Quetiapine use: Science or clever marketing?

To the Editor

It is with interest, but not with surprise, that we read about the substantial increase in quetiapine-related harm in metropolitan Melbourne between 2000-2001 and 2009-2010 (Heilbronn et al., 2012). It is well recognised in the literature that there has been a rapid growth in the use of atypical antipsychotic (AAP) medications over the past ten to fifteen years, with a disproportionate increase in off-label prescribing. Part of the rapid diffusion of AAPs has been achieved by large increases in the rate of use in certain sub-populations, most notably youths for whom long term data on safety and efficacy are still lacking, and due to persisting use of AAPs over long periods of time (Crystal et al., 2009).

Antipsychotic global sales were US$25.4 billion and the seventh biggest therapeutic group in 2010; Seroquel™ (quetiapine), Zyprexa™ (olanzapine) and Abilify™ (aripiprazole) were the 5^th, 10^th and 13^th biggest selling pharmaceuticals worldwide (IMS Health, 2011). The authors conducted a survey on the characteristics of off-label AAP use by psychiatrists in Christchurch, New Zealand in 2010; we found that quetiapine was the preferred choice of 94% of prescribers, and that 58% of all respondents prescribed this medication off-label every week, generally in situations where there was little scientific evidence of safety and efficacy (Monasterio and McKean, 2011).

Using data supplied by PHARMAC (the pharmaceutical funding agency in New Zealand), the authors looked at trends in prescribing of quetiapine over the last ten years in New Zealand. This has increased by almost 700% and prescribing has moved from specialists to general practitioners (GPs). GPs prescribed 2.5 times more quetiapine than specialists in 2011, whereas in 2002 specialist prescribing was 4 times larger than GP prescribing.

The prescription of low dose quetiapine (which is suggestive of off label usage) is more likely to be conducted by GPs. In 2011, 36% and 19% of GP and specialist prescribing was for daily doses of ≤100mg and 11% and 11% for daily doses >100mg and ≤200mg, respectively.

Abuse of quetiapine is increasingly recognised as an area of concern in clinical practice (Pierre et al., 2004; Waters and Joshi, 2007). In recent years strong evidence of inappropriate and problematic use (increased demand for vague indications, intra-nasal and intravenous use and diversion) of quetiapine in correctional settings has led one of the author’s (EM) to markedly limit its use in prisons.

Psychosis and psychotic spectrum disorders are relatively rare conditions in the general population. Yet AAPs, designed for the treatment of these conditions and licensed for few indications outside of psychosis, have become some of the most commonly prescribed medications in modern medicine. Off-label use of quetiapine has become particularly popular. The extent of its use contrasts sharply with the limited evidence base for its safety and efficacy. The reason for the popularity of AAPs and in particular the off-label use of quetiapine is not well understood and warrants urgent investigation. Part of the reason may be that quetiapine is a well tolerated sedative agent, without obvious short term side-effects such as the extrapyramidal problems associated with the predecessor typical agents. However, it is particularly important to bear in mind when prescribing this medication that the FDA declined to approve the licensing of quetiapine for the management of generalised anxiety disorder and major depressive disorder, citing concerns about the public health ramifications of exposing a larger population of individuals to the drug, noting that it is associated with long term metabolic problems, tardive dyskinesia and increased risk of sudden cardiac death (Kuehn, 2009).

In addition it is also clear that pharmaceutical companies have influenced prescriber choices and have strongly encouraged off label prescribing as it increases their total sales, despite this type of marketing not being permitted by the regulators (Kmietowicz, 2009). Pharmaceutical companies have extended sales into unapproved diseases, unapproved disease subtypes and unapproved drug doses; a series of recent publications based on the analysis of whistleblower complaints, and civil and criminal charges have exposed the use of systematic, sophisticated and far-reaching promotional methods, some of which may be resistant to external regulatory approaches (Kesselheim et al., 2011).