Evaluation of the effectiveness and acceptability of the long-acting oral antipsychotic penfluridol: Illustrative case series.

AIM: In this study, we sought to determine clinical outcomes at 1 year for patients prescribed penfluridol in an inner London National Health Service Trust. Using noninterventional data, we describe the use, effectiveness and safety of this treatment modality. RESULTS: We retrospectively followed up 17 patients prescribed penfluridol as part of routine clinical practice. All patients took penfluridol once weekly. Of these patients, 12 (70.6%) were considered treatment resistant. The average duration of illness for this cohort was 10 years (SD = 6.7). At 1 year, nine (53%) patients remained on treatment. Median survival time was not reached at 1-year follow-up; mean time on penfluridol was 251 days (95% confidence interval (CI), 184-318). The mean number of admissions to hospital in the year following penfluridol initiation was 0.6 compared with 0.8, 1 year before initiation (p = 0.465). The median number of bed days 1 year before penfluridol initiation was 24, whereas in the year following penfluridol initiation, it was 0 (p = 0.514). CLINICAL IMPLICATIONS: Although penfluridol is unlicensed in the United Kingdom, limited data suggest that this long-acting oral therapy has the potential to be used safely and effectively for the treatment of psychotic disorders. However, more data are required to establish the place of penfluridol and other potential long-acting oral antipsychotic formulations in the treatment of psychotic disorders.

Penfluridol overcomes paclitaxel resistance in metastatic breast cancer.

Paclitaxel is a first line chemotherapeutic agent for the patients with metastatic breast cancer. But inherited or acquired resistance to paclitaxel leads to poor response rates in a majority of these patients. To identify mechanisms of paclitaxel resistance, we developed paclitaxel resistant breast cancer cell lines, MCF-7 and 4T1 by continuous exposure to paclitaxel for several months. Western blot analysis showed increased expression of HER2 and ß-catenin pathway in resistant cell lines as compared to parent cells. Hence, we hypothesized that HER2/ß-catenin mediates paclitaxel resistance in breast cancer and suppression of HER2/ß-catenin signaling could overcome paclitaxel resistance. Our data showed that penfluridol (PFL) treatment significantly reduced the survival of paclitaxel-resistant cells. Western blot analysis revealed that PFL treatment suppressed HER2, as well as, ß-catenin pathway. In vivo data confirmed that PFL significantly potentiated tumor growth suppressive effects of paclitaxel in an orthotropic breast cancer model. In addition, tumors from paclitaxel and PFL-treated mice showed reduced HER2 and ß-catenin expression, along with increased apoptosis. Taken together our results demonstrate a novel role of HER2/ß-catenin in paclitaxel resistance and open up new avenues for application of PFL as a therapeutic option for overcoming paclitaxel resistance.

Chlorpromazine versus penfluridol for schizophrenia.

BACKGROUND: The efficacy of chlorpromazine, a benchmark antipsychotic, has not been fully assessed in direct comparison with different individual antipsychotics. Penfluridol is another old antipsychotic with a long half-life so one oral dose may last up to one week. This could confer advantage. OBJECTIVES: To assess the clinical effects of chlorpromazine compared with penfluridol for adults with schizophrenia. SEARCH METHODS: On 31 March 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitations for inclusion of records in the register. SELECTION CRITERIA: We included all randomised clinical trials focusing on chlorpromazine versus penfluridol for adults with schizophrenia or related disorders. Outcomes of interest were death, service utilisation, global state, mental state, adverse effects and leaving the study early. We included trials meeting our selection criteria and reporting useable data. DATA COLLECTION AND ANALYSIS: We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we planned to estimate the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS: The review includes three studies with a total of 130 participants. Short-term results for hospital admissions showed no clear difference between chlorpromazine and penfluridol (1 RCT, n = 29, RR 0.19, 95% CI 0.01 to 3.60, low-quality evidence). No clear difference in the incidence of akathisia was found at medium term (2 RCTs, n = 85, RR 0.19, 95% CI 0.04 to 1.06, low-quality evidence), and similar numbers of participants - nearly half - from each treatment group left the study early (3 RCTs, n = 130, RR 1.21, 95% CI 0.83 to 1.77, low-quality evidence). The risk of needing additional antiparkinsonian medication was less in the chlorpromazine group (2 RCTs, n = 74, RR 0.70, 95% CI 0.51 to 0.95). No useable data reported clinically important change in global or mental state. No data were reported for relapse. No deaths were reported by the trials. AUTHORS' CONCLUSIONS: Only three small studies provided data and the quality of reporting and evidence is low. Limited data indicate the efficacy and adverse effects profiles of chlorpromazine and penfluridol are generally similar. Penfluridol, however, may confer advantage by needing to be given only once per week. Firm conclusions are not possible without good-quality trials, and where these treatments are used, such trials are justified.

