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PubMed1989

The relationship between perphenazine plasma levels and clinical response in acute schizophrenia.

1. Twelve patients with schizophrenia according to RDC participated in a double-blind study, comparing two dose levels of perphenazine, 16 or 32 mg, during four weeks. 2. The patients were assessed with a subscale to CPRS and global scores, measuring improvement of regular intervals during four weeks. 3. Blood samples for assay of plasma perphenazine were collected once a week. 4. These results are in many respects in accordance with earlier published data with perphenazine, that is a good clinical response is achieved with a plasma concentration of perphenazine between 1-5 nmol/L. 5. No incidence of severe adverse symptoms were observed.

Adult↗

PubMed1996

The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol.

BACKGROUND: Most antidepressant and neuroleptic agents are metabolized by the polymorphic cytochrome P450 enzyme CYP2D6. This study evaluates the importance of the CYP2D6 genotype for the disposition of the neuroleptic agents perphenazine and zuclopenthixol. METHODS: Patients treated with neuroleptic agents (n = 36) were studied prospectively with regard to CYP2D6 genotype and neuroleptic plasma concentration during oral treatment. Because no patient provided enough samples for individual kinetic modeling, a bayesian approach was used for determination of the clearance. Population kinetic parameters for this procedure were collected from retrospective therapeutic drug monitoring data (n = 113) by use of a nonparametric approach. RESULTS: The CYP2D6 genotype significantly predicted the oral clearance of perphenazine and zuclopenthixol (p < 0.01 by multiple regression). The difference in clearance between homozygous extensive metabolizers and poor metabolizers was threefold for perphenazine and twofold for zuclopenthixol. CONCLUSION: The results show that the genotype for CYP2D6 is closely related to the oral clearances of perphenazine and zuclopenthixol. If this finding can be confirmed in a larger population, genotyping may become an important tool for the dosing of these two neuroleptic agents.

Administration, Oral↗

PubMed1999

Anti-emetic efficacy of prophylactic granisetron compared with perphenazine for the prevention of post-operative vomiting in children.

We have compared the efficacy of granisetron with perphenazine in the prevention of vomiting after tonsillectomy with or without adenoidectomy in children. In a prospective, randomized, double-blind study, 90 paediatric patients, ASA I, aged 4-10 years, received granisetron 40 mg kg-1 or perphenazine 70 mg kg-1 (n = 45 each) intravenously immediately after an inhalation induction of anaesthesia. A standard general anaesthetic technique was employed throughout. A complete response, defined as no emesis with no need for another rescue antiemetic, during the first 3 h (0-3 h) after anesthesia was 87% with granisetron and 78% with perphenazine (P = 0.204). The corresponding incidence during the next 21 h (3-24 h) after anaesthesia was 87% and 62% (P = 0.007). No clinically serious adverse events were observed in any of the groups. We conclude that granisetron is a better anti-emetic than perphenazine for the long-term prevention of post-operative vomiting in children undergoing general anaesthesia for tonsillectomy.

Adenoidectomy↗

PubMedDate not supplied

Perphenazine distribution in a postmortem case.

The case of a 34-year-old, mentally challenged, Caucasian female found dead in a group home is presented. Empty containers of perphenazine and valproic acid were found next to her bed. The perphenazine had been prescribed to another patient. No anatomic cause of death was determined at autopsy. Comprehensive testing of the heart blood for ethanol and drugs identified perphenazine at a concentration of 4.4 mg/L and valproic acid at a concentration of 950 mg/L. The distribution of perphenazine in other specimens was consistent with previously reported phenothiazine cases. The medical examiner ruled that the cause of death in this case was multiple drug intoxication and the manner of death was suicide.

Adult↗

PubMed1993

High-performance liquid chromatographic determination of perphenazine in plasma.

