Comparison of efficacy of a new butyrophenone derivative, timiperone and perphenazine in schizophrenia by a multicentre controlled study. Pimozide versus fluphenazine in ambulatory schizophrenics: A 12-month comparison study. A double-blind randomized comparison of nortriptyline plus perphenazine versus nortriptyline plus placebo in the treatment of psychotic depression in late life. [Study of the clinical effects of sulpiride and perphenazine in 82 schizophrenic patients by the double blind method]. Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics. Sulpiride and perphenazine in schizophrenia. A double-blind clinical trial. Loxapine versus perphenazine in psychotic patients. A double-blind, randomized, multicentre trial. Risperidone, quetiapine, and fluphenazine in the treatment of patients with therapy-refractory schizophrenia. Amitriptyline-perphenazine interaction in ambulatory schizophrenic patients. A controled study of drug interaction. A comparison of the effects of quetiapine ('seroquel') and haloperidol in schizophrenic patients with a history of and a demonstrated, partial response to conventional antipsychotic treatment. PRIZE Study Group. Double-blind comparison of bromperidol and perphenazine. Dose of fluphenazine, familial expressed emotion, and outcome in schizophrenia. Results of a two-year controlled study. Treatment of secondary depression in schizophrenia. A double-blind, placebo-controlled trial of amitriptyline added to perphenazine. Zuclopenthixol and perphenazine in patients with acute psychotic states. A double-blind multicentre study.
The efficacy of timiperone in schizophrenia as compared with perphenazine was assessed in a double-blind fashion in 205 patients throughout a 12-week treatment period. More than half of the subjects were chronic schizophrenics. Global improvement in the timiperone treatment group was superior to that in the perphenazine group in view of a lower rate of aggravation. With regard to overall safety and general usefulness rating, there were no significant differences between the two drug treatments. However, timiperone showed less frequency of excitability, irritability, anxiety and anorexia than perphenazine on occasions during the 12 week treatment period. From these results it may be concluded that the efficacy of timiperone could be superior or equivalent to that of perphenazine which has been confirmed to be of use as an antipsychotic. In this study, chronic schizophrenic outpatients who had been maintained on various neuroleptics for an average of about 4 years had their previous medications (approximately equivalent to 695 mg of chlorpromazine per day) changed abruptly to either pimozide or fluphenazine given in single daily oral doses on a double-blind basis for a period of 52 weeks. Average daily doses were pimozide 9.6 mg and fluphenazine 12.5 mg. Measurements of the therapeutic effects of the two drugs were made immediately prior to starting the study, at the end of the 2nd and 4th weeks, and thereafter every 4th week to the end of the study. Three psychometric scales were used for evaluation: Brief Psychiatric Rating Scale (BPRS); Evaluation of Social Functioning (ESFR); and Clinical Global Impressions (CGI). In addition, patients participated in a Social Adjustment Inventory (SAI) evaluation. Statistical analysis with the use of several statistical techniques for between- and within-drug group comparisons revealed that pimozide and fluphenazine were equally effective in maintaining control of symptomatology of chronic schizophrenics at a level commensurate with or better than that provided by their previous medication. Side effects were characteristic of marketed neuroleptics, similar in severity and occurrence between study-drug groups, mainly extrapyramidal symptoms, and readily controlled with antiparkinsonian medication. Pimozide, slightly more potent than fluphenazine, proved to be equally effective for the long-term management of chronic schizophrenic patients. To conduct the first randomized study comparing the efficacy of an antidepressant alone versus an antidepressant plus a neuroleptic in the treatment of late-life psychotic depression.
                The efficacy of nortriptyline plus placebo versus nortriptyline plus perphenazine was compared in 36 patients aged 50 years or older presenting with a major depressive episode with psychotic features (DSM-III-R criteria). Patients were started openly on nortriptyline treatment titrated to therapeutic levels. They were then randomly assigned under double-blind conditions to addition of perphenazine or placebo. Outcomes were compared in the 2 treatment groups using measures including the Hamilton Rating Scale for Depression (HAM-D) and the Brief Psychiatric Rating Scale (BPRS); side effects were assessed with the Geriatric Movement Disorder Assessment.
                Both treatments were well tolerated. Of the 36 randomly assigned patients, 2 (1 in each group) dropped out due to treatment-related adverse effects. Four additional patients dropped out for administrative reasons. Thirty patients received nortriptyline for at least 4 weeks combined with either perphenazine (N = 14) or placebo (N = 16) for at least 2 weeks (median = 9 weeks). There was no significant difference between the completers in the 2 treatment groups when comparing their scores on the HAM-D, the BPRS, its psychoticism subscale, or any side effects measure. Rates of response (defined as resolution of both depression and psychosis) did not differ significantly in the 2 groups (nortriptyline-plus-perphenazine group, 50% vs. nortriptyline-plus-placebo group, 44%).