Penfluridol for schizophrenia.

BACKGROUND: Penfluridol, available since 1970, is an unusual long acting oral antipsychotic agent for the treatment of schizophrenia. It may be considered a depot medication as it is administered once a week. OBJECTIVES: To review the effects of penfluridol for treatment of those with schizophrenia and schizophrenia-like illnesses in comparison to placebo, other antipsychotic medication or no intervention. SEARCH STRATEGY: We undertook electronic searches of the Cochrane Schizophrenia Group's Register (2005), the Cochrane Central Register of Controlled Trials (2003-5) and LILACS (1982-2005). We hand searched references of all identified studies and sought citations of these studies in the Science Citation Index. We contacted the authors of trials and the manufacturer of penfluridol. SELECTION CRITERIA: We reliably selected all randomised clinical trials comparing penfluridol to placebo or typical or atypical antipsychotic drugs for schizophrenia or serious mental illness. DATA COLLECTION AND ANALYSIS: We independently extracted and analysed data on an intention-to-treat basis. We calculated the relative risk (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data using a random effects model, and where possible calculated the number needed to treat. We calculated weighted mean differences (WMD) for continuous data. MAIN RESULTS: We included twenty-five studies with a total of 1024 participants. Most of these studies were undertaken in the 1970s when penfluridol was launched. Ten studies, with 365 patients, compared penfluridol to placebo. In the meta-analysis of medium-term lasting studies, penfluridol was superior to placebo in the main efficacy measures: 'improvement in global state' (n=159, 4 RCTs, RR 0.69 CI 0.6 to 0.8, NNT 3 CI 2 to 10) and 'needing additional antipsychotic' (n=138, 5 RCTs, RR 0.43 CI 0.2 to 0.8, NNT 3 CI 1.8 to 20).A total of 449 patients from eleven studies were randomised to penfluridol or oral typical antipsychotics. There were no particular differences between penfluridol versus chlorpromazine, fluphenazine, trifluoperazine, thioridazine, or thiothixene for the main outcome measures in medium-term trials: 'improvement on global state' (N=2 studies), 'leaving the study early' (N=6), 'needing additional antipsychotic' (N=3), needing antiparkinsonian medication (N=2), and side-effects. Six studies, with 274 patients, compared penfluridol to depot typical antipsychotics. In general, for the efficacy and safety measures, no differences were established, but penfluridol was superior in keeping the patients in treatment; 'leaving the study early' (n=218, 5RCTs, RR 0.55 CI 0.3 to 0.97, NNT 6 CI 3.4 to 50). AUTHORS' CONCLUSIONS: Although there are shortcomings and gaps in the data, there appears to be enough overall consistency for different outcomes. The efficacy and adverse effects profile of penfluridol are similar to other typical antipsychotics; both oral and depot. Furthermore, penfluridol is shown to be an adequate treatment option for people with schizophrenia, especially those who do not respond to oral medication on a daily basis and do not adapt well to depot drugs. One of the results favouring penfluridol was a lower drop out rate in medium term when compared to depot medications. It is also an option for chronic sufferers of schizophrenia with residual psychotic symptoms who nevertheless need continuous use of antipsychotic medication. An additional benefit of penfluridol is that it is a low-cost intervention.

