Chronic pain and depression commonly occur together: antidepressant and chronic pain-relief medications, such as opioids, are therefore often prescribed together. The majority of antidepressant medications work by increasing levels of the chemical serotonin in the brain. While the opioid tramadol is prescribed as a painkiller, it also increases levels of a transmitter called serotonin in the brain. This can result in "Serotonin syndrome", when there is too much serotonin in the brain and can lead to serious complications and even death. Drugs that increase brain serotonin levels, such as antidepressants and tramadol, should therefore not be prescribed together. However, data from the UK National Program on Substance Abuse Deaths indicates that these drugs are being prescribed together, leading to at least one death every ten days.
Therefore, tramadol-antidepressant co-prescriptions must be examined urgently. Anonymised data from a primary care database will be analysed to find out how common tramadol-antidepressant co-prescriptions are in the UK, and whether patients being co-prescribed these drugs are at a higher risk of unplanned admissions to hospital and death. This research could influence how tramadol and antidepressants are prescribed, to prevent complications and deaths, and to increase awareness of the dangers of combining tramadol and antidepressants to healthcare professionals and the public.
Chronic pain and depression are common comorbidities, especially amongst older adults. Antidepressants and opioid analgesics, are therefore often co-prescribed in primary care. Tramadol relieves pain via mu-opioid receptor activation, and enhancement of serotonergic and noradrenergic transmission. Combining tramadol with other serotonergic enhancers, such as antidepressants, could therefore induce serotonin syndrome - a potentially fatal complication. However, it is not known how widespread co-prescribing is, nor what excess risk might be associated with co-prescribing. Data from the National Program on Substance Abuse Deaths reports 144 UK deaths in 2012-15 where tramadol-antidepressant co-consumption was directly implicated, equating to one death every ten days.
The proposed research aims to use the Clinical Practice Research Datalink (CPRD) to firstly ascertain the prevalence of tramadol-antidepressant co-prescribing in the UK over the last 20 years. Secondly, it will use linked hospital admissions and mortality data to determine to what extent tramadol-antidepressant co-prescriptions are associated with adverse outcomes such as emergency hospital admissions and death. We will carry out statistical analyses that compare prescribing periods when patients are prescribed both drugs with periods when only one drug is prescribed. To add robustness to the findings, we will use different statistical methods (time-to-event, self- controlled case series) as well as carrying out a comparison to the co-prescribing of antidepressants with codeine. This research has the potential to inform tramadol-antidepressant prescribing practice to prevent adverse outcomes and raise awareness amongst healthcare professionals and the public about dangers of tramadol-antidepressant combined use.
Mortality (Primary)
Emergency Hospital Admissions (Secondary)
A&E attendance (Secondary)
Caroline Copeland - Chief Investigator - St George's, University of London
Iain Carey - Corresponding Applicant - St George's, University of London
Derek Cook - Collaborator - St George's, University of London
Stephen DeWilde - Collaborator - St George's, University of London
Tess Harris - Collaborator - St George's, University of London
HES Accident and Emergency;HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation