Background
Methods
Search strategy
Study selection
Data extraction and quality assessment
Data synthesis and analysis
Results
Evidence from RCTs
Study | Diagnosis (criteria for diagnosis) | Treatment(s) | Treatment duration, weeks | Inclusion criteria |
---|---|---|---|---|
Randomized controlled trials | ||||
Findling et al. 2012 [21] | Schizophrenia (DSM-IV-TR + K-SADS-PL) | Quetiapine 400 mg/day Quetiapine 800 mg/day Placebo | 6 | Inpatients or outpatients aged 13–17 years; PANSS ≥ 60 |
Findling et al. 2008 [22] | Schizophrenia (DSM-IV) | Aripiprazole 10 mg/day Aripiprazole 30 mg/day Placebo | 6 | Aged 13–17 years; PANSS ≥ 70 |
Haas et al. 2009a [23] | Schizophrenia (DSM-IV + K-SADS-PL) | Risperidone 1–3 mg/day Risperidone 4–6 mg/day Placebo | 6 | Aged 13–17 years; PANSS 60–120 |
Haas et al. 2009b [26] | Schizophrenia (DSM-IV + K-SADS-PL) | Risperidone 1.5–6 mg/day Risperidone 0.15–0.6 mg/day | 8 | Aged 13–17 years; PANSS 60–120 |
Kryzhanovskaya et al. 2009 [24] | Schizophrenia (DSM-IV-TR) | Olanzapine 2.5–20 mg/day Placebo | 6 | Aged 13–17 years; BPRS ≥ 35 |
Singh et al. 2011 [25] | Schizophrenia (DSM-IV + K-SADS-PL) | Paliperidone 1.5 mg/day Paliperidone 3–6 mg/day Paliperidone 6–12 mg/day Placebo | 6 | Aged 12–17 years; Weight ≥ 29 kg; PANSS 60–120 |
Observational studies | ||||
Duval et al. 2008 [27] | Schizophreniform disorder (DSM-IV) | Risperidone 1–6 mg/day | 3 | Aged 14–18 years |
Kumra et al. 2008 [28] | Schizophrenia, schizoaffective disorder (K-SADS-PL) | Clozapine 25–900 mg/day Olanzapine 30 mg/day | 12 | Aged 10–18 years |
Pandina et al. 2012 [29] | Schizophrenia (DSM-IV + K-SADS-PL) | Risperidone 2–6 mg/daya | 24 or 48a | Aged 13–17 years; PANSS 40–120 |
Ruan et al. 2010 [30] | Schizophrenia (DSM-IV-TR) | Risperidone 25–50 mg biweekly | 24 | Aged 13–18 years; PANSS ≤ 80 |
Schimmelmann et al. 2007 [31] | Schizophrenia, schizoaffective and schizophreniform disorder (DSM-IV) | Quetiapine 200–800 mg/day | 12 | Aged 12–17 years; PANSS ≥ 60 |
Baseline patient characteristics
Study | N (ITT) | Treatment | Age, mean (SD) | Male, n (%) | Caucasian, n (%) | Baseline prolactin, both sexes, (ng/mL), mean (SD) | Baseline prolactin, males, (ng/mL), mean (SD) | Baseline prolactin, females, (ng/mL), mean (SD) | Previous antipsychotic use, n (%) | Proportion diagnosed as paranoid schizophrenia, n (%) | Baseline PANSS score, mean (SD) |
---|---|---|---|---|---|---|---|---|---|---|---|
Randomized controlled trials | |||||||||||
