Rivastigmine treatment for the prevention of electroconvulsive therapy-induced memory deficits in patients with schizophrenia.

Electroconvulsive therapy (ECT) is an effective strategy in some treatment-resistant patients with schizophrenia. However, ECT is associated with cognitive adverse effects, most notably, memory loss. This study examined the effects of rivastigmine, a selective central nervous system acetylcholinesterase inhibitor, with benefits on cognition in Alzheimer disease, on memory performance in patients with schizophrenia treated with ECT. Thirty inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision schizophrenia treated with ECT were coadministered rivastigmine (3-4.5 mg/d) or placebo in a prospective, randomized, double-blind, placebo-controlled trial (maximum period of 4 weeks). Over the ECT course, scores on the cognitive subscale of the Alzheimer's Disease Assessment in subjects receiving placebo showed no significant change, whereas subjects receiving rivastigmine displayed decreased cognitive subscale of the Alzheimer's Disease Assessment scores, indicating cognitive improvement (P < 0.05). Findings suggest possible involvement of the acetylcholinergic system in mediation of cognitive deficits after ECT and indicate possible beneficial effects of rivastigmine coadministration in minimizing some of these ECT-induced cognitive impairments.

Idiom of distress or delusional state? Cultural clash as the cause of misdiagnosis: a case report.

The Beta Israel (House of Israel) represent a total number of more than 100,000 individuals. Ethiopian Jewish culture is based on a tribal cultural model. With their arrival in Israel, many difficulties surfaced. Ethiopian Jews had to deal with cultural choices that challenged their traditions. It has been suggested that the trauma of their journey coupled to the difficulties of the adaptation process to Israeli society, ( the culture shock), was directly responsible for psychopathology found among this population. It also appeared that culture plays a central role in the construction of the clinical picture, blurring at times the boundary between expressions of distress and pathology. It became increasingly difficult to draw the line between culturally normative behavior and psychopathology. The following case report underlines the importance of socio cultural considerations in both staff and patients, and illustrates the dangers of misdiagnosis due to patient therapeutic team cultural clash. A 41 year old woman of Ethiopian origin was hospitalized for suspected schizophrenia. Because of the striking contrast between the patients behavior, responses and so called psychotic content, possible misunderstanding based on cultural differences was considered by the clinical management team. This case underlines the dangers of the psychiatric diagnostic process, emphasizes the important role of sociocultural backgrounds of both staff and patients in patient management and encourages the consideration of cultural factors in all patient evaluations.

Trazodone for the treatment of neuroleptic-induced acute akathisia: a placebo-controlled, double-blind, crossover study.

INTRODUCTION: Neuroleptic-induced acute akathisia (NIA) is a common and distressing extrapyramidal symptom usually resulting from the use of antipsychotic medication.Despite its high incidence (20%-45%), the underlying mechanism of NIA has not yet been adequately explained. Although treatment strategies for NIA have traditionally included anticholinergic agents, γ-aminobutyric acid agents, dopamine enhancers, and the ß-adrenergic antagonists, many patients fail to respond. Trazodone (Trz) is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. In a recent pilot open-label trial, Trz demonstrated to be strongly effective in the treatment of NIA in 9 female schizophrenic patients. OBJECTIVE: On the basis of the results of this pilot study, we investigate further the efficacy of Trz in the treatment of NIA in a double-blind, placebo (Pla)-controlled, crossover design. METHODS: Thirteen inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia or schizo-affective disorder and with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition NIA with a severity of at least mild akathisia according to the Barnes Akathisia Rating Scale participated in the study. Patients were randomly assigned to either the order Trz-Pla or the order Pla-Trz in the treatment periods. Each period lasted for 3 consecutive days (days 1-3 and 4-6). Eight patients were treated with the Trz-Pla order (100 mg/d before bedtime); and 5, with the opposite order (Pla-Trz). RESULTS: Statistically significant improvement in most symptoms of NIA, as measured by the Barnes Akathisia Rating Scale, was detected with Trz compared with Pla treatment. CONCLUSIONS: The findings of this double-blind, placebo-controlled, crossover study indicate the efficacy of Trz in the management of NIA, corroborating the results of a preliminary pilot study. We suggest that Trz's property of serotonin 2A postsynaptic receptor antagonism may be its principal mechanism for the improvement of NIA.

Analysis of clinical characteristics and antipsychotic medication prescribing practices of first-episode schizophrenia in Israel: a naturalistic prospective study.

