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Meta-Analysis
. 2016 Jul 2;7(7):CD010832.
doi: 10.1002/14651858.CD010832.pub2.

Fluphenazine (oral) versus atypical antipsychotics for schizophrenia

James R Sampford  1 , Stephanie Sampson, Bao Guo Li, Sai Zhao, Jun Xia, Vivek A Furtado
Affiliations
Meta-Analysis

Fluphenazine (oral) versus atypical antipsychotics for schizophrenia

James R Sampford et al. Cochrane Database Syst Rev. .

Abstract

Background: Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years.

Objectives: To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost-effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia.

Search methods: We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics.

Data collection and analysis: Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence.

Main results: Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness.Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost-effectiveness.

Authors' conclusions: Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics.

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Conflict of interest statement

James Sampford: none known.

Stephanie Sampson: employed by the National Health Service to undertake Cochrane Programme Grant Reviews (SR ‐ 10/4001/15: Cost‐effective treatments and diagnostic approaches for people with schizophrenia within the NHS).

Sai Zhao: received payment from the NIHR funding detailed above.

Jun Xia: received payment from the NIHR funding detailed above.

Bao Guo Li: none known.

Vivek Furtado: none known

Figures

1
1
Fluphenazine structure
2
2
Study flow diagram: 2013 study search
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
4
4
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 FLUPHENAZINE (ORAL) vs AMISULPRIDE, Outcome 1 Global state: 1. Average endpoint score of CGI scales (high = poor).
1.2
1.2. Analysis
Comparison 1 FLUPHENAZINE (ORAL) vs AMISULPRIDE, Outcome 2 Mental state: 2a. Average endpoint score of various scales (high = poor).
1.4
1.4. Analysis
Comparison 1 FLUPHENAZINE (ORAL) vs AMISULPRIDE, Outcome 4 Adverse effects: 1. Extrapyramidal effects.
1.5
1.5. Analysis
Comparison 1 FLUPHENAZINE (ORAL) vs AMISULPRIDE, Outcome 5 Leaving the study early.
2.1
2.1. Analysis
Comparison 2 FLUPHENAZINE (ORAL) vs RISPERIDONE, Outcome 1 Clinically important response (defined by study).
2.2
2.2. Analysis
Comparison 2 FLUPHENAZINE (ORAL) vs RISPERIDONE, Outcome 2 Global state: 1. Average endpoint score of CGI scales (high = poor).
2.3
2.3. Analysis
Comparison 2 FLUPHENAZINE (ORAL) vs RISPERIDONE, Outcome 3 Mental state: 2a. Average endpoint scores (BPRS, high = poor).
2.5
2.5. Analysis
Comparison 2 FLUPHENAZINE (ORAL) vs RISPERIDONE, Outcome 5 Adverse effects: 1. Anticholinergic effect.
2.6
2.6. Analysis
Comparison 2 FLUPHENAZINE (ORAL) vs RISPERIDONE, Outcome 6 Adverse effects: 2. Central nervous system.
2.7
2.7. Analysis
Comparison 2 FLUPHENAZINE (ORAL) vs RISPERIDONE, Outcome 7 Adverse effects: 3. Gastrointestinal.
2.8
2.8. Analysis
Comparison 2 FLUPHENAZINE (ORAL) vs RISPERIDONE, Outcome 8 Adverse effects: 4. Other adverse events.
2.10
2.10. Analysis
Comparison 2 FLUPHENAZINE (ORAL) vs RISPERIDONE, Outcome 10 Leaving the study early.
3.1
3.1. Analysis
Comparison 3 FLUPHENAZINE (ORAL) vs QUETIAPINE, Outcome 1 Clinically important response (defined by study).
3.2
3.2. Analysis
Comparison 3 FLUPHENAZINE (ORAL) vs QUETIAPINE, Outcome 2 Global state: 1. CGI: Average endpoint CGI‐SI (high = poor).
3.3
3.3. Analysis
Comparison 3 FLUPHENAZINE (ORAL) vs QUETIAPINE, Outcome 3 Mental state: 2a. General ‐ average endpoint score (BPRS total, high = poor).
3.4
3.4. Analysis
Comparison 3 FLUPHENAZINE (ORAL) vs QUETIAPINE, Outcome 4 Mental state: 2b. Positive symptoms ‐ average endpoint score (BPRS positive sub‐score, high = poor).
3.5
3.5. Analysis
