Do patients with paranoid and disorganized schizophrenia respond differently to antipsychotic drugs?

OBJECTIVE: The aim of this study was to compare the differential response to amisulpride in patients with paranoid versus disorganized schizophrenia. METHOD: We reanalyzed the original data from five different randomized drug trials comparing Brief Psychiatric Rating Scale (BPRS) scores in a database containing 427 paranoid and 296 disorganized patients with schizophrenia. RESULTS: Both the disorganized and the paranoid group showed a substantial improvement of the BPRS total score within the first 4 weeks. In the paranoid group, mean (±SD) BPRS reduction was 16.9 (±14.6) (t = 24.06, df = 426, P < 0.001) and in the disorganized group 17.0 (±15.9) (t = 18.49, df = 295, P < 0.001). An analysis of covariance (ancova) controlling for BPRS at baseline and the influence of different trial protocols showed significant differences between diagnostic groups (F = 13.47, df = 1, P < 0.001), Cohen's D 0.31 (CI = 0.16-0.46). Paranoid patients improved by 4.8 BPRS points more than disorganized patients (adjusted means 18.90 (CI = 17.33-20.37) for the paranoid and 14.1 (CI = 12.04 - 16.11) for the disorganized group. CONCLUSION: We conclude that amisulpride is effective in disorganized as well as in paranoid schizophrenia, but that symptom reduction in the disorganized subtype is less pronounced.

Quantitative motor activity differentiates schizophrenia subtypes.

BACKGROUND: Motor symptoms are frequent in schizophrenia and relevant to the diagnosis of subtypes. However, the assessment has been limited to observations recorded in scales and experimental designs. The aim of this study was to use wrist actigraphy to obtain motor activity data in 3 schizophrenia subtypes. METHODS: In total, 60 patients with schizophrenia (35 paranoid, 12 catatonic, 13 disorganized) were investigated using continuous wrist actigraphy over 24 h in an inpatient setting on average 38 days after admission. Data of the wakeful hours of the day were analyzed. RESULTS: The activity level was predicted by schizophrenia subtype and by the type of antipsychotic medication. The movement index and mean duration of uninterrupted immobility were found to be predicted only by the schizophrenia subtype. Age, gender, duration of illness and chlorpromazine equivalents did not contribute to the variance of the activity data. A MANOVA demonstrated the significant differences in the 3 parameters between schizophrenia subtypes (p = 0.001). Patients with catatonic schizophrenia had lower activity levels, a lower movement index and a longer duration of immobility than those with paranoid schizophrenia. CONCLUSIONS: Schizophrenia subtypes can be differentiated using objective measures of quantitative motor activity. The increased duration of immobility appears to be the special feature of catatonic schizophrenia.

Delay of gratification and executive performance in individuals with schizophrenia: putative role for eating behavior and body weight regulation.

OBJECTIVE: Impairment in executive functions and disturbed weight regulation are common features in individuals with schizophrenia on antipsychotics. Still, the clinical management of weight gain, including educational programs, is insufficient. Therefore, we hypothesized that distinct executive impairment is associated with the inability to self-control food intake. METHOD: In the present study we investigated the performance in a paradigm analyzing the executive subfunction "delay of gratification" in individuals with schizophrenia (n=29) compared with controls (n=23) and the interrelationship between delay of gratification, overall executive functioning, reported eating behavior and the BMI. We applied a board-game paradigm to operationalize delay of gratification: on designated fields individuals need to decide about a small amount of immediate reinforcement versus double the amount in the end. Appetite and eating behavior were assessed by self-report scales, executive functioning by BADS. RESULTS: We found that the patients performed significantly worse in our paradigm and that this is associated with lower executive functioning. However, the interrelationship between all parameters is complex: there is a significant positive correlation between the reported perceived appetite and executive functioning whereas the reported restrained eating behavior, significantly more frequent in patients, is correlated with low executive functioning and high disinhibition in eating situations. CONCLUSIONS: We conclude that executive functions are necessary to successfully manage eating behavior. Thus, better understanding of the cognitive mechanisms might help to support the patients more efficiently in their tough job to keep control.

