Use of quetiapine in child and adolescent populations – Response to letter from Dr Lambe

We are grateful to be given an opportunity to comment on the letter by Dr Lambe (Lambe, 2013) in response to our previous correspondence (Monasterio and McKean, 2013), which outlined our concern about the extensive off-label use of quetiapine in primary and specialist psychiatric care, despite the limited evidence base for its safety and efficacy (Monasterio and McKean, 2011).

Dr Lambe acknowledges that there are many potential adverse effects associated with the use of quetiapine, particularly in child and adolescent psychiatry, but, despite this, comments that: ‘off-label prescribing of quetiapine for excessive anxiety and insomnia is often the best alternative, as long as one monitors for side effects’ (Lambe, 2013).

In considering the appropriateness of off-label prescribing of atypical antipsychotic (AAP) medications in child and adolescent psychiatry, we encourage close attention to recent findings in the literature, which indicate that there has been a particularly rapid expansion in the use of these agents in this age group for reasons which remain largely unknown.

• An analysis of drug dispensing data from community pharmacies in The Netherlands found that between 1997 and 2005 the use of antipsychotics increased from 3.0 to 6.8 per thousand for youths to 19 years of age; the use of AAPs increased almost ninefold. The increase in AAPs was most pronounced for 5–9 year olds (almost 10-fold) and for 10–14 year olds (almost 12-fold). The median duration of AAP use was 2.9 years and 5.1 years for 5–9 year olds and 10-14 year olds respectively. (Kalverdijk et al., 2008).

• An analysis of Medical Expenditures Panel Survey (MEPS) data on non-institutionalized individuals in the USA found that the proportion of antipsychotic users who were under age 18 doubled between 1996/1997 and 2004/ 2005 from 7% to 15% of all users (Domino and Swartz, 2008). Analysis of data from the National Ambulatory Medical Care Survey (NAMCS), which collects information from office-based physician practices, found that the annual number of US office visits by those under age 21 that included prescription of an antipsychotic medication jumped more than fivefold from 1993/1995 to 2002 (Olfson et al., 2006). Amongst privately insured 2–5-year-old children in the USA, the rate of antipsychotic use doubled in the period of 1999/2001 to 2007; this occurred at the same time that the use of antidepressants decreased (1.6 times less common in 2007) in this age group (Olfson et al., 2010). Data from long-term US trends in office-based physician use of antipsychotic medications found that there was an eightfold increase in the number of treatment visits for children between 1995 and 2008 (Alexander et al., 2011). In British Columbia, there has been a 10-fold increase in the prescription of AAPs to children under 14 between 1997 and 2007 (Panagiotopoulos et al., 2010).

• Data supplied by PHARMAC (the pharmaceutical funding agency in New Zealand) indicates that there has been a 56% increase in the use of antipsychotic medications in 10–19 year olds from 2008 to 2012 in New Zealand.

• Children and adolescents may be at a higher risk of antipsychotic-associated weight gain, as well as sedation and movement disorders, when compared to adults (McKinney and Renk, 2011). Among 257 children taking second-generation antipsychotics for the first time, weight increased during the first 12 weeks of treatment. Among subjects taking olanzapine, the mean weight gain was 8.5 kg, or 18.7 pounds; for those taking quetiapine, it was 6.1 kg (13.4 pounds); for risperidone, 5.3 kg (11.7 pounds); for aripiprazole, 4.4 kg (9.7 pounds) (Correll et al., 2009). The study also found olanzapine to significantly worsen glucose and lipid parameters, and quetiapine and risperidone to significantly increase triglycerides (Correll et al., 2009). Moreover, it is important to note that children from lower socioeconomic groups may be at elevated risk for metabolic side effects because ‘the risk of childhood obesity is inversely related to socioeconomic status, and low-income children who are already at high risk for obesity and related metabolic disorders may be especially vulnerable to the adverse effects of weight gain’ (Crystal et al., 2009).

• A recent literature review summarizing randomized controlled evidence for the efficacy of AAPs in children under 18 found no evidence of efficacy for these agents in the management of anxiety, depression or insomnia, but clear evidence for a wide range of metabolic complications (Panagiotopoulos et al., 2010).

• Pharmaceutical companies have conducted carefully considered advertising campaigns to illegally promote AAPs to children (as well as the elderly, veterans and prisoners). For example, AstraZeneca settled for $520 million, but denied misconduct, after it was sued by the US Government for illegally promoting the use of AAPs in children (Wilson, 2010). Documents unearthed as part of the legal process showed that the company tried to hide the risks of diabetes and weight gain associated with quetiapine. Positive studies were hyped, the documents show; negative ones were filed away (Wilson, 2010). New Zealand is one of only two developed countries (the other is the USA) that permit direct to consumer pharmaceutical advertising, which includes product claims via television, print (magazines, newspapers), radio, the Internet, and other forms of mass media.

The authors have already provided a critique of the trends of off-label use of AAPs across all patient groups over the past 15 years, highlighting the disconnect between their popularity, the evidence base for common off-label uses and their safety (McKean and Monasterio, 2012). In this context, children and adolescents represent a particularly vulnerable group with limited capacity to engage in shared decision-making or provide informed consent, and for whom long-term safety and efficacy is far from established. For any treatment intervention, proven benefits define the parameters of acceptable risks; it is therefore incumbent on the prescriber to ensure that the benefits of AAP treatment in children outweigh their risks. In most instances this has not been established with any degree of confidence.

See Letter by Lambe, 2013, 47(11): 1086.