A reversed-phase high-performance liquid chromatographic (HPLC) method for the analysis of perphenazine in rabbit plasma was developed. Amitriptyline HCl was used as the internal standard. The chromatography was performed using a Microsorb-CN column; the mobile phase consisted of 85:15 methanol/0.005 M ammonium acetate buffer; flow rate of 1.6 ml/min; and ultraviolet detection at 254 nm. Retention times were 10.8 and 18.1 min for perphenazine and amitriptyline HCl, respectively. The recovery of perphenazine added to plasma in the concentration range of 0.05-5 micrograms/ml was found to be greater than 80%. This procedure was used for the analysis of plasma samples collected over time following the oral administration of perphenazine tablets in rabbits.

Animals↗

PubMed1980

Clopenthixol decanoate and perphenazine enanthate in schizophrenic patients. A double-blind Nordic multicentre trial.

The clinical properties of clopenthixol decanoate has been investigated versus perphenazine enanthate in a double-blind clinical multicentre trial including 14 psychiatric hospitals in Finland, Sweden, Norway, and Denmark. Test treatment was initiated in 172 chronic schizophrenic patients and the planned 6 months test period was completed by 57 patients receiving clopenthixol decanoate and 48 receiving perphenazine enanthate. The therapeutic effect was assessed by means of CGI, BPRS, and NOSIE-30 and was found significant with both test drugs. Significant differences in the effect were seen only in "Hostile-suspiciousness" (BPRS) and "Social interest" (NOSIE-30). For these items clopenthixol decanoate was found superior to perphenazine enanthate. The influence of side effects on the patients' functioning was found to be slightly, but not significantly more troublesome in the perphenazine enanthate patients.

Adult↗

PubMed1989

Sulpiride and perphenazine in schizophrenia. A double-blind clinical trial.

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.

Acute Disease↗

PubMed1977

Interaction of perphenazine with the kinetics of nortriptyline.

The kinetics of nortriptyline in four patients were investigated before and during treatment with perphenazine (24-36 mg/day) by administering 57 mg nortriptyline hydrochloride as an intravenous infusion and evaluating the resulting plasma concentration data according to a two compartment open model. In all patients an increased biological half-life as well as a decreased systemic clearance and rate of metabolism were found in the perphenazine-period, thus confirming the inhibitory effect of perphenazine on the metabolism of nortriptyline found in earlier studies. Some interaction with distribution parameters was also indicated, but on the whole the model parameters did not provide much further information about the interaction. Although the most pronounced changes were found with the patient getting the highest dose of perphenazine, the dose-effect relationship remains obscure.

Dose-Response Relationship, Drug↗

PubMed1978

Double-blind comparison of bromperidol and perphenazine.

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.

Adult↗

PubMed1982

Comparison of efficacy of a new butyrophenone derivative, timiperone and perphenazine in schizophrenia by a multicentre controlled 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.

Adolescent↗

PubMed1978

Loxapine versus perphenazine in psychotic patients. A double-blind, randomized, multicentre trial.

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.

Acute Disease↗

PubMed1975

Influence of anaesthetics on basal, perphenazine-induced and thyrotrophin releasing hormone-induced prolactin secretion in ovariectomized, oestrogen-treated rats.

Plasma levels of prolactin were determined, by radioimmunoassay, in ovariectomized, oestrogen-treated rats after administration of ether, sodium pentobarbitone, urethane, chloral hydrate or ketamine. These anaesthetics, when administered alone, induced sustained increases in the plasma level of prolactin (continuous ether inhalation), no change in prolactin secretion (urethane), or depressions in the level of prolactin (sodium pentobarbitone, chloral hydrate and ketamine). These same anaesthetics when given before perphenazine failed to alter the stimulatory effect of this phenothiazide on prolactin secretion. Sodium pentobarbitone did not alter the normal increase in prolactin concentration after intra-arterial administration of synthetic thyrotrophin releasing hormone (TRH). These results indicated that anaesthetics do not affect the response of either the central nervous system or the anterior pituitary to perphenazine or TRH although they affect prolactin secretion when administered alone. The site of action of anaesthetics must, therefore, be different from that of perphenazine or perphenazine must be capable of overcoming their influence by direct action on the pituitary.

