Schizophrenia affects ~1% of the population and is associated with enormous personal suffering, family distress and burden, and tremendous healthcare and societal costs. Although considerable progress has been made in treating this illness enormous challenges remain.

Early detection and treatment are at present a distant goal. There is undue delay between the onset of full-blown psychosis and appropriate diagnosis and treatment. Continuity of care is often spoken about rather than truly implemented. Adverse effects remain a critical challenge, and comorbid medical conditions as well as suicide result in a markedly diminished life expectancy. Substance abuse affects a substantial proportion of patients, creating an impediment to optimum outcome. Nonadherence remains a very common, but inadequately appreciated obstacle to adequate and sustained treatment response and contributes enormously to a high rate of preventable relapse and rehospitalization.

The focus of this CNS Spectrums supplement is to address many of these topics in a clinically relevant manner by reviewing the latest research findings in pharmacologic and behavioral treatments, with an emphasis on evaluating appropriate treatment for each patient while considering the host of issues that should inform our clinical decision-making. Historically, a major focus of treatment has been positive symptom control. Though this is clearly important, negative symptoms, cognitive dysfunction, depression, demoralization, and comorbid substance abuse are also critical targets in enhancing functional outcome. Concepts such as remission and recovery are useful metrics to help establish targets and goals for treatment planning and for creating a framework for assessing outcome.

Agitation can present as an emergency in the course of numerous psychiatric conditions including intoxication, schizophrenia, bipolar disorder, and delirium. This article reviews relevant literature regarding the definition, etiology, measurement, and management of episodic agitation and pays particular attention to intramuscular treatments. The impact of changes in methodology between the era of first- and second-generation antipsychotics, the implications of those changes for external validity of studies of second-generation studies, and the recent evolution of expert consensus are discussed.

Balancing efficacy with tolerability and safety of prescribed treatments is critical to optimizing antipsychotic treatment outcomes in the mentally ill. Symptom control, symptom remission, and functional recovery are only realistic goals when treatments are both effective and well tolerated. The consideration of predictable differences in antipsychotic adverse-effect profiles is central to successful illness management. Minimizing adverse effects on alertness, motivation, cognition, sexual/reproductive functioning, and physical health enhancesmental health outcomes, partly through improving treatment adherence. Neuroendocrine and metabolic side effects of antipsychotics for cardiovascular morbidity and mortality need to be addressed proactively and aggressively. In view of the widespread lack of primary care engagement and the adverse effects of psychotropic medications on cardiovascular health, psychiatric care providers should function as key facilitators of an integrated mental and physical health management approach. In addition to psychoeducation and healthy lifestyle counseling, clinicians can improve psychiatric and physical health by selecting medications carefully, routinely screening and monitoring for reversible cardiovascular risk factors, and playing an active role in the prevention and interdisciplinary management of cardiovascular risk factors and medical illness in the vulnerable mentally ill.

The successful management of schizophrenia is an enormous public health issue. Although antipsychotic medications can be very helpful in reducing rates of relapse and rehospitalization, nonadherence to medication is a frequent cause of exacerbations in psychopathology, psychotic relapse, and rehospitalization. Relapses can have devastating consequences in a variety of clinical and functional domains. Nonadherence can result from a variety of factors that vary from patient to patient and vary over time in individual patients. A number of strategies have been developed to assess and facilitate adherence. The first critical step is clinician awareness of the scope of the problem and consideration of appropriate strategies to address it.

Substance use disorder is the most frequent and clinically significant comorbidity among schizophrenia patients today. All schizophrenia patients should be assessed and monitored carefully regarding their substance use. Those with any regular use of alcohol or other drugs should be considered at risk for multiple adverse effects. As therapies for co-occurring substance use disorders have evolved over the past 20 years, medication management, psychosocial interventions, and rehabilitation models have increasingly emphasized the integration of mental health and substance abuse treatments, attention to group and residential interventions, matching interventions to stage of treatment, comprehensiveness, and long-term perspectives on recovery. Clinicians should understand the implications of each of these principles of care.