Safety of haloperidol and penfluridol in pregnancy: a multicenter, prospective, controlled study.

OBJECTIVE: To assess the safety of the butyrophenone neuroleptics haloperidol and penfluridol in pregnancy. METHOD: The rate of major anomalies was compared between a cohort of pregnant women counseled for gestational exposure to haloperidol or penfluridol and a control group counseled for nonteratogen exposure. This multicenter, prospective, controlled study was conducted within the European Network of Teratology Information Services (ENTIS) and included women who contacted 1 of 4 teratology information services for counseling between January 1989 and December 2001. RESULTS: We followed up on the outcomes of 215 pregnancies exposed to haloperidol (N = 188) or penfluridol (N = 27)-78.2% (of 206) were in the first trimester-and compared to outcomes of 631 ENTIS controls. The rate of congenital anomalies did not differ between the haloperidol/penfluridol-exposed group and the control group (6/179 = 3.4% vs. 22/581 = 3.8%, p = .787). No difference was found by limiting the analysis to those exposed to butyrophenones during the first trimester. There were 2 cases of limb defects in the butyrophenone-exposed group (1 after haloperidol and 1 after penfluridol exposure) and none in the controls. A higher rate of elective terminations of pregnancy (8.8% vs. 3.8%, p = .004), a higher rate of preterm birth (13.9% vs. 6.9%, p = .006), a lower median birth weight (3155 g vs. 3370 g, p < .001), and a lower median birth weight of full-term infants (3250 g vs. 3415 g, p = .004) were found in the butyrophenone-exposed group compared to the controls. CONCLUSION: This study suggests that haloperidol and penfluridol do not represent a major teratogenic risk. Since a possible association between butyrophenone exposure and limb defects cannot be ruled out with this sample size, a level II ultrasound with emphasis on the limbs should be considered in pregnancies with first trimester exposure.

Comparative short-term evaluation of penfluridol and trifluoperazine in chronic schizophrenia.

A double blind comparative study was conducted to evaluate the efficacy and safety of penfluridol and trifluoperazine in patients of chronic schizophrenia. Penfluridol was administered once weekly while trifluoperazine was administered twice daily by preparing identical capsules. The data revealed that both the compounds were similarly effective in maintaining control of symptoms of chronic schizophrenia. However, penfluridol has a definite advantage over trifluoperazine since it is administered once a week instead of twice a day.

Study of penfluridol and chlorpromazine in the treatment of chronic schizophrenia.

This study presents data on the use of penfluridol, a once-a-week orally administered, antipsychotic agent, in the treatment of chronic schizophrenic patients. Fifty-nine patients participated in the initial dose titration segment during which doses of penfluridol were adjusted weekly until the patients' condition became stabilized. The starting dose did not exceed 60 mg per week, and the maximum weekly dose did not exceed 140 mg. Forty-one of these patients continued on to participate in a double-blind comparison of penfluridol with chlorpromazine. Maximum doses did not exceed 140 mg per dose per week for penfluridol and 7350 mg per week for chlorpromazine in the double-blind segment. Patients were abruptly switched from their previous neuroleptic medication to penfluridol without loss of control. Side effects, mainly extrapyramidal in nature, were readily alleviated with benztropine mesylate. Penfluridol, administered orally once a week, appeared to be well tolerated; it was comparable to daily chlorpromazine in treating and maintaining schizophrenic patients.

Penfluridol: a long acting oral antipsychotic drug.

Penfluridol is a diphenylbutylpiperdine derivative with a half-life of sixty-six (66) hours. The present study was designed to determine its efficacy for the maintenance of schizophrenia. In a 52 week double-blind study, once weekly doses of penfluridol were compared with once daily doses of chlorpromazine in 56 schizophrenic patients receiving maintenance treatment on an outpatient basis. Both drugs were similar in their clinical effectiveness; no major side effects occurred with either drug.

A controlled study of penfluridol in the treatment of chronic schizophrenia.

