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Scott T Stroup - One of the best experts on this subject based on the ideXlab platform.
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inflammatory markers in schizophrenia comparing antipsychotic effects in phase 1 of the clinical antipsychotic trials of intervention effectiveness study
Biological Psychiatry, 2009Co-Authors: Marvin S. Swartz, Sonia M. Davis, Jonathan M Meyer, Joseph P Mcevoy, Vicki G Davis, Donald C Goff, Henry A Nasrallah, John K Hsiao, Scott T StroupAbstract:Background C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin are systemic inflammatory markers (IM) that positively correlate with cardiovascular (CV) risk. Despite the known CV effects of atypical antipsychotics, there is limited prospective data on IM changes during treatment. Methods The IM outcomes were compared between antipsychotic treatment groups in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial phase 1 with subjects with laboratory assessments at baseline and 3 months ( n = 789). Results There were significant treatment differences in CRP, E-selectin, and ICAM-1 at 3 months, with a differential impact of baseline values on the CRP and ICAM-1 results. In overall comparisons, quetiapine and olanzapine had the highest median levels for CRP, and olanzapine for E-selectin and ICAM-1. Olanzapine was significantly different after baseline adjustment than Perphenazine ( p = .001) for E-selectin, and in those with low baseline CRP ( p p p = .002) for CRP. Perphenazine had the lowest 3-month ICAM-1 levels in subjects with baseline ICAM-1 above the median, but the differences were not statistically significant versus olanzapine ( p = .010), quetiapine ( p = .010), and risperidone ( p = .006) after controlling for multiple comparisons. The 18-month repeated measures CRP analysis confirmed the significantly higher values for olanzapine in those with low baseline CRP. Conclusions This analysis provides further evidence for differential antipsychotic metabolic liabilities as measured by changes in systemic inflammation. C-reactive protein might emerge as a useful target for CV risk outcomes in schizophrenia patients.
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neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the catie trial
Archives of General Psychiatry, 2007Co-Authors: Richard S.e. Keefe, Philip D Harvey, Sonia M. Davis, Robert M Bilder, Barton W Palmer, James M Gold, Herbert Y Meltzer, Michael F Green, George Capuano, Scott T StroupAbstract:change in a neurocognitive composite score after 2 months of treatment. Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains. Results: At 2 months, treatment resulted in small neurocognitive improvements of z= 0.13 for olanzapine (P.002), 0.25 for Perphenazine (P.001), 0.18 for quetiapine (P.001), 0.26 for risperidone (P.001), and 0.12 for ziprasidone (P.06), with no significant differences between groups. Results at 6 months were similar. After 18 months of treatment, neurocognitive improvement was greater in the Perphenazine group than in the olanzapine and risperidone groups. Neurocognitive improvement predicted longer time to treatment discontinuation, independently from symptom improvement, in patients treated with quetiapine or ziprasidone. Conclusions: After 2 months of antipsychotic treatment, all groups had a small but significant improvement in neurocognition. There were no differences between any pair of agents, including the typical drug Perphenazine. These results differ from the majority of previous studies, and the possible reasons are discussed.
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effectiveness of olanzapine quetiapine and risperidone in patients with chronic schizophrenia after discontinuing Perphenazine a catie study
American Journal of Psychiatry, 2007Co-Authors: Scott T Stroup, Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Richard S.e. Keefe, Jeffrey A. Lieberman, George Capuano, Alexander L Miller, Irving BelzAbstract:Objective: The relative effectiveness of newly started antipsychotic drugs for individuals with schizophrenia may depend on multiple factors, including each patient’s previous treatment response and the reason for a new medication trial. This randomized, double-blind study compared olanzapine, quetiapine, and risperidone in patients who had just discontinued the older antipsychotic Perphenazine. Method: Subjects with schizophrenia (N=114) who had been randomly assigned to and then discontinued Perphenazine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study were reassigned randomly to double-blinded treatment with olanzapine, 7.5–30.0 mg/day (N=38); quetiapine, 200–800 mg/day (N=38); or risperidone, 1.5–6.0 mg/day (N=38). The primary aim was to determine whether there were differences among these three treatments in effectiveness, as measured by time to treatment discontinuation for any reason. Secondary outcomes included reasons for treatment disconti...
