New developments in the pharmacological treatment of schizophrenia.

The ability to use pharmacological treatment for schizophrenia is progressing in a most efficacious fashion, while the risk of adverse effects is declining. An important reevaluation of minimal effective antipsychotic drug dosages for both acute and extended treatment has taken place. Clozapine has provided clinical practitioners with a useful new alternative for treatment-refractory patients, and new research has helped clarify the role of different maintenance and prophylactic medication strategies. The author summarizes recent progress in these areas.     

New drug treatment strategies in schizophrenia: editorial introduction

The recognition of both the value and limitations of antipsychotic drug treatment has led to research on effective alternative strategies for treatment. The authors review assumptions underlying such strategies and introduce five articles pertinent to the topic. These articles address: the use of drugs other than antipsychotic neuroleptics; the use of reduced dosages of antipsychotic drugs; the initiation of antipsychotic drugs early during periods of symptom exacerbation to prevent full relapse; the use of psychosocial treatment strategies in relation to drug treatment; and the development of antipsychotic drugs following models based on restitutive systems in the brain.     

Schizophrenia research in Japan: editor's introduction.

The aim and circumstances of the special theme on "Schizophrenia Research in Japan" are described. The six articles included in the issue cover the history, epidemiology, psychophysiology, animal as well as human models, and neurochemistry of schizophrenia.     

New developments in the pharmacotherapy of schizophrenia

This review summarizes current key research strategies and the most prominently pursued new potential treatments for schizophrenia. First, new routes of administration for second generation antipsychotics are presented. These include rapidly dissolving tablets, drops and sirups as well as new intramuscular formulations. Newly available short acting and long acting (depot) antipsychotics complement oral antipsychotics so that the full spectrum of routes of administration is now available for second generation antipsychotics. Next to antipsychotic polypharmacy, in which two or more antipsychotics are combined, pharmacological add-on treatments, mainly with benzodiazepines, antidepressants and mood stabilizers enjoy increasing popularity. Most of this practice is driven by personal preferences, clinical experience and marketing rather than evidence based medicine. New pharmacological mechanisms currently utilized in advanced states of development include partial dopamine D2-receptor agonism, supplementation with glutamatergic agents, estrogen and omega-3-fatty acids. While the concept of partial D1-agonism has already led to the successful launch of a new antipsychotic, aripiprazole, the other attempts to improve therapeutic response in schizophrenia patients have so far provided equivocal results. It is argued that they may be helpful for certain subgroups or specific symptoms of schizophrenia patients. In conclusion, many exciting new pharmacological leads are currently pursued and this will very likely augment the options for treating patients with schizophrenia.     

The pharmacologic treatment of schizophrenia: a progress report

Pharmacologic agents currently used or being studied for the treatment of schizophrenia are reviewed. Neuroleptic medications are still the mainstay of treatment, but recent studies suggest new approaches to dosage and to the treatment of acute psychosis. Lithium is beneficial in psychotic illnesses with acute onset and a remitting course, regardless of the acute psychotic symptoms. Antidepressant agents may ameliorate depression in psychotic patients, but do not improve psychotic symptoms or social withdrawal. Propranolol's reported antipsychotic action has not been confirmed by controlled studies, but the drug may have a role in treating organic psychoses. The benzodiazepines, clonidine, and carbamazepine all merit more investigation as possible treatments for psychosis. The implications of differential treatment response among schizophrenic patients are discussed.     

Reducing variation in the pharmacologic treatment of schizophrenia: Defining acceptable standards of treatment

Clinicians are exhorted to improve the quality of care for patients with schizophrenia by applying evidence-based medication treatment guidelines. Unfortunately, although there are many guidelines, they are all more or less out of date, and their recommendations often are inconsistent, leaving clinicians uncertain about the definition of acceptable standards of care. This paper reviews existing guideline recommendations and recently published research related to two parameters of care: 1) first-line treatment of multiepisode psychosis and 2) the care of treatment-resistant patients. Its purpose is to help clinicians understand the implications of the latest research for the content of schizophrenia guidelines and for the clinical practice they are supposed to inform.     

