Faina Bar

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.

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, &ggr;-aminobutyric acid agents, dopamine enhancers, and the &bgr;-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 Trzs property of serotonin 2A postsynaptic receptor antagonism may be its principal mechanism for the improvement of NIA.

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

AbstractElectroconvulsive 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.

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.