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Biomedical subjects

S R Marder

Publications and source records attributed to S R Marder.

At least 19 recordsLinked to original sources
PubMed1992

The determination of the steady-state pharmacokinetic profile of fluphenazine decanoate by gas chromatography/mass spectrometry detection.

This study uses the highly sensitive method of gas chromatography/mass spectrometry to compare the basic steady-state pharmacokinetic parameters of two fluphenazine decanoate formulations. Sixteen stable outpatients participated in a two-way crossover design study of the bioavailability of a new formulation of FPZ Dec, i.e., 10 mg/ml, to the standard 25 mg/ml formulation. When compared to a 1 ml injection of the standard formulation (25 mg/ml) over a two-week, steady-state period, we found bioequivalence as evidenced by similar mean areas under the curve (hrs x ng/ml). We did find that the injection volume of the same dose (2.5 ml of a 10 mg/ml formulation) results in a statistically significantly higher maximum serum level of parent fluphenazine. A tendency toward faster time to peak level was observed with the 10 mg/ml formulation but the difference was not statistically significant. Both of these differences are considered too small to be clinically significant. In a subgroup of 10 patients, pre-injection serum fluphenazine levels correlated significantly (Pearson r = 0.78, p < 0.05) with serum prolactin levels.

Adult↗
PubMed1992

Risperidone: clinical development: north American results.

This multicenter trial indicates that risperidone is an effective treatment for the positive and negative symptoms of schizophrenia. The most effective dose appears to be about 6 mg of risperidone daily. This dose was more effective than 20 mg of haloperidol. In addition, this dose was associated with very low rates of extrapyramidal side effects.

Adolescent↗
PubMed1992

Technique for training schizophrenic patients in illness self-management: a controlled trial.

OBJECTIVE: To determine whether schizophrenic outpatients receiving low-dose neuroleptic therapy could learn and retain complex information and skills related to self-management of their illness, a novel technique of teaching, using cognitive and behavioral methods, was designed to compensate for the patients' learning disabilities. METHOD: The subjects were 41 patients with DSM-III-R schizophrenia who were receiving constant maintenance neuroleptic drug therapy. They were randomly assigned to structured, modularized skills training or to supportive group psychotherapy. RESULTS: The patients who received skills training made significant gains in each of the areas taught, while those participating in group therapy did not. The skills learned during training were retained without significant erosion over a 1-year follow-up period. CONCLUSIONS: The effectiveness of modularized teaching of illness self-management skills to schizophrenic patients appears to be largely independent of baseline psychology and symptom improvement. Such an approach is useful for overcoming or compensating for the enduring cognitive and information processing deficits commonly found in schizophrenia.

Activities of Daily Living↗
PubMed1992

Haloperidol plasma levels and clinical response: a therapeutic window relationship.

OBJECTIVE: The purpose of the study was to assess the relationship between plasma haloperidol and clinical response. METHOD: Sixty-nine newly admitted drug-free schizophrenic men were randomly assigned to receive haloperidol, 5, 10, or 20 mg daily for 4 weeks, and clinical response was measured at the end of the fixed-dose period. Haloperidol was assayed by a sensitive and specific radioimmunoassay. RESULTS: The authors found a curvilinear relationship between clinical response and plasma haloperidol during fixed-dose treatment, with an apparent optimum between 5 and 12 ng/ml. When plasma levels above 12 ng/ml were lowered to the 5-12 ng/ml range, all patients improved to varying degrees and no patient deteriorated. When plasma levels of nonresponders within this therapeutic window were raised above 12 ng/ml (as in routine practice), they, on balance, deteriorated in that they became more dysphoric. With the 20-mg dose, half the patients had plasma levels above 12 ng/ml. CONCLUSIONS: In this sample of newly admitted schizophrenic men, optimal clinical response occurred with a plasma haloperidol range of 5-12 ng/ml.

Adult↗
PubMed1992

Neuroleptic medication and prescription practices with sheltered-care residents: a 12-year perspective.