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cost effectiveness of second generation antipsychotics and Perphenazine in a randomized trial of treatment for chronic schizophrenia
American Journal of Psychiatry, 2006Co-Authors: Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Richard S.e. Keefe, Scott T Stroup, Douglas L Leslie, Jody L Sindelar, Edward Alan Miller, Diana O PerkinsAbstract:Background: Second-generation antipsychotics have largely replaced firstgeneration antipsychotics for the treatment of schizophrenia, but a large-scale cost/effectiveness analysis has not been attempted. Method: Patients with schizophrenia (N=1,493) were assigned to treatment with a first-generati on antipsychotic (Perphenazine) or one of four secondgeneration drugs (olanzapine, quetiapine, risperidone, or ziprasidone) and followed for up to 18 months. Patients with tardive dyskinesia were prohibited from assignment to Perphenazine. Patients could be reassigned at any time to another second-generation drug, including clozapine, but not to Perphenazine. The cost analysis included medications plus health services use. Qualityadjusted life year (QALY) ratings were assessed on the basis of Positive and Negative Syndrome Scale (PANSS) subscale scores and side effects. An intention-totreat analysis included all available observations, classified by initial drug assignment, and costs of reassignment of most patients to another second-generation drug. The analysis was repeated considering only treatment on initially assigned medications. Results: Although QALY ratings, PANSS scores, and other quality of life measures indicated modest improvement over 18 months, there were no significant differences between Perphenazine and any second-generation medication. Average total monthly health care costs were $300–$600 (20%–30%) lower for Perphenazine than for second-generation antipsychotics because of lower drug cost. Differences in costs remained when maximally discounted drug prices were used for all patients and when only observations during treatment with the first medication were included. Conclusions: Treatment with Perphenazine was less costly than treatment with second-generation antipsychotics with no significant differences in measures of effectiveness. However, the trial was limited by a high dropout rate, and longer-term neurological and metabolic side effects require further study.
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effectiveness of antipsychotic drugs in patients with chronic schizophrenia
The New England Journal of Medicine, 2005Co-Authors: Jeffrey A. Lieberman, Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Richard S.e. Keefe, Scott T Stroup, Diana O Perkins, C E DavisAbstract:background The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, Perphenazine, with several newer drugs in a double-blind study. methods A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), Perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. results Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to Perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the Perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and Perphenazine was associated with more discontinuation for extrapyramidal effects. conclusions The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent Perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.
Sonia M. Davis - One of the best experts on this subject based on the ideXlab platform.
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inflammatory markers in schizophrenia comparing antipsychotic effects in phase 1 of the clinical antipsychotic trials of intervention effectiveness study
Biological Psychiatry, 2009Co-Authors: Marvin S. Swartz, Sonia M. Davis, Jonathan M Meyer, Joseph P Mcevoy, Vicki G Davis, Donald C Goff, Henry A Nasrallah, John K Hsiao, Scott T StroupAbstract:Background C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin are systemic inflammatory markers (IM) that positively correlate with cardiovascular (CV) risk. Despite the known CV effects of atypical antipsychotics, there is limited prospective data on IM changes during treatment. Methods The IM outcomes were compared between antipsychotic treatment groups in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial phase 1 with subjects with laboratory assessments at baseline and 3 months ( n = 789). Results There were significant treatment differences in CRP, E-selectin, and ICAM-1 at 3 months, with a differential impact of baseline values on the CRP and ICAM-1 results. In overall comparisons, quetiapine and olanzapine had the highest median levels for CRP, and olanzapine for E-selectin and ICAM-1. Olanzapine was significantly different after baseline adjustment than Perphenazine ( p = .001) for E-selectin, and in those with low baseline CRP ( p p p = .002) for CRP. Perphenazine had the lowest 3-month ICAM-1 levels in subjects with baseline ICAM-1 above the median, but the differences were not statistically significant versus olanzapine ( p = .010), quetiapine ( p = .010), and risperidone ( p = .006) after controlling for multiple comparisons. The 18-month repeated measures CRP analysis confirmed the significantly higher values for olanzapine in those with low baseline CRP. Conclusions This analysis provides further evidence for differential antipsychotic metabolic liabilities as measured by changes in systemic inflammation. C-reactive protein might emerge as a useful target for CV risk outcomes in schizophrenia patients.
