Over the last few years, we have seen more and more children and young people being prescribed antipsychotic drugs. The theory behind this increase is that the newer antipsychotic drugs have fewer side effects than the older typical antipsychotics.

However, some small and relatively short duration studies have shown that the newer drugs may also cause weight gain, metabolic disorders, prolactin changes, and extrapyramidal symptoms.

We have been waiting for a well conducted meta-analysis of these small studies and a research team from the Université Pierre et Marie Curie in Paris have come up trumps with a recent systematic review published in the Journal of Clinical Psychopharmacology.

The researchers searched a range of databases for published and unpublished trials from 1980-2010. They included prospective controlled clinical trials (randomised and non-randomised) of second-generation antipsychotics in children and adolescents that had a placebo or control group, were up to 12 weeks in length and reported on side effects. Studies were excluded if they had poor design, small sample sizes or incomplete reporting of key outcomes.

They found 41 trials to include in their analysis (including a total of 4,015 patients), which ranged from 3-12 weeks in length. The studies involved patients with a wide range of health conditions including schizophrenia, bipolar disorder, Tourette syndrome and conduct disorders.

The authors used Bayesian methods to meta-analyse the data and produce odds ratios and mean average effects.

The second-generation antipsychotics (SGAs) that were included in the review (and there patient numbers) were:

• Risperidone (n=1040)
• Aripiprazole (n=671)
• Quetiapine (n=446)
• Olanzapine (n=413)
• Ziprasidone (n=228)
• Clozapine (n=79)

Here’s what they found:

Compared with placebo, significant treatment-related increases were observed for a number of outcomes:

• Weight gain
  • Olanzapine (mean ± SD = 3.99 ± 0.42 kg; 95% credible interval, 3.17-4.84 kg)
  • Clozapine (2.38 ± 1.13 kg; 95% credible interval, 0.19-4.62 kg)
  • Risperidone (2.02 ± 0.32 kg; 95% credible interval, 1.39-2.66 kg)
  • Quetiapine (1.74 ± 0.38 kg; 95% credible interval, 0.99-2.5 kg)
  • Aripiprazole (0.89 ± 0.32 kg; 95% credible interval, 0.26-1.51 kg)
• Glucose levels
  • Risperidone (3.7 ± 1.36 mg/dL; 95% credible interval, 1.08-6.42 mg/dL)
  • Olanzapine (2.09 ± 1.08 mg/dL; 95% credible interval, 0.13-4.32 mg/dL)
• Cholesterol levels
  • Quetiapine (10.77 ± 2.14 mg/dL; 95% credible interval, 6.6-14.95 mg/dL)
  • Olanzapine (4.46 ± 1.65 mg/dL; 95% credible interval, 1.24-7.73 mg/dL)
• Triglyceride levels
  • Olanzapine (20.18 ± 5.26 mg/dL; 95% credible interval, 9.85-30.53 mg/dL)
  • Quetiapine (19.5 ± 3.92 mg/dL; 95% credible interval, 11.84-27.17 mg/dL)
• Hyperprolactinaemia
  • Risperidone (OR, 38.63; 95% credible interval, 8.62-125.6)
  • Olanzapine (OR, 15.6; 95% credible interval, 4.39-41.1)
  • Ziprasidone (OR, 9.35; 95% credible interval, 1.24-37.03)
• Extrapyramidal symptoms (EPS)
  • Ziprasidone (OR, 20.56; 95% credible interval, 3.53-68.94)
  • Olanzapine (OR, 6.36; 95% credible interval, 2.43-13.84)
  • Aripiprazole (OR, 3.79; 95% credible interval, 2.17-6.17)
  • Risperidone (OR, 3.71; 95% credible interval, 2.18-6.02)
• There was not enough data to include clozapine in the metabolic analyses, the prolactin analysis, and the EPS analysis
• All SGAs increased the risk of somnolence/sedation

The reviewers concluded:

Short-term metabolic effects and extrapyramidal symptoms are frequent in children treated with second-generation antipsychotics (SGAs). SGAs have distinct profiles of secondary effects, which should be considered in making treatment decisions.

This excellent piece of work begins to show us some of the unique side-effects profiles of the short-term use of second-generation antipsychotics in children and young people, which will be vital information for clinicians making treatment decisions for this population.

Link

Cohen D, Bonnot O, Bodeau N, Consoli A, Laurent C. Adverse effects of second-generation antipsychotics in children and adolescents: a Bayesian meta-analysis. J Clin Psychopharmacol. 2012 Jun;32(3):309-16. [PubMed abstract]