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Free Radical Biology & Medicine Aug 2016Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by progressive loss of motor neurons, gliosis, neuroinflammation and...
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by progressive loss of motor neurons, gliosis, neuroinflammation and oxidative stress. The aim of this study was to evaluate the involvement of NADPH oxidases (NOX) in the oxidative damage and progression of ALS neuropathology. We examined the pattern of NOX expression in spinal cords of patients and mouse models of ALS and analyzed the impact of genetic deletion of the NOX1 and 2 isoforms as well as pharmacological NOX inhibition in the SOD1(G93A) ALS mouse model. A substantial (10-60 times) increase of NOX2 expression was detected in three etiologically different ALS mouse models while up-regulation of some other NOX isoforms was model-specific. In human spinal cord samples, high NOX2 expression was detected in microglia. In contrast to previous publications, survival of SOD1(G93A) mice was not modified upon breeding with constitutive NOX1 and NOX2 deficient mice. As genetic deficiency of a single NOX isoform is not necessarily predictive of a pharmacological intervention, we treated SOD1(G93A) mice with broad-spectrum NOX inhibitors perphenazine and thioridazine. Both compounds reached in vivo CNS concentrations compatible with NOX inhibition and thioridazine significantly decreased superoxide levels in the spinal cord of SOD1(G93A) mice in vivo. Yet, neither perphenazine nor thioridazine prolonged survival. Thioridazine, but not perphenazine, dampened the increase of microglia markers in SOD1(G93A) mice. Thioridazine induced an immediate and temporary enhancement of motor performance (rotarod) but its precise mode of action needs further investigation. Additional studies using specific NOX inhibitors will provide further evidence on the relevance of NOX as drug targets for ALS and other neurodegenerative disorders.
Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Animals; Disease Models, Animal; Female; Gene Expression Regulation; Humans; Male; Mice; Middle Aged; Motor Neurons; NADPH Oxidase 1; NADPH Oxidase 2; Perphenazine; Spinal Cord; Superoxide Dismutase-1; Thioridazine
PubMed: 27212019
DOI: 10.1016/j.freeradbiomed.2016.05.016 -
The Journal of Clinical Psychiatry Mar 2011We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD.
METHOD
This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with χ(2) tests. Data were collected from January 2001 to December 2004.
RESULTS
Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (χ(2)(1) = 0.11, P = .743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ≥ 50% decrease in AIMS score, and 7% showed a ≥ 50% increase in AIMS score.
CONCLUSIONS
Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00014001.
Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chi-Square Distribution; Dibenzothiazepines; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Movement Disorders; Olanzapine; Perphenazine; Piperazines; Proportional Hazards Models; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Thiazoles; Treatment Outcome
PubMed: 20816031
DOI: 10.4088/JCP.09m05793yel -
Fertility and Sterility Apr 1984Six euprolactinemic polycystic ovary syndrome (PCOS) patients were subjected to a 24-hour study with serum sampling every 30 minutes and a perphenazine stimulation test....
Six euprolactinemic polycystic ovary syndrome (PCOS) patients were subjected to a 24-hour study with serum sampling every 30 minutes and a perphenazine stimulation test. The serum prolactin (PRL) levels were compared with those of five healthy normoprolactinemic women whose cases were evaluated in a similar fashion. In addition to evaluating the PRL secretory pattern and lactotroph response, the PCOS individuals were given dopamine agonist therapy in a graduated dosage schedule, increasing each month, over a 3-month interval. The PCOS patients exhibited parallel but lower PRL levels than the control subjects during the late evening and early morning hours (P less than 0.0001) and were less responsive to perphenazine at the 6-hour sampling (P less than 0.05). Only one PCOS individual had suggestive evidence of ovulation over the 15 cycles the group was monitored. Therefore, we conclude that euprolactinemic PCOS patients who are nocturnal hyposecretors of PRL and who hyporespond to a perphenazine stimulation test are not likely to ovulate on bromocriptine in the dosages used in this study.
Topics: Adult; Bromocriptine; Circadian Rhythm; Drug Administration Schedule; Female; Humans; Ovulation; Ovulation Induction; Perphenazine; Polycystic Ovary Syndrome; Prognosis; Prolactin
PubMed: 6538517
DOI: No ID Found -
JAMA Psychiatry Apr 2018Mood stabilizers and antipsychotics are the main maintenance treatments for bipolar disorder. Lithium is considered to be the most effective mood stabilizer, but very... (Comparative Study)
Comparative Study
IMPORTANCE
Mood stabilizers and antipsychotics are the main maintenance treatments for bipolar disorder. Lithium is considered to be the most effective mood stabilizer, but very little is known about overall health outcomes associated with specific treatments and the comparative long-term effectiveness of specific psychotropics or routes of administration in the prevention of rehospitalizations.