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The effects of antipsychotic medications on emotion perception in patients with chronic schizophrenia in the CATIE trial
Schizophrenia research, 2009Co-Authors: David L. Penn, Sonia M. Davis, Richard S.e. Keefe, Diana O Perkins, Piper S. Meyer, Diane Losardo, Jeffrey A. LiebermanAbstract:Few pharmacological intervention studies have examined the impact of medication on social cognition, particularly emotion perception. The goal of this randomized, double-blind study is to compare the effects of several second generation antipsychotics and a first generation antipsychotic, Perphenazine, on emotion perception in individuals with schizophrenia. Patients were assigned to receive treatment with olanzapine, queitapine fumarate, risperidone, ziprasidone or Perphenazine for up to 18 months. Eight hundred and seventy three patients completed an emotion perception test immediately prior to randomization and after 2 months of treatment. We also examined baseline predictors of emotion perception change. Most treatments were associated with a small, non-statistically significant improvement in emotion perception at two months, although they did not differ from one another. Greater improvement in emotion perception at 2 months was significantly predicted by lower baseline emotion perception and higher baseline neurocognitive functioning, and marginally predicted by less time on an antipsychotic.
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extrapyramidal side effects of antipsychotics in a randomised trial
British Journal of Psychiatry, 2008Co-Authors: Del D Miller, Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Stanley N Caroff, Bruce L Saltz, Silvana Riggio, Miranda Chakos, Richard S.e. KeefeAbstract:Background There are claims that second-generation antipsychotics produce fewer extrapyramidal side-effects (EPS) compared with first-generation drugs. Aims To compare the incidence of treatment-emergent EPS between second-generation antipsychotics and Perphenazine in people with schizophrenia. Method Incidence analyses integrated data from standardised rating scales and documented use of concomitant medication or treatment discontinuation for EPS events. Mixed model analyses of change in rating scales from baseline were also conducted. Results There were no significant differences in incidence or change in rating scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when comparing second-generation antipsychotics with Perphenazine or comparing between second-generation antipsychotics. Secondary analyses revealed greater rates of concomitant antiparkinsonism medication among individuals on risperidone and lower rates among individuals on quetiapine, and lower rates of discontinuation because of parkinsonism among people on quetiapine and ziprasidone. There was a trend for a greater likelihood of concomitant medication for akathisia among individuals on risperidone and Perphenazine. Conclusions The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and Perphenazine or between second-generation antipsychotics in people with schizophrenia.
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neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the catie trial
Archives of General Psychiatry, 2007Co-Authors: Richard S.e. Keefe, Philip D Harvey, Sonia M. Davis, Robert M Bilder, Barton W Palmer, James M Gold, Herbert Y Meltzer, Michael F Green, George Capuano, Scott T StroupAbstract:change in a neurocognitive composite score after 2 months of treatment. Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains. Results: At 2 months, treatment resulted in small neurocognitive improvements of z= 0.13 for olanzapine (P.002), 0.25 for Perphenazine (P.001), 0.18 for quetiapine (P.001), 0.26 for risperidone (P.001), and 0.12 for ziprasidone (P.06), with no significant differences between groups. Results at 6 months were similar. After 18 months of treatment, neurocognitive improvement was greater in the Perphenazine group than in the olanzapine and risperidone groups. Neurocognitive improvement predicted longer time to treatment discontinuation, independently from symptom improvement, in patients treated with quetiapine or ziprasidone. Conclusions: After 2 months of antipsychotic treatment, all groups had a small but significant improvement in neurocognition. There were no differences between any pair of agents, including the typical drug Perphenazine. These results differ from the majority of previous studies, and the possible reasons are discussed.