Past and present progress in the pharmacologic treatment of schizophrenia

Despite treatment advances over the past decades, schizophrenia remains one of the most severe psychiatric disorders that is associated with a chronic relapsing course and marked functional impairment in a substantial proportion of patients. In this article, a historical overview of the pharmacologic advances in the treatment of schizophrenia over the past 50 years is presented. This is followed by a review of the current developments in optimizing the treatment and outcomes in patients with schizophrenia. Methodological challenges, potential solutions, and areas of particular need for further research are highlighted. Although treatment goals of response, remission, and recovery have been defined more uniformly, a good "effectiveness" measure mapping onto functional outcomes is still lacking. Moreover, the field must advance in transferring measurement-based approaches from research to clinical practice. There is an ongoing debate regarding whether and which first- or second-generation antipsychotics should be used. However, especially when considering individual adverse effect profiles, the differentiation into first- and second-generation antipsychotics as unified classes cannot be upheld, and a more differentiated view and treatment selection are required. The desired, individualized treatment approach needs to consider current symptoms, comorbid conditions, past therapeutic response, and adverse effects, as well as patient choice and expectations. Acute and long-term goals and effects of medication treatment should be balanced. To date, clozapine is the only evidence-based treatment for refractory patients, and the role of antipsychotic polypharmacy and other augmentation strategies remains unclear, at best. To discover novel treatments with enhanced/broader efficacy and improved tolerability, and to enable personalized treatment, the mechanisms underlying illness development and progression, symptomatic improvement, and side effect development need to be elucidated.     

Best practice pharmacologic treatment of schizophrenia: Applying principles of evidence-based medicine

Despite substantial advances, schizophrenia remains an extremely challenging illness to treat. Clinicians are often placed in situations in which they have to make treatment decisions when they believe that there is little information to guide them. Despite gaps, there is in fact a large body of useful information about the treatments that we utilize. Accessing this information and applying it to specific treatment decisions about individual patients is often difficult. In this article, approaches to the application of principles of evidence-based medicine to the pharmacologic treatment of schizophrenia are outlined, with a view to helping practitioners sort through the existing body of information and make the best possible decisions for their patients’ greatest gain. Hopefully this will encourage clinicians and treatment systems to consider how best to employ evidence-based information to provide patients suffering from schizophrenia with the best currently available pharmacologic treatment.     

New developments in the treatment of malignant gliomas

Malignant gliomas represent an heterogeneous group of brain tumors both in terms of natural history and response to treatment. The standard therapeutic approach for treating glioblastomas is a combination of radiotherapy and concomitant/adjuvant temozolomide, and methylguanine-DNA methyltransferase promoter methylation is now recognized as an important factor for predicting both prognosis and response to alkylating agents. In the future, the discovery of targeted therapies will increasingly allow personalized medical treatments. Anaplastic oligodendroglial tumors display a better prognosis and are more chemosensitive than glioblastomas; the discovery of molecular factors of prognostic significance, such as 1p/19q codeletion, will lead to different treatment strategies for different subgroups of patients. Gliomatosis cerebri is a rare diffuse glioma, and upfront chemotherapy is increasingly being employed instead of whole-brain radiotherapy to avoid/delay cognitive defects in long surviving patients, despite the lack of data to support this.     

What have we learned from CATIE about the pharmacologic treatment of schizophrenia?

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study sponsored by the National Institute of Mental Health compared the effectiveness of four second-generation antipsychotics (olanzapine, risperidone, quetiapine, and ziprasidone), and one first-generation antipsychotic (perphenazine) in 1460 individuals with chronic schizophrenia. A hybrid of effectiveness and efficacy study design, the primary outcome was antipsychotic “effectiveness,” as measured by discontinuation of the assigned antipsychotic because of inadequate efficacy, inadequate tolerability, patient decision, or other reason. Most (64% to 82%) patients discontinued the phase-I antipsychotic before 18 months of treatment (approximately two-thirds subjects continued treatment with a different antipsychotic in phase 2). The five antipsychotics varied significantly in effectiveness, efficacy, and side-effect profiles. CATIE baseline results also find the general health of individuals with chronic schizophrenia to be poor, highlighting concerns about added risk from metabolic side effects of some antipsychotics. Analysis of comparative cost effectiveness, impact on cognition, rates of recovery, phase 2 results, and many other analyses are forthcoming, and the cumulative findings from the CATIE study will provide an evidence base for clinicians, health care administrators, patients and their families to make pharmacologic treatment choices.     

Advances in the genetics of schizophrenia: editors' introduction

In view of the rapid advances in the application of molecular genetics to research in schizophrenia, an effort was made to put these studies into a wider perspective. This issue of the Schizophrenia Bulletin is devoted to the expanded presentation of some of the early genetic linkage findings in schizophrenia, and a broader discussion of the impact of these new techniques on schizophrenia research, as well as the limitations of this approach in a complex disorder.