BACKGROUND: Investigation of the clinical presentation and treatment of first-episode psychosis is important in order to exclude effects of age, chronic illness, long-term treatment and institutionalization. The aim of this descriptive study was to investigate the management practices of first-episode schizophrenia in a cohort of patients in Israel and to document use of the various "typical" or "atypical" antipsychotic agents. METHOD: Fifty-one consecutive patients (26 M, 25 F) with first-episode psychosis were recruited for study participation and were administered either typical or atypical antipsychotic medications in a naturalistic manner. RESULTS: While an approximately equal number of subjects received typical and atypical medications at illness onset, a prominent shift to atypical antipsychotic treatment occurred over the study course; 18 subjects had medication class shifts: 17 from typical to atypical, and one from atypical to typical. Negative symptoms did not affect length of hospitalization, but were associated with aggression. Higher depression rates were noted in patients with long hospitalizations who received typical antipsychotic medications. Immigrants were admitted at an age approximately four years older than native-born Israelis. CONCLUSIONS: The prominent shift from "typical" to "atypical" antipsychotic medications may indicate sensitivity of first-episode psychotic patients to side-effects of "typical" medications and prominence of use of atypical medications in this patient subpopulation be it due to improved efficacy over time or successful marketing. Unique cultural and population characteristics may contribute to the manifestation of first-episode psychosis and suggest the importance of more effective outreach to the immigrant population in order to manage an apparent treatment delay.

Donepezil augmentation of clozapine monotherapy in schizophrenia patients: a double blind cross-over study.

Increasing evidence suggests that the cholinergic system is involved in the pathogenesis of schizophrenia. Donepezil, a central cholinesterase inhibitor, improves psychotic symptomatology in demented patients, however, evidence for its role in the management of active psychosis in schizophrenia remains limited. An 18-week double blind cross-over study was conducted in which eight patients were randomly assigned to either donepezil (5 mg/day for the first 4 weeks and 10 mg/day for the following 4 weeks) or placebo as augmentation treatment to clozapine. After this initial phase, there was a 2-week washout period of the study medication after which the same regimen was crossed over at the same dose and for the same period (8 weeks). No significant difference was noted in the total positive and negative symptom scale scores when donepezil was compared with placebo (16.7%+12.97% vs 3.20%+13.94% respectively, p = 0.18). However, three patients improved (>15%) in the total PANSS scores (37.03%, 16.6% and 25.33%) during the donepezil treatment phase, while only one patient improved (20.87%) during the placebo phase. No differences were noted in the Calgary depression scale (p = 0.305), Simpson Angus scale (p = 0.374), clinical global impression-improvement scale (p = 0.23) and clinical global impression-severity of illness scores (p = 0.116). Although this preliminary study failed to demonstrate a clear effect of donepezil augmentation in clozapine treated chronic schizophrenia patients, it seems that the subtle positive effect of donepezil observed in some of our patients should encourage further investigation in a larger sample of this patient subpopulation.

Alterations in QT dispersion in medicated schizophrenia patients following electroconvulsive therapy.

QT dispersion (QTd) is a measure of interlead variations of the surface 12-lead electrocardiogram (ECG). Increased QTd, found in various cardiac diseases, reflects cardiac instability and is associated with increased risk for cardiac death. Research suggests a link between antipsychotics, ECG abnormalities (QT prolongation) and increased sudden cardiac mortality rates. However, QTd analysis has been scarcely investigated in schizophrenia patients. We calculated QTd in 20 medicated psychotic inpatients with schizophrenia, before and 3 days after electroconvulsive therapy (ECT), concomitantly with Brief Psychiatric Rating Scale (BPRS) assessment. QT interval and the rate-corrected QT (QTc) were abnormally prolonged before ECT. However, although QT was significantly shortened, QTc showed only a marginal decrease after ECT. QTd, the rate-corrected QTd, as well as BPRS, showed a significant decrease after ECT. Further large-scale studies are warranted to determine if QTd can serve as a marker for response to ECT, and if it is a risk factor for sudden cardiac death in schizophrenia patients.

DSM-IV self-report and subjective evaluation by psychiatrists in Israel.

