Dextromethorphan intoxications: Data from the French Toxicovigilance and Poison Control Centers from 1999 to 2014

Abstract

The French National Agency for Medicines and Health Products Safety (ANSM) has requested the Committee for Coordination of Toxicovigilance to analyze all dextromethorphan (DXM)-containing formulations cases reported to the French Toxicovigilance and Poison Control Centers (CAPTV). The main objective of this retrospective study was to complete the evaluation of the potential for abuse and dependence of DXM. DXM is indicated as antitussive therapy, mediated by agonist activity at the sigma receptors, however, mainly at larger doses, DXM may cause euphoria, hallucinations and a dissociative state. These effects are mostly due to its primary metabolite, dextrorphan, which is a potent N-methyl-D-aspartate (NDMA) receptor antagonist. This last pharmacological action may contribute to a recreational abuse of DXM-containing formulations [1] , [2] . We conducted a retrospective review analyzing all cases involving DXM-containing formulations reported to the CAPTV from January, 1999, through December, 2014. The severity of poisonings was graded using Poisoning Severity Score. We mainly focused our study on cases related to the intentional use of DXM, including addictive behaviors, misuse, and suicide attempts. Over the study period, 1474 DXM-containing formulations exposures were recorded. Among them, 478 were associated with symptoms and 14 serious cases were identified. One case of death related to the intentional use of DXM in combination with other psychoactive substances was also reported. The number of exposures as well as symptomatic cases gradually increased over the study period, especially from 2007. But if we take into account variables (i.e. circumstances of exposure, total number of cases reported to the CAPTV and total sales of DXM), a continuous increase was only observed for addictive cases. An increase in suicide attempts involving DXM was also highlighted until 2012, but then followed a downward trend. Among the 478 symptomatic cases, 196 (41.0%) were an intentional use of DXM-containing formulations: 67 addictive behaviors, 63 misuses and 66 suicide attempts; 135 of the 196 cases of intentional exposure involved only DXM use (and no other drugs). Among these 135 cases, addictive behaviors ( n = 51) were over represented in men (64.7%) and younger subjects as compared with misuses ( n = 56) or suicide attempts ( n = 28) (median age 16 versus 38 and 18-year-old, respectively). Solid dose forms of DXM-containing formulations were the most used in the addictive behaviors ( n = 38 among the 54 cases with DXM only). In addition, doses of DXM were of the same order of magnitude for suicidal attempt and addictive behavior cases (mean and median respectively 500 and 375 mg versus 450 and 360 mg), while they were lower for cases of misuse (mean and median 200 and 180 mg). This retrospective study of cases highlighted the increasing recreational use of DXM for hallucinogenic effects confirming addictovigilance network data. Further assessments of exposures are necessary to evaluate the impact of preventive measures set up at the end of 2014.