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Around 4 million Australians (16% of the population) are living with back problems, with about 4 out of 5 people experiencing low back pain at some point in their lives.
Antidepressants are widely prescribed for low back pain and sciatica, with up to one in seven Australians with low back pain dispensed an antidepressant – most commonly the tricyclic antidepressant amitriptyline.
However, there is inconsistency across international clinical guidelines around their use for this indication, said Michael Ferraro, lead author of a review into Antidepressants for low back pain and spine‐related leg pain and Doctoral candidate at the Centre for Pain IMPACT, NeuRA, and the School of Health Sciences UNSW.
‘These medicines are very widely used clinically for sciatica, but there’s barely any trial evidence to inform their use.’
Michael Ferraro
‘The general thought was that they might be useful in some patients,’ he said. ‘At an individual prescriber level, clinicians are more likely to prescribe an antidepressant as a second-line treatment, particularly where there might be issues with sleep or mood.’
The review looked at the effects of any antidepressant class – including serotonin–norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants – on low back pain or spine-related leg pain (encompassing full nerve compression or referred pain into the leg).
While not all patients with low back pain have spine-related leg pain, those who do generally have worse pain and poorer long-term outcomes, Mr Ferraro said.
‘These medicines are very widely used clinically for sciatica, but there’s barely any trial evidence to inform their use,’ he said.
One class of antidepressant is beneficial for low back pain
The main outcomes of the review were impacts on patient-reported pain intensity, adverse events and function 3 months after initiation of treatment – enough time for the medicine to have a therapeutic effect.
The review is an update of an older Cochrane review, published in 2008, with the newer review incorporating results from industry-sponsored trials that tested the SNRI duloxetine.
‘Those trials, which were run across multiple international sites and recruited large patient populations, focused on low back pain patients,’ Mr Ferraro said.
While the review found that only SNRIs were effective over placebo for low back pain intensity, this effect was marginal.
‘When we think about the average effect in the patients that received an SNRI versus those who received the placebo, there was only a difference of around five points out of 100,’ he said.
‘That’s what we would consider small, and it might even be so small that it’s not really a benefit that your average patient would appreciate.’
Another antidepressant helps for disability
While the evidence is uncertain on the impact of SSRIs for low back pain or spine-related pain, tricyclic antidepressants were found to have no effect on pain.
However, there was one unexpected benefit unearthed.
‘They had a small effect on disability,’ Mr Ferraro said. ‘Normally we would expect any effects on disability to be mediated via pain, so that was a little surprising.’
But to demonstrate clinical benefit, there should be evidence of effects on both pain and disability, he said.
Antidepressants probably do more harm than good in back pain
The review found a lack of evidence to determine whether use of SSRIs and tricyclic antidepressants for low back pain and spine-related leg pain lead to adverse events.
However, there was an increased risk of experiencing any adverse event when using SNRIs.
‘While we didn’t look at adverse events formally, nausea, dry mouth and dizziness – the typical effects you’d have with an antidepressant – would be the ones that are most likely,’ Mr Ferraro said.
The next step for the research team is further investigation into the effects of SNRIs for spine-related leg pain.
‘Members of the author team are about to commence recruitment for a randomised trial of duloxetine for spine-related leg pain or sciatica, Mr Ferraro said. ‘That will be a critical study, as it will be large enough to fill the evidence gap we identified.’
Should antidepressants still be prescribed for this indication?
Cessation of antidepressants, including tapering too quickly, can come with withdrawal effects. So should patients be initiated on a treatment that could have little or no benefit, with the potential for adverse events down the line?
‘None of the trials we included in the review actually assessed adverse events after the treatment had ceased, so that’s a really key research item that must be addressed in the future,’ Mr Ferraro said.
However, when prescribing or dispensing antidepressants for low back pain or sciatica, it’s important to point patients to evidence that the benefits, on average, are small and may not be appreciable.
‘[Pharmacists and GPs] should explain that there’s a risk of side effects – and extrapolating from other data sources – that some of those effects may be related to tapering an antidepressant if it’s not effective.’
Pharmacists are also advised to check in with patients to see how they are coping with their pain.
‘The evidence we included found a benefit [of SNRIs] within 14 weeks, after a course of 2–3 months,’ he said. ‘So if there’s no benefit within the first 3 months, it would be critical to have a discussion with the pharmacist and then the GP.’
What are the alternative treatment options?
In terms of pharmacological treatments, the Australian Commission on Safety and Quality in Health Care’s Low Back Pain Clinical Care Standard recommends non-steroidal anti-inflammatory drugs (NSAIDs) for patients with low back pain who are at low risk of NSAID-related harm.
Along with antidepressants, anticonvulsants and benzodiazepines should generally be avoided – with the risks outweighing the benefits and little evidence for their effectiveness. Opioid analgesics should only be considered in carefully selected patients, using the lowest effective dose for the shortest possible duration.
Overall, medicines should be used judiciously, with physical and psychological interventions recommended first line to improve function.
