Effects of sustained-release bupropion and supportive group therapy on cigarette consumption in patients with schizophrenia.

OBJECTIVE: The study examined the efficacy, tolerability, and safety of supportive group psychotherapy and adjunctive sustained-release bupropion for nicotine addiction in patients with schizophrenia. METHOD: Eight patients participated in a 14-week open-label trial. End expired breath carbon monoxide level, symptom levels, neuropsychological performance, and suppression of the P50 event-related potential were measured before and after the 14-week trial. RESULTS: Patients showed a decrease in carbon monoxide levels that was not associated with any worsening in symptom, neuropsychological, or P50 suppression measures. CONCLUSIONS: Use of sustained-release bupropion in combination with supportive group therapy may help patients with schizophrenia decrease their cigarette consumption.

Comparative effectiveness of fluphenazine decanoate injections every 2 weeks versus every 6 weeks.

OBJECTIVE: Dose reduction strategies for the maintenance treatment of schizophrenia are designed to maintain the benefits of antipsychotic drug therapy while reducing risks. Previous strategies with decanoate preparations have been based on the use of lower doses per injection to achieve dose reduction; these strategies have achieved dose reduction but have resulted in some increase in symptoms. The authors tested a new dose reduction approach: increasing the interval between injections during intramuscular decanoate antipsychotic treatment. METHOD: Fifty outpatients with schizophrenia or schizoaffective disorder were randomly assigned to receive 25 mg of fluphenazine decanoate intramuscularly either every 2 weeks or every 6 weeks for 54 weeks in a double-blind design. RESULTS: The two dose regimens did not differ significantly in relapse, symptom, or side effect measures. The every-6-weeks regimen was associated with a significant reduction in total antipsychotic exposure. CONCLUSIONS: The use of injections every 6 weeks instead of every 2 weeks may increase compliance and improve patients' comfort as well as decrease cumulative antipsychotic exposure, without increasing relapse rates or symptoms.

The Maryland Psychiatric Research Center scale and the characterization of involuntary movements.

The Maryland Psychiatric Research Center involuntary movement scale (MPRC scale) has been used in the evaluation of 1107 patients referred for drug-induced movement disorders. The scale has increased discrimination of body area and severity compared to other scales. Validity was examined using principal component analyses, pharmacologic response studies and associations with AIMS, global judgement and motor diagnosis. Reliability was examined using Cronbach's alpha, intraclass correlation coefficient (ICC) between raters and test-retest measurements. The prevalence of dyskinetic and parkinsonian signs at several levels of severity are reported. Total dyskinesia was strongly correlated with AIMS score, r = 0.97. Inter-rater reliability was 0.81-0.90 for total dyskinesia score. Receiver Operating Characteristic (ROC) analysis shows a total dyskinesia score of 4 or above to predict tardive dyskinesia, consistent with RDC-TD criteria. Hand dyskinesia showed a high prevalence comparable to that of oral dyskinesias. The MPRC scale is a valid, sensitive and reliable instrument for the rating of neuroleptic-induced dyskinetic and parkinsonian syndromes and may offer advantages over other scales in neurophysiologic research and brain imaging with its ease of use, uniform structure and greater discrimination of anatomic place and severity in the rating of involuntary movements.

Borna disease virus antibodies and the deficit syndrome of schizophrenia.

We detected anti-Borna disease virus (BDV) antibodies at a 14.4% rate in patients with schizophrenia. The hypothesis of a higher rate of BDV seropositivity in deficit syndrome was borne out in a subset of 64 patients categorized according to the Schedule for the Deficit Syndrome with 5/15 seropositive deficit and 4/49 seropositive nondeficit (p < 0.05). This suggests that the antibodies and possibly a BDV-like virus are pathogenetically linked to this form of schizophrenia.

Borna disease virus and schizophrenia.

The development of a new serological assay method to detect antibodies in human sera recognizing Borna disease virus (BDV) proteins and a clinical pilot study are presented. Psychiatric patients from a schizophrenia research clinic in Baltimore, Maryland, were examined for antibodies to BDV antigen with traditional indirect immunofluorescence assays (IFA) that used both single and double labeling techniques and also with a Western blot assay capable of detecting antibodies to the three BDV proteins from a human neuroblastoma cell line. Thirteen of 90 (14.4%) patients and 0/20 control subjects had antibodies that recognized more than one BDV protein on the Western blot. Three patients had antibodies that recognized all three BDV proteins. Magnetic resonance imaging assessments of the volume of the putamen (with controls for total cranial volume) differentiated BDV+ from BDV- patients, and there were trend differences for bilateral amygdalae and the left amygdala-hippocampal process. We conclude that: (1) the Western blot assay is superior to IFA assays in BDV serology studies, (2) detection of antibodies to more than one BDV protein is a useful working criterion for seropositivity, (3) the 14.5 kDa BDV protein is 10 times more predictive of seropositivity than either the 38/40 kDa or the 24 kDa protein, (4) there is tentative evidence for a schizophrenia-control difference in the prevalence of anti-BDV antibodies, and (5) it is likely that there are neuroanatomical/behavioral features that differentiate seropositive from seronegative schizophrenic patients.