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effectiveness of olanzapine quetiapine and risperidone in patients with chronic schizophrenia after discontinuing Perphenazine a catie study
American Journal of Psychiatry, 2007Co-Authors: Scott T Stroup, Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Richard S.e. Keefe, Jeffrey A. Lieberman, George Capuano, Alexander L Miller, Irving BelzAbstract:Objective: The relative effectiveness of newly started antipsychotic drugs for individuals with schizophrenia may depend on multiple factors, including each patient’s previous treatment response and the reason for a new medication trial. This randomized, double-blind study compared olanzapine, quetiapine, and risperidone in patients who had just discontinued the older antipsychotic Perphenazine. Method: Subjects with schizophrenia (N=114) who had been randomly assigned to and then discontinued Perphenazine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study were reassigned randomly to double-blinded treatment with olanzapine, 7.5–30.0 mg/day (N=38); quetiapine, 200–800 mg/day (N=38); or risperidone, 1.5–6.0 mg/day (N=38). The primary aim was to determine whether there were differences among these three treatments in effectiveness, as measured by time to treatment discontinuation for any reason. Secondary outcomes included reasons for treatment disconti...
Richard S.e. Keefe - One of the best experts on this subject based on the ideXlab platform.
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The effects of antipsychotic medications on emotion perception in patients with chronic schizophrenia in the CATIE trial
Schizophrenia research, 2009Co-Authors: David L. Penn, Sonia M. Davis, Richard S.e. Keefe, Diana O Perkins, Piper S. Meyer, Diane Losardo, Jeffrey A. LiebermanAbstract:Few pharmacological intervention studies have examined the impact of medication on social cognition, particularly emotion perception. The goal of this randomized, double-blind study is to compare the effects of several second generation antipsychotics and a first generation antipsychotic, Perphenazine, on emotion perception in individuals with schizophrenia. Patients were assigned to receive treatment with olanzapine, queitapine fumarate, risperidone, ziprasidone or Perphenazine for up to 18 months. Eight hundred and seventy three patients completed an emotion perception test immediately prior to randomization and after 2 months of treatment. We also examined baseline predictors of emotion perception change. Most treatments were associated with a small, non-statistically significant improvement in emotion perception at two months, although they did not differ from one another. Greater improvement in emotion perception at 2 months was significantly predicted by lower baseline emotion perception and higher baseline neurocognitive functioning, and marginally predicted by less time on an antipsychotic.
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extrapyramidal side effects of antipsychotics in a randomised trial
British Journal of Psychiatry, 2008Co-Authors: Del D Miller, Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Stanley N Caroff, Bruce L Saltz, Silvana Riggio, Miranda Chakos, Richard S.e. KeefeAbstract:Background There are claims that second-generation antipsychotics produce fewer extrapyramidal side-effects (EPS) compared with first-generation drugs. Aims To compare the incidence of treatment-emergent EPS between second-generation antipsychotics and Perphenazine in people with schizophrenia. Method Incidence analyses integrated data from standardised rating scales and documented use of concomitant medication or treatment discontinuation for EPS events. Mixed model analyses of change in rating scales from baseline were also conducted. Results There were no significant differences in incidence or change in rating scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when comparing second-generation antipsychotics with Perphenazine or comparing between second-generation antipsychotics. Secondary analyses revealed greater rates of concomitant antiparkinsonism medication among individuals on risperidone and lower rates among individuals on quetiapine, and lower rates of discontinuation because of parkinsonism among people on quetiapine and ziprasidone. There was a trend for a greater likelihood of concomitant medication for akathisia among individuals on risperidone and Perphenazine. Conclusions The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and Perphenazine or between second-generation antipsychotics in people with schizophrenia.
