, and war scenarios were used. Some of the subjects received 1000 mg of paracetamol one hour before the experiment and the others received a placebo. The treatment group assessed the shocking or pleasing photos significantly less positively or negatively in an emotional ranking scale.

A study by Eisenberger et al looked at the effect of paracetamol on “social pain”, specifically lovesickness. This and the pain from rejection are both improved by taking paracetamol. Paracetamol also intervenes in the serotonergic nervous system and acts with cannabis receptors. Whether these are reasons for the psychotropic effects, we can only speculate.

The new findings do not put the reliable effect of paracetamol with other pain or fever conditions in question. Nevertheless, they can encourage practitioners to use the analgesic in more targeted and more restrictive manner.

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