Schizophrenia: when clozapine fails.

Purpose Of Review: This article reviews the recent evidence for therapeutic strategies for patients with treatment-resistant schizophrenia (TRS) not responding to or only partially responding to clozapine.

Recent Findings: A number of pharmacological and nonpharmacological biological approaches for clozapine-resistant TRS have been evaluated in clinical trials. Among these, the evidence supporting clozapine augmentation by pharmacological approaches is weak and the reported benefits were modest at best.

A naturalistic comparison of the long-term metabolic adverse effects of clozapine versus other antipsychotics for patients with psychotic illnesses.

Objective: Clozapine, an evidence-based treatment of refractory schizophrenia, is associated with increased weight gain and metabolic dysregulation compared with most antipsychotics in short-term clinical trials. However, there are limited data describing comparative long-term metabolic risks. In this report, we examined whether short-term differences persist with long-term exposure to clozapine.

Intranasal oxytocin blocks alcohol withdrawal in human subjects.

Background: The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain.

Methods: In a randomized, double-blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol-dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score-driven PRN administration of lorazepam.

Prenatal infection and risk for schizophrenia: IL-1beta, IL-6, and TNFalpha inhibit cortical neuron dendrite development.

Prenatal exposure to infection increases risk for schizophrenia, and we have hypothesized that inflammatory cytokines, generated in response to maternal infection, alter neuron development and increase risk for schizophrenia. We sought to study the effect of cytokines generated in response to infection-interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNFalpha), and interleukin-6 (IL-6)-on the dendritic development of cortical neurons. Primary mixed neuronal cultures were obtained from E18 rats and exposed to 0, 100, or 1000 units (U)/ml of IL-1beta, TNFalpha, IL-6, or IL-1beta+TNFalpha for 44 h.