Fluphenazine decanoate (depot) and enanthate for schizophrenia (Review) Maayan N, Quraishi SN, David A, Jayaswal A, Eisenbruch M, Rathbone J, Asher R, Adams CE This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2015, Issue 2 http://www.thecochranelibrary.com Fluphenazine decanoate (depot) and enanthate for schizophrenia (Review) Copyright © 2015 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 . ..... 4 BACKGROUND .................................... 6 OBJECTIVES ..................................... 6 METHODS ...................................... 6 RESULTS....................................... 11 Figure1. ..................................... 13 Figure2. ..................................... 16 Figure3. ..................................... 17 ADDITIONALSUMMARYOFFINDINGS . 24 DISCUSSION ..................................... 30 AUTHORS’CONCLUSIONS . 32 ACKNOWLEDGEMENTS . 33 REFERENCES ..................................... 33 CHARACTERISTICSOFSTUDIES . 50 DATAANDANALYSES. 160 Analysis 1.1. Comparison 1 FLUPHENAZINE DECANOATE vs PLACEBO, Outcome 1 Death. 170 Analysis 1.2. Comparison 1 FLUPHENAZINE DECANOATE vs PLACEBO, Outcome 2 Global state: 1. Relapse. 171 Analysis 1.3. Comparison 1 FLUPHENAZINE DECANOATE vs PLACEBO, Outcome 3 Global state: 2. GAS (short term - 6 weeks to 5 months) (high score = worse). 172 Analysis 1.4. Comparison 1 FLUPHENAZINE DECANOATE vs PLACEBO, Outcome 4 Leaving the study early. 173 Analysis 1.5. Comparison 1 FLUPHENAZINE DECANOATE vs PLACEBO, Outcome 5 Mental state: 1. BPRS (endpoint scores - high score = worse). 174 Analysis 1.6. Comparison 1 FLUPHENAZINE DECANOATE vs PLACEBO, Outcome 6 Mental state: 2. Depression (mediumterm-6monthsto1year).. 174 Analysis 1.7. Comparison 1 FLUPHENAZINE DECANOATE vs PLACEBO, Outcome 7 Adverse effects: 1. Movement disorders - tardive dyskinesia (longer term - more than 1 year).................. 175 Analysis 1.8. Comparison 1 FLUPHENAZINE DECANOATE vs PLACEBO, Outcome 8 Adverse effects: 2. Toxicity. 175 Analysis 2.1. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 1 Global state: 1. No clinically important global change. 176 Analysis 2.2. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 2 Global state: 2. Relapse..................................... 177 Analysis 2.3. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 3 Global state: 3. Clinical Global Impression (short term - 6 weeks to 5 months) (high score = worse). 178 Analysis 2.4. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 4 Leaving the studyearly.................................... 179 Analysis 2.5. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 5 Behaviour: 1. NOSIE-30 - endpoint scores (high score = poor). 180 Analysis 2.7. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 7 Mental state: 1. BPRS - endpoint scores (longer term - more than 1 year) (high score =poor).. ... ... ... .. 181 Analysis 2.8. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 8 Mental state: 2. Depression. .................................. 182 Analysis 2.9. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 9 Adverse effects: 1a.Movementdisorders-general. 183 Analysis 2.10. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 10 Adverse effects: 1b. Movement disorders - akathisia. .......... 184 Analysis 2.11. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 11 Adverse effects: 1c. Movement disorders - needing anticholinergic drugs. ................ 185 Fluphenazine decanoate (depot) and enanthate for schizophrenia (Review) i Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Analysis 2.12. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 12 Adverse effects: 1d. Movement disorders - tardive dyskinesia. ............... 186 Analysis 2.13. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 13 Adverse effects: 1e. Movement disorders - tremor (longer term - more than1year).. 187 Analysis 2.14. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 14 Adverse effects: 1f. Movement disorders - average score (Simpson & Angus, 0 to 5 weeks, high = poor). 187 Analysis 2.15. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 15 Adverse effects: 2. Blurred vision - medium term (6 months to 1 year). .............. 188 Analysis 2.16. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 16 Adverse effects: 3. Toxicity - medium term (6 months to 1 year). .......... 