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Biomedical subjects

F R Frankenburg

Publications and source records attributed to F R Frankenburg.

At least 19 recordsLinked to original sources
PubMed1996

Serum levels of clozapine and norclozapine in patients treated with selective serotonin reuptake inhibitors.

OBJECTIVE: The selective serotonin reuptake inhibitor (SSRI) fluoxetine can increase serum levels of clozapine and norclozapine, but effects of other SSRIs are unknown. Thus, the authors evaluated interactions of clozapine with fluoxetine, paroxetine, and sertraline. METHOD: Serum clozapine and norclozapine concentrations were assayed in 80 psychiatric patients, matched for age and clozapine dose, given clozapine (mean dose = 279 mg/day) alone or with fluoxetine (mean dose = 39.3 mg/day), paroxetine (mean = 31.2 mg/day), or sertraline (mean = 92.5 mg/ day). Each patient's dose of clozapine was stable for at least a month before serum sampling. RESULTS: Concentrations of clozapine plus norclozapine averaged 43% higher, and the risk of levels higher than 1000 ng/ml was 10-fold greater (25%), in the patients taking SSRIs, with minor differences between patients taking the individual SSRIs. CONCLUSIONS: SSRIs can increase circulating concentrations of clozapine and norclozapine, sometimes to potentially toxic levels.

1-Naphthylamine↗
PubMed1995

Relation of leukocyte counts during clozapine treatment to serum concentrations of clozapine and metabolites.

OBJECTIVE: This study was done to test the hypothesis that serum concentration of norclozapine is a risk factor for leukopenia during treatment with clozapine. METHOD: Maximum decreases in leukocyte counts in 44 unselected patients treated with clozapine were determined and then correlated with drug doses and serum concentrations of clozapine, norclozapine, and clozapine-N-oxide. RESULTS: White cell and granulocyte counts decreased by up to 60%-73%, but there were no positive correlations between these decrements and drug dose, drug level, ratio of drug level to drug dose, or ratio of norclozapine level to clozapine level, nor were the decreases related to age or gender. CONCLUSIONS: While these results do not suggest in vivo hemotoxicity of norclozapine, further study of patients with clinically significant leukopenia is required.

Clozapine↗
PubMed1995

Clozapine-caused eosinophilic colitis.

Four patients with diarrhea and eosinophilia associated with clozapine therapy are presented. In two cases clozapine therapy was interrupted but then restarted; all patients eventually tolerated clozapine well. A syndrome of clozapine-induced eosinophilic colitis is suggested.

Adult↗
PubMed1994

Serum concentrations of clozapine and its major metabolites: effects of cotreatment with fluoxetine or valproate.

Serum concentrations of clozapine, norclozapine, and clozapine-N-oxide were assayed in psychotic patients treated with clozapine alone (N = 17), clozapine with fluoxetine added (N = 6), or clozapine with valproic acid added (N = 11). Subjects were matched for age and other treatments, and concentrations were corrected for daily dose of clozapine (milligrams per kilogram of body weight). With valproic acid, there was a minor increase in total clozapine metabolites, which was even less with dose correction. Fluoxetine increased all clozapine analytes, in some cases to twice the levels in the subjects given only clozapine.

Adult↗
PubMed1994

Clozapine and seizures: a review.

Clozapine, a novel antipsychotic agent, is an alternative to standard neuroleptic therapy for psychotic disorders. Some advantages of clozapine over neuroleptics are that it may be a more effective antipsychotic in treatment resistant patients and has a lower incidence of extrapyramidal side effects. However, seizures associated with clozapine treatment occur at a rate of about three percent. Factors which seem to increase the likelihood of seizures include high doses of clozapine, rapid dose titration, the concurrent use of other epileptogenic agents and a previous history of neurological abnormalities. A strategy that has been proposed to reduce the occurrence of seizures is the addition of an anticonvulsant agent. At present, little rigorous scientific evidence exists to establish the effectiveness of this strategy or the choice of an anticonvulsant. However, based on what evidence there is and the side effect profiles of the various anticonvulsants, the authors propose the use of valproic acid for the prophylaxis and management of clozapine related seizures.

Anticonvulsants↗
PubMed1994

History of the development of antipsychotic medication.

The story of the development of effective antipsychotic medications involves the collaboration of many people and organizations, ranging from Ayurvedic physicians to pharmaceutical companies, and the confluence of many quests, from that for improved synthetic dyes to that for an improved antimalarial agent. The disturbed behavior of patients and their evident anguish fueled the development of these drugs, which in turn has led to more research into the biochemistry of psychotic illnesses. Double-blind, placebo-controlled trials have established the true although partial utility of these new treatments. Most patients with schizophrenia--even those who have good responses to antipsychotic agents--continue to have some psychotic symptoms and to require a great deal of rehabilitation. It is hoped that physicians in the future will not find today's therapies as harmful as we find those of the past.

Antipsychotic Agents↗
PubMed1994

Clozapine and metabolites: concentrations in serum and clinical findings during treatment of chronically psychotic patients.