Effects of clozapine on positive and negative symptoms in outpatients with schizophrenia.

OBJECTIVE: Clozapine is an atypical neuroleptic with superior efficacy in severely ill, treatment-resistant inpatients with schizophrenia. To determine if clozapine's differential efficacy generalizes to less ill, outpatients populations, the authors examined the effects of clozapine on positive and negative symptoms in outpatients with schizophrenia. METHOD: Outpatients with schizophrenia who had histories of partial response to conventional neuroleptics and who had not responded to a prospective 6-week trial of fluphenazine participated in a 10-week, double-blind, parallel-groups comparison of clozapine and haloperidol. Thirteen men and six women were given clozapine, and 15 men and five women were given haloperidol. Clinical response rates were determined and effects on primary versus secondary negative symptoms were addressed. Doses of clozapine and haloperidol at the end of the 10-week trial were 410.5 mg/day (SD = 45.8) and 24.8 mg/day (SD = 5.5), respectively. RESULTS: Clozapine was superior to haloperidol for treating positive symptoms. In addition, eight of the patients given clozapine and only one of the patients given haloperidol fulfilled clinical responder criteria. Clozapine was also superior to haloperidol for treating negative symptoms, although these effects were relatively minor. Negative symptoms were significantly affected in the subgroup of patients with nondeficit schizophrenia but not in the subgroup with deficit schizophrenia. Overall, clozapine was well tolerated. CONCLUSIONS: Clozapine has superior efficacy for treating positive symptoms in partially responsive outpatients with chronic schizophrenia, suggesting that it has utility for a broad spectrum of patients with schizophrenia beyond the most severely ill.

Clinical predictors of relapse following neuroleptic withdrawal.

The validity of previously hypothesized predictors of elapse following neuroleptic discontinuation was examined. One hundred sixty-two outpatients, with either Research Diagnostic Criteria schizophrenia or schizoaffective disorder, were discontinued from neuroleptic medication for a 28-day period or until judged to be relapsed. Pre-discontinuation neuroleptic dosage level, the severity of psychotic symptoms, and the presence of dyskinetic movements prior to neuroleptic discontinuation were the predictor variables. Of the 162 patients, 62.7% did not relapse during the study period. There were no differences in the survival rates between the patients withdrawn from oral versus depot neuroleptics. Neuroleptic dosage, but not severity of psychotic symptoms or dyskinetic movements, predicted relapse. These results support the hypothesis that pre-withdrawal neuroleptic dosage level predicts relapse, but fail to validate either severity of psychotic symptoms or presence of dyskinetic movements as predictors of relapse.

Reduction of perseverative errors in patients with schizophrenia using monetary feedback.

The influence of monetary feedback on Wisconsin Card Sort Test (WCST) performance of 14 male schizophrenics was investigated. Patients were administered the test under standard instructions and with monetary feedback in counterbalanced order. Monetary reinforcement reduced perseverative errors and increased correct responses (p less than .05). These findings suggest that the WCST perseverative errors of schizophrenics reflect motivational as well as cognitive factors.

ROUNDS, a new time-sampling methodology for the quantitative behavioral assessment of schizophrenic withdrawal. Reliability and validity.

Negative symptoms in schizophrenia have been the subject of much research interest. However, there has been a need for a way to measure withdrawal behavior quantitatively over time. We have developed a behavioral time-sampling methodology performed by nursing staff on a schizophrenia inpatient unit. Called ROUNDS, it gathers reliable and valid quantitative data about specific withdrawal behaviors such as posture, daytime sleep and levels of social interaction and activity. This paper describes the development of the method, its implementation, the statistical analysis of its reliability and validity, and the degree to which the data can be replicated with different sampling frequencies. We contend that this method can be applied to the analysis of a wide variety of questions about the nature and treatment response of schizophrenic withdrawal in an inpatient setting.

Meal order reversal: effects of eating a sweet course first or last.