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neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the catie trial
Archives of General Psychiatry, 2007Co-Authors: Richard S.e. Keefe, Philip D Harvey, Sonia M. Davis, Robert M Bilder, Barton W Palmer, James M Gold, Herbert Y Meltzer, Michael F Green, George Capuano, Scott T StroupAbstract:change in a neurocognitive composite score after 2 months of treatment. Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains. Results: At 2 months, treatment resulted in small neurocognitive improvements of z= 0.13 for olanzapine (P.002), 0.25 for Perphenazine (P.001), 0.18 for quetiapine (P.001), 0.26 for risperidone (P.001), and 0.12 for ziprasidone (P.06), with no significant differences between groups. Results at 6 months were similar. After 18 months of treatment, neurocognitive improvement was greater in the Perphenazine group than in the olanzapine and risperidone groups. Neurocognitive improvement predicted longer time to treatment discontinuation, independently from symptom improvement, in patients treated with quetiapine or ziprasidone. Conclusions: After 2 months of antipsychotic treatment, all groups had a small but significant improvement in neurocognition. There were no differences between any pair of agents, including the typical drug Perphenazine. These results differ from the majority of previous studies, and the possible reasons are discussed.
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effectiveness of olanzapine quetiapine and risperidone in patients with chronic schizophrenia after discontinuing Perphenazine a catie study
American Journal of Psychiatry, 2007Co-Authors: Scott T Stroup, Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Richard S.e. Keefe, Jeffrey A. Lieberman, George Capuano, Alexander L Miller, Irving BelzAbstract:Objective: The relative effectiveness of newly started antipsychotic drugs for individuals with schizophrenia may depend on multiple factors, including each patient’s previous treatment response and the reason for a new medication trial. This randomized, double-blind study compared olanzapine, quetiapine, and risperidone in patients who had just discontinued the older antipsychotic Perphenazine. Method: Subjects with schizophrenia (N=114) who had been randomly assigned to and then discontinued Perphenazine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study were reassigned randomly to double-blinded treatment with olanzapine, 7.5–30.0 mg/day (N=38); quetiapine, 200–800 mg/day (N=38); or risperidone, 1.5–6.0 mg/day (N=38). The primary aim was to determine whether there were differences among these three treatments in effectiveness, as measured by time to treatment discontinuation for any reason. Secondary outcomes included reasons for treatment disconti...
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cost effectiveness of second generation antipsychotics and Perphenazine in a randomized trial of treatment for chronic schizophrenia
American Journal of Psychiatry, 2006Co-Authors: Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Richard S.e. Keefe, Scott T Stroup, Douglas L Leslie, Jody L Sindelar, Edward Alan Miller, Diana O PerkinsAbstract:Background: Second-generation antipsychotics have largely replaced firstgeneration antipsychotics for the treatment of schizophrenia, but a large-scale cost/effectiveness analysis has not been attempted. Method: Patients with schizophrenia (N=1,493) were assigned to treatment with a first-generati on antipsychotic (Perphenazine) or one of four secondgeneration drugs (olanzapine, quetiapine, risperidone, or ziprasidone) and followed for up to 18 months. Patients with tardive dyskinesia were prohibited from assignment to Perphenazine. Patients could be reassigned at any time to another second-generation drug, including clozapine, but not to Perphenazine. The cost analysis included medications plus health services use. Qualityadjusted life year (QALY) ratings were assessed on the basis of Positive and Negative Syndrome Scale (PANSS) subscale scores and side effects. An intention-totreat analysis included all available observations, classified by initial drug assignment, and costs of reassignment of most patients to another second-generation drug. The analysis was repeated considering only treatment on initially assigned medications. Results: Although QALY ratings, PANSS scores, and other quality of life measures indicated modest improvement over 18 months, there were no significant differences between Perphenazine and any second-generation medication. Average total monthly health care costs were $300–$600 (20%–30%) lower for Perphenazine than for second-generation antipsychotics because of lower drug cost. Differences in costs remained when maximally discounted drug prices were used for all patients and when only observations during treatment with the first medication were included. Conclusions: Treatment with Perphenazine was less costly than treatment with second-generation antipsychotics with no significant differences in measures of effectiveness. However, the trial was limited by a high dropout rate, and longer-term neurological and metabolic side effects require further study.
