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Clozapine response in chronic schizophrenia not associated with brain morphology on MRI: A preliminary report
742
BIOLPSYCHIATRY 1994;35:615-747
groups, but one patient developed a reversible delirium associated with combined lithium/haloperidol treatment. For these long-term, severely ill patients, combined treatment afforded no advantage over treatment with haloperidol alone.
459. IS THERE RAPID RELAPSE AFTER DISCONTINUATION OF CLOZAPlNE?
W.S. Musser, C.D. Wills, & V.L. Nimgaonkar Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara St., Pittsburgh, PA 15213 Psychotic relapse within a week of discontinuation of ciozapine has been described before, but the studies were anecdotal (Perenyi et al., 1985; Alphs et al., 1991; Parson et al., 1993). We have conducted a systematic survey of patients discontinued from clozapine at Westeru Psychiatric Institute and Clinic, a large tertiary care center. Of 97 patients treated with clozapine between 1989 and 1993, treatment was discontinued in 20 cases. Adequate infommtion concerning relapse was obtained on ten individuals. Half of them were of Caucasian ethnicity, and nine were male. All of them had a diagnosis of schizophrenia (n=8) or schizoaffeetive psychosis (n-2) (DSM-IiI-R criteria). Relapse (defined as time to onset of psychotic features) occurred after a median period of 7.5 days (range 5-30 days). In all cases, the patients exhibited florid psychotic features. These consisted predominantly of paranoid delusions, auditory hallucinations and suicidal ideation. Since half the individuals had responded poorly to prior medication, it is difficult to compare the rapidi~ of relapse during the index episode to that during previous episodes. Our results suggest that recurrence of psychotic features occurs rapidly in a substantial proportion of patients for whom clozapine is discontinued. These findings have important clinical implications.
460. REDUCED HOSPITALIZATION WITH CLOZAPINE IN A COMMUNFFY MENTAL HEALTH SETFINO
R. Ganguli, J.S. Brar, M. DeLeo, M. Allen, & R. Sarma University of Pittsburgh Medical School, Western Psychiatric Institute & Clinic, Pittsburgh, PA 15213 The Pittsburgh Schizophrenia Treatment and Research Center (STRC) is a University based, comprel~nsive facility with inpatient, outpatient, and partial hospital programs, servinga definedgeographicalcatchment area. We reviewed the course and outcome of all 85 patients who began treatment with clozapine, at the STRC, following its general release in the US in February, 1990. Seventeen patients (20%) had been discontinued due to non-response, intolerance, or poor comp|iance. Of the 68 patients stiill receiving clozapine, 49 (72%) were started t~sinpatients, and 19 (28%) as outpatients. The patients' treating cliniciansrated the changes in positive and negative symptoms and compliance in response to clozapine. The rates of rehospitalization following the instiultion of clozapine were compared for identical time periods preceding clozapine in a mirror image design. There was a significant reduction, following clozapine in both the number (p~.0001) and length (p-0.01) of ho,~pimlizations.These effects were significantly greater for patients who h ~ received >6 months of clozapine versus those exposed for a shorter period. Seventy nine percent of patients had improvements in positive symptoms, 39% in negative symptoms, 31% in compliance and 47% in social function. Most previous US studies of clozapine have involved severely ill, institutionalized patient~ These data, though from an open and uncontrolled study, indicate
SATURDAY, MAY 21
that clozapine offers significant benefits to patients in community settings.
