It’s all atypical: Can clozapine cause atypical neuroleptic malignant syndrome?

Australian & New Zealand Journal of Psychiatry, 46(3) the growing use (including off-label prescribing) relate to its sedative properties and favourable extrapyramidal and metabolic profile, as well as emerging evidence of positive outcomes at low doses for a range of mental disorders (Hollingworth et al., 2010). While the toxicity profile of atypical antipsychotics is considered preferable to typical agents, particularly regarding overdose risk, recent literature has called the relative safety of quetiapine into question. In one study, quetiapine-related overdoses were more likely to result in hypotension, respiratory depression, coma, or death than all the other antipsychotics combined (Ngo et al., 2008). This is particularly concerning given the growing number of case reports citing quetiapine as a potential substance of misuse, a phenomenon unseen with other atypical antipsychotic preparations (Sansone and Sansone, 2010). A recent study (Lloyd and McElwee, 2011) identified a non-significant increase in antipsychotic-related ambulance attendances over 2000−2009 in metropolitan Melbourne. While demographic characteristics remained relatively consistent over the period, there was a significant increase in antipsychoticrelated attendances where other drugs (both licit and illicit) were also implicated in presentations. However, differential harms across different antipsychotic preparations have not been adequately explored at a community level. To further our understanding of this emerging issue, we analysed ambulance attendance data from metropolitan Melbourne across different antipsychotic preparations to provide a preliminary quantification of quetiapine-related harms. Data were derived from the Ambo Project database (Lloyd and McElwee, 2011), utilizing data from patient care records completed by paramedics, with additional coding undertaken to identify involvement of alcohol or other drugs in ambulance presentations. While there was a small increase in antipsychotic-related ambulance attendances between 2000/01 and 2009/10 (from 783 to 1074 attendances), quetiapinerelated attendances increased substantially over the same period (from 32 in 2000/01 to 598 in 2009/10). Similar increases were not found for other antipsychotic preparations. Anecdotal reports from Victorian alcohol and drug agencies participating in the Earlier Identification of Drug Harms Project (unpublished data) indicate that quetiapine demand, use, diversion, misuse, and harms are ongoing issues, particularly for clients with a history of illicit drug use. Over the course of this project involving bi-monthly data collection, quetiapine was the only antipsychotic consistently reported as being used in a problematic manner, regardless of source of supply. Such an increase in acute quetiapine-related harm represents a growing public health issue. Further exploration is required to identify the nature and magnitude of quetiapinerelated harms, population groups at increased risk of harm, prescribing trends, and strategies to ensure benefits of quetiapine are balanced against potential risks to patients, and costs to the community. In the meantime, it is important that clinicians are aware of growing misuse and diversion of quetiapine, and adopt prescribing practices that minimize the risk of harms.