OBJECTIVES: Most adult residents of sheltered-care facilities (board and care, family care, psychosocial rehabilitation, and other supported housing arrangements) for the chronically mentally ill receive neuroleptics. These facilities house over 300,000 mentally ill residents, but neuroleptic prescription practices with this population have not been studied. METHODS: A probability sample (n = 393) of all adult former psychiatric patients in sheltered care in California was surveyed in 1973; 94% of the located survivors (n = 243) were reinterviewed 12 years later. RESULTS: In 1973, 79% received neuroleptics; in 1985, 76%. Polypharmacy decreased, and the elderly remained less medicated than adults. Yet, mean daily neuroleptic doses doubled, more persons received higher doses, and 62% reported adverse effects. Furthermore, high dosing was attributed to psychiatrists rather than other physicians, even when controlling for residents clinical and sociodemographic characteristics. CONCLUSIONS: Neuroleptic drugs became the staple pharmacological treatment for mentally ill sheltered-care residents. While physicians more cautiously medicated the elderly, they had not reduced doses by 1985, even after a decade of treatment. The specialty of the prescriber was an important factor in preference for high-dose treatment.

Adolescent↗
PubMed1992

Acquisition and retention of skills training methods in chronic schizophrenic outpatients.

Forty-one DSM-III-R schizophrenic subjects on constant, low-dose maintenance neuroleptic drug therapy (5-10 mg of fluphenazine decanoate intramuscularly every 2 weeks) were randomly assigned to structured and modularized skills training or to supportive group psychotherapy. The skills training was designed by using cognitive and behavioral methods to compensate for the learning disabilities that plague many schizophrenic patients. Skill acquisition was assessed by using quantified performance on standardized role-play tests. Subjects who received skills training made significant gains in each of the areas taught, whereas those who participated in the control psychotherapy group did not. The knowledge and skills learned during training were retained without significant erosion over a 1-year followup period. These results suggest that the use of structured principles of learning and cognitive therapy can effectively train schizophrenics in skill areas pertinent to the self-management of their illness.

Adult↗
PubMed1991

T2 hyperintense foci on magnetic resonance images of schizophrenic patients and controls.

High resolution magnetic resonance imaging (MRI) of the brain was performed on 18 male schizophrenic patients and 15 male normal control subjects using an identical imaging protocol. The number and size of T2 hyperintense foci were clinically quantified by an academic radiologist. Large foci (greater than or equal to 3 mm in diameter) were observed more frequently on patient images (7/18) than on control images (1/15). The imaging protocol detected high rates of focal hyperintensities, but no differences between patients and controls were noted in the total affected brain area (sum of focal areas) or in the presence or absence of foci.

Adult↗
PubMed1991

Controlled information processing resources and the development of automatic detection responses in schizophrenia.

The relation between resource limitations and the type of processing (automatic vs. controlled) on a multiple-frame search task (MFST) was examined in 15 schizophrenic and 15 normal control subjects. After 320 trials of consistently mapped practice, the patients' detection accuracy was normalized, and the effect of processing load (letter array size) on their detection accuracy was eliminated, which suggests automatization. Changes in load effects with practice could not be used as an index of automatization in control subjects, because of their unexpected lack of load effects at the beginning of practice. In a dual-task (MFST during auditory shadowing) condition after MFST practice, patients' MFST accuracy deteriorated nonsignificantly, and patients' shadowing declined significantly. The findings suggest schizophrenics have reduced available processing resources, but research is needed to determine whether this is due to abnormal automatization.

Adult↗
PubMed1991

Neuroleptic plasma levels.

There is enormous variation in plasma levels of most neuroleptics in patients on the same dose. Much of the past research on the relation between plasma levels of antipsychotic drugs and clinical change, however, has been difficult to interpret. It does appear that decreased bioavailability, at least in public institutions, is rarely the cause of treatment failure. Aberrantly low plasma levels are more likely due to surreptitious noncompliance or drug interactions with enzyme inducers such as carbamazepine. Therapeutic plasma level ranges, in which good antipsychotic effect occurs without undue side effects, have been tentatively identified for perphenazine, haloperidol, fluphenazine, and chlorpromazine. The extent to which aberrantly high plasma levels are associated with inferior antipsychotic response is unclear. Antipsychotic plasma levels may be most useful when the distinction between side effects and worsening psychosis is unclear. The utility of high neuroleptic plasma levels in the treatment-resistant patient is unclear.