The aim of the experiment was to determine the effects of eating a sweet food either as a first course or as a third course on intake during a three-course lunch. Twenty normal weight, non-dieting male subjects were run twice in a counter-balanced design. The first and third courses were interchanged and consisted of either a sweet (candy bar) or savory (cheese or crackers) food, both of similar palatabilities and energy densities. Intake of these foods, when they were eaten as a first course, was the same. The two first courses had no differential effects on intake of the middle course (spaghetti with meat sauce and a salad), which was the same in both conditions. Intakes in the third course did not differ significantly between conditions, but intake was slightly higher when the candy was eaten. Intake of the candy bar was similar in the first and third courses, but intake of the cheese on crackers was significantly lower (p less than 0.0007) as the third course. Total energy intake over the entire meal was 6% higher when the candy bar was eaten last, but this was not significant. Thus, there was no indication that eating candy as a first course affected appetite and food intake differently from eating the same amount of a non-sweet food such as cheese on crackers, which was similar in energy density and palatability. However, more studies with different foods in a situation more similar to a normal meal are needed before it can be concluded that sweet and savory foods at the start or end of a meal always have the same effects on appetite and food intake.

Carbamazepine maintenance treatment in outpatient schizophrenics.

A double-blind crossover trial was used to evaluate carbamazepine as the sole maintenance treatment of chronic, nonmanic schizophrenic outpatients whose conditions had been stabilized with the use of neuroleptics prior to study. Criteria of treatment effectiveness included the number of patients relapsing and time to relapse over a 95-day neuroleptic-free period during which either carbamazepine or placebo was administered. Relapse was determined by the concordance of psychiatric ratings and independent clinical judgements indicating significant worsening. Results for 27 patients (13 receiving carbamazepine and 14 receiving placebo) involved in the first phase of this treatment comparison were nondifferentiating. Corroborating descriptive findings in the second phase were available for 14 of these patients. There was no evidence supporting the existence of a treatment-relevant subgroup defined by episodic dyscontrol phenomena.

Continuous versus targeted medication in schizophrenic outpatients: outcome results.

The authors report on the outcome of treatment of 116 outpatients with chronic schizophrenia who were assigned to a 2-year, single-blind course of treatment with either targeted or continuous medication. These patients were not restricted to those who were good candidates for a medication reduction strategy. Continuous medication was superior to targeted medication in preventing decompensations and hospitalizations and in extent of employment at 2 years. Other measures of psychopathology and functioning at 1 and 2 years did not differentiate the two groups of patients. The targeted approach achieved a substantial reduction in total medication through a reduction in the number of days of medication administration.

Hunger and food intake following consumption of low-calorie foods.

Although high-intensity sweeteners are widely used to decrease the energy density of foods, little is known about how this affects hunger and food intake. We have studied the effects of consumption of commercially available foods sweetened with either sucrose or aspartame on subjective appetite ratings and food intake. When normal-weight non-dieting males and females were given large portions of either a high- or low-calorie pudding or jello and instructed to eat as much as they liked, they ate similar weights of the different caloric versions of each food. Despite the resulting difference in caloric intake (up to 206 kcal), subjects showed only a non-significant trend towards caloric compensation when presented with a variety of foods 2 h later. Total caloric intake (preload plus test meal) did not differ between conditions. Ratings of hunger, desire to eat, the amount subjects wanted to eat, and the pleasantness of the taste of the eaten food were similarly decreased and fullness similarly increased by consumption of the different caloric versions of the foods. Awareness of the caloric content of the foods did not influence intake or appetite in that both informed and uniformed subjects responded similarly in the tests. Thus reduced calorie foods suppressed ratings of hunger for several hours after consumption, but were not associated with a significant reduction in total energy intake.

Rating affective flattening from videotaped interviews.

Semistructured interviews with 28 schizophrenic patients were videotaped. The affective flattening section of the Scale for the Assessment of Negative Symptoms (SANS) was rated after each interview. At a later date, each videotape was rated by three raters as well as the interviewer. Reliability was estimated within and across rating conditions by intraclass correlation. Comparison of reliability scores across rating conditions indicated that the videotape medium had little effect on the ability of raters to rate affective flattening similarly.

Food intake in dieters and nondieters after a liquid meal containing medium-chain triglycerides.

Medium-chain triglycerides (MCT) may be of benefit in the control of body weight by reducing food intake but this has not been established in humans. The effect of three doses (100, 200, and 300 kcal) of preloads of two complete liquid diets containing either 30% long-chain triglycerides (LCT) or 24% MCT with 6% LCT on subsequent intake was tested in dieting and nondieting females. Thirty minutes after consuming these preloads, subjects were offered a varied self-selection lunch. The major finding was that in the nondieters MCT at all doses was followed by a significantly decreased caloric intake in the lunch. Dieters were unresponsive to the type of dietary fat and tended to eat the same number of calories regardless of the preload. Although MCT can reduce short-term food intake in some individuals, further experiments are required to establish the possible benefit of MCT in weight control.