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Meta-Analysis
. 2014 Aug 3;2014(8):CD009230.
doi: 10.1002/14651858.CD009230.pub2.

Fluphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia

Magdolna Tardy  1 , Maximilian Huhn, Rolf R Engel, Stefan Leucht
Affiliations
Meta-Analysis

Fluphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia

Magdolna Tardy et al. Cochrane Database Syst Rev. .

Abstract

Background: Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between any other antipsychotic compounds, however, low-potency antipsychotic drugs are often perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side effects. This review examined the effects of the high-potency antipsychotic fluphenazine compared to those of low-potency antipsychotics.

Objectives: To review the effects of fluphenazine and low-potency antipsychotics for people with schizophrenia.

Search methods: We searched the Cochrane Schizophrenia Group Trials Register (November 2010).

Selection criteria: We included all randomised controlled trials (RCTs) comparing fluphenazine with first-generation low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis.

Data collection and analysis: We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model.

Main results: The review currently includes seven randomised trials and 1567 participants that compared fluphenazine with low-potency antipsychotic drugs. The size of the included studies was between 40 and 438 participants. Overall, sequence generation, allocation procedures and blinding were poorly reported. Fluphenazine was not significantly different from low-potency antipsychotic drugs in terms of response to treatment (fluphenazine 55%, low-potency drug 55%, 2 RCTs, n = 105, RR 1.06 CI 0.75 to 1.50, moderate quality evidence). There was also no significant difference in acceptability of treatment with equivocal numbers of participants leaving the studies early due to any reason (fluphenazine 36%, low-potency antipsychotics 36%, 6 RCTs, n = 1532, RR 1.00 CI 0.88 to 1.14, moderate quality evidence). There was no significant difference between fluphenazine and low-potency antipsychotics for numbers experiencing at least one adverse effect (fluphenazine 70%, low-potency antipsychotics 88%, 1 RCT, n = 65, RR 0.79 CI 0.58 to 1.07, moderate quality evidence). However, at least one movement disorder occurred significantly more frequently in the fluphenazine group (fluphenazine 15%, low-potency antipsychotics 10%, 3 RCTs, n = 971, RR 2.11 CI 1.41 to 3.15, low quality of evidence). In contrast, low-potency antipsychotics produced significantly more sedation (fluphenazine 20%, low-potency antipsychotics 64%, 1 RCT, n = 65, RR 0.31 CI 0.13 to 0.77, high quality evidence). No data were available for the outcomes of death and quality of life. The results of the primary outcome were robust in a number of subgroup and sensitivity analyses.Adverse effects such as akathisia (fluphenazine 15%, low-potency antipsychotics 6%, 5 RCTs, n = 1209, RR 2.28 CI 1.58 to 3.28); dystonia (fluphenazine 5%, low-potency antipsychotics 2%, 4 RCTs, n = 1309, RR 2.66 CI 1.25 to 5.64); loss of associated movement (fluphenazine 20%, low-potency antipsychotics 2%, 1 RCT, n = 338, RR 11.15 CI 3.95 to 31.47); rigor (fluphenazine 27%, low-potency antipsychotics 12%, 2 RCTs, n = 403, RR 2.18 CI 1.20 to 3.97); and tremor (fluphenazine 15%, low-potency antipsychotics 6%, 2 RCTs, n = 403, RR 2.53 CI 1.37 to 4.68) occurred significantly more frequently in the fluphenazine group.For other adverse effects such as dizziness (fluphenazine 8%, low-potency antipsychotics 17%, 4 RCTs, n = 1051, RR 0.49 CI 0.32 to 0.73); drowsiness (fluphenazine 18%, low-potency antipsychotics 25%, 3 RCTs, n = 986, RR 0.67 CI 0.53 to 0.86); dry mouth (fluphenazine 11%, low-potency antipsychotics 18%, 4 RCTs, n = 1051, RR 0.63 CI 0.45 to 0.89); nausea (fluphenazine 4%, low-potency antipsychotics 15%, 3 RCTs, n = 986, RR 0.25 CI 0.14 to 0.45); and vomiting (fluphenazine 3%, low-potency antipsychotics 8%, 3 RCTs, n = 986, RR 0.36 CI 0.18 to 0.72) results favoured fluphenazine with significantly more events occurring in the low-potency antipsychotic group for these outcomes.

Authors' conclusions: The results do not show a clear difference in efficacy between fluphenazine and low-potency antipsychotics. The number of included studies was low and their quality moderate. Therefore, further studies would be needed to draw firm conclusions about the relative effects of fluphenazine and low-potency antipsychotics.

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Conflict of interest statement

Magdolna Tardy: none known. Maximilian Huhn: none known. Rolf Engel: none known. Stefan Leucht‐has received honoraria for lectures from Abbvie, Astra Zeneca, BristolMyersSquibb, ICON, EliLilly, Janssen, Johnson & Johnson, Roche, SanofiAventis, Lundbeck and Pfizer; honoraria for consulting/advisory boards from Roche, EliLilly, Medavante, BristolMyersSquibb, Alkermes, Janssen, Johnson & Johnson and Lundbeck. EliLilly has provided medication for a study with SL as primary investigator.

Figures

1
1
Fluphenazine structure
2
2
Study flow diagram.
3
3
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Comparison 1: FLUPHENAZINE versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 1 Clinical response: Response to treatment‐short term.
1.2
1.2. Analysis
Comparison 1 Comparison 1: FLUPHENAZINE versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 2 Leaving the study early: 1. Due to any reason.
1.3
1.3. Analysis
Comparison 1 Comparison 1: FLUPHENAZINE versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 3 Leaving the study early: 2. Due to adverse effects.
1.4
1.4. Analysis
Comparison 1 Comparison 1: FLUPHENAZINE versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 4 Leaving the study early: 3. Due to inefficacy.
1.5
1.5. Analysis
Comparison 1 Comparison 1: FLUPHENAZINE versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 5 Adverse effects: 1. General‐at least one adverse effect.
1.6
1.6. Analysis
Comparison 1 Comparison 1: FLUPHENAZINE versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 6 Adverse effects: 2a. Specific‐movement disorders.
1.7
1.7. Analysis
Comparison 1 Comparison 1: FLUPHENAZINE versus LOW‐POTENCY ANTIPSYCHOTIC DRUGS, Outcome 7 Adverse effects: 2b. Specific‐other.
2.1
2.1. Analysis
Comparison 2 Subgroup analysis, Outcome 1 Response to treatment‐each low‐potency antipsychotic separately.
3.1
3.1. Analysis
Comparison 3 Sensitivity analysis, Outcome 1 Response to treatment‐exclusion of non double‐blind studies.
3.2
3.2. Analysis
Comparison 3 Sensitivity analysis, Outcome 2 Response to treatment‐fixed effects model.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD009230

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