Anesthetics↗

PubMed1976

Prolactin stimulation test with perphenazine: an evaluation of plasma prolactin levels and pituitary secretory activity in the rat.

Many investigations of the regulation of prolactin synthesis and release are based on single plasma prolactin determinations. The purpose of the present experiment was to ascertain whether groups of rats (i.e. young or adult, male or female animals, being either intact, gonadectomized or gonadectomized and treated with oestrone), differing in age and/or endocrine status, will react to a single dose of perphenazine by an acute release of pituitary prolactin in proportion to their initial plasma prolactin levels. No consistent relation existed between the classification of the twelve groups of rats into three categories of basal plasma prolactin levels (i.e. less than 20, 25-50, greater than 125 ng/ml) and their response to perphenazine. Even though all groups showed a highly significant increase of plasma prolactin levels the magnitude of the maximum prolactin response at 30 min varied greatly within the groups of one category and thus was not related to the initial prolactin levels. The effect of 14 days of oestrone treatment in increasing plasma prolactin levels in gonadectomized animals was greatest in young and adult male rats, less in young females and not significant in adult females. The results obtained after perphenazine treatment in the latter group made it clear that the effect of oestrogen treatment on prolactin release can be completely blocked by increasing synthesis and/or release of the prolactin-release inhibiting factor (PIF). Since perphenazine induces decrease of pituitary prolactin and a concomitant increase of plasma prolactin levels through lowered PIF-action, the positive effect of oestrogens on prolactin release (as observed in gonadectomized male and young female rats) apparently is caused by a different mode of action. The implications of these findings for the regulation of prolactin release, as affected by the endocrine status of the rat, is discussed. Moreover, comparison of prolactin lost from the pituitary and gained in the circulation of the experimental animals, with amounts of prolactin that were observed to disappear from plasma during the experiment, provided suggestive evidence that the capacity to synthesize and/or eliminate prolactin, after a sudden provoked release of the hormone, differed among the groups. The rates of synthesis by the pituitary, of release from the pituitary into the circulation as well as of elimination of the hormone from the circulation (equally involved in determing actual plasma levels) are thought, therefore, to be far more important for the elucidation of prolactin regulation than single plasma prolactin determinations.

Animals↗

PubMed1975

Prolactin and growth hormone synthesis: effects of perphenazine, alpha-methyltyrosine and estrogen in different thyroid states.

The effects of thyroid hormones on prolactin (PRL) and growth hormone (GH) synthesis by the rat anterior pituitary gland were assessed in vitro. A marked reduction (84-87%) in the rate of H3-leucine incorporation into GH was evident 2-4 weeks after thyroidectomy, while incorporation into PRL was 52-71% less than that measured in glands from intact rats. A single injection of T4 (200 mug/kg) administered to thyroidectomized (THX) rats 48 hr before sacrifice significantly increased incorporation into both pituitary hormones, although the stimulation of GH synthesis was much more dramatic. Perphenazine, alpha-methyltyrosine and estrogen enhanced the rate of PRL synthesis in intact rats. Thyroid ablation did not affect the response to perphenazine, but significantly increased the response to alpha-methyltyrosine and estrogen. On the other hand, administration of T4 to THX rats receiving perphenazine, alpha-methyltyrosine or estrogen diminished the stimulatory influence of these treatments on PRL synthesis. Perphenazine, alpha-methyltyrosine and estrogen had no effect on the rate of GH synthesis in THX rats, nor did they alter the ability of T4 to restore GH synthesis in these animals. These results indicate that GH synthesis in the rat is dependent upon thyroid hormones and support the concept that these hormones exert their stimulatory effect directly on pituitary somatotrophs. Pituitary lactotrophs, however, appear to retain much of their capacity to synthesize PRL under conditions of thyroid deficiency. The changes in pituitary PRL levels and synthesis rate induced by thyroid ablation might reflect differences in the number rather than the activity of these cells.

