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.
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).
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:
- 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
- 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
- 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
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).
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.
@Mental_Elf too right they can 3stone i have put on(:o(
Atypical antipsychotics can lead to weight gain in children and adolescents, but more evidence needed about me… http://t.co/hqG8X1iGiN
My latest blog post for @Mental_Elf on weight gain in children and adolescents taking atypical antipsychotics: http://t.co/GVBa6yNyfo
RT @ellyob: My latest blog for @Mental_Elf on weight gain in children and adolescents taking atypical antipsychotics: http://t.co/EXXdXChuuH
SR finds statistically significant increase in weight in young people taking risperidone, olanzapine or aripiprazole http://t.co/4MVAeeOuHI
@Mental_Elf I was severely bulimic and was put on Olanzapine. Brutal.
Olanzapine was associated with most weight gain, then risperidone, then aripiprazole. #antipsychotics #adolescents http://t.co/4MVAeeOuHI
@Mental_Elf @MarkOneinFour over 2004-9 NHS atypical prescribing increased 49% to £59.2M. Have atypicals/SGAs been overrated? #mentalhealth
Read @ellyob blog about a systematic review on atypical antipsychotics and weight gain in children & young people http://t.co/4MVAeeOuHI
Pls RT @YoungMindsUK Atypical antipsychotics can lead to weight gain in children & adolescents, says new review http://t.co/4MVAeeOuHI
Don’t miss: Atypical antipsychotics can lead to weight gain in children and adolescents, says systematic review http://t.co/4MVAeeOuHI
@Mental_Elf don’t I know it. My son has gained 3 stone!! :-/
@Mental_Elf Adults also have a problem with weight gain on these medications. Stabilise psychosis but some depressed because of weight gain
Mental Elf: Atypical antipsychotics can lead to weight gain in children and adolescents, but more evidence needed… http://t.co/IIZm3ILEPR
What do studies show for adults taking this sort of medication ? My experience of patients in hospital complaining to psychiatrists that they (the patients) are putting on weight is that the psychiatrists do nothing.