Review of risperidone for the treatment of pediatric and adolescent bipolar disorder and schizophrenia

Figures & data

Table 1 Summary of risperidone treatment studies in children and adolescents with bipolar disorder or schizophrenia

Author (Year)	Diagnosis	Design	Age range (N)	Duration	Efficacy/Effectiveness
(Armenteros et al 1997)	Schizophrenia	Open label treatment with risperidone	11–18 (10)	6 weeks	PANSS, BPRS, CGI assessments – PANSS (total score) improvement = 19.9 points (p < 0.001 vs baseline) – BPRS improvement = 12.2 points (p = 0.003 vs baseline) – CGI improvement = 1.4 points (p = 0.007 vs baseline)
(Zalsman et al 2003)	Schizophrenia	Open label treatment with risperidone	15.5–20 (11)	6 weeks	PANSS, BPRS, CGI assessments – PANSS (total score) improvement = 26.5 points (p < 0.01 vs baseline) – BPRS improvement = 13.5 points (p < 0.01 vs baseline) – CGI improvement = 1.46 (p < 0.001 vs baseline)
(Gothelf et al 2003)	Schizophrenia	Open label treatment with risperidone (n = 17), olanzapine (n = 19), or haloperidol (n = 7)	14–20.5 (43)	8 weeks	PANSS assessment – PANSS (total score) improvement at week 8 = 16.3 points (risperidone), 10 points (olanzapine), and 19.9 points (haloperidol) (p < 0.001 for effect of time); no differences between medication groups (p = 0.99)
(Mozes et al 2006)	Schizophrenia	Open label treatment with risperidone (n = 13) or olanzapine (n = 12)	9–14 (25)	12 weeks	PANSS, BPRS, CGAS assessments – PANSS (total score) improvement at week 12 = 30.4 points (risperidone; p < 0.001 vs baseline) and 42.3 points (olanzapine; p < 0.001 vs baseline) – BPRS improvement at week 12 = 18.2 points (risperidone; p < 0.001) and 23.9 (olanzapine; p < 0.001) – CGAS improvement at week 12 = 1.85 (risperidone; p < 0.001 vs baseline) and 2.42 (olanzapine; p < 0.001 vs baseline) – p > 0.24 for all risperidone vs olanzapine comparisons
(van Bruggen et al 2003)	Schizophrenia	Randomized, fiexible dose treatment of risperidone 1– 8 mg/day (n = 24) or olanzapine 5–30 mg/day (n = 18)	16–28 (42)	6 weeks	PANSS assessment – PANSS (total score) improvement at week 6 = 15.0 points (risperidone; p < 0.05 vs baseline) and 15.1 points (olanzapine; p < 0.05 vs baseline) – No significant differences between treatment groups
(Sikich et al 2004)	Schizophrenia spectrum (n = 26), and psychosis spectrum affective disorders (bipolar disorder or major depressive disorder with psychotic features; n = 24)	Randomized, double blind fiexible dose study of risperidone 4.0 ± 1.2 mg/day (n = 19), olanzapine 12.3 ± 3.5 mg/day (n = 16) or haloperidol 5.0 ± 2.0 mg/day (n = 15)	8–19 (50)	8 weeks	BPRS-C, CGI-I, and CPRS assessments – BPRS-C improvement = 27 points (risperidone; p = 0.0018 vs baseline), 28 points (olanzapine; p = 0.0018 vs baseline), and 16 points (haloperidol; p = 0.012 vs baseline) – CPRS (total) improvement = 54 points (risperidone; p = 0.0018 vs baseline), 52 points (olanzapine; p = 0.0036 vs baseline), and 40 points (haloperidol; p = 0.285 vs baseline) – CGI Improvement = 1.9 points (risperidone; p = 0.0018 vs baseline), 2.0 points (olanzapine; p = 0.0018 vs baseline), and 1.3 points (haloperidol p = 0.075 vs baseline) – No statistically significant differences between treatment groups for any outcomes
(Haas et al 2007)	Schizophrenia	Randomized, double blind, placebo- controlled study of placebo (n = 15), risperidone 1– 3 mg/day (n = 55), or risperidone 4– 6 mg/day (n = 51)	13–17 (160)	6 weeks	PANSS assessment – Placebo improvement = 8.9 points – Risperidone 1–3 mg/day improvement = 21.3 points – Risperidone 4–6 mg/day improvement = 21.2 points – Risperidone (either dose range) improvement 3 placebo (p < 0.001)
(Frazier et al 1999)	Bipolar disorder	Retrospective study of risperidone 1.7 ± 1.3 mg/day	4–17 (28)	0.25–34 months	CGI-Severity assessments – CGI-Severity Mania score improvement = 2.5 points (p < 0.01 vs baseline) – CGI-Severity Aggression score improvement = 2.1 points (p < 0.01 vs baseline)
(Biederman et al 2005a)	Bipolar disorder	Open-label study of risperidone 0.25–2.0 mg/day (n = 16) or olanzapine 1.25–10 mg/day (n = 15)	4–6 (31)	8 weeks	YMRS, BPRS, CDRS – YMRS score improvement = 18.8 points (risperidone; p < 0.05 vs baseline), 12.1 points (olanzapine; p < 0.05 vs baseline) – BPRS score improvement = 13.1 points (risperidone; p < 0.05 vs baseline), 8.9 points (olanzapine; p < 0.05 vs baseline) – CDRS score improvement = 12.7 points (risperidone; p < 0.05 vs baseline), 8.3 points (olanzapine; p = NS vs baseline) – p = NS between treatment groups for primary outcomes
(Biederman et al 2005b)	Bipolar disorder	Open label study of risperidone 0.25–4.0 mg/day	6–17 (30)	8 weeks	YMRS, BPRS, and CDRS assessments – YMRS score improvement = 14.4 points (p < 0.0001 vs baseline) – BPRS score improvement = 12.6 points (p = 0.0002 vs baseline) – CDRS score improvement = 10.2 points (p = 0.0001 vs baseline)
(Pavuluri et al 2004a)	Bipolar disorder	Open label study of risperidone 0.25–3 mg/day+ lithium 0.6–1.0 mEq/day or divalproex sodium 50–120 μg/mL	5–18 (37)	6 months	YMRS and CGI-BP assessments – YMRS score improvement = 23.53 (risperidone + lithium), 22.0 (risperidone + divalproex sodium) (p < 0.0001 for effect of time; p = NS between treatments) – CGI-BP score improvement = 3.56 (risperidone + lithium) and 3.82 (risperidone + divalproex sodium) (p < 0.001 for effect of time; p = NS between treatments)