Antipsychotic Agents↗
PubMed1991

Plasma levels of fluphenazine in patients receiving fluphenazine decanoate. Relationship to clinical response.

The levels of fluphenazine and fluphenazine sulphoxide in schizophrenic patients who were randomly assigned to receive either 5 mg or 25 mg of fluphenazine decanoate every two weeks were monitored. Patients treated with 25 mg of fluphenazine decanoate required three months to reach a steady-state plasma level, indicating that those patients who are being converted from oral to depot fluphenazine should continue to receive oral supplementation during the first three months of treatment with fluphenazine decanoate. Plasma levels of fluphenazine sulphoxide were lower than levels of fluphenazine. At six and nine months following randomisation, there was a statistically significant relationship between lower fluphenazine plasma levels and an increased risk of psychotic exacerbations. A relatively weak relationship was found between fluphenazine plasma levels and akinesia, but non-significant relationships between fluphenazine levels and other neurological side-effects including akathisia, retardation, and tardive dyskinesia. Monitoring the plasma levels may be helpful to clinicians who are attempting to treat stabilised patients with the lowest effective dose of fluphenazine decanoate.

Adult↗
PubMed1991

Serum prolactin as a correlate of clinical response to haloperidol.

The rise in serum prolactin concentration in patients treated with neuroleptic drugs is well documented, but attempts to relate this rise to clinical response have yielded conflicting results. These conflicting results could be explained by design flaws in those studies attempting to relate prolactin to clinical response. Seventy-three newly (re)admitted drug-free schizophrenic men were randomly assigned to receive haloperidol either 5, 10, or 20 mg daily for 4 weeks. Prolactin levels post-treatment were significantly (p less than 0.02) related to global outcome by logistic regression. A serum prolactin level may be a useful guide to the lowest effective dose of haloperidol in newly treated schizophrenic men. Above a plasma prolactin level of approximately 30 ng/ml there was very little increase in response. Patients on the 5, 10, and 20 mg daily haloperidol doses had mean prolactin levels of 16, 32, and 34 ng/ml, respectively.

Adult↗
PubMed1991

Early prediction of relapse in schizophrenia: an application of receiver operating characteristic (ROC) methods.

We compared different methods of identifying prodromal periods with regard to their ability to predict relapse in schizophrenia. Fifty stabilized schizophrenic patients, who received a low dose of schizophrenic patients, who received a low dose of fluphenazine decanoate (5 to 10 mg every 2 weeks) were monitored with weekly evaluations to determine whether they met criteria for nonpsychotic prodromal episodes. We evaluated three different scales: (1) the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS); (2) a modification of the patient self-report Early Signs Questionnaire and (3) the Idiosyncratic Prodromal Scale (IPS). We used receiver operating characteristic (ROC) methods for comparing the different instruments as methods for predicting whether patients would or would not demonstrate a psychotic exacerbation in the 4 weeks following the assessment. Both the IPS and the BPRS cluster scores were better than chance at correctly identifying periods of vulnerability to psychotic exacerbation. The ROC analyses suggest that relatively small changes in the signs and symptoms of chronic schizophrenic patients in maintenance treatment may be clinically meaningful.

Humans↗
PubMed1991

Plasma fluphenazine levels and clinical response in newly admitted schizophrenic patients.