Clozapine (CLZ) and metabolites norclozapine and clozapine-N-oxide were assayed with a new, sensitive (2 pmol), and selective method in 68 serum samples from 44 psychotic subjects, 20 to 54 years old, ill 16 years, and treated with CLZ for 2.2 years (currently at 294 mg, 3.4 mg/kg daily). CLZ levels averaged 239 ng/ml (0.73 microM; 92 ng/ml per mg/kg dose) or 48% of total analytes (norclozapine = 41% [91% of CLZ] and clozapine-N-oxide = 11%); metabolite and CLZ levels were highly correlated (rs = 0.9), and CLZ levels varied with daily dose (rs = 0.7). Sampling twice yielded similar within-subject analyte levels (r = 0.8 to 0.9; difference = 24% to 33%). Range and variance narrowed when levels were expressed per weight-corrected dose (ng/ml per mg/kg). Levels per dose were 40% higher in nonsmoking women than men, despite a 60% lower milligram per kilogram dose in women, and did not vary by diagnosis or age in this limited sample. Fluoxetine increased serum CLZ analytes by 60%; valproate had less effect. Patients rated treatment very positively; observer-assessed benefits typically were more moderate. Common late side effects were sialorrhea (80%), excess sedation (58%), obesity (55% > 200 lb), mild tachycardia (51%), constipation (32%), and enuresis (27%); there were no seizures or leukopenia. There was little evident relationship of drug dose or serum level to current clinical measures or side effect risks.

Adult↗
PubMed1993

Determination of clozapine, norclozapine, and clozapine-N-oxide in serum by liquid chromatography.

We report a new assay to measure the serum concentrations of the atypical antipsychotic drug clozapine and two major metabolites, norclozapine and clozapine-N-oxide. The analytes and an internal standard (triprolidine) were extracted from alkalinized samples into ethyl acetate and back-extracted into 0.1 mol/L HCl. The acid extracts were chromatographed on a reversed-phase liquid chromatographic column with photodiode array detection (210-340 nm). With the 254-nm signal, between-run imprecision (CV) was < 2% for clozapine and norclozapine at 400 micrograms/L, and 4.1% for clozapine-N-oxide at 100 micrograms/L. Absolute recovery exceeded 65%, and the detection limit was approximately 3-4 micrograms/L. In 25 patients at steady state at a mean daily clozapine dosage of 269 mg (3.09 mg/kg), clozapine averaged 231 +/- 144 micrograms/L (mean +/- SD); norclozapine and clozapine-N-oxide concentrations averaged 84% and 23% that of clozapine. Analyte concentrations were significantly correlated with daily dose. The method's ability to quantify clozapine and two major metabolites simultaneously with precision and sensitivity makes it useful in pharmacokinetic studies and therapeutic monitoring.

Adult↗
PubMed1991

The face validity of the DSM-III and DSM-III-R criteria sets for borderline personality disorder.

OBJECTIVE: The main objective of this study was to determine the congruence between DSM-III and DSM-III-R diagnoses of borderline personality disorder derived through the use of semistructured research interviews or given by experienced clinicians after lengthy consultations with an interdisciplinary team. METHOD: The presence of the DSM-III and DSM-III-R criteria sets for borderline personality disorder was assessed in a study group of 253 patients with personality disorders (148 inpatients and 105 outpatients) by raters who were blind to clinical diagnoses and who used information from two semistructured interviews of proven reliability. These diagnoses were then compared with "longitudinal expert all data" (LEAD) standard clinical diagnoses provided by therapists specifically asked to base their diagnoses on DSM criteria. RESULTS: Both criteria sets were found to be overinclusive when compared with the LEAD standard. Most criteria were also found to lack specificity. However, the three DSM-III-R criteria that are new or revisions of DSM-III criteria were found to be more specific, and raising the cutoff on the DSM-III-R criteria from five to six improved specificity. CONCLUSIONS: Both the DSM-III and DSM-III-R criteria sets for borderline personality disorder as assessed by semistructured interview lack face validity because they are nonspecific when compared with a rigorous but representative clinical standard, and the results of studies using these criteria sets may prove misleading to researchers and clinicians because they seem to define a nonspecific type of serious character pathology.

Adolescent↗
PubMed1990

Progressive ventricular enlargement in schizophrenia: comparison to bipolar affective disorder and correlation with clinical course.

Previous studies of long-term serial changes in ventricular size in schizophrenia (SCZ) have yielded mixed, albeit predominantly negative results. The current study examined ventricular changes in CT scans over intervals of 1-to 4 1/2 years in chronic schizophrenic and bipolar patients. The results indicated significant progression of ventricular size from initial to final scan in the schizophrenia group but not in the bipolar or control groups; the percent increase in VBR over baseline was 25% (p less than 0.01) in the schizophrenia group as compared with 11% (n.s.) in the bipolar group. The increases in ventricular enlargement in the schizophrenic group did not correlate with duration of illness but did appear to show an irregular stepwise pattern in several patients. It is concluded that progressive ventricular enlargement after onset of illness does occur in a subgroup of schizophrenic patients characterized by a chronic or deteriorating clinical course. The etiological implications of this finding are discussed.

Adult↗