Twenty patients were treated with penfluridol and 21 with fluphenazine for a period of up to 1 year. Penfluridol, an oral neuroleptic administered weekly was as efficacious as fluphenazine administered twice daily and appeared to be superior to fluphenazine in improving emotional withdrawal and anergia. The low incidence of side effects and other signs of toxicity, coupled with an effective prophylactic activity, suggests that penfluridol is an important addition to our therapeutic armamentarium for the treatment of chronic schizophrenia.

Side effects in the neonate from psychotropic agents excreted through breast-feeding.

Neuroleptics, antidepressants, lithium, anxiolytics, and hypnotics may be excreted in breast milk. Because of the danger to the neonate, drugs such as diazepam, lithium, bromides, reserpine, and opium alkaloids should not be given to lactating women, and barbiturates, haloperidol, and penfluridol should be administered with caution. The side effects produced as a result of breast-feeding of the infant by mothers consuming psychotropic drugs are reviewed and possible preventive measures are discussed.

A twelve month comparison of penfluridol and trifluoperazine in chronic schizophrenic outpatients.

This investigation is a 52-week double-blind study comparing the efficacy and safety of penfluridol and trifluoperazine in 25 chronic schizophrenic outpatients. Penfluridol was administered once weekly and trifluoperazine daily. Measurements were made at baseline, various fixed intervals during the study period and termination. The data reveals that both agents were similarly effective in maintaining control of the symptoms of chronic schizophrenic patients at a level commensurate with or better than that provided by their previous medication. Besides being effective, medications were also well tolerated. The side effects were characteristic of marketed neuroleptics. Akathisia was more common with penfluridol but readily controlled with anti-parkinsonian medication. Other side effects were similar in severity and occurrence between study-drug groups. Both agents had low autonomic liability, and neither agent was depressogenic.

A long term comparative trial of penfluridol and fluphenazine decanoate in schizophrenic outpatients.

Penfluridol, a diphenylbutylpiperidene derivative, is a new long acting neuroleptic, administered orally, once weekly. It is marketed in several European countries and has been used successfully in the treatment of various acute psychoses, for severely ill chronic schizophrenic patients, and as maintenance therapy for chronic schizophrenic patients. The present study was designed to compare, in a double-blind fashion, the efficacy of penfluridol and fluphenazine decanoate in the maintenance therapy of schizophrenic outpatients.

[Penfluridol. Results of a year-long clinical trial]. / Penfluridol. ergebnisse einer einjährigen klinischen prüfung.

During an open clinical trial, 51 schizophrenic patients were treated with Penfluirdol, 34 for 1 year and 17 for a shorter time. The mean dosage of Penfluirdol was 22 up to 28 mg per week. Assessments were made on days 0, 14, 28, 56, 90, 180, 270, and 365 using the AMP system and the EPRS scale of Simpson and Angus. The symptomatology was mainly reduced during the first 3 months of treatment and remained afterwards relative unchanged. Penfluridol showed a good antipsychotic effect on productive schizophrenic symptoms (thought disorders and paranoid symptoms, autism and schizophrenic affective disorders). The dosage used showed only a slight sedative effect and was well tolerated concerning autonomic and extrapyramidal side-effects.

Penfluridol: an open phase III study in acute newly admitted hospitalized schizophrenic patients.

An open study was carried out in 17 acutely ill, newly admitted, floridly psychotic schizophrenic patients to a city hospital in New York. Penfluridol was given on a daily basis up to doses of 120 mg and patients were rated objectively by means of different psychometric evaluations; vital signs were monitored daily as were side effects. The drug was found to be a rapid acting, well-tolerated, and highly effective antipsychotic agent within the population of patients explored and within the dose range used. It was particularly effective in acutely agitated floridly paranoid schizophrenics; a statistically significant impact was achieved by 7 days and usually within 72 h after initiating treatment. The drug appears unique in that (1) its effects are realized without the untoward and usually troublesome effects of nonspecific sedation attendant upon the use of many other 'neuroleptic' medications, and (2) even within the relatively high doses used it produced no hypotensive effects. It is concluded that this appears to be a unique antipsychotic agent and a potentially important addition to the treatment armamentarium of both acute and chronic schizophrenic individuals.