Seventy-two newly readmitted, drug-free men with the diagnosis of schizophrenia by DSM-III were assigned randomly to receive fluphenazine hydrochloride at 5 mg, 10 mg, or 20 mg daily for 4 weeks. Fluphenazine (FLU), fluphenazine sulfoxide, 7-hydroxyfluphenazine, and fluphenazine N-oxide were measured by highly specific and sensitive radioimmunoassays. Data were analyzed by logistic regression using the Clinical Global Impressions Disabling Side Effects and Global Improvement as the outcome measures. Disabling side effects were defined as "side effects that significantly interfered with patient's functioning" or "side effects that outweigh therapeutic effects" (National Institute of Mental Health 1985, p. 839). Higher plasma FLU levels (up to 4.23 ng/mL) were significantly (p = .015) associated with a higher rate of global improvement. However, close to 90 percent of these acute patients had disabling side effects at a plasma FLU level of 2.7 ng/mL. At least in the patient's view, these disabling side effects negated or compromised the improvement in psychosis. Fluphenazine N-oxide may be a toxic metabolite in that it was more powerfully associated with side effects than was the parent FLU.

Adult↗
PubMed1990

MRI in tardive dyskinesia: shortened left caudate T2.

High-resolution magnetic resonance imaging of the brain was performed on 18 male schizophrenic patients, 14 with a cumulative exposure to neuroleptics of more than 1 year and 4 with less than 3 months of exposure. Calculated T2 relaxation time values were obtained for the basal ganglia. Patients with tardive dyskinesia (n = 9) had significantly shortened left caudate T2 relaxation times when compared to patients without tardive dyskinesia (n = 5). The group of four patients with fewer than 3 months' exposure to neuroleptics demonstrated a significantly greater variability of their left caudate T2 values. T2 relaxation time shortening may be related to iron levels in the basal ganglia and may be of predictive value in evaluating risk of tardive dyskinesia.

Adult↗
PubMed1990

A controlled dose comparison of haloperidol in newly admitted schizophrenic patients.

Eighty newly admitted or readmitted men with DSM-III schizophrenia were assigned to receive 5, 10, or 20 mg/d of haloperidol for 4 weeks. Staff were not "blind" to dose. By Clinical Global Impression Scale ratings, the 20-mg dose appeared to be superior to both the 5- and 10-mg doses for the first 2 weeks of treatment but not thereafter. On the Brief Psychiatric Rating Scale Schizophrenia factor, the 20-mg dose was superior to the 5-mg dose throughout the trial and tended to be marginally superior to the 10-mg dose after the first 2 weeks of treatment. By the second week of treatment, however, the group receiving the 20-mg dose deteriorated significantly with regard to Brief Psychiatric Rating Scale ratings of Withdrawal-Retardation (blunted affect, motor retardation, and emotional withdrawal) as well as akinesia and akathisia ratings. Furthermore, 35% of patients given 20 mg/d of haloperidol insisted on leaving the hospital against medical advice vs only 4% of those given 5 or 10 mg/d of haloperidol. A 20-mg/d dose of haloperidol, therefore, may have substantial "psychotoxic" effects by the second week of treatment.

Adult↗
PubMed1990

Social skills and relapse history in outpatient schizophrenics.

Persons with schizophrenia commonly have impaired social functioning (Wallace 1984). Those with greater impairments, particularly as measured by premorbid social attainment, have a poorer clinical prognosis (Strauss and Carpenter 1972). Interventions designed to improve social competence, such as social skills training, have yielded generalizable and durable effects and may have reduced relapse rates (Wallace and Liberman 1985; Liberman et al. 1986; Hogarty et al. 1986). Thus, a valid measure of social skills should be a useful clinical and research tool. This research explores the validity of a new instrument for measuring such skills, the Assessment of Interpersonal Problem Solving Skills (AIPSS) (Donahoe et al., this issue). The AIPSS differs from more conventional social functioning measures because it 1) utilizes observations of role-playing, rather than self-report or third-party report; 2) provides a rating of the patient's current rather than past functioning; 3) involves videotaped simulated "real life" situations that pose challenges to the patient's ability to solve socially relevant problems; 4) permits assessment of patient's social perception, processing of social information for action planning, and verbal and nonverbal social responses. In this study, we examined the relationship between these parameters of schizophrenic patients' social functioning and their recent relapse history.

Adult↗