Three cases of schizophrenia for which olanzapine was effective after early acute phase.

AIMS: It clarifies a difference between early acute phase and late acute phase in medication. METHODS: The present report describes three patients with schizophrenia who presented with restlessness and excitement requiring hospitalization. RESULTS: Treatment with risperidone solution orally or parenteral haloperidol until the day after admission, followed by olanzapine, successfully improved the clinical condition of the patients. In the early stage of hospitalization, selection of fast-acting drugs that can be administered to uncooperative patients is considered preferable, focusing on rapid control of symptoms and behavioral disorders, whereas after this early stage, olanzapine is preferable for improving patient compliance in addition to stabilizing symptoms. CONCLUSIONS: Because the target symptoms differ between the early and late acute phases, the term 'acute phase' used in the broad sense should be divided into two units, each requiring a different therapeutic strategy, and independent clinical approaches should be considered in order to provide more suitable treatment.

The clinical dilemma--prescribing in pregnancy.

Antipsychotic prescription in pregnancy is a complex topic and raises a great deal of anxiety in professionals. There is limited data about atypical antipsychotic prescription in pregnancy and its possible teratogenicity. There are no randomised controlled studies of atypical antipsychotic use in pregnancy due to obvious reasons of ethical issues. We present two cases where a choice had to be made as to whether to prescribe Olanzapine during pregnancy, with different results.

Characteristics and use patterns of patients taking first-generation depot antipsychotics or oral antipsychotics for schizophrenia.

OBJECTIVE: Investigators compared patient characteristics and antipsychotic use patterns between individuals with schizophrenia treated in usual care with first-generation depot antipsychotics and those treated with oral antipsychotics (first- or second-generation or both). METHODS: Analyses used data from the U.S. Schizophrenia Care and Assessment Program, a large, prospective study of treatment for schizophrenia conducted July 1997 through September 2003. Participants were assessed at enrollment and every six months thereafter with patient self-report, validated psychiatric measures, and systematic extraction of medical records. Individuals treated with a first-generation depot antipsychotic at any time during the three-year study (N=569) were compared with those treated with only oral antipsychotics (N=1,617) on characteristics at enrollment and medication use pattern during the year after enrollment. RESULTS: Compared with patients receiving only oral antipsychotics, participants treated with depot medications (haloperidol or fluphenazine decanoate) were more likely to be African American (p<.001); less likely to be a veteran (p=.005); had more psychiatric hospitalizations in the year before enrollment (p<.001); and were more likely to have been arrested (p<.001), to use alcohol and illicit substances (p<.001), and to show higher psychopathology, particularly psychotic symptoms and disorganized thinking (p<.01 for both). In the year after enrollment, participants treated with depot medications had a high mean medication possession ratio (91%), and most of the medication regimens (68%) were augmented with oral antipsychotics for prolonged durations (median of 144 days). CONCLUSIONS: Patients with schizophrenia treated with first-generation depot antipsychotics differed from those treated with only oral antipsychotics. Findings suggest that first-generation depot antipsychotics might address some unmet needs of a unique subgroup of patients with schizophrenia.

[The cardiovascular risk of schizophrenic patients]. / Das kardiovaskuläre Risiko schizophrener Patienten.

OBJECTIVE: Schizophrenia is associated with increased cardiovascular mortality. The deceleration capacity of heart rate is discussed to be a predictor of mortality, more powerful than conventional measures of heart rate variability (HRV) or the left ventricular ejection fraction. The aim of this study was to determine whether patients with schizophrenia, receiving antipsychotic medication have a reduced HRV indicating an elevated mortality risk. METHODS: We quantified HRV and the deceleration capacity in 24-hour electrocardiogram recordings from 28 medicated patients with schizophrenia and 28 matched controls. In addition to the evaluation of the 24-hour recording, 4-hour periods of "sleep" and "wake" recordings were evaluated separately, as activity has a major influence on HRV. Actigraphy was used to identify coherent sleep and wake phases and to ensure comparable levels of activity in patients and controls. RESULTS: Medicated patients showed a significant reduction of the HRV. The HRV was reduced significantly according to the time domain and frequency domain measures. The deceleration capacity of medicated patients was 5.36 compared with 8.26 for the controls (p < .05). CONCLUSIONS: Heart rate deceleration capacity is significantly reduced in schizophrenic patients treated with antipsychotics and may serve as an indicator of increased cardiovascular mortality risk.