Findling et al. 2012 [21] | 73 | Quetiapine 400 mg/day | 15.5 (1.3) | 43 (58.9) | 45 (61.6) | 20.8 (17.0) | NR | NR | NR | NR | 96.2 (17.7) |
74 | Quetiapine 800 mg/day | 15.5 (1.3) | 44 (59.5) | 44 (59.5) | 18.1 (20.1) | NR | NR | NR | NR | 97.0 (15.3) | |
73 | Placebo | 15.3 (1.4) | 42 (57.5) | 46 (63.0) | 28.7 (29.1) | NR | NR | NR | NR | 96.7 (18.0) | |
Findling et al. 2008 [22] | 100 | Aripiprazole 10 mg/day | 15.6 (1.3) | 45 (45.0) | 5]4 (54.0) | NR | NR | NR | 53 (53.0) | NR | 93.7 (15.7) |
102 | Aripiprazole 30 mg/day | 15.4 (1.4) | 65 (63.7) | 62 (60.8) | NR | NR | NR | 47 (46.1) | NR | 94.9(15.5) | |
100 | Placebo | 15.4 (1.4) | 61 (61.0) | 64 (64.0) | NR | NR | NR | 46 (46.0) | NR | 95.0(15.5) | |
Haas et al. 2009a [23] | 55 | Risperidone 1–3 mg/day | 15.7 (1.3) | 30 (54.5) | 33 (60.0) | 29.6 (38.2) | 21.6 (15.2) | 39.2 (53.0) | NR | 38 (69.1) | NR |
51 | Risperidone 4–6 mg/day | 15.7 (1.3) | 37 (72.5) | 24 (47.1) | 24.1 (23.0) | 22.7 (19.9) | 27.9 (28.3) | NR | 34 (66.7) | NR | |
54 | Placebo | 15.5 (1.4) | 35 (64.8) | 27 (50.0) | 22.6 (23.3) | 21.5 (21.1) | 24.6 (25.9) | NR | 38 (70.4) | NR | |
Haas et al. 2009b [26] | 125 | Risperidone 1.5–6 mg/day | 15.6 (1.3) | 65 (52.0) | 104 (83.2) | NR | NR | NR | NR | 83 (66.4) | 96.4 (15.4) |
132 | Risperidone 0.15–0.6 mg/day | 15.6 (1.3) | 80 (60.6) | 111 (84.9) | NR | NR | NR | NR | 92 (69.7) | 93.3 (14.1) | |
Kryzhanovskaya et al. 2009 [24] | 72 | Olanzapine 2.5–20 mg/day | 16.1 (1.3) | 51 (70.8) | 52 (72.2) | 15.6 (12.3) | NR | NR | 51 (70.8) | NR | 95.3 (14.1) |
35 | Placebo | 16.3 (1.6) | 24 (68.6) | 25 (71.4) | 18.7 (16.2) | NR | NR | 30 (85.7) | NR | 95.5 (14.1) | |
Singh et al. 2011 [25] | 54 | Paliperidone 1.5 mg/day | 15.1 (1.5) | 30 (55.6) | 35 (64.8) | 25.1 (32.8) | 14.7 (14.5) | 38.0 (45.5) | 47 (87.0) | NR | 91.6 (12.5) |
48 | Paliperidone 3–6 mg/day | 15.3 (1.6) | 31 (64.6) | 34 (70.8) | 26.6 (43.2) | 16.1 (1.8) | 45.67 (71.0) | 44 (91.7) | NR | 90.6 (14.0) | |
47 | Paliperidone 6–12 mg/day | 15.5 (1.6) | 33 (70.2) | 32 (68.1) | 20.8 (22.3) | 18.2 (13.7) | 26.88 (33.9) | 40 (85.1) | NR | 91.5 (13.9) | |
51 | Placebo | 15.7 (1.4) | 23 (45.1) | 35 (68.6) | 24.5 (30.5) | 13.6 (13.6) | 33.43 (38.5) | 48 (94.1) | NR | 90.6 (12.1) | |
Observational studies | |||||||||||
Duval et al. 2008 [27] | 16 | Risperidone 1–6 mg/day | 15.7 (1.3) | 10 (62.5) | 16 (100.0) | 16 (9) | NR | NR | NR | NR | NR |
Kumra et al. 2008 [28] | 14 | Clozapine 25–900 mg/day | 15.3 (2.3) | 5 (35.7) | 1 (7.1) | NR | NR | NR | 14 (100.0) | NR | NR |
19 | Olanzapine 30 mg/day | 15.6 (1.7) | 11 (57.9) | 5 (26.3) | NR | NR | NR | 19 (100.0) | NR | NR | |