Animals↗

PubMed1999

Effectiveness of antipsychotic therapy in a naturalistic setting: a comparison between risperidone, perphenazine, and haloperidol.

BACKGROUND: Therapeutic ineffectiveness and noncompliance with antipsychotic agents are major contributors to rehospitalization in patients with psychotic disorders. It is unknown whether risperidone's favorable side effect profile compared with that of the conventional antipsychotics results in improved compliance and reduced hospitalizations in a naturalistic setting. The purpose of this study was to test the hypothesis that treatment with risperidone reduces readmission rates and associated costs when compared with treatment with perphenazine or haloperidol. METHOD: Inpatients prescribed either risperidone, perphenazine, or haloperidol between January 1, 1995, and December 31, 1995, as a single oral antipsychotic at discharge were retrospectively identified. Data were collected for that index hospitalization and for a 1-year follow-up period. Primary outcome measures included re-admission rates, changes in antipsychotic therapy, anticholinergic drug use, and costs. RESULTS: There were 202 evaluable patients (81 treated with risperidone, 78 with perphenazine, and 43 with haloperidol). Baseline demographics were similar between groups except that more patients in the risperidone group had a primary diagnosis of psychotic disorder or had been hospitalized in the year prior to study. The percentage of patients readmitted during the 1-year follow-up period was similar among drug groups (41% risperidone, 26% perphenazine, and 35% haloperidol) when controlled for baseline differences in diagnosis and hospitalization history (p = .32). Anticholinergic drug use was more common in the haloperidol group (p = .004). Mean yearly cost (drug + hospitalization) in the risperidone group was $20,317, nearly double that in the other treatment groups (p < .001). CONCLUSION: The results from this naturalistic study indicate that the high cost of risperidone is not offset by a reduction in readmission rates when compared with conventional antipsychotics.

Adolescent↗

PubMed2001

A double-blind randomized comparison of nortriptyline plus perphenazine versus nortriptyline plus placebo in the treatment of psychotic depression in late life.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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%). CONCLUSION: 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.

Affective Disorders, Psychotic↗

PubMed1975

Effects of perphenazine on imipramine metabolism in man.

In previous studies we have shown that perphenazine inhibits the metabolism of nortriptyline and imipramine. In this study the metabolism of 14C-imipramine and 14C-desipramine was studied before and during treatment with perphenazine. Studies on the imipramine and desipramine metabolites in urine showed that the major effect of perphenazine is an inhibition of the 2-hydroxylation of imipramine and desipramine. This causes a decreased formation and excretion of non-conjugated and glucuronide bound hydroxy metabolites and accumulation of imipramine and desipramine. There was some relationship between the dose of perphenazine and the decrease in total urinary excretion but the individual variations in response were pronounced (2-3-fold).

Adult↗

PubMed1991

[Experience with using etaperazine (perphenazine) in the treatment of patients with schizophrenia in a preschool psychiatric department].

The results of the treatment with perphenazine of 58 patients aged 5 to 7 years suffering from different forms of schizophrenia have been analyzed. Perphenazine was used in doses of 6 to 45 mg a day. The dosage was progressively increased until the optimal clinical effect was attained. The relationship was discovered between the range of psychopharmacological activity (from stimulating, organizing to antipsychotic and sedative) and the drug doses. The efficacy of the treatment with perphenazine correlated with the forms of schizophrenia, predominant syndromes in the disease clinical picture, and different stages of the process by the treatment commencement. Low toxicity and good tolerance of perphenazine, no pronounced side effects and complications were recorded. This made it possible to administer a wide range of the drug doses in the patients of the age group under study.

Child↗