Benefits of combining aripiprazole to clozapine: three case reports.

OBJECTIVE: A substantial number of patients treated with clozapine shows insufficient response. The author presents the results of adding aripiprazole in patients resistant to clozapine. METHOD: Three cases of individuals with psychotic symptoms despite clozapine use and with significant side effects that were treated via this combination are presented. Response was evaluated by clinical assessment. RESULTS: Good clinical results were obtained in all three patients, with improvement of psychotic symptoms and of some of the side effects of clozapine. CONCLUSION: The findings from this case series suggest that adjunctive therapy with aripiprazole can be of benefit for treating clozapine resistant schizophrenic patients.

Severe hypernatraemia due to nephrogenic diabetes insipidus - a life-threatening side effect of chronic lithium therapy.

Renal toxicity of long-term lithium therapy is a common problem. Nephrogenic diabetes insipidus is the most frequently encountered complication, but often remains unrecognised because of the rather benign symptoms. We present a patient with long-term lithium therapy who developed life-threatening hypernatraemia due to insufficient oral fluid intake after elective spinal surgery. Careful daily substitution of up to 25 l of hypotonic fluids led to full recovery within 9 days. Nephrogenic diabetes insipidus should always be considered in lithium-treated patients undergoing elective surgery in order to avoid severe hypernatraemia.

The Curse of the Dolphins: Cognitive Decline and Psychosis.

CASE: Isela is an 11-year-old Mexican-American girl with mild intellectual disability. During a vacation with her family, she went swimming with dolphins. A few days later, Isela awoke at night with laughing spells; during the day, she was pacing, aggressive, and had a decline in self-care and communication skills. Her parents attributed the symptoms to the dolphins. She was evaluated by a pediatric neurologist. The sleep-deprived electroencephalogram, brain magnetic resonance imaging, lumbar puncture, and thyroid function tests were normal. A genomic microarray was sent. The neurologist initiated empirical therapy for seizures with lamotrigine, which caused a rash. It was discontinued. She was then treated with oxcarbazepine followed by topiramate for several months without any change in symptoms. Comparative genomic hybridization revealed a small deletion at 14q13.1, which includes the NPAS3 gene. Psychiatry was consulted after several months of persistent symptoms. Isela seemed to be laughing in response to internal stimuli. Owing to the decline in communication and her apparent preoccupation with visual and auditory internal stimuli, Isela could not be interviewed adequately to confirm that she was experiencing hallucinations, but her laughter seemed to be in response to hallucinations. Isela was diagnosed with disorganized schizophrenia with psychosis. Risperidone was prescribed. A psychology evaluation was completed a few months later. Parents noted significant improvement after starting risperidone with reduced inappropriate laughing spells, reduced pacing, as well as improved eating, sleeping, communication, and self-care. Cognitive assessment with the Wechsler Abbreviated Scale of Intelligence-II indicated the following: verbal estimated intelligence quotient (IQ) = 70, perceptual estimated IQ = 71, and full-scale estimated IQ = 68. There was no cognitive decline compared with testing at school 4 years previously. Although psychotic symptoms were significantly improved on antipsychotic medication and function appeared to have been restored to her previous level, her parents continued to perceive a significant decline of functioning, and they continued to attribute the psychosis to swimming with the dolphins.

Acute and subchronic effects of low-dose bromocriptine in haloperidol-treated schizophrenics.

The effects of the acute (within 24 hr) and subchronic (21 days) addition of low-dose bromocriptine (2.5 mg/day) were compared to placebo in schizophrenic patients treated concomitantly with haloperidol. After 24 hr patients on bromocriptine (n = 15) showed a mean improvement of 29% in the total score of the Brief Psychiatric Rating Scale (BPRS) as compared to 14% in the placebo group (n = 15) (p less than 0.10). The acute improvement correlated negatively with bromocriptine plasma levels; patients with the highest reduction in BPRS score had the lowest plasma levels (between 50 and 150 pg/ml) at 60, 90, and 120 min after intake. The improvement in the bromocriptine group continued until the 10th day of the trial, when a nonsignificant increase in the total BPRS score took place. Analysis of Variance of the overall BPRS improvement during the 21 days revealed no significant difference between both patient groups. Our results give modest support to the idea of an acute antipsychotic response to low-dose dopamine agonists in neuroleptic-treated patients, but fail to support their clinical usefulness in the subchronic treatment of schizophrenia.