Pandina et al. 2012 [29] | 48 | Risperidone 2–6 mg/day (treatment-naïve) | 15.4 (1.4) | 30 (62.5) | 25 (52.1) | 17.0 (20.4) | 18.6 (24.7) | 14.3 (6.7) | NR | 33 (68.8) | 84.7 (16.8) |
292 | Risperidone 2–6 mg/day (treatment-experienced) | 15.5 (1.7) | 178 (61.0) | 218 (74.7) | 53.4 (33.9) | 40.4 (26.3) | 73.6 (43.0) | 292 (100.0) | 195 (66.8) | 72.1 (19.4) | |
50 | Risperidone 2–6 mg/day (open-label) | 15.5 (1.4) | 30 (60.0) | 42 (84.0) | 73.6 (44.9) | 55.8 (25.3) | 100.3 (62.3) | NR | 35 (70.0) | 83.9 (13.5) | |
Ruan et al. 2010 [30] | 31 | Risperidone 25–50 mg biweekly | 15.9 (3.3) | 13 (41.9) | NR | 54.8 (17.7) | NR | NR | NR | 24 (77.4) | 57.8 (1.8) |
Schimmelmann et al. 2007 [31] | 56 | Quetiapine 200–800 mg/day | 15.9 (1.3) | 38 (67.9) | 47 (83.9) | 15.9 (23.3) | 12.6 (6.3) | 22.9 (41.4) | 13 (23.2) | NR | 91.5 (17.2) |
Outcomes
Study | N (ITT) | Treatment | Prolactin-related adverse events, n (%) | Gynecomastia/ galactorrhea, n (%) | Amenorrhea/ dysmenorrhea, n (%) | Impotence/decreased libido, n (%) |
---|---|---|---|---|---|---|
Randomized controlled trials | ||||||
Findling et al. 2012 [21] | 73 | Quetiapine 400 mg/day | NR | NR | NR | NR |
74 | Quetiapine 800 mg/day | NR | NR | NR | NR | |
73 | Placebo | NR | NR | NR | NR | |
Findling et al. 2008 [22] | 100 | Aripiprazole 10 mg/day | 0 (0.0) | NR | NR | NR |
102 | Aripiprazole 30 mg/day | 0 (0.0) | NR | NR | NR | |
100 | Placebo | 0 (0.0) | NR | NR | NR | |
Haas et al. 2009a [23] | 55 | Risperidone 1–3 mg/day | 0 (0.0) | NR | NR | NR |
51 | Risperidone 4–6 mg/day | 0 (0.0) | NR | NR | NR | |
54 | Placebo | 0 (0.0) | NR | NR | NR | |
Haas et al. 2009b [26] | 125 | Risperidone 1.5–6 mg/day | 7 (5.6) | 3 (2.4) | 1 (1.0) | NR |
132 | Risperidone 0.15–0.6 mg/day | 2 (1.5) | 2 (1.5) | 0 (0.0) | NR | |
Kryzhanovskaya et al. 2009 [24] | 72 | Olanzapine 2.5–20 mg/day | NR | NR | NR | NR |
35 | Placebo | NR | NR | NR | NR | |
Singh et al. 2011 [25] | 54 | Paliperidone 1.5 mg/day | NR | NR | NR | NR |
48 | Paliperidone 3–6 mg/day | NR | NR | NR | NR | |
47 | Paliperidone 6–12 mg/day | NR | NR | NR | NR | |
51 | Placebo | NR | NR | NR | NR | |
Observational studies | ||||||
Duval et al. 2008 [27] | 16 | Risperidone 1–6 mg/day | NR | NR | NR | NR |
Kumra et al. 2008 [28] | 14 | Clozapine 25–900 mg/day | NR | NR | NR | NR |
19 | Olanzapine 30 mg/day | NR | NR | NR | NR | |
Pandina et al. 2012a [29] | 48 | Risperidone 2–6 mg/day (treatment-naïve) | 36 (9.3) | 14 (3.6) | 3 (1.0) | 1 (<0.5) |
