Implications of combining tramadol with serotonergic transmission enhancer drugs

H. E. Brennan, H. Claridge, C. S. Copeland. St George's University of London, London, United Kingdom.

Introduction: A total of 64.7 million antidepressants were prescribed and dispensed in the UK in 2016 alone (1). All commonly prescribed antidepressants (Selective Serotonin Re-Uptake Inhibitors [SSRIs], Monoamine Oxidase Inhibitors [MAOIs], Tricyclic Antidepressants [TCAs]) act to increase serotonergic transmission (2). Consequentially, their co-ingestion with other drugs needs to be carefully considered due to the potential of Serotonin Syndrome. Symptoms of Serotonin Syndrome include changes in mental state, neuromuscular changes, and, in extreme cases, can lead to death (3). Tramadol is an opioid analgesic. Along with its main metabolite, O-desmethyl-tramadol, their primary mechanism of action is at μ-opioid receptors to provide pain relief (4). However, Tramadol also has a secondary mechanism of action where it inhibits serotonin and noradrenaline reuptake, which adds to its analgesic effects (4). Combining tramadol with serotonergic enhancers, such as antidepressant drugs, would therefore increase the chance of Serotonin Syndrome. In this study, we have investigated the prevalence of tramadol and antidepressant drug co-ingestion and implication in deaths in England and Wales in 2012-2015.

Method: Data was extracted from the Voluntary Coroners Reporting Database using filters. Total deaths related to tramadol were examined, with sub-group analysis on deaths where anti-depressant drugs were co-ingested, with further focus on instance of accidental or deliberate death. Where appropriate, paired t-tests were performed for statistical analysis, and data are presented as mean ±STDEV).

Results: A total of 144 deaths were reported in 2012-2015 where co-ingestion of tramadol and antidepressants were directly implicated. This represents 30% of total reported tramadol-related deaths (n=480). Of the 144 deaths, 37.5% of them were classified as accidental or misadventure by the coroner, and 14.6% were classed as a suicide. There was no gender bias found in these cases (male n=75; female n=71) or specific age skew (mean age 45.03±12.41; age range 15-76 years old), suggesting this is an issue across many demographics.

Conclusions: The pharmacological interaction and subsequent physiological consequences of these drugs needs to be made clearer, both to prescribing doctors and patients themselves. A visible label on the outside of tramadol packaging warning people of the risks of co-ingesting antidepressants and tramadol could also help to prevent accidental death relating to co-consumption of these drugs.

References:

(1) NHS Digital (2017). ‘Antidepressants were the area with largest increase in prescription items in 2016.’

(2) Feighner (1999). J Clin Psychiatry, 60:4-11.

(3) Volpie-Abadie et al., (2013). Ochsner J, 13:533-540.

(4) Dayer et al., (1997). Drugs, 53:18-24.