Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide. Use of clozapine in this population should lead to a significant reduction in suicidal behavior.

As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.

Objectives To assess the efficacy and safety of varenicline (Chantix®) for the treatment of alcohol use disorders. Varenicline is a partial α4β2 nicotinic acetylcholine agonist approved by the Food and Drug Administration for smoking cessation. It has reduced drinking in animal studies and in small studies of humans who were both heavy drinkers and smokers. This is the first multisite clinical trial of varenicline in a population of smokers and nonsmokers with alcohol use disorders. Methods Men and women (n=200) meeting the criteria for alcohol dependence were recruited across 5 clinical sites. Patients received double-blind varenicline or placebo and a computerized behavioral intervention. Varenicline was titrated during the first week to 2 mg/day, which was maintained during weeks 2–13. Results The varenicline group had significantly lower weekly percent heavy drinking days (primary outcome) (adjusted mean difference=10.4), drinks per day, drinks per drinking day, and alcohol craving compared with the placebo group (p values < 0.05). The average treatment effect on alcohol use was similar for smokers and nonsmokers. Varenicline was well-tolerated; adverse events were expected and mild. Conclusions Varenicline significantly reduced alcohol consumption and craving, making it a potentially viable option for the treatment of alcohol use disorders.

National attention continues to focus on the need to improve care for individuals with co-occurring mental illnesses and substance use disorders, as emphasized in the 2003 President's New Freedom Commission Report on Mental Health and recent publications from the Substance Abuse and Mental Health Services Administration (SAMHSA). These reports document the need for best practice recommendations that can be translated into routine clinical care. Although efforts are underway to synthesize literature in this area, few focused recommendations are available that include expert opinion and evidence-based findings on the management of specific co-occurring disorders, such as schizophrenia and addiction. In response to the need for user-friendly recommendations on the treatment of schizophrenia and addiction, a consensus conference of experts from academic institutions and state mental health systems was organized to 1) frame the problem from clinical and systems-level perspectives; 2) identify effective and problematic psychosocial, pharmacological, and systems practices; and 3) develop a summary publication with recommendations for improving current practice. The results of the consensus meeting served as the foundation for this publication, which presents a broad set of recommendations for clinicians who treat individuals with schizophrenia. "Integrated treatment" is the new standard for evidence-based treatment for this population and recommendations are given to help clinicians implement such integrated treatment. Specific recommendations are provided concerning screening for substance use disorders in patients with schizophrenia, assessing motivation for change, managing medical conditions that commonly occur in patients with dual diagnoses (e.g., cardiovascular disease, liver complications, lung cancer, HIV, and hepatitis B or C infections) and selecting the most appropriate medications for such patients to maximize safety and minimize drug interactions, use of evidence-based psychosocial interventions for patients with dual diagnoses (e.g., Dual Recovery Therapy, modified cognitive-behavioral therapy, modified motivational enhancement therapy, and the Substance Abuse Management Module), and key pharmacotherapy principles for treating schizophrenia, substance use disorders, and comorbid anxiety, depression, and sleep problems in this population. Finally the article reviews programmatic and systemic changes needed to overcome treatment barriers and promote the best outcomes for this patient population. An algorithm summarizing the consensus recommendations is provided in an appendix.

Olanzapine was associated with significantly greater weight gain than haloperidol, with both leading to greater weight gain than previously described.

Several case studies indicate that clozapine use is associated with reductions in the use of nicotine, alcohol, or illicit drugs. Although not designed to assess clozapine, this study explored a posteriori the effects of clozapine on alcohol and drug use disorders among schizophrenia patients. Among 151 patients with schizophrenia or schizoaffective disorder and co-occurring substance use disorder who were studied in a dual-disorder treatment program, 36 received clozapine during the study for standard clinical indications. All participants were assessed prospectively at baseline and every 6 months over 3 years for psychiatric symptoms and substance use. Alcohol-abusing patients taking clozapine experienced significant reductions in severity of alcohol abuse and days of alcohol use while on clozapine. For example, they averaged 54.1 drinking days during 6-month intervals while off clozapine and 12.5 drinking days while on clozapine. They also improved more than patients who did not receive clozapine. At the end of the study, 79.0 percent of the patients on clozapine were in remission from alcohol use disorder for 6 months or longer, while only 33.7 percent of those not taking clozapine were remitted. Findings related to other drugs in relation to clozapine were also positive but less clear because of the small number of patients with drug use disorders. This study was limited by the naturalistic design and the lack of prospective, standardized measures of clozapine use. The use of clozapine by patients with co-occurring substance disorders deserves further study in randomized clinical trials.

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