Sleep analysis during drug-free weekends in chronic schizophrenic patients.

The authors made a polygraphic registration of the night sleep in a sample of 14 chronic schizophrenic patients who for several months (mean 8 months) have been on a stable, relatively low maintenance dosage of neuroleptics administered according to the drug-free weekend schedule (two consecutive drug-free days at the weekend). During this treatment none of them showed a relapse or deterioration (BPRS, CGI, and NOSIE rating scales were applied periodically). Their only complaint was of sleep deterioration during the drugfree weekend nights, especially during the second night. The polygraphic night-sleep pattern of each patient was studied during two consecutive weeks. No difference was found between the adaptation night on medication and the consecutive night on medication during the first week, and between the adaptation and readaptation nights on medication during two consecutive weeks. There was no difference in any sleep parameters between the nights on medication and the first drug-free nights. There was a signifcant difference in the total sleep time between the nights on medications and the second drug-free nights. No difference was found in any other sleep parameters in nights analysed as a blocks and in the distribution of NREM and REM stages in the first vs. the second half of the night when B3 was compared with A2. The practical implication is, that to avoid any change in nocturnal behavior it is preferable to withdraw the medication on two nonconsecutive days in the week. The evaluation of both daily and nocturnal behavior seems to be a useful tool in evaluating the first sign of the drug-withdrawal syndrome.

Negative and deficit symptoms in schizophrenia do respond to neuroleptics.

Five large-scale placebo-controlled studies are cited to show that, contrary to the contention of Johnstone et al. (1976) and Crow (1980), negative and/or deficit symptoms in schizophrenia do indeed respond to neuroleptic treatment. Further evidence is given that it is the "organic-like" symptoms (visual and olfactory hallucinations, disorientation, and memory deficit) that do not respond to neuroleptics. This would more sensibly reformulate the hypothesis of Johnstone et al. (1976) and Crow (1980) to state that schizophrenic patients with enlarged ventricles tend to show symptoms of organicity and tend not to respond to neuroleptics.

Clinical, biochemical, and hormonal aspects of treatment with Des-tyr1-gamma-endorphin in schizophrenia.

Des-tyr1-gamma-endorphin (DT gamma E) was administered intramuscularly in a dose of 1 mg/day for 10 days to 18 neuroleptic-free schizophrenic patients in a double-blind crossover design. Six patients showed either a slight or no antipsychotic response; seven patients showed a moderate antipsychotic response; and the remaining five patients showed a marked antipsychotic response. DT gamma E led to a decrease of plasma prolactin levels in patients treated with DT gamma E in the first period of experimental treatment as compared to those treated with placebo. Neither plasma levels of growth hormone and cortisol nor cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylglycol were affected by DT gamma E. Patients suffering from a hebephrenic or paranoid type of schizophrenia and those presenting relatively fewer negative symptoms were most susceptible to treatment with DT gamma E. These data confirm and extend previous findings that DT gamma E has antipsychotic properties in a number of schizophrenic patients.

SPECT imaging, clinical features, and cognition before and after low doses of amisulpride in schizophrenic patients with the deficit syndrome.

The aim of the study was to examine the action of low-dose amisulpride (100 mg/d), an atypical antipsychotic from the benzamide class with a high affinity for the D2 and D3 dopamine receptors, given for 4 weeks in 19 schizophrenic patients with the deficit syndrome, in terms of clinical response, modifications in their cognitive performance and changes in brain perfusion values. A secondary objective was to distinguish between primary and secondary deficit, according to Carpenter's definition. Both efficacy and a relatively low rate of side effects of low-dose amisulpride in the deficit forms of schizophrenia were found as expected from earlier placebo-controlled studies. Our study found significant changes in the cerebral blood flow, before and after treatment, more marked in the frontal area and particularly in the dorso-lateral frontal area. A significant improvement of cognitive function was found after treatment, without a link to any particular changes in a loco-regional perfusion value. Finally, a distinction between primary and secondary deficit showed a higher percentage of clinical improvement in the patients with a secondary deficit. The psychometric and cerebral perfusion changes were no different in the two groups.

