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Some antipsychotics better than others for young people: review

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Despite widespread use of antipsychotics in children, evidence regarding the comparative benefits and harms of first-generation (FGAs) and second-generation antipsychotics (SGAs) are “limited,” conclude the authors of a review published February 20 in Pediatrics.

The analysis does show that some SGAs have a better side effect profile that others, first author Jennifer C. Seida, MPH, from the Alberta Research Centre for Health Evidence, University of Alberta in Edmonton and colleagues say.

In 1996, about 9 of every 1,000 children in the United States were prescribed an antipsychotic; by 2002 that number had risen to 39. “Prescribing practices have been under ongoing scrutiny due to the marked increase in on-label and off-label use, concerns regarding medication safety, and the comparative efficacy of available medications,” the authors say.

Several recent systematic reviews have looked at the effect of antipsychotic drug therapy for specific indications in children. What makes their review different, they say, is that it examines the evidence on both effectiveness and safety of all FDA-approved FGAs and SGAs in children, adolescents, and young adults aged 24 or younger across a variety of psychiatric and behavioral conditions.

The researchers identified and included in their analysis 62 randomized clinical trials, two non-randomized clinical trials and 17 cohort studies. They report that 90% of the RCTs and both non-RCTs had a high risk of bias. Most had inadequate sequence generation, allocation concealment, blinding and incomplete outcome data. Seventy-eight percent of the trials were funded by industry.

For most comparisons, the strength of evidence was “low or insufficient,” the authors say, particularly for FGAs vs SGAs and FGAs vs other FGAs. They did find moderate strength of evidence that olanzapine (Zyprexa) caused more dyslipidemia and weight gain, but fewer prolactin-related events, than risperidone (Risperdal) and that olanzapine caused more weight gain than quetiapine (Seroquel).

[Olanzapine, risperidone and quetiapine are currently approved in the US for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adolescents aged 13-17 years old. Risperidone and quetiapine are approved as an option for manic or mixed episodes of bipolar I disorder in children as young as age 10.]

There was also moderate strength of evidence that SGAs “consistently” resulted in greater symptom improvement in disruptive behavior disorders (behaviors, clinical global impressions [CGI]), bipolar disorder (CGI), schizophrenia (CGI, positive and negative symptoms), and tic severity than placebo.

As expected, say the researchers, SGAs posed a greater risk for adverse events compared with placebo. However, several “patient-important” outcomes, such as health-related quality of life, social and school performance, and legal involvement, were rarely assessed and had insufficient strength of evidence.

The researchers note in their report that the “rapid rise in the use of SGAs reflected the expectation of greater safety and tolerability compared with FGAs, particularly with respect to extrapyramidal symptoms. The low strength of evidence in this review regarding FGAs versus SGAs makes it difficult to draw conclusions.”

“Among SGAs, the tolerability profile appears to vary by drug, particularly with regard to endocrine effects (ie, prolactin-related events) (favoring olanzapine), lipid effects (ie, dyslipidemia) (favoring risperidone), and body weight (favoring quetiapine and risperidone).”

What’s needed, say the researchers, are high-quality trials that focus on comparisons that reflect everyday clinical practice decisions. “This includes more head-to-head comparisons of different antipsychotics, both between and within classes, and different doses to define clear parameters on the efficacy, safety, and tolerability of this pharmacotherapy for children and adolescents,” they write.

In their opinion, “One of the greatest priorities for future research is the systematic evaluation of adverse events given that such events may have greater long-term impact in children. A high proportion of the studies reported some adverse events; however, few systematically evaluated harms using standardized measures.”


Antipsychotics for Children and Young Adults: A Comparative Effectiveness Review

Pediatrics 2012;129:e771-e784.