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New drugs for chronic pain: The search continues for something better than opioids

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By Barbara Greenwood Dufour

When seeking treatment for chronic pain, many Canadians will be prescribed an opioid medication. However, the current opioid crisis in Canada has called attention to the significant risks associated with these drugs. Furthermore, despite being such a common treatment for chronic pain, opioids don’t tend to be very effective over the long term. This has led to increased interest in alternatives to opioids for managing chronic pain that are not only safer but are also more effective.

A number of non-opioid drugs have been suggested as alternatives for chronic pain, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitor antidepressants, and anticonvulsants. But none of these drugs appears to have reduced the need for opioids in managing pain, and they also come with their own risk of adverse events. There are, however, some emerging non-opioid drugs in development. Might they offer safer and more effective treatment options for chronic pain?

CADTH — an independent agency that finds, assesses, and summarizes the research on drugs and medical devices — recently conducted an Environmental Scan to identify and review the available evidence on non-opioid drugs for chronic non-cancer pain that will likely enter the Canadian market in the near future. CADTH identified several such drugs that have either been approved by a regulatory agency in another country or are in clinical development, including three that could become available in Canada in the near future and potentially play a role in addressing the opioid crisis. They are ziconotide for severe, treatment-refractory chronic pain, tanezumab for chronic pain caused by osteoarthritis or chronic low back pain, and the capsaicin 8% patch for neuropathic pain associated with post-herpetic neuralgia.

Ziconotide is an analgesic that was approved by the US FDA in 2004 for the management of severe chronic pain in patients who are intolerant of or not responding to other treatments. It’s injected into the spinal cord to block the transmission of pain signals. The evidence produced so far shows that ziconotide might be effective for these patients. It was, however, also found to be associated with some adverse events, including abnormal gait, dizziness, rapid involuntary eye movements, confusion, urinary retention, nausea, and vomiting.


Tanezumab, a treatment for osteoarthritis-related pain or chronic low back pain, is said to target and stop the nerve growth factor activity to reduce pain signals. The drug was previously studied as an intravenous infusion but is now being studied as a subcutaneous injection. Tanezumab has not yet been approved by the FDA — in 2010, the FDA put a hold on clinical trials of the drug when some participants developed rapidly progressive osteoarthritis and osteonecrosis that led to the need for joint replacements. However, the hold has since been lifted, and tanezumab has now been granted Fast Track designation for an expedited review. The evidence from studies conducted so far suggest that tanezumab may be effective for reducing pain related to both indications, with the main adverse effects reported to be abnormal peripheral sensations (e.g., numbness and tingling), especially at higher doses, and, in the one study in patients with chronic low back pain joint pain, pain in the extremities, and headache. It also appeared to result in a small number of patients requiring joint replacements in the osteoarthritis-related studies.

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A topical treatment — the capsaicin 8% patch — was approved by the FDA in 2009 for the management of neuropathic pain associated with post-herpetic neuralgia, a complication of shingles. The patch contains a high concentration of synthetic capsaicin (the substance that naturally occurs in chilli peppers and gives them their heat) and is applied to the skin for an hour. The evidence produced so far on the capsaicin 8% patch shows that it could be effective for pain management in these patients. The most common adverse effects associated with this patch are redness and pain in the area where the patch is applied.


There are several other non-opioid drugs that are in clinical development for the management of chronic non-cancer pain and may become available in the future. The majority of them are for neuropathic pain, pain related to osteoarthritis, and chronic migraine prevention. Until additional studies of any of the emerging treatments are conducted to further evaluate their safety and effectiveness, we can’t tell how likely they are to replace or reduce the use of opioids. However, staying familiar with what’s in the pipeline can give decision-makers advance knowledge to help them be better prepared, should these drugs eventually come on the Canadian market.


If you’d like to learn more about CADTH or this environmental scan, visit www.cadth.ca. You can find more evidence to help address the opioid crisis in Canada at www.cadth.ca/opioids and www.cadth.ca/pain, follow us on Twitter @CADTH_ACMTS, or speak to the CADTH Liaison Officer in your region.


Barbara Greenwood Dufour is a Knowledge Mobilization Officer at CADTH.


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