Search

Combining clozapine with a long-acting injectable antipsychotic (LAI) or using different, nonstandard formulations of the compound may improve treatment outcomes. We aimed to investigate the utility of the clozapine-LAI combination and different formulations of clozapine for compliance problems of clozapine treatment, and to describe a case series on the combined treatment.We conducted a PubMed search with no date restriction. The number and length of hospitalizations, the results of clinical scales, and adverse events were recorded. We also present a case series of 18 patients using the clozapine-LAI combination. Data were collected from the medical charts and electronic records.We extracted 9 records describing the use of the clozapine-LAI combination. The case reports and mirror-image studies showed a significant reduction in the number of hospitalizations, length of hospital stays, and number of visits to the emergency department on the combined treatment with no serious adverse events. We included 11 articles for clozapine formulations. The case reports and retrospective data suggested that short-acting intramuscular clozapine was often well tolerated and resulted in an increased acceptance of oral clozapine in the acute phase of illness. In our case series, illness severity and the number of hospitalization per year significantly decreased after the combined treatment, besides a significant improvement in the functioning scores. Hyperprolactinemia and extrapyramidal side effects were reported due to concomitant LAIs.Despite the encouraging evidence, the present data are preliminary and mostly based on retrospective studies, and oral-dissolving tablets or oral liquid formulations of clozapine have insufficient evidence for clinical practice. Well-designed, controlled, follow-up studies are needed for both clozapine-LAI combination and different formulations of clozapine.

The term epigenetic refers to long-lasting changes in gene expression that are beyond the DNA base sequence. Understanding the dynamic role of epigenetic mechanisms in the regulation of gene expression in adulthood has led researchers to investigate epigenetic mechanisms in psychiatric disorders. The aim of this review was to describe epigenetic mechanisms and to discuss the role of epigenetic modifications in stress, depression, schizophrenia, and substance dependence. For this purpose PubMed was searched using the keywords epigenetic, stress, depression, schizophrenia, and substance dependence; studies published between 2000 and 2011 were reviewed. Different maternal behavioral patterns and early life stress have been reported to yield heritable changes in gene expression via epigenetic mechanisms, which are reversible. Studies that investigated the role of epigenetic modifications in stress and depression focused on the proteins involved in the regulation of the hypothalamo-pituitary adrenal (HPA) axis, whereas epigenetic studies of schizophrenia primarily focused on changes in the GABAergic system. Studies on substance dependence, on the other hand, showed that substance use might change the expression of many genes by causing short- or long-lasting epigenetic modifications. These findings have led to the development of new therapeutic strategies that target epigenetic mechanisms. Among these strategies, histone deacetylase inhibitors are especially promising. More studies are needed to improve our understanding of the role of epigenetic modifications in the development of psychiatric disorders, and to aid in the development of new treatment strategies that focus on epigenetic mechanisms.