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Meta-Analysis
. 2018 Jun 12;6(6):CD006352.
doi: 10.1002/14651858.CD006352.pub3.

Fluphenazine (oral) versus placebo for schizophrenia

Hosam E Matar  1 , Muhammad Qutayba Almerie, Stephanie J Sampson
Affiliations
Meta-Analysis

Fluphenazine (oral) versus placebo for schizophrenia

Hosam E Matar et al. Cochrane Database Syst Rev. .

Abstract

Background: Fluphenazine is one of the first drugs to be classed as an 'antipsychotic' and has been widely available for five decades.

Objectives: To compare the effects of oral fluphenazine with placebo for the treatment of schizophrenia. To evaluate any available economic studies and value outcome data.

Search methods: We searched the Cochrane Schizophrenia Group's Trials Register (23 July 2013, 23 December 2014, 9 November 2016 and 28 December 2017 ) which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There is no language, date, document type, or publication status limitations for inclusion of records in the register.

Selection criteria: We sought all randomised controlled trials comparing oral fluphenazine with placebo relevant to people with schizophrenia. Primary outcomes of interest were global state and adverse effects.

Data collection and analysis: For the effects of interventions, a review team inspected citations and abstracts independently, ordered papers and re-inspected and quality assessed trials. We extracted data independently. Dichotomous data were analysed using fixed-effect risk ratio (RR) and the 95% confidence interval (CI). Continuous data were excluded if more than 50% of people were lost to follow-up, but, where possible, mean differences (MD) were calculated. Economic studies were searched and reliably selected by an economic review team to provide an economic summary of available data. Where no relevant economic studies were eligible for inclusion, the economic review team valued the already-included effectiveness outcome data to provide a rudimentary economic summary.

Main results: From over 1200 electronic records of 415 studies identified by our initial search and this updated search, we excluded 48 potentially relevant studies and included seven trials published between 1964 and 1999 that randomised 439 (mostly adult participants). No new included trials were identified for this review update. Compared with placebo, global state outcomes of 'not improved or worsened' were not significantly different in the medium term in one small study (n = 50, 1 RCT, RR 1.12 CI 0.79 to 1.58, very low quality of evidence). The risk of relapse in the long term was greater in two small studies in people receiving placebo (n = 86, 2 RCTs, RR 0.39 CI 0.05 to 3.31, very low quality of evidence), however with high degree of heterogeneity in the results. Only one person allocated fluphenazine was reported in the same small study to have died on long-term follow-up (n = 50, 1 RCT, RR 2.38 CI 0.10 to 55.72, low quality of evidence). Short-term extrapyramidal adverse effects were significantly more frequent with fluphenazine compared to placebo in two other studies for the outcomes of akathisia (n = 227, 2 RCTs, RR 3.43 CI 1.23 to 9.56, moderate quality of evidence) and rigidity (n = 227, 2 RCTs, RR 3.54 CI 1.76 to 7.14, moderate quality of evidence). For economic outcomes, we valued outcomes for relapse and presented them in additional tables.

Authors' conclusions: The findings in this review confirm much that clinicians and recipients of care already know, but they provide quantification to support clinical impression. Fluphenazine's global position as an effective treatment for psychoses is not threatened by the outcome of this review. However, fluphenazine is an imperfect treatment and if accessible, other inexpensive drugs less associated with adverse effects may be an equally effective choice for people with schizophrenia.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram: 2006 search.
2
2
Study flow diagram: 2012 update search (no additional studies).
3
3
Study flow diagram: economic Cochrane Schizophrenia Group’s Health Economic Database (CSzGHED) search 23 July 2013.
4
4
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
5
5
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 1: Global state: 1. Not improved or worsened
1.2
1.2. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 2: Global state: 2. Relapse
1.5
1.5. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 5: Global state: 5. average score: CGI ‐ severity of illness score (high = poor)
1.6
1.6. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 6: Leaving the study early: 1. Non‐specific reasons
1.7
1.7. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 7: Leaving the study early: 2. Specific reason ‐ short term
1.8
1.8. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 8: Leaving the study early: 3. Marked improvement/ hospital discharge
1.9
1.9. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 9: Adverse effects: 1. Anticholinergic effects ‐ short term
1.10
1.10. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 10: Adverse effects: 2. Cardivascular effects ‐ short term
1.11
1.11. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 11: Adverse effects: 3. CNS ‐ short term
1.12
1.12. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 12: Adverse effects: 4. Death ‐ long term
1.13
1.13. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 13: Adverse effects: 5. Endocrine ‐ short term
1.14
1.14. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 14: Adverse effects: 6a. Extrapyramidal effects ‐ short term
1.15
1.15. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 15: Adverse effects: 6b. Extrapyramidal effects ‐ medium term
1.16
1.16. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 16: Adverse effects: 7. Others ‐ short term
1.17
1.17. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 17: Sensitivity analysis: 1. CHRONIC versus ACUTE
1.18
1.18. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 18: Sensitivity analysis: 2. LOW DOSES (1‐5 mg/day) versus HIGH DOSES (5mg/day>)
1.19
1.19. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 19: Sensitivity analysis: 3. OPERATIONAL CRITERIA versus LOOSE DEFINITIONS
1.20
1.20. Analysis
Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 20: Sensitivity analysis: 4. BEFORE 1990 versus AFTER 1990
See this image and copyright information in PMC

Update of

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References to other published versions of this review

Matar 2007a
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