Marvin S. Swartz - One of the best experts on this subject based on the ideXlab platform.
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inflammatory markers in schizophrenia comparing antipsychotic effects in phase 1 of the clinical antipsychotic trials of intervention effectiveness study
Biological Psychiatry, 2009Co-Authors: Marvin S. Swartz, Sonia M. Davis, Jonathan M Meyer, Joseph P Mcevoy, Vicki G Davis, Donald C Goff, Henry A Nasrallah, John K Hsiao, Scott T StroupAbstract:Background C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin are systemic inflammatory markers (IM) that positively correlate with cardiovascular (CV) risk. Despite the known CV effects of atypical antipsychotics, there is limited prospective data on IM changes during treatment. Methods The IM outcomes were compared between antipsychotic treatment groups in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial phase 1 with subjects with laboratory assessments at baseline and 3 months ( n = 789). Results There were significant treatment differences in CRP, E-selectin, and ICAM-1 at 3 months, with a differential impact of baseline values on the CRP and ICAM-1 results. In overall comparisons, quetiapine and olanzapine had the highest median levels for CRP, and olanzapine for E-selectin and ICAM-1. Olanzapine was significantly different after baseline adjustment than Perphenazine ( p = .001) for E-selectin, and in those with low baseline CRP ( p p p = .002) for CRP. Perphenazine had the lowest 3-month ICAM-1 levels in subjects with baseline ICAM-1 above the median, but the differences were not statistically significant versus olanzapine ( p = .010), quetiapine ( p = .010), and risperidone ( p = .006) after controlling for multiple comparisons. The 18-month repeated measures CRP analysis confirmed the significantly higher values for olanzapine in those with low baseline CRP. Conclusions This analysis provides further evidence for differential antipsychotic metabolic liabilities as measured by changes in systemic inflammation. C-reactive protein might emerge as a useful target for CV risk outcomes in schizophrenia patients.
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extrapyramidal side effects of antipsychotics in a randomised trial
British Journal of Psychiatry, 2008Co-Authors: Del D Miller, Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Stanley N Caroff, Bruce L Saltz, Silvana Riggio, Miranda Chakos, Richard S.e. KeefeAbstract:Background There are claims that second-generation antipsychotics produce fewer extrapyramidal side-effects (EPS) compared with first-generation drugs. Aims To compare the incidence of treatment-emergent EPS between second-generation antipsychotics and Perphenazine in people with schizophrenia. Method Incidence analyses integrated data from standardised rating scales and documented use of concomitant medication or treatment discontinuation for EPS events. Mixed model analyses of change in rating scales from baseline were also conducted. Results There were no significant differences in incidence or change in rating scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when comparing second-generation antipsychotics with Perphenazine or comparing between second-generation antipsychotics. Secondary analyses revealed greater rates of concomitant antiparkinsonism medication among individuals on risperidone and lower rates among individuals on quetiapine, and lower rates of discontinuation because of parkinsonism among people on quetiapine and ziprasidone. There was a trend for a greater likelihood of concomitant medication for akathisia among individuals on risperidone and Perphenazine. Conclusions The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and Perphenazine or between second-generation antipsychotics in people with schizophrenia.
