Table 1.
Study, Patient, and Treatment Characteristics
| Study/ Sponsor |
Design | Total N |
Time (wks) |
Population | Mean Age |
Male Sex (%) |
Illness duration (years) |
Treatments | Mean Dose (mg/d) |
Primary Outcome(s) |
Secondary Outcomes |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Selective Serotonin Reuptake Inhibitor | |||||||||||
| Dawes 2012/Zisook 2009a/Zisook 2010/Kasckow 2010 NIMH Department of Veterans Affairs | DBRPCT | 212 | 8 | Schizophrenia (n=117) or schizoaffective D/O (n=81) All subjects had “subsyndromal depression” Outpatients Baseline total PANSS or CGI-S score NR | 52.5 (n=198) | 78.3 (n=198) | NR | AP+citalopram AP+PBO |
AP doses not provided Citalopram = 28.9 |
Cognitive Tests; Psycho-pathology; Suicidality | EPS; Quality of Life; Metabolic side effects |
| Friedman 2005a Forest Laboratories | DBRPCT Cross overb | 19 | 12 | Chronic schizophrenia (n=17) or schizoaffective D/O (n=2) Stable Inpatients (42.1%) and outpatients (57.9%) Baseline total PANSS score = 78.90±14.46 Baseline CGI-S score = 4.00±0.69 | 45.0 | 68.4 | 25.6 | AP+citalopram SGA+PBO |
AP doses not provided Citalopram = 40 |
Cognitive Tests | Psycho-pathology; EPS |
| Niitsu 2012a No external funding | DBRPCT | 47 | 8 | Chronic schizophrenia Outpatients Baseline total PANSS score = 74.6 ± 10.7 | 37.4 | 61.7 | 11.5 | SGA+fluvoxamine SGA+PBO |
SGA = 257.9 CPZ equivalents Fluvoxamine = 150 |
Cognitive Tests | Psycho-pathology; EPS; Quality of Life |
| Serotonin-Norepinephrine Reuptake Inhibitor | |||||||||||
| Mico 2011 Funding source not specified | DBRPCT | 40 | 16 | Chronic schizophrenia Active positive and negative symptoms Outpatients Baseline total PANSS score = 65.7±12.6 | 35.0 | 60.0 | 6.5 | Clozapine+duloxetine Clozapine+PBO |
Clozapine = 518.3 (1036.6 CPZ equivalents) Duloxetine = 60 |
Total Psycho-pathology | Psycho-pathology; Cognitive Tests |
| Norepinephrine Reuptake Inhibitor | |||||||||||
| Poyurovsky 2009/Poyurovsky 2007 Stanley Medical Research Institute | DBRPCT | 33 | 6 | First-episode schizophrenia or schizophreniform D/O Remitted Inpatients Baseline CGI-S score = 4.18±0.64 | 31.1 | 63.6 | 3.6 | Olanzapine+reboxetine Olanzapine+PBO |
Olanzapine = 10 (200 CPZ equivalents) Reboxetine = 4 |
Cognitive Tests | Psycho-pathology; EPS |
| Dopamine-Norepinephrine Reuptake Inhibitor | |||||||||||
| Bloch 2010a National Alliance for Research on Schizophrenia and Depression Phillip Morris | DBRPCT | 61 | 14 | Schizophrenia (n=41), Schizoaffective D/O (n=19) or Diagnosis unclear (n=1) Smokers Stable Outpatients Baseline total PANSS = 72.90±21.63 (n=60) | 41.67 (n=60) | 75.4 | NR | AP+bupropion SR AP+PBO |
AP doses not provided Bupropion = 300 |
Smoking Cessation; Genetic Testing | Psycho-pathology; Cognitive Tests |
| Alpha 2 Antagonist | |||||||||||
| Berk 2009a Organon Australia | DBRPCT | 38 | 6 | Schizophrenia NR Inpatients (39.5%) or outpatients (39.5%) with unreported data for 21.1% of patients Baseline total PANSS score = 84.76±19.85 Baseline CGI-S score = 4.13±0.89 | 36.8 | 84.2 | NR | SGA+mirtazapine SGA+PBO |
SGA = 333.6 CPZ equivalents (n=27) Mirtazapine = 30 |
Total Psycho-pathology | Psycho-pathology; Cognitive Tests |
| Caforio 2013a Stanley Medical Research Institute Organon Italy (Schering Plough) | DBRPCT | 28 | 8 | Schizophrenia Recent exacerbation of psychotic symptoms requiring hospitalization Inpatients Baseline total PANSS score = 67.05±18.40 | 29.3 (n=20) | 75.0 (n=20) | 7.1 (n=20) | Olanzapine+mirtazapine Olanzapine+PBO |
