Thirty-five RCTs were included in the review (number of participants not stated). Overall, trial quality was considered to be high (32 trials received a rating of good or fair).
Risperidone (19 RCTs): Trial durations ranged from three weeks to six months and trial quality ranged from low to good. In trials shorter than 12 weeks, significant increased risk was found (compared with placebo) for weight gain (10 RCTs), body mass index, blood pressure (minor), extrapyramidal symptoms (seven RCTs) and elevated prolactin (three RCTs). Trials of 12 weeks or more demonstrated a significant increase in weight gain (three RCTs) when compared with placebo. Outcomes with only one RCT were also stated in the review.
Olanzapine (seven RCTs): Trial durations ranged from three to eight weeks and were of good quality. Compared with placebo, significant increased risk was found for weight gain (three RCTs), clinically significant weight gain, increased body mass index (two RCTs), extrapyramidal symptoms, increased blood pressure (minor) and elevation in triglycerides (two RCTs), total cholesterol (two RCTs), low-density lipoprotein cholesterol, insulin, prolactin (two RCTs), aspartate and alanine transaminase (two RCTs). Compared with risperidone, greater weight gain and metabolic laboratory abnormalities were found with olanzapine (two RCTs). Compared with clozapine, no significant between group differences were found in terms of weight gain and metabolic laboratory abnormalities.
Quetiapine (four RCTs): Trial durations ranged from six to eight weeks and were of good quality. Significant increased risk was found for weight gain (three RCTs), increase in blood pressure and heart rate (minor) and elevated triglycerides compared with placebo.
Clozapine (three RCTs): Trials durations ranged from six to 12 weeks and were of good quality. All comparisons were with an active comparator: olanzapine (two RCTs, see above) and haloperidol (one RCT). A greater proportion of patients receiving clozapine demonstrated a decrease in absolute neutrophil count compared with haloperidol. No change in either group in total score on the Abnormal Involuntary Movement Scale was found. In addition, a similar mean weight gain in both groups was also found.
Aripiprazole (five RCTs): Trial durations ranged from four to eight weeks and were of good quality. Significant increased risk was found for weight gain (five RCTs), clinically significant weight gain, increase in body mass index (three RCTs) and extrapyramidal symptoms compared with placebo (five RCTs). Evidence of metabolic laboratory abnormalities were not found and prolactin levels were found to decrease (four RCTs).
Ziprasidone (one RCT): No significant between group differences were observed for the main endpoints in this eight week trial in children with Tourette's syndrome.
Paliperidone: no trials meeting the inclusion criteria were found.