                When treating older patients with psychotic depression, the addition of a moderate dose of a traditional neuroleptic to a tricyclic antidepressant was well tolerated but did not improve efficacy. This finding supports existing data suggesting that the pathophysiology (and thus the required treatment) of psychotic depression may be different early and late in life. Our clinical and statistical evaluation of Sulpiride and Perphenazine was carried out over a 10 week period, in 82 patients of both sexes, aged 20 to 56 years. All were chronic patients with a symptomatic profile of apathy, lack of initiative but with the personality relatively well preserved in 56 patients. The daily dosage varied from 300 to 1,200 mg Sulpiride orally and 12 to 48 mg Perphenazine. The effects of therapy have been received globally and individually at the beginning, 4th, 8th, and the end of the 10th week using the B.P.R.S. modified by the clinic of Neurology and Psychiatry of the University of Hiroshima. Using "Armitage's Restricted Sequential Design", there was no significant difference between the therapeutic effects of these 2 neuroleptics. However, Sulpiride appeared more beneficial following the review during the 8th week and the 4th week. In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome.
                The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug.
                Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings.
                Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies. Seventeen patients with acute schizophrenia and 30 with chronic schizophrenia were included in a randomized, double-blind parallel-group trial comparing sulpiride and perphenazine. Patients were evaluated using the 16-item Brief Psychiatric Rating Scale (BPRS) prior to the onset of treatment and 1 and 2 weeks, and 1, 2, 3, and 4 months thereafter. In patients with acute schizophrenia, total BPRS scores declined significantly at the end of the trial compared with pretreatment values in sulpiride-treated patients but not in schizophrenics treated with perphenazine. Differences in response between the groups did not reach statistical significance, however. For patients suffering from chronic schizophrenia, a statistically significant decline was observed in total BPRS scores at 4 months compared with pretreatment scores in both sulpiride and perphenazine groups. There was no significant difference in the treatment response between the groups. Sulpiride appeared to be somewhat more effective than perphenazine for treatment of acute schizophrenia. Efficacy of both compounds was less marked in chronic forms of schizophrenia. A double-blind, randomized, multicentre trial was carried out in 47 psychotic patients to evaluate the efficacy of oral treatment with loxapine compared with perphenazine. In total, 22 patients were included in diagnostic Group I (cases of acute schizophrenia and psychogenic (reactive) psychoses). The average maximum daily dose was 60.0 mg in the loxapine group and 36.8 mg in the perphenazine group. After 3-weeks' treatment, no significant differences were found between the two treatment groups according to the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) Scale or side-effect records. Twenty-five patients were included in diagnostic Group II (cases of chronic schizophrenia). The average daily dosage was 81.1 mg in the loxapine group and 90.1 mg in the perphenazine group. After 10 to 12-weeks' treatment, no significant differences between the two treatment groups could be found according to BPRS, CGI scale, Nurses' Observation Scale for In-patient Evaluation (NOSIE) or side-effect records. The diastolic blood pressure (lying and standing) tended to increase slightly in both treatment groups. In conclusion, it was found that loxapine and perphenazine seemed to be equally effective and, based on experience with parenteral loxapine treatment, it is suggested that further investigation of oral loxapine should be carried out in psychotic patients in whom agitation is a feature. 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. In a double-blind placebo, controlled clinical study, lasting 12 weeks, 48 male and 48 female ambulatory schizophrenic patients were randomly assigned to one of four treatments: placebo; amitriptyline hydrochloride, 125 mg/day; perphenazine, 20 mg/day; or amitriptyline-perphenazine, 20 mg/day. Treatment groups contained an equal number of male and female patients. Perphenazine alone or in combination was substantially more effective in reducing psychopathological disorder than was the placebo, but there was no evidence to indicate the superiority of the amitriptyline-perphenazine combination over perphenazine alone. Amitriptyline alone was not substantially better than placebo and could not be considered an efficacious medication for the maintenance treatment of these patients. Less response to treatment was made by patients with longer-term records of prior hospitalization. Quetiapine ('Seroquel') is a well-tolerated, novel, atypical antipsychotic with consistent efficacy in the treatment of schizophrenia. To date, no clinical studies have evaluated the effect of quetiapine in patients who only partially respond to conventional antipsychotics, yet this type of patient is most frequently seen by psychiatrists. Therefore, this international, multicentre, double-blind study was conducted to compare the efficacy and tolerability of 8 weeks' treatment of quetiapine 600 mg/day with haloperidol 20 mg/day in 288 patients who had a history of partial response to conventional antipsychotics and displayed a partial or no response to 1 month of fluphenazine (20 mg/day) treatment. Patients on quetiapine tended to have greater improvement than those on haloperidol in the primary efficacy measure, mean Positive and Negative Symptom Scale (PANSS) score, after 4 weeks' treatment (-9.05, -5.82, respectively, P = 0.061) and at study end (-11.50, -8.87, respectively, P = 0.234). Similarly, there was a trend towards patients on quetiapine demonstrating greater improvements in the secondary efficacy measures (Clinical Global Impression, PANSS subscale and Brief Psychiatric Rating Scale scores) [week 4 (baseline) to