Deaths involving contraindicated and inappropriate combinations of serotonergic drugs

In the Australian state of Victoria, all fatalities that were recorded from 2002 through to 2008 involving the use of certain serotonin active drugs (tramadol, venlafaxine, fluoxetine, sertraline, citalopram and paroxetine), were reviewed to assess the incidence of contraindicated or ill advised drug combinations. More than 1,000 were identified of which 326 cases formed the basis of this study. These cases involved contraindicated or inappropriate drug combinations that can lead to adverse drug reactions (ADRs) and subsequent fatal toxicity. Of these, 46% were drug-related, 35% were a result of natural disease and 13% were classified as external injury cases. The remaining cases were those where the cause of death (COD) was unascertained. Tramadol was the most common drug, usually detected alongside a serotonergic antidepressant (in 20% of cases). Twenty-five (8%) cases involved contraindicated drug combinations while the remainder (301 cases, 92%) involved drug combinations that are associated with adverse interactions ranging from minor to major severity. Of these 326 cases, the Coroner determined 166 cases (51%) to be acts of intentional self-harm or drug misuse, with the remainder unascertained or attributed to natural disease. Very few post-mortem reports and Coroners’ findings made mention of possible ADRs when such combinations were actually present. The majority of cases comprising contraindicated drug combinations involved the combined use of five drugs (24%) at the time of death. A combination of three to five drugs was most common in cases involving inadvisable drug combinations. Combined drug toxicity was the most common COD, with heart disease the most common co-morbidity.