Risperidone, quetiapine, and fluphenazine in the treatment of patients with therapy-refractory schizophrenia. Fluphenazine vs placebo in patients with remitted, acute first-episode schizophrenia. Fluphenazine vs placebo supplementation for prodromal signs of relapse in schizophrenia. A double-blind comparison of fluspirilene and fluphenazine decanoate in schizophrenia. Outpatient maintenance of chronic schizophrenic patients with long-acting fluphenazine: double-blind placebo trial. Report to the Medical Research Council Committee on Clinical Trials in Psychiatry.
This 12-week, double-blind study evaluated the effectiveness of risperidone (4 mg/day), quetiapine (400 mg/day), or fluphenazine (12.5 mg/day) in a stringently defined treatment-resistant population of people with schizophrenia. No differences were noted in total Brief Psychiatric Rating Scale (BPRS) or Clinical Global Impression scores among the drug groups (n = 38). More subjects tended to complete the study on risperidone (69%) or quetiapine (58%) than those treated with fluphenazine (31%; P value not significant). Eighty-nine percent of those who discontinued on fluphenazine (8 of 9) were due to lack of efficacy. Discontinuation due to adverse effects was low, with only 2 subjects (both on quetiapine) stopping due to side effects. Three of 13 risperidone-treated subjects (23%) and 3 of 12 quetiapine-treated subjects (25%) met response criteria (decrease of 20% of total BPRS score), whereas 2 of 13 subjects (15%) responded to fluphenazine. Side effect occurrence was similar among drug groups and EPS ratings on the Simpson Angus Scale improved in all drug groups (quetiapine, 1.64; risperidone, 1.30; fluphenazine, 0.69; P value not significant). Despite the newer class of second-generation antipsychotic medications, this treatment-resistant population remains difficult to treat. Many people have only minimal to modest improvements with antipsychotic treatment and most continue to have residual psychotic symptoms. Treatment with first- and second-generation antipsychotics may demonstrate similar efficacy; however, patients treated with second-generation antipsychotics may be more likely to adhere to treatment. Twenty-eight patients who had recently recovered from an acute-onset, first-episode schizophrenic illness were randomly given fluphenazine hydrochloride or decanoate or placebo for a one-year period in a double-blind study. Seven of 17 patients(14%) receiving placebo experienced a psychotic relapse, whereas none of 11 drug-treated patients experienced a relapse. Eighteen (69%) of the 26 patients available for follow-up (mean interval, 3.5 years) experienced a second psychotic relapse either during the study or afterward, and 50% (14/28) of the original sample experienced a third episode. We studied the effectiveness of treating patients with low doses of fluphenazine decanoate and supplementing them with oral fluphenazine when there was evidence of prodromal symptoms of psychotic exacerbations.
                Eighty schizophrenic patients who were receiving 5 to 10 mg of fluphenazine decanoate every 2 weeks were monitored for prodromal symptoms using an idiosyncratic prodromal rating scale. When patients met our criteria for a prodromal episode, they were randomly assigned to a double-blind comparison of oral fluphenazine hydrochloride (5 mg twice daily) or a placebo for the current and future prodromal episodes. We compared rates of psychotic exacerbations in the two treatment groups.
                Thirty-six patients (45%) met the criteria for a prodrome at some point during the trial and were randomized to drug or placebo. Using survival analysis during the entire 2 years, we did not find a significant difference between fluphenazine and placebo in the likelihood that a prodrome would continue to an exacerbation. Survival analysis beginning at the start of the second year of treatment did indicate a significant reduction in exacerbation risk for patients receiving drug supplementation (P = .032). Similarly, there was no difference between the two groups in the proportion of time at risk spent in exacerbation during the first year, but patients receiving active drug supplementation spent less time in an exacerbated state in the second year (P = .05).
                Our treatment strategy appeared to be effective for some patients, particularly those who were able to remain in the study beyond the first year. Although the occurrence of a prodrome was a fairly good marker that a patient was at high risk of ultimate exacerbation with our low-dose maintenance protocol, prodromes were not highly sensitive indicators of imminent exacerbation. A double-blind comparison of fluspirilene and fluphenazine decanoate in 28 schizophrenic patients over six months showed equal improvement and the same incidence of side-effects in each group of patients. It would be expected from the literature that a better ratio of therapeutic to side-effects would appear with fluspirilene than with fluphenazine. The absence of such an effect in this study may be attributable to an initial lack of familiarity by the investigators with the use of fluspirilene, indicating an important potential variable in the comparison of a new drug with an established one. A double-blind placebo trial of fluphenazine decanoate, a long-acting phenothiazine, was carried out to determine its value in maintenance therapy of chronic schizophrenic outpatients already established on the drug for a minimum period of eight weeks. In low doses it was significantly more effective than placebo in preventing relapse and admission to hospital. Relapse was accompanied by a resurgence of specifically schizophrenic symptoms and by an increase in abnormalities described by the relatives. There was no difference between the experimental and control groups in the treatment required for depression. The group on active medication required more treatment for Parkinsonism, but this difference did not reach statistical significance.In the context of a well-run special clinic for outpatient follow-up of chronic schizophrenic patients these results confirm the usefulness of long-acting fluphenazine. By inference, the benefit of this treatment highlights the need for adequate community services to deal with the residual chronic disabilities which are characteristic of these patients.
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.
The addition of seven studies to awaiting classification may alter the conclusions of this review once assessed.