Oral fluphenazine versus placebo for schizophrenia: a Cochrane systematic review of 40 years of randomised controlled trials Flufenazina oral vs. placebo, en el tratamiento de la esquizofrenia. Una revisión sistemática de Cochrane de 40 años de estudios controlados aleatorizados

Introducción: La flufenazina, uno de los tres antipsicóticos de la lista de drogas esenciales de la OMS, está disponible desde hace 5 décadas. Las revisiones cuantitativas de sus efectos vs. placebo son escasas y desactualizadas. Método: Buscamos estudios controlados aleatorizados relevantes que compararan la administración de flufenazina oral contra placebo, en los registros de ensayos de los grupos de esquizofrenia de Cochrane (oct. 2006) y en referencias incluidas en los estudios. Los estudios consistentes y confiables muestran datos de ensayos clínicos aleatorizados (ECA). Calculamos el RR mediante un modelo de efectos fijos, el número necesario por tratar (NNT) y su intervalo de confianza de 95porciento. Resultados: En flufenazina vs. placebo, a corto plazo, el resultado “no mejoría” no fue muy diferente (n=75, 2 ECA, RR 0,71, IC 0,5 a 1,1). La flufenazina oral, a corto plazo, aumenta el riesgo de manifestaciones extrapiramidales, como la acatisia (n=227, 2 ECA, RR 3,43, IC 1,2 a 9,6, NNT 13, IC 4 a 128) y rigidez (n=227, 2 ECA, RR 3,54, IC 1,8 a 7,1, NNT 6, IC 3 a 17). La deserción fue más baja en el grupo de la flufenazina oral, pero los datos no fueron estadísticamente significativos (n=227, 2 ECA, RR 0,70 CI 0,4 a 1,1). Conclusión: La flufenazina es un tratamiento imperfecto con muy pocos datos que sustenten su uso. Otras drogas de bajo costo y pocos efectos adversos pueden ser mejor opción para pacientes psicóticos. La OMS debe revisar su lista de antipsicóticos esenciales...

Background: Fluphenazine, one of only three antipsychotics on WHO’s list of essential drugs, has been widely available for five decades. Quantitative reviews of its effects compared with placebo are rare and out of date. Methods: We searched for all relevant randomised controlled trials comparing oral administration of fluphenazine with placebo on the Cochrane Schizophrenia Group’s register of trials (October 2006) and in reference lists of included studies. Data were extracted from reliably selected trials. Where possible, we calculated fixed effects relative risk (RR), the number needed to treat (NNT), and their 95% confidence intervals (CI). Results: We found over 1200 electronic records for 415 studies. Ninety papers were acquired; 59 were excluded and the remainder were reports of the seven trials we could include (total participants=349). Compared with placebo, in the short-term, global state outcomes for ‘not improved’ were not significantly different (n=75, 2 RCTs, RR 0.71 CI 0.5 to 1.1). There is evidence that oral fluphenazine, in the short term, increases a person’s chances of experiencing extrapyramidal effects such as akathisia (n=227, 2 RCTs, RR 3.43 CI 1.2 to 9.6, NNH 13 CI 4 to 128) and rigidity (n=227, 2 RCTs, RR 3.54 CI 1.8 to 7.1, NNH 6 CI 3 to 17). We found study attrition to be lower in the oral fluphenazine group, but data were not statistically significant (n=227, 2 RCTs, RR 0.70 CI 0.4 to 1.1). Conclusions: Fluphenazine is an imperfect treatment with surprisingly few data from trials to support its use. If accessible, other inexpensive drugs, less associated with adverse effects, may be a better choice for people with schizophrenia. It is time for the World Health Organisation to revise their list of essential antipsychotic drugs...

The Effects of Acetazolamide and Fluphenazin on CSF Formation

The purpose of this study was to invstigate the effect of acetazolamide and fluphenazine on the formation of CSF. Studis were performed in 12 cats those were divided into 2 groups;A-F group included animals received initial acetazolamide infusion and additional infusion of fluphenazine to the initial infusion and the F-A group for vice versa. The rate of CSF formation was measured at 3cm above zero outflow pressure by force transducer which connected to personal computer. After obtaining steady value of CSF formation rate, the drugs were infused intravenously according to the protocol. Base line CSF formation rate, 18.87+/-6.52 microliter/min. is reduced to 6.67+/-2.45 microliter/min after acetazolamide infusion and further reduced to 3.48+/-4.06 microliter/min after additional fluphenazine. In fluphenazine group, the base line CSF formation rate, 16.34+/-4.58 microliter/min is reduced to 9.63+/-4.58 microliter/min after initial infusion of fluphenazine and further to 6.45+/-3.64 microliter/min. after additional infusion of acetazolamide. Mean reduction of CSF formation after initial intravenous infusion of acetazolamide and fluphenazine were 59% and 37% respectively. Although statistically insignificant, the CSF formation reduction in A-F group revealed more even and profound value comparing with that of F-A group. These date suggest that in addition to the effect of acetazolamide to reduce the formation of CSF, some other mechanism may exist in CSF formation that major tranquilizer exert the effect on CSF formation.