BACKGROUND: Psychiatric disorder, with the range of both subsyndromal and syndromal manifestation, is an important, yet often unrecognized and unacknowledged, problem among physicians. It is a subject that remains understudied, particularly among psychiatrists. The purpose of this study was to explore the subjective perception of mental illness among members of the psychiatric profession. METHOD: Psychiatrists attending an educational symposium completed, anonymously, a self-evaluation questionnaire in which they were asked to self-diagnose the presence of DSM-IV disorders. RESULTS: 110 responses were received (response rate: 52.1%); 90% of respondents indicated the presence of at least one syndrome or trait. The most common disorders on axis I and axis II were "mood disorder" and "narcissistic traits" respectively, with the least common being "psychotic disorder" and "schizotypal traits." Female psychiatrists reported more impairment, particularly among axis I disorders. The reported number of axis I and II conditions decreased with subjects' age. CONCLUSIONS: Manifestations of psychiatric conditions including the range of subthreshold phenomena, as self-diagnosed according to DSM-IV criteria, appear to be prominently reported, albeit with low severity, in a subjective manner by psychiatrists. Our findings may be of importance in encouraging the implementation of special programs in training and ongoing occupational support.

Treatment of neuroleptic-induced akathisia with the 5-HT2A antagonist trazodone.

Akathisia is a common and distressful extrapyramidal adverse side effect usually resulting from the use of antipsychotic medications. Early management of akathisia is important because it may be associated with poor treatment response and medication noncompliance. Unfortunately many patients fail to respond to standard management of akathisia. In addition to dopaminergic mechanisms, it has been hypothesized that serotonin may play a prominent role in the pathophysiology of akathisia. Trazodone is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. This open-label pilot study investigates the efficacy of trazodone in the management of akathisia. Nine female patients with a score of at least "mild akathisia" on the Barnes Akathisia Scale, and receiving a stable dose of antipsychotic medication, were administered trazodone, titrated up to a dosage of 100 mg/day over a period of 5 days. The patients demonstrated marked improvement in symptoms of akathisia. In addition, some improvement was noted in symptomatology of anxiety, depression, and psychosis. These observations suggest the use of trazodone as a beneficial and relatively safe medication for the treatment of antipsychotic medication-induced akathisia. Further study in the context of a double-blind, placebo-controlled trial is mandated to substantiate these preliminary findings.

Amantadine as augmentation therapy in the management of treatment-resistant depression.

Treatment-resistant depression is an important clinical problem presenting a major challenge to clinical psychiatry. While several strategies have been attempted, including medication switch, antidepressant polypharmacy and various augmentative regimens, success remains limited. Amantadine (AMN), an agent traditionally used in the treatment and prophylaxis of influenza, is now known to exhibit prominent effects at the level of dopaminergic, monoamine oxidase and N-methyl-D-aspartate systems. The present reports on the efficacy of AMN as augmentation to standard antidepressant treatment in patients with treatment-resistant depression. Eight patients with treatment-resistant depression consented to receive AMN, titrated up to a dose of 300 mg, over a period of 4 weeks in a non-blinded fashion. Improvement in both depression and anxiety scores were observed from week 1, with patients exhibiting improvement of depressive scores of up to 49% by study completion. Females appeared to exhibit a stronger response, and within a shorter period of time. Side-effects reported included dry mouth and sedation. AMN appears to demonstrate efficacy as a safe and effective augmentative agent in treatment-resistant depression. Further studies are clearly mandated to test these preliminary observations in a double-blinded manner.

Beneficial effect of donepezil augmentation for the management of comorbid schizophrenia and dementia.

Comorbid schizophrenia and dementia is a common clinical phenomenon; however, management of the coexisting illnesses remains incomplete. Donepezil, a cholinesterase inhibitor, may be beneficial for the management of symptoms of Alzheimer's disease, a disease in which cholinergic pathways in the cerebral cortex and basal forebrain are well known to be compromised. Furthermore, impaired cognition in elderly schizophrenic patients has been observed to be more than two thirds; however, there are no published controlled studies reporting the use of cholinesterase inhibitors in the management of schizophrenia in patients with associated dementia. In this study, six patients with chronic schizophrenia and comorbid dementia were administered donepezil, 5 mg, in single-blind fashion as augmentation to their standard antipsychotic medication for a 4-week period. Patients were evaluated with the Mini Mental State Examination (MMSE); Alzheimer's Disease Assessment Scale, Cognitive subscale; Positive and Negative Symptom Scale (PANSS); and the Clinical Global Impression (CGI) scales. A significant improvement was noted in MMSE scores (P < 0.01) and for CGI scores (P < 0.01). In addition, three patients demonstrated improvement on the PANSS. Donepezil appears to be an effective treatment for the management of symptoms of dementia accompanying patients with comorbid schizophrenia and dementia. Since cholinergic dysfunction may be present in some patients with schizophrenia, the authors' findings further demonstrate the possibility that this disorder may be managed with cholinergic medications as augmenting agents, at least in this specific subpopulation of patients with comorbid dementia. To confirm the findings of this preliminary trial, further investigation is mandated with a larger sample of subjects in the context of a double-blind medication trial.