New developments in the pharmacotherapy of cocaine dependence

New possibilities with medications for the treatment of cocaine dependence have begun to emerge. For example, in a randomised controlled study, disulfiram succeeded for the first time in significantly reducing cocaine consumption. In October 2003, a phase IIb study was started in the USA testing active immunisation against cocaine dependence. There is also an ongoing study in Switzerland testing methylphenidate treatment in combination with cognitive behavioural therapy. Pilot studies indicate that vigabatrin, selegiline, and topiramate are promising candidates for further clinical substance testing.     

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.     

Short-term inpatient pharmacotherapy of schizophrenia

There is much practice variation in the pharmacotherapy of schizophrenia on short-term acute inpatient units, where the length of stay may be 1 week or less. We surveyed relevant practice guidelines, review articles, and individual studies and developed summary statements regarding evidence-supported procedures for short-term inpatient stabilization. If the patient requires parenteral treatment, the combination of intramuscular haloperidol 2-5 mg and lorazepam has the earliest effect. For initial oral treatment, monotherapy with one of the new "atypical" antipsychotics is favored. Some evidence suggests that risperidone may have an earlier onset of action. Olanzapine seems to have a relatively more rapid effect when started at a daily dose of 15 mg, rather than 5 or 10 mg. The role of quetiapine is somewhat unclear. In the event of nonresponse to the initial antipsychotic after 3-7 days, alternatives may include increasing the dose, switching to a different antipsychotic, or adding a mood stabilizer.     

New developments in the pharmacologic treatment of schizophrenia: editor's introduction.

In this issue we have tried to bring together a series of reviews describing new developments in the pharmacologic management of schizophrenia. Important progress is being made not only in medication development, but also in furthering our ability to use available treatments and treatment combinations in the most effective manner. Topics discussed include: the role of blood levels; alternative somatic treatments for nonresponding patients; the role of clozapine; putative mechanisms of action of novel antipsychotics; an overview of potential antipsychotic drugs under development; new findings in maintenance treatment; a review of the impact of neuroleptic treatment on the long-term course of schizophrenia; and a discussion of obstacles which must be overcome to ensure that the promise of treatment research can be fully realized.     

Optimizing pharmacotherapy of schizophrenia for individuals

Decisions regarding the pharmacotherapy of schizophrenia are based on a number of individual patient characteristics, including their clinical signs and symptoms, sensitivity to side effects, and psychiatric and medical comorbidities. The publication of recent guidelines from the American Psychiatric Association and the Schizophrenia Patient Outcome Research Team provides guidance for clinicians who are attempting to individualize pharmacologic treatment. Guidance is also provided from clinical studies that have demonstrated the effectiveness of new formulations of second-generation antipsychotics and studies that evaluated the effectiveness of these agents in long-term studies. Recent data have also focused on important side effects of second-generation agents that can affect the long-term health of patients. These studies as well as recommendations from experts can assist clinicians who are selecting an antipsychotic for patients with serious medical problems such as sexual dysfunction, diabetes, obesity, and hyperlipidemias.     

Recent developments in the genetics of schizophrenia

Schizophrenia, which is also called "split personality," is a complex and multifactorial mental disorder with variable clinical manifestations. It perhaps represents several diseases and occurs throughout the world. It is a more-prevalent disorder among homeless people and is clinically characterized by hallucinations and delusions. The pathophysiology of schizophrenia is not localized to a single region of the brain and the etiology of this illness is not understood. Because of its complex pattern of inheritance, genetic techniques are not readily applicable in identifying the genes responsible for this disorder. Family, twin, and adoption studies, however, provide strong but indirect support for genetic components in the etiology of schizophrenia. Extensive linkage analyses now suggest that susceptibility genes may be present on chromosomes 5q, 6p, 8p, 13q, 18p, and 22q. Identification and characterization of these and other genes, as well as non-genetic factors, is one of the greatest challenges in biomedicine. This may ultimately lead to the development of a new line of effective and safe drugs or treatments for its prevention or cure. Received: June 24, 1999 / Accepted: July 22, 1999 / Published online: September 27, 1999     

