Maintenance treatment with antipsychotic drugs for schizophrenia (Review) Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Davis JM This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 5 http://www.thecochranelibrary.com Maintenance treatment with antipsychotic drugs for schizophrenia (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 3 BACKGROUND .................................... 5 OBJECTIVES ..................................... 5 METHODS ...................................... 5 RESULTS....................................... 10 Figure1. ..................................... 12 Figure2. ..................................... 15 Figure3. ..................................... 16 Figure4. ..................................... 18 Figure5. ..................................... 23 Figure6. ..................................... 24 Figure7. ..................................... 26 DISCUSSION ..................................... 27 AUTHORS’CONCLUSIONS . 32 ACKNOWLEDGEMENTS . 32 REFERENCES ..................................... 33 CHARACTERISTICSOFSTUDIES . 43 DATAANDANALYSES. 143 Analysis 1.1. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 1 Relapse:upto3months.. 147 Analysis 1.2. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 2 Relapse:4to6months. 149 Analysis 1.3. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 3 Relapse:7to12months.. 151 Analysis 1.4. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 4 Relapse:>12months.. 152 Analysis 1.5. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 5 Relapse: independent of duration. 153 Analysis 1.6. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 6 Leaving the study early: due to any reason. ......... 156 Analysis 1.7. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 7 Leaving the study early: due to adverse events. ............ 159 Analysis 1.8. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 8 Leaving the study early: due to inefficacy. ....... 161 Analysis 1.9. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 9 Global state: number of participants improved. ........... 164 Analysis 1.10. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 10 Service use: number of participants hospitalised. ............. 165 Analysis 1.11. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 11 Service use: number of participants discharged. .......... 167 Analysis 1.12. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 12 Death:any.................................... 168 Analysis 1.13. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 13 Death:duetonaturalcauses. 169 Analysis 1.14. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 14 Suicide..................................... 171 Analysis 1.15. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 15 Suicideattempts.. 172 Maintenance treatment with antipsychotic drugs for schizophrenia (Review) i Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Analysis 1.16. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 16 Suicideideation.. 173 Analysis 1.17. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 17 Violent/aggressive behaviour. 174 Analysis 1.18. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 18 Adverse effects: at least one adverse event. .......... 175 Analysis 1.19. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 19 Adverse effects: movement disorders: at least one movement disorder. 176 Analysis 1.20. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 20 Adverse effects: movement disorders: akathisia. ............. 178 Analysis 1.21. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 21 Adverse effects: movement disorders: akinesia. ............. 179 Analysis 1.22. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 22 Adverse effects: movement disorders: dyskinesia. .............. 180 Analysis 1.23. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 23 Adverse effects: movement disorders: dystonia. ............ 181 Analysis 1.24. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 24 Adverse effects: movement disorders: rigor. ........... 183 Analysis 1.25. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 25 Adverse effects: movement disorders: tremor. ........... 184 Analysis 1.26. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 26 Adverse effects: movement disorders: use of antiparkinson medication. 185 Analysis 1.27. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 27 Adverseeffects:sedation. 186 Analysis 1.28. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 28 Adverseeffects:weightgain. 187 Analysis 1.29. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 29 Qualityoflife. ................................. 188 Analysis 1.30. Comparison 1 Maintenance treatment with antipsychotic drugs versus placebo/no treatment, Outcome 30 Number of participants employed: 7 to 12 months. .......... 189 Analysis 2.1. Comparison 2 Subgroup analysis (relapse at 12 months), Outcome 1 Subgroup analysis: participants with a firstepisode. .................................. 190 Analysis 2.2. Comparison 2 Subgroup analysis (relapse at 12 months), Outcome 2 Subgroup analysis: participants in remission. ................................... 192 Analysis 2.3. Comparison 2 Subgroup analysis (relapse at 12 months), Outcome 3 Subgroup analysis: various durations of stability before entering the study. ........ 194 Analysis 2.4. Comparison 2 Subgroup analysis (relapse at 12 months), Outcome 4 Subgroup analysis: abrupt withdrawal versustapering. ... ... ... ... ... ... ... ... ... ... .. 196 Analysis 2.5. Comparison 2 Subgroup analysis (relapse at 12 months), Outcome 5 Subgroup analysis: single antipsychotic drugs. .................................... 198 Analysis 2.6. Comparison 2 Subgroup analysis (relapse at 12 months), Outcome 6 Subgroup analysis: depot versus oral drugs. .................................... 200 Analysis 2.7. Comparison 2 Subgroup analysis (relapse at 12 months), Outcome 7 Subgroup analysis: first- versus second- generation antipsychotic drugs. 201 Analysis 2.8. Comparison 2 Subgroup analysis (relapse at 12 months), Outcome 8 Subgroup analysis: appropriate versus unclearallocationconcealment.. 203 Analysis 2.9. Comparison 2 Subgroup analysis (relapse at 12 months), Outcome 9 Subgroup analysis: blinded versus open trials...................................... 205 Analysis 3.1. Comparison 3 Sensitivity analysis (relapse at 12 months), Outcome 1 Exclusion of studies that were not explicitly described as randomised. 207 Analysis 3.2. Comparison 3 Sensitivity analysis (relapse at 12 months), Outcome 2 Exclusion of non-double-blind studies..................................... 208 Analysis 3.3. Comparison 3 Sensitivity analysis (relapse at 12 months), Outcome 3 Fixed-effects model. 210 Maintenance treatment with antipsychotic drugs for schizophrenia (Review) ii Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Analysis 3.4. Comparison 3 Sensitivity analysis (relapse at 12 months), Outcome 4 Original authors’ assumptions on dropouts. ................................... 211 Analysis 3.5. Comparison 3 Sensitivity analysis (relapse at 12 months), Outcome 5 Inclusion of only large studies (> 200 participants). .................................. 212 Analysis 3.6. Comparison 3 Sensitivity analysis (relapse at 12 months), Outcome 6 Exclusion of studies with clinical diagnosis. ................................... 213 Analysis 3.7. Comparison 3 Sensitivity analysis (relapse at 12 months), Outcome 7 Three months stable. 214 Analysis 3.8. Comparison 3 Sensitivity analysis (relapse at 12 months), Outcome 8 Six months stable. 215 Analysis 3.9. Comparison 3 Sensitivity analysis (relapse at 12 months), Outcome 9 Nine months stable. 216 Analysis 3.10. Comparison 3 Sensitivity analysis (relapse at 12 months), Outcome 10 Exclusion of studies with unclear randomisationmethod. 217 Analysis 3.11. Comparison 3 Sensitivity analysis (relapse at 12 months),