Comparison 3 FLUPHENAZINE (ORAL) vs QUETIAPINE, Outcome 5 Mental state: 2c. Negative symptoms ‐ average endpoint score (BPRS negative sub‐score, high = poor).
3.7
3.7. Analysis
Comparison 3 FLUPHENAZINE (ORAL) vs QUETIAPINE, Outcome 7 Mental state: 2e. Hostility symptoms ‐ average endpoint score (BPRS hostility sub‐score, high = poor).
3.9
3.9. Analysis
Comparison 3 FLUPHENAZINE (ORAL) vs QUETIAPINE, Outcome 9 Adverse effects: 1. Anticholinergic effect.
3.10
3.10. Analysis
Comparison 3 FLUPHENAZINE (ORAL) vs QUETIAPINE, Outcome 10 Adverse effects: 2. Central nervous system.
3.11
3.11. Analysis
Comparison 3 FLUPHENAZINE (ORAL) vs QUETIAPINE, Outcome 11 Adverse effects: 3. Gastrointerstinal adverse effects.
3.12
3.12. Analysis
Comparison 3 FLUPHENAZINE (ORAL) vs QUETIAPINE, Outcome 12 Adverse effects: 4a. Other adverse events.
3.14
3.14. Analysis
Comparison 3 FLUPHENAZINE (ORAL) vs QUETIAPINE, Outcome 14 Leaving the study early.
4.1
4.1. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 1 Clinically important response (defined by author).
4.2
4.2. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 2 Global state: 1. CGI: Average change CGI‐SI (high = poor).
4.3
4.3. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 3 Mental state: 2a. General ‐ average change score (BPRS total, high = poor).
4.4
4.4. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 4 Mental state: 2b. General ‐ average change score (PANSS total, high = poor).
4.5
4.5. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 5 Mental state: 2c. Positive symptoms ‐ average change score (BPRS positive sub‐score, high = poor).
4.6
4.6. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 6 Mental state: 2d. Positive symptoms ‐ average endpoint score (PANSS positive sub‐score, high = poor).
4.7
4.7. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 7 Mental state: 2e. Negative symptoms ‐ average change score (BPRS negative sub‐score, high = poor).
4.8
4.8. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 8 Mental state: 2f. Negative symptoms ‐ average change score (PANSS negative sub‐score, high = poor).
4.9
4.9. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 9 Mental state: 2g. General psychopathology ‐ average change score (PANSS general psychopathology sub‐score, high = poor).
4.10
4.10. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 10 Mental state: 2h. Anxiety ‐ average change score (HAMA, high = poor).
4.11
4.11. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 11 Satisfaction with treatment: 1. Average change score (DAI, low = poor).
4.12
4.12. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 12 Adverse effects: 1. General.
4.13
4.13. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 13 Adverse effects: 2. Anticholinergic effect.
4.14
4.14. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 14 Adverse effects: 3a. Central nervous system.
4.15
4.15. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 15 Adverse effects: 3b. CNS (LSEQ, low = poor).
4.16
4.16. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 16 Adverse effects: 4a. Extrapyramidal effects.
4.17
4.17. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 17 Adverse effects: 4b. Extrapyramidal effects ‐ average change score (SAS, high = poor).
4.18
4.18. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 18 Adverse effects: 4c. Extrapyramidal effects ‐ average change score (HAS, high = poor).
4.19
4.19. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 19 Adverse effects: 4d. Extrapyramidal effects ‐ average change score (AIMS, high = poor).
4.20
4.20. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 20 Adverse effects: 5. Other adverse events.
4.21
4.21. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 21 Adverse effects: 5b. Other adverse events.
4.23
4.23. Analysis
Comparison 4 FLUPHENAZINE (ORAL) vs OLANZAPINE, Outcome 23 Leaving the study early.
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