Table 1.

Characteristics of Studies Included in the Review

Authors	Drugs, Mean Daily Dose (SD)	Duration	Participants	Effectiveness	Adverse Effects	Limitations
Pool et al30	Loxapine, 87.5 mg; haloperidol, 9.8 mg; placebo	4 weeks	N = 75, mean age: ∼15.5 years	Both treatments significantly reduced BPRS total ratings compared with placebo. No significant differences observed between active treatment groups.	EPS (eg, muscle rigidity) noted in 19 (73%) of 26 receiving loxapine and 18 (72%) of 25 subjects receiving haloperidol. Sedation also problematic.	Short duration of treatment; small sample size
Realmuto et al31	Thiothixene, 16.2 mg; thioridazine, 178 mg	6 weeks	N = 21, mean age: ∼15.5 years	Both treatments significantly reduced BPRS total scores. Clinical improvement noted within the first 7 days of treatment.	Marked sensitivity to sedative effects of medication, dose reductions required for both medications	Short duration of treatment, small sample size
Spencer et al29	Crossover design: haloperidol, 1.8 mg, vs placebo	6 weeks	N = 16, mean age (SD): ∼8.9 years	CGI-I much/very much improved: 12 (75%) of 16; marked reduction in severity of persecutory ideation and hallucinations	Sedation observed at optimal doses	Short duration of treatment, small sample size
Kumra et al69	Clozapine, 176 mg (149); haloperidol, 16 mg (8)	6 weeks	N = 21, mean age (SD): 14.0 ± 2.3 years	Clozapine > haloperidol in terms of positive (SAPS total) and negative symptoms (SANS total)	One third of clozapine-treated patients discontinued treatment prematurely due to neutropenia or seizures	Short duration of treatment
Sikich et al64	Risperidone, 4 mg (1.2); olanzapine, 12.3 mg (3.5); haloperidol, 5.0 mg (2)	8 weeks	N = 50, mean age (SD): 14.7 ± 2.7 years; broad range of children with psychotic disorders included	All treatments significantly reduced BPRS-C total scores from baseline to end point; CGI-I much/very much improved and ≥ 20% BPRS-C reduction: 74% risperidone, 88% olanzapine, 54% haloperidol	Prevalence of extrapyramidal symptoms and weight gain higher and more severe in youth compared with published data from adult studies	Short duration of treatment, differences in the diagnosis across the treatment groups, concomitant use of antidepressants and/or mood stabilizers
Shaw et al68	Clozapine, 327 mg (113); olanzapine, 18.1 mg (4.3)	8 weeks	N = 25, mean age: ∼12 years	Clozapine > olanzapine with respect to improvement in negative symptoms (SANS)	Marked weight gain at 4 kg during the 8-week trial noted in both groups, at 2-year follow-up, 6 (40%) of 15 patients were observed to have dyslipidemia	Short duration of treatment, study powered to detect only large treatment effects
Kumra et al70	Clozapine, 403.1 mg (201.8); olanzapine, 26.2 mg (6.5)	12 weeks	N = 39, mean age (SD): 15.6 (2.1)	Clozapine > “high-dose” olanzapine with respect to improvement in negative symptoms (SANS) for 12 weeks, CGI much/very much improved and ≥30% BPRS reduction: 66% clozapine, 33% olanzapine	Five (13%) of 39 patients (3 clozapine, 2 olanzapine) gained >7% of their baseline body weight; high incidence of dyslipidemia and prediabetes seen with both drugs	Short duration of treatment, small sample size
Robb et al,58 Findling et al57	Aripiprazole, 10 mg; aripiprazole, 30 mg; PBO	6 weeks	N = 302, mean age: 15.5 years (range, 13–17)	Aripiprazole (10-mg and 30-mg doses) > PBO in terms of improvement from baseline to end point on the PANSS Total Score compared with placebo (−26.7 and −28.6, respectively; placebo, -21.2; Last Observation Carried Forward (LOCF)	Mild to moderate severity of spontaneously reported Adverse Events (AEs): extrapyramidal disorder, somnolence, akathisia; mean change in weight from baseline was minimal (10 mg, no change; 30 mg, 0.2 kg)	No data available from drug-naive subjects to assess whether aripiprazole is truly “weight neutral”; high placebo response rate
Haas et al52	Risperidone, 1–3 mg; risperidone, 4–6 mg; PBO	6 weeks	N = 160, mean age (SD): 15.6 years (1.3)	Both risperidone groups > PBO on the PANSS Total Score (risperidone 1- mg: −19.9 and risperidone 4–6 mg: −20.7, respectively; placebo, −7.8; LOCF)	Higher dose risperidone group had a greater incidence of EPS, dizziness, and hypertonia compared with lower dose group	Short duration of treatment
Kryzhanovskaya et al50	Olanzapine, 11.1 mg (4.0); PBO	6 weeks	N = 107, mean age (SD): 16.2 years (1.3)	Olanzapine > PBO in terms of improvement from baseline to end point on the BPRS-C (P = .003) and CGI-S (P = .004), respectively. Treatment response rate was not significantly different between olanzapine (37.5%) and PBO (25.7%).	Mean olanzapine-induced weight gain (4.3 ± 3.3 kg) higher and more severe in youth compared with adult studies	Short duration of treatment, high placebo response rate

Note: EPS, Extrapyramidal side effects; BPRS, Brief Psychiatric Rating Scale; CGI-I, Clinical Global Impression—Improvement Scale; CGI-S, Clinical Global Impression—Severity of Illness; BRPS-C, Brief Psychiatric Rating Scale for Children; SAPS, Scale for the Assessment of Positive Symptoms, SANS, Scale for the Assessment of Negative Symptoms; PBO, placebo; PANSS, Positive and Negative Syndrome Scale.