OBJECTIVE
To study the comparative effectiveness of pharmacologic treatments in the prevention of rehospitalization in a nationwide cohort of patients with bipolar disorder.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study examined the risk of psychiatric, cardiovascular, and all-cause hospitalization from January 1, 1987, to December 31, 2012, among all patients in Finland who had been hospitalized for bipolar disorder (N = 18 018; mean follow-up time, 7.2 years) using prospectively gathered nationwide databases for hospitalization and dispensed medications. The primary analysis was within-individual analysis, in which each individual was used as his or her own control to eliminate selection bias. The study adjusted for the effect of concomitant psychotropic medications, duration of illness, and the temporal orders of exposure and nonexposure periods. Statistical analysis was conducted from January 1, 1996, to December 31, 2012.
MAIN OUTCOMES AND MEASURES
Adjusted hazard ratios (HRs) for rehospitalization were calculated.
RESULTS
Among the cohort (9558 women and 8460 men; mean [SD] age, 46.6 [17.0] years), 9721 patients (54.0%) had at least 1 psychiatric rehospitalization. In comparison between use and no use among specific agents reaching nominal statistical significance, risperidone long-acting injection (HR, 0.58 [95% CI, 0.34-1.00]), gabapentin (HR, 0.58 [95% CI, 0.44-0.77]), perphenazine long-acting injection (HR, 0.60 [95% CI, 0.41-0.88]), and lithium carbonate (HR, 0.67 [95% CI, 0.60-0.73]) were associated with the lowest risk of psychiatric rehospitalization. Concerning all-cause hospitalization, lithium (HR, 0.71 [95% CI, 0.66-0.76]) was associated with the lowest risk. The most frequently used antipsychotic treatment, quetiapine fumarate, showed only modest effectiveness (risk of psychiatric rehospitalization: HR, 0.92 [95% CI, 0.85-0.98]; risk of all-cause hospitalization: HR, 0.93 [95% CI, 0.88-0.98]). Long-acting injections were associated with substantially better outcomes compared with identical oral antipsychotics (risk of psychiatric rehospitalization: HR, 0.70 [95% CI, 0.55-0.90]; risk of all-cause hospitalization: HR, 0.70 [95% CI, 0.57-0.86]). Results from sensitivity analyses showed consistent beneficial effects only for lithium and for long-acting injections compared with their oral counterparts.
CONCLUSIONS AND RELEVANCE
Lithium was the most effective mood stabilizer, and long-acting injections the most effective antipsychotics, in preventing hospitalization due to mental or physical illness.
Topics: Administration, Oral; Adult; Bipolar Disorder; Cohort Studies; Delayed-Action Preparations; Drug Therapy, Combination; Female; Follow-Up Studies; Gabapentin; Humans; Injections, Intramuscular; Lithium Carbonate; Male; Middle Aged; Patient Readmission; Perphenazine; Prospective Studies; Psychotropic Drugs; Quetiapine Fumarate; Risk; Risperidone; Treatment Outcome
PubMed: 29490359
DOI: 10.1001/jamapsychiatry.2017.4711 -
Schizophrenia Research Aug 2008Recent literature documents a stronger association between nonfasting triglycerides (TG) and cardiovascular risk compared to fasting TG. Given concerns over... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Recent literature documents a stronger association between nonfasting triglycerides (TG) and cardiovascular risk compared to fasting TG. Given concerns over antipsychotic effects on serum TG, this analysis explored changes in nonfasting TG in phase 1 of the CATIE Schizophrenia Trial.
METHODS
Change in nonfasting TG, adjusted for baseline value, was compared between antipsychotic treatment groups using subjects with nonfasting laboratory assessments at baseline and 3 months.
RESULTS
Among the 246 subjects there were significant treatment differences in 3-month change from baseline (p=0.009). The greatest increases in median and adjusted mean nonfasting TG levels were seen among those randomized to quetiapine (mean+54.7 mg/dl, median+26 mg/dl) and olanzapine (mean+23.4 mg/dl, median+26.5 mg/dl), while ziprasidone was neutral (mean+0.0 mg/dl, median+8 mg/dl), and decreases were seen with risperidone (mean -18.4 mg/dl, median -6.5 mg/dl) and perphenazine (mean -1.3 mg/dl, median -22 mg/dl). Pairwise comparisons indicated a significant between-group difference for perphenazine vs. olanzapine (p=0.002) and a trend for perphenazine vs. quetiapine (p=0.006).