461. CLOZAPINE RESPONSE IN CHRONIC SCHIZOPHRENIA NOT ASSOCIATED WITH BRAIN MORPIIOLOGY ON MRI: A PRELIMINARY REPORT
J. Aronowitz l, H. Wu I, S. Pollack l,a, R. Bilder I, J. Kane l, A. Safferman l, & J. Lieberman I tHiliside Hospital, a division of Long Island Jewish Medical Center, affiliated with Albert Einstein College of Medicine, Glen Oaks, NY 11004; 2St. John's University, Dept. of Quantitative Analysis, Jamaica, NY I 1439 Clozapine is a dibenzodiazepineatypical antipsychotic agent with demonstrated efficacy in treatment resistant and treatment intolerant schizophrenic populations (Kane 1988; Pickax 1992). Previous reports suggest clozapine's efficacy in schizophrenia may be related to morphologic abnormalities in lateral frontal and prefrontal cortices as measured on CT (Friedman 1991; Honer 1993) and MR! (Breier 1983). To examine this issue further, 18 chronic schizophrenic (DSM-III-R) patients (mean age 27 years, 89% male) who received standmdized ~atment with ciozapine (mean duration of treatment = 30 months 4- 19,43), underwent assessmerits for psychopathology (BPRS, CGI, SANS) and brain morphology with magnetic resonance imaging. MRIs were acquired using a gradient echo pulse sequence OD flash) on a Siemens-Magneton (l.0 tesla) system. Images were analyzed under blind conditions by trained personnel using quantitative (total brain volume, integhemispberie fissure volume) and qualitative (evaluation of sulcal prominence, cerebral cortex, lateral ventricles, third ventricle, medial temporal lobe structures) measures. Data analyses examined the relationship between brain morphologic variables and measures of psychopathology at baseline and during clozapine treatment, l~,liminary analyses to date have found no significant associations between the specific morphologic variables described above and treatment outcome. Mean severity of psychopathology at baseline was associated with increased interhemispheric fissure volume (r-0.54, p=0.02), due to positive symptom factors on the BPR$. These results do not replicare previous findings of abnormal brain morphology being associated with poorer response to clozapine. Reasons may include differences in patient samples and the limited number of patients studied. This issue will be reexamined in the context of a larger patient sample as data become available.
462. CSF HVA:5HIAA RATIO INCREASES WITH ANTIPSYCHOTIC RESPONSE TO CLOZAPINE S.C. Risch 1, C.A. Haden 2, J. Caudle 2, & R.R.J. Lewine 2 1Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425; aDepartment of Psychiatry, Emery University, Atlanta, GA Kahn and colleagues, 1993 have reported that increases in the cerebrospinal fluid (CSF) homovanillic acid (HVA) to 5-hydroxyindoleacetic acid (5HIAA) ratio (HVA:SHIAA ratio) were correlated with antipsychotic response to the "typical" neuroleptic haloperidol in 19 patients with schizophrenia or schizoaffective disorder. We now report preliminary data suggesting that antipsychotic improvement on the "atypical" neuroleptic
BIOLPSYCHIATRY 1994;35:615-747
groups, but one patient developed a reversible delirium associated with combined lithium/haloperidol treatment. For these long-term, severely ill patients, combined treatment afforded no advantage over treatment with haloperidol alone.
459. IS THERE RAPID RELAPSE AFTER DISCONTINUATION OF CLOZAPlNE?
W.S. Musser, C.D. Wills, & V.L. Nimgaonkar Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara St., Pittsburgh, PA 15213 Psychotic relapse within a week of discontinuation of ciozapine has been described before, but the studies were anecdotal (Perenyi et al., 1985; Alphs et al., 1991; Parson et al., 1993). We have conducted a systematic survey of patients discontinued from clozapine at Westeru Psychiatric Institute and Clinic, a large tertiary care center. Of 97 patients treated with clozapine between 1989 and 1993, treatment was discontinued in 20 cases. Adequate infommtion concerning relapse was obtained on ten individuals. Half of them were of Caucasian ethnicity, and nine were male. All of them had a diagnosis of schizophrenia (n=8) or schizoaffeetive psychosis (n-2) (DSM-IiI-R criteria). Relapse (defined as time to onset of psychotic features) occurred after a median period of 7.5 days (range 5-30 days). In all cases, the patients exhibited florid psychotic features. These consisted predominantly of paranoid delusions, auditory hallucinations and suicidal ideation. Since half the individuals had responded poorly to prior medication, it is difficult to compare the rapidi~ of relapse during the index episode to that during previous episodes. Our results suggest that recurrence of psychotic features occurs rapidly in a substantial proportion of patients for whom clozapine is discontinued. These findings have important clinical implications.