188 Analysis 2.17. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 17 Adverse effects:4.Generaladverseeffects. 189 Analysis 2.18. Comparison 2 FLUPHENAZINE DECANOATE vs ORAL NEUROLEPTICS, Outcome 18 SENSITIVITY ANALYSIS Global state: 2. Relapse. .......... 190 Analysis 3.1. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 1 Death. .................................... 191 Analysis 3.2. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 2 Global state: 1. No clinically important global change. .............. 191 Analysis 3.3. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 3 Globalstate:2.Relapse. 192 Analysis 3.4. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 4 Global state: 3. Severly ill (medium term 6 months to 1 year). ............... 194 Analysis 3.5. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 5 Global state: 4. Needing additional antipsychotic treatment(6monthsto1year). 194 Analysis 3.7. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 7 Global state: 6. Clinical Global Impression. (medium term - 6 monthsto1year). 195 Analysis 3.8. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 8 Global state: 7. Clinical Global Impression - not improved (high score = poor). 196 Analysis 3.9. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 9 Leavingthestudyearly. 197 Analysis 3.10. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 10 Behaviour: 1. NOSIE-30 - endpoint scores (high score = poor). ............. 199 Analysis 3.11. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 11 Mental state: 1. BPRS (endpoint scores - high score = poor). ............. 199 Analysis 3.12. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 12 Mental state: 2. BPRS (endpoint scores 6 months to 1 year - dichotomous data). 200 Analysis 3.13. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 13 Mental state: 3. Depression (6 months to 1 year). ......... 201 Analysis 3.15. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 15 Adverse effects: 1a. Movement disorders - general. ............. 202 Analysis 3.16. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 16 Adverse effects: 1b. Movement disorders - needing anticholinergic drugs. 203 Analysis 3.17. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 17 Adverse effects: 1c. Movement disorders - parkinsonism. ............... 204 Analysis 3.18. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 18 Adverse effects: 1d. Movement disorders - tardive dyskinesia: longer term (more than 1 year). 205 Analysis 3.19. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 19 Adverse effects: 1e. Movement disorders - tremor. ............ 206 Analysis 3.21. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 21 Adverseeffects:2.Blurredvision. 207 Analysis 3.22. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 22 Adverse effects: 3. Dry mouth: longer term (more than 1 year). ............... 208 Fluphenazine decanoate (depot) and enanthate for schizophrenia (Review) ii Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Analysis 3.23. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 23 Adverseeffects:4.Generaladverseeffects. .......... 208 Analysis 3.24. Comparison 3 FLUPHENAZINE DECANOATE vs OTHER DEPOT NEUROLEPTICS, Outcome 24 SENSITIVITY ANALYSIS Global state: 2. Relapse. .......... 209 Analysis 4.1. Comparison 4 FLUPHENAZINE DECANOATE - DOSAGE STUDIES - HIGH DOSE vs STANDARD, Outcome 1 Global state: 1. Relapse (medium term - 6 months to 1 year). ............. 210 Analysis 4.2. Comparison 4 FLUPHENAZINE DECANOATE - DOSAGE STUDIES - HIGH DOSE vs STANDARD, Outcome 2 Global state: 2. Needing additional antispsychotic treatment (medium term - 6 months to 1 year). 211 Analysis 4.3. Comparison 4 FLUPHENAZINE DECANOATE - DOSAGE STUDIES - HIGH DOSE vs STANDARD, Outcome 3 Global state: 3. Not improved (medium term - 6 months to1year).. 212 Analysis 4.4. Comparison 4 FLUPHENAZINE DECANOATE - DOSAGE STUDIES - HIGH DOSE vs STANDARD, Outcome 4 Leaving the study early (medium term - 6 months to 1 year). ............. 213 Analysis 4.5. Comparison 4 FLUPHENAZINE DECANOATE - DOSAGE STUDIES - HIGH DOSE vs STANDARD, Outcome 5 Mental state: BPRS endpoint scores (medium term - 6 months to 1 year, high score = poor). 213 Analysis 4.6. Comparison 4 FLUPHENAZINE