Practical pharmacotherapy for acute schizophrenia patients

Well‐organized clinical guidelines of pharmacotherapy for schizophrenia are not necessarily applicable to emergency and acute‐phase situations. Thus, practical pharmacotherapy for acute schizophrenia patients should be based on data from real clinical practice and be independent of pharmaceutical companies. This study investigated the current guidelines being used to determine the initially preferred antipsychotics, durations required before an antipsychotic is viewed as being ineffective, and the strategies utilized for early non‐responders that include switching, high dose, and augmentation. In patients who develop side‐effects to the preferred antipsychotic drug, continued use may depend on the specific characteristics of the side‐effects. For acute‐phase patients, antipsychotics with high efficacy and effectiveness may be chosen based on meta‐analysis findings for not only double‐blinded but also rater‐blinded randomized controlled trials. Many previous studies have reported being able to make an early prediction at 2 weeks regarding the later response. These predictions were supported by the findings of a recent meta‐analysis of 34 studies that examined 9975 participants. In early non‐responders to the initial antipsychotic, the effectiveness of the switching strategy appears to depend on the initial antipsychotic administered and the antipsychotic the patient is subsequently switched to. Furthermore, the effectiveness of the strategy between switching and augmentation might also depend on the initial antipsychotic administered. The current findings might serve as the basis for the use of dosing above the licensed range versus continuing the use of conventional dosing in non‐responders, provided there is close monitoring of the side‐effects. Further research is required before any modifications of routine practices are undertaken regarding the direction of new potential treatments.     

Optimizing pharmacotherapy of schizophrenia: Tools for the psychiatrist

The pharmacologic treatment of schizophrenia presents several challenges: 1) available treatments are incompletely and variably effective; 2) treatments take time to show their full effects; and 3) different benefits and adverse effects of treatment appear over different time frames. To aid in treatment decisions, clinicians are inundated with information that can be difficult to digest and integrate. Treatment often is provided within systems of care that limit the range of available treatment options. To preserve broad treatment options and facilitate optimal care, the State of Florida has developed a comprehensive program to provide several tools to the treating physician, and systems of care to promote optimally effective and efficient pharmacotherapy for each individual with schizophrenia. Although a formal evaluation of its effectiveness is underway, the program has been uniformly well received and considered to be very useful in helping clinicians and treatment systems efficiently provide schizophrenia patients with the best currently available pharmacologic treatment. Elements of the program and its evolution and operation are described.     

The Mount Sinai conference on the pharmacotherapy of schizophrenia

This report summarizes the recommendations from a consensus meeting that focused on specific questions regarding the pharmacotherapy of schizophrenia. The issues were selected because there was evidence that experts had recently disagreed about the evidence supporting a particular practice or when there were substantial variations in a clinical practice indicating that there was disagreement among clinicians. The group of experts was able to reach a consensus regarding the evidence base pertaining to the following issues: First generation (FGAs) and second generation (SGAs) antipsychotics as first line agents; the duration of antipsychotic trials; the effectiveness of clozapine and other agents for treatment refractory schizophrenia; risk of tardive dyskinesia on FGAs and SGAs; differences among antipsychotics for different dimensions of psychopathology; and side effect monitoring for various antipsychotics.     

Pathophysiology of schizophrenia and its impact on pharmacotherapy

Schizophrenia is a severe psychiatric illness with a lifetime morbidity risk of around 1 %. Symptoms include hallucinations, delusions, poverty of thought and emotion and social withdrawal and cognitive deficits. Although newer antipsychotics affecting multiple neurotransmitter receptors facilitate therapy, many patients still do not achieve full response. Despite intensive study, the molecular etiology of schizophrenia remains enigmatic in many ways. The dopamine hypothesis of schizophrenia still plays an important role, although pharmacological studies, brain imaging analyses and genetic research indicate additional dysfunctions of glutamate, GABA and serotonin transmission. This article reviews the pathophysiological background of the disorder, its implications for pharmacological treatment and possible directions for future research.     

The new and evolving pharmacotherapy of schizophrenia.

Based on the evidence presented here, the following tentative conclusions can be drawn. Atypical antipsychotics (except amisulpride) have shown superiority over placebo in acute schizophrenia. Compared with conventional antipsychotics, they are at least as effective. Generally, analyses employing conservative criteria (e.g., Cochrane reviews) report few efficacy differences between atypical and conventional agents. There are now many well-controlled studies indicating modest advantages for the atypical antipsychotics, however, particularly in specific symptom domains. For the treatment of negative symptoms, olanzapine and to a lesser extent amisulpride seem most promising. Risperidone, olanzapine, and quetiapine display advantages in improving cognitive and depressive symptoms. There are indications that the atypical antipsychotics are associated with decreased likelihood of rehospitalization and improved quality of life. In head-to-head comparisons of atypical antipsychotics, none have shown consistent efficacy advantages. In severely refractory samples, no atypical antipsychotics have consistently been shown to be as effective as clozapine or superior to conventional agents. There are indications, however, that risperidone, olanzapine, and quetiapine have advantages over conventional agents in less severely refractory patients. Few maintenance RCTs have been published, and efficacy advantages for atypical antipsychotics in prospective RCTs in first-episode schizophrenia have not been reported.