460. REDUCED HOSPITALIZATION WITH CLOZAPINE IN A COMMUNFFY MENTAL HEALTH SETFINO
R. Ganguli, J.S. Brar, M. DeLeo, M. Allen, & R. Sarma University of Pittsburgh Medical School, Western Psychiatric Institute & Clinic, Pittsburgh, PA 15213 The Pittsburgh Schizophrenia Treatment and Research Center (STRC) is a University based, comprel~nsive facility with inpatient, outpatient, and partial hospital programs, servinga definedgeographicalcatchment area. We reviewed the course and outcome of all 85 patients who began treatment with clozapine, at the STRC, following its general release in the US in February, 1990. Seventeen patients (20%) had been discontinued due to non-response, intolerance, or poor comp|iance. Of the 68 patients stiill receiving clozapine, 49 (72%) were started t~sinpatients, and 19 (28%) as outpatients. The patients' treating cliniciansrated the changes in positive and negative symptoms and compliance in response to clozapine. The rates of rehospitalization following the instiultion of clozapine were compared for identical time periods preceding clozapine in a mirror image design. There was a significant reduction, following clozapine in both the number (p~.0001) and length (p-0.01) of ho,~pimlizations.These effects were significantly greater for patients who h ~ received >6 months of clozapine versus those exposed for a shorter period. Seventy nine percent of patients had improvements in positive symptoms, 39% in negative symptoms, 31% in compliance and 47% in social function. Most previous US studies of clozapine have involved severely ill, institutionalized patient~ These data, though from an open and uncontrolled study, indicate
SATURDAY, MAY 21
that clozapine offers significant benefits to patients in community settings.
461. CLOZAPINE RESPONSE IN CHRONIC SCHIZOPHRENIA NOT ASSOCIATED WITH BRAIN MORPIIOLOGY ON MRI: A PRELIMINARY REPORT
J. Aronowitz l, H. Wu I, S. Pollack l,a, R. Bilder I, J. Kane l, A. Safferman l, & J. Lieberman I tHiliside Hospital, a division of Long Island Jewish Medical Center, affiliated with Albert Einstein College of Medicine, Glen Oaks, NY 11004; 2St. John's University, Dept. of Quantitative Analysis, Jamaica, NY I 1439 Clozapine is a dibenzodiazepineatypical antipsychotic agent with demonstrated efficacy in treatment resistant and treatment intolerant schizophrenic populations (Kane 1988; Pickax 1992). Previous reports suggest clozapine's efficacy in schizophrenia may be related to morphologic abnormalities in lateral frontal and prefrontal cortices as measured on CT (Friedman 1991; Honer 1993) and MR! (Breier 1983). To examine this issue further, 18 chronic schizophrenic (DSM-III-R) patients (mean age 27 years, 89% male) who received standmdized ~atment with ciozapine (mean duration of treatment = 30 months 4- 19,43), underwent assessmerits for psychopathology (BPRS, CGI, SANS) and brain morphology with magnetic resonance imaging. MRIs were acquired using a gradient echo pulse sequence OD flash) on a Siemens-Magneton (l.0 tesla) system. Images were analyzed under blind conditions by trained personnel using quantitative (total brain volume, integhemispberie fissure volume) and qualitative (evaluation of sulcal prominence, cerebral cortex, lateral ventricles, third ventricle, medial temporal lobe structures) measures. Data analyses examined the relationship between brain morphologic variables and measures of psychopathology at baseline and during clozapine treatment, l~,liminary analyses to date have found no significant associations between the specific morphologic variables described above and treatment outcome. Mean severity of psychopathology at baseline was associated with increased interhemispheric fissure volume (r-0.54, p=0.02), due to positive symptom factors on the BPR$. These results do not replicare previous findings of abnormal brain morphology being associated with poorer response to clozapine. Reasons may include differences in patient samples and the limited number of patients studied. This issue will be reexamined in the context of a larger patient sample as data become available.
462. CSF HVA:5HIAA RATIO INCREASES WITH ANTIPSYCHOTIC RESPONSE TO CLOZAPINE S.C. Risch 1, C.A. Haden 2, J. Caudle 2, & R.R.J. Lewine 2 1Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425; aDepartment of Psychiatry, Emery University, Atlanta, GA Kahn and colleagues, 1993 have reported that increases in the cerebrospinal fluid (CSF) homovanillic acid (HVA) to 5-hydroxyindoleacetic acid (5HIAA) ratio (HVA:SHIAA ratio) were correlated with antipsychotic response to the "typical" neuroleptic haloperidol in 19 patients with schizophrenia or schizoaffective disorder. We now report preliminary data suggesting that antipsychotic improvement on the "atypical" neuroleptic