Abbreviations: PANSS, (Positive and Negative Symptoms Scale); BPRS, (Brief Psychiatric Rating Scale); CGI, (Clinical Global Impression Scale – Improvement); CGAS, (Children’s Global Assessment Scale); BPRS-C, (Brief Psychiatric Rating Scale for Children); CPRS, (Children’s Psychiatric Rating Scale); YMRS, (Young Mania Rating Scale); CGI-BP, (Clinical Global Impression Scale for Bipolar Disorder); CDRS-R, (Child Depression Rating Scale-Revised).

Table 2 Weight gain

Reference	Study duration (wks)	Population	Sample size (# on risperidone if comparison trial)	Mean age (SD)	Mean maximum (or endpoint) daily dose (SD)	Weight gain kg (SD)
(Armenteros et al 1997)	6	Schizophrenia	10	15.10 (1.90)	6.6 (1.56)	4.85 (NA)
(Zalsman et al 2003)	6	Schizophrenia	11	17.27 (1.27)	3.14 (1.6)	8.66 (6.53)
(Ratzoni et al 2002)	12	Schizophrenia-spectrum and conduct disorder	21	17.21 (2.1)	3.2 (1.1)	3.9 (4.8)
(Mozes et al 2006)	12	Schizophrenia	13	10.71 (1.43)	1.62 (1.02)	4.45 (2.87)
(van Bruggen et al 2003)	6	Schizophrenia	26	20.6 (3.0)	4.4 (1.5)	4.5 (5.2)
(Sikich et al 2004)	8	Schizophrenia-spectrum and mood disorder with psychosis	19	14.6 (2.9)	4.0 (1.2)	4.9 (3.6)
(Biederman et al 2005b)	8	Bipolar	30	10.1 (2.5)	1.25 (1.5)	2.1 (2.0)
(Biederman et al 2005a)	8	Bipolar	16	5.3 (0.8)	1.4 (0.5)	2.2 (0.4)
(McDougle et al 1997)	12	Pervasive developmental disorders	18	10.2 (3.7)	1.8 (1.0)	8.1 (3.4)
(Malone et al 2002)	24	Autism	22	7.1 (3.3)	1.8 (1.1)	3.3 (1.7)
(Findling et al 2000)	10	Conduct disorder	10	9.2 (2.9)	0.75-1.5	4.2 (0.7)
(Gaffney et al 2002)	8	Tourette’s	9	10.4 (2.7)	1.5 (0.9)	2.1 (2.3)
(Aman et al 2002)	6	Disruptive Behaviorsa	55	8.7 (2.1)	2.2 (1.8)	1.16 (0.57)
(Snyder et al 2002)	6	Conduct and disruptive disordersb	53	8.6 (0.26)	0.98 (0.06)	2.2 (NA)
(McCracken et al 2002)	8	Autism	49	8.8 (2.7)c	1.8 (0.7)	2.7 (2.9)

a Disruptive behaviors: oppositional defiant disorder ± ADHD, conduct disorder ± ADHD, disruptive behavior NOS ± ADHD.

b Conduct disorder ± AHDD, oppositional defiant disorder ± ADHD

c Mean (SD) for entire study sample (risperidone + placebo).

Abbreviations: NA, Not available; NOS, Not otherwise specified.

Figure 1 Percent of subjects receiving anticholinergic medications in risperidone monotherapy trials of children and adolescents.

Table 3 Monitoring recommendations for risperidone (modified recommendations developed from ADA, APA [2004])

Measure	Baseline	1 Month	2 Months	3 Months	4 Months	Yearly
Personal/Family Hxa	X					X
Vitals	Every visit
BMI (ht/wt)	Every visit
Waist circumference	X					X
Blood pressure	X			X		X
Fasting plasma glucose	X			X		X
Fasting lipid profile	X			X		X
Prolactin (a.m. preferred)b	Xb			X
LFTs	X
CBC/dif	X
Electrolytes	X
AIMS/EPS	X	Increase frequency to monthly if exhibiting signs of tardive dyskinesia				X
Drug interactions	X	After dose changes or when considering additional agents

a Assess for history of cardiovascular disease, diabetes, dyslipidemia, obesity.

b Follow-up prolactin indicated if signs of breast tenderness, gynecomastia (males), menstrual changes/irregularities (not associated with normal development), or galactorrhea.

Abbreviations: Hx, history; Ht, height; Wt, weight; LFTs, liver function tests; CBC/dif, complete blood count with differential.

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