Olanzapine = 17.3 (346.0 CPZ equivalents) (n=20) Mirtazapine = 30 (n=20) |
Negative symptoms; Cognitive Tests | Psycho-pathology |
| Cho 2011/Lee 2011 Funding source not specified | DBRPCT | 21 | 8 | Schizophrenia Stable Outpatients Baseline total PANSS score = 83.65±13.55 | 35.7 (n=20) | 50.0 (n=20) | 6.5 (n=20) | Risperidone+mirtazapine Risperidone+PBO |
Risperidone = 3.5 (175 CPZ equivalents) (n=20) Mirtazapine = 30 (n=20) |
Negative Symptoms; Cognitive Tests; EPS; Metabolic side effects | Cognitive Tests; Psycho-pathology; Adherence |
| Poyurovsky 2003a Funding source not specified but author states in a personal communication “This trial was not funded by any external sources.” | DBRPCT | 30 | 4 | Chronic schizophrenia Stable Inpatients Baseline CGI-S score = 3.5±0.6 (n=24) | 44.1 (n=24) | 70.8 (n=24) | 17.2 (n=24) | FGA+mianserin FGA+PBO |
FGA Defined Daily Dosage = 4.0 (n=24) Mianserin = 15 (n=24) |
Cognitive Tests | Psycho-pathology; EPS |
| Stenberg 2010a/Joffe 2009a/Terevnikov 2011 Stanley Medical Research Institute | DBRPCT | 39 | 6 | Chronic schizophrenia (n=38) or schizoaffective D/O, depressive type (n=1) Active positive and/or negative symptoms; at least moderate illness severity Inpatients (46.2%) and outpatients (53.8%) Baseline total PANSS score = 102.92±13.77 Baseline CGI-S score = 4.33±0.54 | 45.7 | 51.3 | 22.4 | FGA+mirtazapine FGA+PBO |
FGA = 323.8 CPZ equivalents Mirtazapine = 30 |
Psycho-pathology; Cognitive Tests | Psycho-pathology; Patient-rated Improvement |
| Total (unweighted means) | |||||||||||
| 11 Trials; Industry: N=4 Foundation: N=4 Government: N=1 Not reported/No external funding : N=4 | DBR PCT: N=11; Parallel: N=10 Cross-over: N=1 | 568 | 8.7±3.7 | SCZ:91.3% SZA:7.7% Chronic SCZ: 88.9%; first-episode SCZ or schizophreniform D/O: 5.8%; Outpatients: 60.1% Baseline total PANSS score = 78.5±12.1 (N=8) Baseline CGI-S score = 4.0±0.34 (N=5) | 39.5±6.9 | 67.2±10.9 | 12.5±8.0 (N=8) | Active: mirtazapine=4 mianserin=1 citalopram=2 duloxetine=1 fluvoxamine=1 reboxetine=1 bupropion=1 Comparator: SGA+PBO=6; FGA+PBO=2; CLO+PBO=1; OLA+PBO=2; RIS+PBO=1 |
Citalopram: 29.7 (weighted mean) Fluvoxamine: 150 Duloxetine: 60 Reboxetine: 4 Bupropion: 300 Mirtazapine: 30 Mianserin: 15
CPZ equivalents = 382.7±285.1 (N=7) |
Cognitive Tests: N=8; Total psycho-pathology: N=2; Psycho-pathology: N=2 Negative symptoms: N=2; Suicidality: N=1 Smoking cessation: N=1 Genetic testing : N=1 EPS:N=1 Metabolic side effects : N=1 | Psycho-pathology: N=10; EPS: N=5; Cognitive Tests: N=4; Patient rated improvement: N=1; Metabolic side effects: N=1; Adherence: N=1 Quality of Life = 2 |
a
additional, unpublished data were obtained from study author
b
pre-crossover data were obtained from study author
Abbreviations: AD=Antidepressant; AP=Antipsychotic; CGI-S=Clinical Global Impression–Severity Scale; CLO=Clozapine; CPZ=Chlorpromazine; DBRPCT=Double-blind, randomized, placebo-controlled trial; EPS=Extrapyramidal symptoms; FGA=First-generation antipsychotic; NR=Not reported; OLA=Olanzapine; PANSS=Positive and Negative Syndrome Scale; PBO=Placebo; RIS=Risperidone; SGA=Second-generation antipsychotic, SCZ=Schizophrenia; SZA=Schizoaffective disorder