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effectiveness of olanzapine quetiapine and risperidone in patients with chronic schizophrenia after discontinuing Perphenazine a catie study
American Journal of Psychiatry, 2007Co-Authors: Scott T Stroup, Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Richard S.e. Keefe, Jeffrey A. Lieberman, George Capuano, Alexander L Miller, Irving BelzAbstract:Objective: The relative effectiveness of newly started antipsychotic drugs for individuals with schizophrenia may depend on multiple factors, including each patient’s previous treatment response and the reason for a new medication trial. This randomized, double-blind study compared olanzapine, quetiapine, and risperidone in patients who had just discontinued the older antipsychotic Perphenazine. Method: Subjects with schizophrenia (N=114) who had been randomly assigned to and then discontinued Perphenazine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study were reassigned randomly to double-blinded treatment with olanzapine, 7.5–30.0 mg/day (N=38); quetiapine, 200–800 mg/day (N=38); or risperidone, 1.5–6.0 mg/day (N=38). The primary aim was to determine whether there were differences among these three treatments in effectiveness, as measured by time to treatment discontinuation for any reason. Secondary outcomes included reasons for treatment disconti...
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cost effectiveness of second generation antipsychotics and Perphenazine in a randomized trial of treatment for chronic schizophrenia
American Journal of Psychiatry, 2006Co-Authors: Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Richard S.e. Keefe, Scott T Stroup, Douglas L Leslie, Jody L Sindelar, Edward Alan Miller, Diana O PerkinsAbstract:Background: Second-generation antipsychotics have largely replaced firstgeneration antipsychotics for the treatment of schizophrenia, but a large-scale cost/effectiveness analysis has not been attempted. Method: Patients with schizophrenia (N=1,493) were assigned to treatment with a first-generati on antipsychotic (Perphenazine) or one of four secondgeneration drugs (olanzapine, quetiapine, risperidone, or ziprasidone) and followed for up to 18 months. Patients with tardive dyskinesia were prohibited from assignment to Perphenazine. Patients could be reassigned at any time to another second-generation drug, including clozapine, but not to Perphenazine. The cost analysis included medications plus health services use. Qualityadjusted life year (QALY) ratings were assessed on the basis of Positive and Negative Syndrome Scale (PANSS) subscale scores and side effects. An intention-totreat analysis included all available observations, classified by initial drug assignment, and costs of reassignment of most patients to another second-generation drug. The analysis was repeated considering only treatment on initially assigned medications. Results: Although QALY ratings, PANSS scores, and other quality of life measures indicated modest improvement over 18 months, there were no significant differences between Perphenazine and any second-generation medication. Average total monthly health care costs were $300–$600 (20%–30%) lower for Perphenazine than for second-generation antipsychotics because of lower drug cost. Differences in costs remained when maximally discounted drug prices were used for all patients and when only observations during treatment with the first medication were included. Conclusions: Treatment with Perphenazine was less costly than treatment with second-generation antipsychotics with no significant differences in measures of effectiveness. However, the trial was limited by a high dropout rate, and longer-term neurological and metabolic side effects require further study.
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effectiveness of antipsychotic drugs in patients with chronic schizophrenia
The New England Journal of Medicine, 2005Co-Authors: Jeffrey A. Lieberman, Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick Mcevoy, Sonia M. Davis, Richard S.e. Keefe, Scott T Stroup, Diana O Perkins, C E DavisAbstract:background The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, Perphenazine, with several newer drugs in a double-blind study. methods A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), Perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. results Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to Perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the Perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and Perphenazine was associated with more discontinuation for extrapyramidal effects. conclusions The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent Perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.
Abraham Weizman - One of the best experts on this subject based on the ideXlab platform.