292 | Risperidone 2–6 mg/day (treatment-experienced) | |||||
50 | Risperidone 2–6 mg/day (open-label) | |||||
Ruan et al. 2010 [30] | 31 | Risperidone 25–50 mg biweekly | 5 (16.1) | 2 (6.5) | 3 (9.7) | NR |
Schimmelmann et al. 2007 [31] | 56 | Quetiapine 200–800 mg/day | NR | 3 (5.4) | 4 (7.1) | 9 (16.1) |
Study | Treatment | Time point, weeks | Prolactin change, both sexes (ng/mL), mean (SD) | Prolactin change, males (ng/mL), mean (SD) | Prolactin change, females (ng/mL), mean (SD) |
---|---|---|---|---|---|
Randomized controlled trials | |||||
Findling et al. 2012 [21] | Quetiapine 400 mg/day | 6 | −10.6 (16.1) | −9.22 (14.4) | −12.4 (18.5) |
Quetiapine 800 mg/day | 6 | −7.8 (26.5) | −3.7 (11.6) | −14.0 (39.1) | |
Placebo | 6 | −18.3 (28.8) | −6.53 (15.1) | −33.9 (34.9) | |
Findling et al. 2008 [22] | Aripiprazole 10 mg/day | 6 | −11.9 (23.3) | NR | NR |
Aripiprazole 30 mg/day | 6 | −15.1 (26.9) | NR | NR | |
Placebo | 6 | −8.5 (24.2) | NR | NR | |
Haas et al. 2009a [23] | Risperidone 1–3 mg/day | 6 | 25.5 (33.5) | 16 (23.7) | 36.9 (41.3) |
Risperidone 4–6 mg/day | 6 | 49.5 (46.9) | 26.4 (28.5) | 77.3 (60.8) | |
Placebo | 6 | −5.9 (24.9) | −3.2 (24.8) | −9.2 (24.1) | |
Haas et al. 2009b [26] | Risperidone 1.5–6 mg/day | 8 | NR | NR | NR |
Risperidone 0.15–0.6 mg/day | 8 | NR | NR | NR | |
Kryzhanovskaya et al. 2009 [24] | Olanzapine 2.5–20 mg/day | 6 | 8.8 (17.9) | NR | NR |
Placebo | 6 | −3.3 (14.8) | NR | NR | |
Singh et al. 2011 [25] | Paliperidone 1.5 mg/day | 6 | 3.3 (36.0) | 3.6 (19.1) | 2.9 (48.6) |
Paliperidone 3–6 mg/day | 6 | 22.7 (34.1) | 22.8 (30.1) | 22.4 (38.7) | |
Paliperidone 6–12 mg/day | 6 | 22.4 (35.5) | 21.3 (31.1) | 24.9 (42.0) | |
Placebo | 6 | 2.7 (15.2) | 0.6 (9.4) | 4.4 (18.3) | |
Observational studies | |||||
Duval et al. 2008 [27] | Risperidone 1–6 mg/day | 3 | 47.9 (23.6) | NR | NR |
Kumra et al. 2008 [28] | Clozapine 25–900 mg/day | 12 | NR | NR | NR |
Olanzapine 30 mg/day | 12 | NR | NR | NR | |
Clozapine 25–900 mg/day | 24 | NR | NR | NR | |
Olanzapine 30 mg/day | 24 | NR | NR | NR | |
Pandina et al. 2012 [29] | Risperidone 2–6 mg/day (treatment-naïve) | 24 | 66.8 (41.8) | 29.1 (32.6) | 83.4 (44.7) |
Risperidone 2–6 mg/day (treatment-experienced) | 24 | −11.6 (43.3) | −6.2 (22.2) | −14.0 (49.3) | |
Risperidone 2–6 mg/day (open-label) | 48 | 6.8 (35.2) | 3.7 (28.5) | 11.5 (43.3) | |
Ruan et al. 2010 [30] | Risperidone 25–50 mg biweekly | 24 | −13.1 (17.1) | NR | NR |
Schimmelmann et al. 2007 [31] | Quetiapine 200–800 mg/day | 12 | −1.4 (21.1) | −4.5 (5.7) | 3.2 (21.7) |