week 12 (end)], but the difference between treatments did not reach significance. Significantly more patients on quetiapine than on haloperidol showed a clinical response-patient response rates, defined as > 20% reduction in PANSS total score between weeks 4 and 12, were 52.2% for quetiapine and 38.0% for haloperidol (P = 0.043). Patients receiving quetiapine required less anticholinergic medication (P < 0.011), had greater reduction in extrapyramidal symptoms (EPS) (P = 0.005) and fewer treatment-emergent EPS-related adverse events compared to those on haloperidol (P < 0.001). Serum prolactin concentrations were elevated at the end of fluphenazine treatment in 73% of patients. Between weeks 4 and 12, elevated serum prolactin concentrations significantly decreased in quetiapine-treated patients compared to those receiving haloperidol (P < 0.001). At the end of quetiapine treatment, 83% of patients had normal prolactin levels while only 21% of patients receiving haloperidol were within the normal range. These results suggest that quetiapine may make a valuable contribution to the management of patients with a history of partial response to conventional antipsychotics. Within the scope of a clinical double-blind study, effects and side effects of Bromperidol and Perphenazine were compared. Forty newly-hospitalized schizophrenic patients were included in the trial. Assessments were made on days 0, 2, 5, 10, 20, and 30. Data were documented by means of the AMP system, the EPRS scale of Simpson and Angus, and a Brief Ward Behaviour Rating Scale. Laboratory tests and ECGs were performed before and after treatment. Treatment was scheduled for 30 days and dosages were established depending on effects and side effects. We found a therapeutic effective mean daily dose of 6 mg for Bromperidol and 20 mg for Perphenazine. Both substances caused autonomic and extrapyramidal side effects and, in a few patients, temproary fatigue. The employed dosage caused no strong sedation. To sum up, Bromperidol and Perphenazine can be described as highly potent and well tolerated antipsychotic drugs. We observed stronger efficacy and earlier onset of action with Bromperidol. The superior effect of Bromperidol cannot be explained by a higher dosage as compared with Perphenazine, since both substances showed a similar severity of extrapyramidal side effects, and the dosage of both substances was established individually for each patient, depending on effects and side effects. Issues regarding the side effects of antipsychotic medication and the possible contribution of the environment to dose requirements led to a two-year controlled dosage study of maintenance antipsychotic medication and familial environment among recently discharged schizophrenic patients. Seventy stable patients, living in high- or low-expressed emotion (EE) households, were randomized, double blind, to receive a standard dose of fluphenazine decanoate (average, 25 mg every two weeks) or a minimal dose representing 20% of the dose prescribed (average, 3.8 mg every two weeks). No differences in relapse were observed among dose, EE, or dose and EE. Patients in the minimal dose/high-EE condition experienced more minor but aborted episodes in year 2. Side effects were fewer on the minimal dose after one year, and low-EE patients were better adjusted than high-EE patients. Over time, minimal-dose recipients were significantly more improved in their instrumental and interpersonal role performance than were standard-dose recipients. The combination of antidepressants and neuroleptics has been widely recommended and commonly used clinically for the schizophrenic patient who becomes depressed. However, the value of the combination for these patients has not been clearly demonstrated. This report presents results of a double-blind, randomized, placebo-controlled clinical trial designed to evaluate the combination of perphenazine and amitriptyline hydrochloride with that of perphenazine alone in the treatment of 35 ambulatory chronic schizophrenic patients in whom depressive symptoms developed. Results showed that the addition of amitriptyline to perphenazine, when compared with perphenazine alone, was more effective in reducing symptoms of depression after four months of treatment, but less effective in reducing thought disorder. The study concludes that the value of adding an antidepressant to the usual neuroleptic in the treatment of secondary depression in schizophrenia should be reviewed. Fifty-four patients with acute psychotic states were included in a double-blind multicentre study of zuclopenthixol and perphenazine given orally. Fourteen patients had not received test preparations for a minimum of 3 weeks as stated in the protocol, and were excluded. The remaining 40 patients received the test preparations for 3 to 12 weeks, with an average of 49 days for patients receiving zuclopenthixol and 45 days for patients receiving perphenazine. Clinical evaluations were done at baseline and at weeks 1, 2, 4, 6, 8, and 12 including the CGI, a CPRS subscale for schizophrenia, and the UKU Side Effects Rating Scale. The patients received on average 37 mg zuclopenthixol or 30 mg perphenazine daily. Statistically, significant reductions on the CGI, severity of illness, and on the CPRS (total score) were found for both drugs when comparing baseline with later scores. No significant differences between the drugs were found. It was also impossible to demonstrate a difference in clinical profile between the two drugs on the basis of the single items on the CPRS. Although small differences between the two drugs were found, as regards number and type of side effects, it is concluded that the pattern of side effects was almost identical in the two treatment groups.
Although perphenazine has been randomised for more than 40 years, incomplete reporting and the variety of comparators used make it impossible to draw clear conclusions. At best we can say that perphenazine showed similar effects and adverse events as several of the other pooled antipsychotic drugs. Since perphenazine is a relatively inexpensive and frequently used compound, further trials are justified to clarify the properties of this classical antipsychotic drug.