Atypical (second-generation) antipsychotics are used to treat a variety of psychiatric conditions. Although they have fewer side effects than first-generation antipsychotics, weight gain and other metabolic problems (such as high blood pressure and diabetes) remain common side effects of taking atypical antipsychotic medication (Mind, 2012).

The Mental Elf has previously blogged about a Canadian report on the optimal use of atypical antipsychotics in children and adolescents with schizophrenia.

This systematic review looks at the effects of atypical antipsychotics on weight gain and other metabolic factors. In their meta-analysis, the authors found a statistically significant increase in weight in children and adolescents taking risperidone, olanzapine or aripiprazole.

Methods

Authors carried out thorough and systematic searches across a range of databases to identify published and on-going randomised controlled trials examining the metabolic effects of atypical antipsychotic use in those aged 18 years and under. The quality of studies was assessed using the Jadad score, with the poorest quality studies excluded from their analysis. A random effects model was used in the meta-analysis of the 21 studies reporting weight outcomes (a total of 2,455 patients). Of the included studies 14 investigated risperidone, 3 olanzapine and 4 aripiprazole, (all compared with placebo).

Results

Here’s what they found for weight gain:

• Risperidone – mean weight gain 1.77kg (95% CI 1.35-2.20, p=<0.00001)
• Olanzapine – mean weight gain 3.45kg (95% CI 2.93-3.98, p=<0.00001)
• Aripiprazole – mean weight gain 0.94kg (95% CI 0.65-1.24, p=<0.00001)

The reporting of the metabolic effects was inconsistent, therefore a meta-analysis was not possible. Where data was reported the results showed:

• Risperidone
  • Six out of fourteen studies reported no data on metabolic outcomes
  • Lipids – only two studies reported data, with both indicating no change
  • Prolactin – a statistically significant increase in 5 studies (although one study showed statistical significance only in boys); a dose-dependent significant increase in 2 studies and a significant increase in the remaining studies (authors report that it was unclear in these three studies whether it was statistical or clinical significance being reported)
  • Glucose – two studies reported no change

• Olanzapine
  • One out of 3 studies reported no data on metabolic outcomes
  • Lipids – statistically significant increase reported in two studies
  • Prolactin – a statistically significant increase in two studies
  • Glucose – one study reported a statistically significant increase, the other no change

• Aripiprazole
  • One out of 4 studies reported no data on metabolic outcomes
  • Lipids – three studies reported no change
  • Prolactin – three studies reported a statistically significant decrease
  • Glucose – three studies reported no change

Conclusions

The authors concluded:

Olanzapine, risperidone, and aripiprazole were all associated with statistically significant weight gain. Olanzapine was associated with the most weight gain and aripiprazole the least. For the secondary outcome, although a number of active comparator trials were identified, data were not available for meta-analysis and were too limited to allow firm conclusions to be drawn.

This systematic review, consistent with other published reviews, highlights the impact of weight gain associated with prescribing atypical antipsychotics to children and adolescents on their mental and physical health.

Although firm conclusions could not be drawn from the review of the metabolic impact of these drugs, the review draws attention to the lack of evidence and the methodological weaknesses (small sample sizes, short treatment duration) of what little evidence is available.

A note on off-label prescribing

This review also highlights the important issue of off-label prescribing in children and young people. Off-label prescribing is where a drug is given outside of the terms of its licence, this may mean it is prescribed for a different condition or that it is given to a different group of patients – such as children (MHRA, 2009).

Because the process of developing and licensing drugs is expensive, and the paediatric market is smaller than the adult market, developing drugs specifically in children is understandably of a lower commercial interest to drug companies (MHRA, 2013). Although guidance exists to inform off-label prescribing (RCPCH, 2010), the extent of off-label psychiatric prescribing in children in the UK is unknown (RCPsych, 2007).

Links

Almandil NB, Liu Y, Murray ML, Besag FM, Aitchison KJ, Wong IC. Weight gain and other metabolic adverse effects associated with atypical antipsychotic treatment of children and adolescents: a systematic review and meta-analysis. Paediatr Drugs. 2013 Apr;15(2):139-50. doi: 10.1007/s40272-013-0016-6. [PubMed abstract]

Making sense of antipsychotics (PDF). Mind, 2012

Off-label or unlicensed use of medicines: prescribers’ responsibilities. MHRA, 2009.

Medicines for children. MHRA, 2013.

Use of licensed medicines for unlicensed applications in psychiatric practice (PDF). Royal College of Psychiatrists, 2007.

The use of unlicensed medicines or licensed medicines for unlicensed applications in paediatric practice (PDF). Royal College of Paediatrics and Child Health, 2010.