CONCLUSIONS
This analysis provides further evidence for differential antipsychotic metabolic liabilities, and confirms signals for the effects of olanzapine and quetiapine on serum TG seen in earlier CATIE analyses. Future consensus recommendations will clarify the role of nonfasting TG monitoring in routine clinical practice.
Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cardiovascular Diseases; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Perphenazine; Piperazines; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; Thiazoles; Triglycerides
PubMed: 18534821
DOI: 10.1016/j.schres.2008.04.023 -
Canadian Medical Association Journal Apr 1979During the last decade there has been a substantial increase in the number of poisonings due to tricyclic antidepressants in both children and adults. The main toxic... (Review)
Review
During the last decade there has been a substantial increase in the number of poisonings due to tricyclic antidepressants in both children and adults. The main toxic manifestations are of anticholinergic origin, and the most frequent constitute the so-called central anticholinergic syndrome. Most of the deaths result from the cardiac complications. Three cases are presented that illustrate chiefly the toxic manifestations related to the central nervous system. The therapeutic management is reviewed in the light of the metabolism of the tricyclic antidepressants, their pharmacologic action and the mechanism of their toxic effects.
Topics: Adolescent; Amitriptyline; Antidepressive Agents, Tricyclic; Cardiovascular Diseases; Central Nervous System Diseases; Diazepam; Female; Gastric Lavage; Humans; Infant; Male; Perphenazine; Physostigmine; Psychoses, Substance-Induced
PubMed: 373877
DOI: No ID Found -
British Journal of Anaesthesia Feb 1998We have compared the effects of ondansetron and perphenazine on vomiting after tonsillectomy in 216 healthy children, aged 2-12 yr. The study was randomized, stratified,... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
We have compared the effects of ondansetron and perphenazine on vomiting after tonsillectomy in 216 healthy children, aged 2-12 yr. The study was randomized, stratified, blocked and double blind. Anaesthesia was induced with propofol i.v. or by inhalation of halothane and nitrous oxide. Ondansetron 150 micrograms kg-1 or perphenazine 70 micrograms kg-1 was administered i.v. after induction of anaesthesia in a double-blind manner. Perioperative management of emesis, pain, fluids and patients discharge were standardized. Ondansetron and perphenazine had similar effects on postoperative vomiting (44% vs 41%; ondansetron vs perphenazine P = 0.77). By logistic regression analysis, the only significant predictor of postoperative vomiting was sex, that is males had a greater incidence of vomiting (49% vs 35%; P = 0.016). In-hospital vomiting was associated with a prolongation of stay in the day-care surgical unit of 7 min per episode of vomiting (P = 0.015). We conclude that ondansetron and perphenazine had similar effects on vomiting in children after tonsillectomy in a day-case setting.
Topics: Ambulatory Surgical Procedures; Anesthesia, Inhalation; Anesthesia, Intravenous; Antiemetics; Child; Child, Preschool; Double-Blind Method; Humans; Ondansetron; Perphenazine; Postoperative Complications; Sex Factors; Tonsillectomy; Vomiting
PubMed: 9602577
DOI: 10.1093/bja/80.2.155 -
Proceedings of the National Academy of... Mar 1999Full term pregnancy early in life is the most effective natural protection against breast cancer in women. Rats treated with chemical carcinogen are similarly protected...
Full term pregnancy early in life is the most effective natural protection against breast cancer in women. Rats treated with chemical carcinogen are similarly protected by a previous pregnancy from mammary carcinogenesis. Proliferation and differentiation of the mammary gland does not explain this phenomenon, as shown by the relative ineffectiveness of perphenazine, a potent mitogenic and differentiating agent. Here, we show that short term treatment of nulliparous rats with pregnancy levels of estradiol 17beta and progesterone has high efficacy in protecting them from chemical carcinogen induced mammary cancers. Because the mammary gland is exposed to the highest physiological concentrations of estradiol and progesterone during full term pregnancy, it is these elevated levels of hormones that likely induce protection from mammary cancer. Thus, it appears possible to mimic the protective effects of pregnancy against breast cancer in nulliparous rats by short term specific hormonal intervention.