Neuropsychological correlates of schizophrenic syndromes in patients treated with atypical neuroleptics.

There is widespread evidence that schizophrenic symptomatology is best represented by three syndromes (positive, negative, disorganized). Both the disorganized and negative syndrome have been found to correlate with several neurocognitive dysfunctions. However, previous studies investigated samples predominantly treated with typical neuroleptics, which frequently induce parkinsonian symptoms that are hard to disentangle from primary negative symptoms and may have inflated correlations with neurocognition. A newly developed psychopathological instrument called the Positive and Negative and Disorganized Symptoms Scale (PANADSS) was evaluated in 60 schizophrenic patients. Forty-seven participants treated with atypical neuroleptics performed several neurocognitive tasks.A three-factor solution of schizophrenic symptomatology emerged. Negative symptomatology was associated with diminished creative verbal fluency and digit span backward, whereas disorganization was significantly correlated with impaired Stroop, WCST and Trail-Making Test B performance.Data suggest that disorganization is associated with tasks that demand executive functioning. Previous findings reporting correlations between negative symptomatology and neurocognition may have been confounded by the adverse consequences of typical neuroleptics.

[Hyperthermia with acute rhabdomyolysis in a psychotic treated with neuroleptics]. / Hyperthermie avec rhabdomyolyse aiguë chez un psychotique traité par neuroleptiques.

A 36 year old psychotic man receiving treatment with slow-release pipotiazine and trihexyphenidyl developed nine days after addition of droperidol signs suggestive of a malignant neuroleptic syndrome: altered general condition, diffuse hypertonia, akinesia, fever and vomiting. Results of biologic tests and a muscle biopsy were suggestive of a severe rhabdomyolysis. Cessation of neuroleptic therapy and the administrative of nifedipine brought a gradual return return to normal conditions, and progressively increasing doses of neuroleptic could be given without complications 12 days later. Onset of hyperthermia during neuroleptic treatment raises two questions: 1) is the etiology related to a malignant neuroleptic syndrome or acute catatonia, or a heat stroke? 2) to what extent are neuroleptics responsible for these disorders?

[Antipsychotic efficacy of neuroleptic neuropeptides in schizophrenia. Review of clinical data]. / Efficacité antipsychotique des neuropeptides neuroleptiques dans la schizophrénie. Revue des données cliniques.

Recently much interest has been shown in the antipsychotic efficacy of neuroleptic-like neuropeptides in schizophrenia. In this article the clinical effects of the non-opioid fragments of gamma-endorphin, the so-called gamma-type endorphins DT gamma E and DE gamma E are reviewed. In addition, preliminary clinical studies of peptides related to cholecystokinin are considered. It is concluded that gamma-type endorphins possess antipsychotic properties in a subgroup of patients who may belong to Type I schizophrenia. With cholecystokinin-related peptides, in particular ceruletide, antipsychotic effects have been reported, which seem to be more or less comparable to those observed with gamma-type endorphins.

[Carpipramine in psychoses]. / La carpipramine au cours des psychoses.

A survey of 131 psychotic subjects treated with carpipramine and a synthesis of the Japanese, German and French publications about this drug were done. The most valuable results were obtained in hebephrenics and in depressed schizophrenics. Carpipramine has a definite desinhibitory action against motor retardation, lack of energy, ideo-motor slowliness and blunting of the affect. At low doses, paranoid schizophrenics become worse. The emerged delusional and anxious phenomena, can be avoided by using higher doses. This drug possesses two kinds of effects: antidelusional and desinhibitory actions. If it does not seem to be a true antidepressant, Carpipramine proves useful in deficits of the psychomotor tone, which were resistant to antidepressant drugs.