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bl 1020 a novel antipsychotic drug with gabaergic activity and low catalepsy is efficacious in a rat model of schizophrenia
European Neuropsychopharmacology, 2009Co-Authors: Yona Geffen, Herbert Y Meltzer, Irit Gilad, Abraham Nudelman, Ada Rephaeli, Mei Huang, Kinneret Savitsky, Leah N Klapper, Ilan Winkler, Abraham WeizmanAbstract:Abstract Reduced brain γ-amino-butyric acid (GABA) participates in the pathogenesis of schizophrenia. GABA scarcely penetrates the brain. We evaluated the pharmacological properties of BL-1020, a novel GABA ester of Perphenazine. Oral BL-1020 or Perphenazine were assessed in acute and subchronic schizophrenia rat models. Catalepsy, serum prolactin, receptor binding profile and cortical (PFC), hippocampal (Hip) and dopamine (DA) levels were determined. Radioactive [14C] labeled BL-1020 was used for pharmacokinetics (PK). Acute and subchronic treatment with BL-1020 antagonized amphetamine-induced hyperactivity, with significantly lower catalepsy and sedation compared to equimolar Perphenazine. At the same time, BL-1020 increased DA release in the PFC and Hip. BL-1020 and Perphenazine stimulated prolactin secretion equally. BL-1020 displayed strong DA and serotonin (5HT) receptor inhibition (D2L Kiz = 0.066 nM, D2S Ki = 0.062 nM, 5-HT2A Ki = 0.21 nM). PK data revealed that BL-1020 penetrated the brain. Conclusions: The advantages of BL-1020 for treatment of schizophrenia stem from its being a DA/5HT antagonist and a GABAergic agsonist that releases cortical DA and antagonizes amphetamine-induced hyperactivity with reduced catalepsy and sedation
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evaluation of the neurotoxic activity of typical and atypical neuroleptics relevance to iatrogenic extrapyramidal symptoms
Cellular and Molecular Neurobiology, 2001Co-Authors: Irit Gilad, Biana Shtaif, Roni Shiloh, Abraham WeizmanAbstract:Typical neuroleptic therapy often results in extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). Recent reports reveal neurotoxic activity in some neuroleptics. We hypothesized that neurotoxicity might be implicated in EPS. This study aims to evaluate the neurotoxic activity of typical and atypical neuroleptics and to determine the possible role of neurotoxicity in neuroleptic-induced EPS. Perphenazine, haloperidol, clozapine, sulpiride, and risperidone (10-100 microM) were administered, either alone or combined with dopamine, to primary mouse neuronal or intact brain culture and to a human neuroblastoma (NB) cell line (SK-N-SH). Cell viability (measured by neutral red and alamar blue), DNA fragmentation (flow cytometry-NB) were determined. Neuroblastoma: Perphenazine, clozapine, and haloperidol (100 microM) decreased viability by 87, 43, and 34% respectively. Sulpiride and risperidone were not toxic. At 10 microM, toxicity decreased markedly. Dopamine (125 microM) potentiated the Perphenazine-induced toxicity. Flow cytometry of NB cells treated with Perphenazine (2.5-40 microM) showed an increase (Perphenazine 20 microM, 40 microM, 48 h) in fragmented DNA (74.7% and 95.0% vs. 8.7% in controls). Lower concentrations increased the G1 phase and decreased S phase in the cell cycle. In primary neurons, Perphenazine, haloperidol, and clozapine, but not risperidone and sulpiride, induced a significant neurotoxic effect, which, in intact brain culture, was absent (haloperidol and clozapine) or lowered (Perphenazine). Dopamine (0.5 mM) did not modify the effect of the drugs in the primary cultures. Neuroleptics possess differential neurotoxic activity with higher sensitivity of neoplasm tissue (NB compared to primary cultures). The order of toxicity was Perphenazine > haloperidol = clozapine:sulpiride and risperidone were not toxic. Neurotoxicity is independent of dopamine and is associated with cell cycle arrest and apoptosis. With the exception of clozapine, neurotoxicity seems relevant to neuroleptic-induced EPS and TD.