Topics: Animals; Anticarcinogenic Agents; Breast Neoplasms; Cell Differentiation; Cell Division; Estradiol; Female; Humans; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Methylnitrosourea; Perphenazine; Pregnancy; Progesterone; Rats; Rats, Inbred Lew
PubMed: 10051675
DOI: 10.1073/pnas.96.5.2520 -
Emergency Medicine International 2023To describe the clinical presentation of acute dystonia (AD) from drug abuse or misuse, as well as the emergency department (ED) management and outcomes in adolescents...
OBJECTIVES
To describe the clinical presentation of acute dystonia (AD) from drug abuse or misuse, as well as the emergency department (ED) management and outcomes in adolescents and young adults.
METHODS
This was a retrospective cohort study of patients aged 10-25 years who were admitted to the ED for AD due to intentional abuse or misuse from January 1, 2014, to June 30, 2017. Data were collected from electronic medical records by three investigators with excellent interrater reliability (0.87).
RESULTS
Sixty-two cases met the criteria with male predominance (85.5%); the mean age was 16.7 years. Perphenazine was the most common cause of AD (38.7%), followed by haloperidol (32.2%). The most common AD manifestations were torticollis (51.6%), oromandibular dystonia (45.2%), and oculogyric crisis (22.6%). Intravenous (IV) diazepam combined with oral trihexyphenidyl and IV diazepam alone were the most frequently used first treatment in our ED (41.7% and 35.0%, respectively). Overall, the improvement rates from IV diazepam alone or combined with trihexyphenidyl ranged from 46.2%-75.0%. These rates were inferior to those observed with IV benztropine (100%) alone or combined with trihexyphenidyl. All patients were treated on an outpatient basis, except for one who was admitted to a pediatric ward.
CONCLUSIONS
In recent years, drug-induced AD caused by intentional abuse among adolescents and young adults has become a concern in Thailand. The most common suspected drugs of abuse were first-generation antipsychotics, perphenazine, and haloperidol. The most effective treatment was benztropine.
PubMed: 37057297
DOI: 10.1155/2023/2725974 -
BMC Psychiatry Feb 2006There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia. This naturalistic study... (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia. This naturalistic study compares atypical and typical antipsychotics on time to all-cause medication discontinuation, a recognized index of medication effectiveness in the treatment of schizophrenia.
METHODS
We used data from a large, 3-year, observational, non-randomized, multisite study of schizophrenia, conducted in the U.S. between 7/1997 and 9/2003. Patients who were initiated on oral atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone) or oral typical antipsychotics (low, medium, or high potency) were compared on time to all-cause medication discontinuation for 1 year following initiation. Treatment group comparisons were based on treatment episodes using 3 statistical approaches (Kaplan-Meier survival analysis, Cox Proportional Hazards regression model, and propensity score-adjusted bootstrap resampling methods). To further assess the robustness of the findings, sensitivity analyses were performed, including the use of (a) only 1 medication episode for each patient, the one with which the patient was treated first, and (b) all medication episodes, including those simultaneously initiated on more than 1 antipsychotic.
RESULTS
Mean time to all-cause medication discontinuation was longer on atypical (N = 1132, 256.3 days) compared to typical antipsychotics (N = 534, 197.2 days; p < .01), and longer on atypicals compared to typicals of high potency (N = 320, 187.5 days; p < .01), medium potency (N = 140, 213.5 days; p < .01), and low potency (N = 74, 208.7 days; p < .01). Among the atypicals, only clozapine, olanzapine, and risperidone had significantly longer time to all-cause medication discontinuation compared to typicals, regardless of potency level, and compared to haloperidol with prophylactic anticholinergic treatment. When compared to perphenazine, a medium-potency typical antipsychotic, only clozapine and olanzapine had a consistently and significantly longer time to all-cause medication discontinuation. Results were confirmed by sensitivity analyses.
CONCLUSION
In the usual care of schizophrenia patients, time to medication discontinuation for any cause appears significantly longer for atypical than typical antipsychotics regardless of the typical antipsychotic potency level. Findings were primarily driven by clozapine and olanzapine, and to a lesser extent by risperidone. Furthermore, only clozapine and olanzapine therapy showed consistently and significantly longer treatment duration compared to perphenazine, a medium-potency typical antipsychotic.
Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bias; Clozapine; Drug Administration Schedule; Episode of Care; Female; Follow-Up Studies; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Perphenazine; Proportional Hazards Models; Research Design; Risperidone; Schizophrenia; Time Factors; Treatment Outcome; United States
PubMed: 16504026
DOI: 10.1186/1471-244X-6-8