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[FROM THE GUEST EDITORS] From the Guest Editors

Kane, J. M., Buckley, P. F., Marder, S. R. — 2008-05-15

[CLINICAL SYNTHESIS] New-Onset Schizophrenia: Pharmacologic Treatment

Kane, J. M. — 2008-05-15

The management of new-onset schizophrenia represents an enormous challenge and opportunity. The evaluation and treatment decisions that are implemented at this phase of illness can have an important impact on subsequent course and outcome. It is important to consider factors that are specific to managing first-episode patients when choosing medication, establishing a treatment plan, and evaluating both therapeutic response and potential adverse reactions. Maintenance treatment strategies and approaches to facilitating adherence with clinical recommendations are also important issues in this context.

[CLINICAL SYNTHESIS] Schizophrenia Host Vulnerability and Risk of Metabolic Disturbances During Treatment with Antipsychotics

Buckley, P. F., Foster, A., Miller, B. — 2008-05-15

People with schizophrenia die prematurely from comorbid physical diseases, particularly from cardiometabolic disturbances. Although some host vulnerability exists, there is also mounting evidence of a relationship between metabolic disturbances and antipsychotic medications. Clinicians must now make a careful appraisal of these risks when choosing an antipsychotic drug. Additionally, clinicians are required to undertake close monitoring for metabolic disturbances during antipsychotic therapy. Although switching antipsychotic medications is currently the preferred strategy if metabolic disturbances occur, there are other pharmacologic and nonpharmacologic approaches that might also prove beneficial for the individual patient. Metabolic disturbance and the detection and management thereof currently hold "center stage" in the psychopharmacology of schizophrenia.

[CLINICAL SYNTHESIS] Neurocognition as a Treatment Target in Schizophrenia

Marder, S. R. — 2008-05-15

Recent attention has focused on the limitations of current antipsychotic medications for improving community functioning in schizophrenia. The strong relationship between neurocognition and functional outcome has led to a focus on developing pharmacological agents that improve cognition. The potential of this target led to a National Institute of Mental Health initiative known as Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS). Through a series of consensus meetings that included representatives from academia, the pharmaceutical industry, and government, this initiative has developed a consensus battery of neuropsychological tests that can be used as an outcome measure in clinical trials, a pathway to drug approval that has been endorsed by the U.S. Food and Drug Administration, a priority list of molecular targets for new drug development, and a consensus regarding the design of clinical trials.

[CLINICAL SYNTHESIS] Ask the Expert: Schizophrenia

Streltzer, J., Tseng, W.-S. — 2008-05-15

[CLINICAL SYNTHESIS] Patient Management Exercise * Schizophrenia

Levine, H., Albucher, R. C. — 2008-05-15

[INFLUENTIAL PUBLICATIONS] Bibliography Schizophrenia

2008-05-15

This section contains a compilation of recent publications that have shaped the thinking in the field as well as classic works that remain important to the subject reviewed in this issue. This bibliography has been compiled by experts in the field and members of the editorial and advisory boards. Entries are listed chronologically and within years by first author. Articles from the bibliography that are reprinted in this issue are in bold type.

[INFLUENTIAL PUBLICATIONS] Abstracts

2008-05-15

[INFLUENTIAL PUBLICATIONS] New Paradigms for Treatment Development

Stover, E. L., Brady, L., Marder, S. R. — 2008-05-15

(Reprinted with permission from the Schizophrenia Bulletin 2007; 33(5):1093–1099)

[INFLUENTIAL PUBLICATIONS] Adding or Switching Antipsychotic Medications in Treatment-Refractory Schizophrenia

Kreyenbuhl, J., Marcus, S. C., West, J. C., Wilk, J., Olfson, M. — 2008-05-15

Objective:

This study compared patients with schizophrenia whose antipsychotic medications were switched to manage treatment-resistant positive psychotic symptoms with those for whom another antipsychotic was added. Psychiatrists' characteristics and perceptions of effectiveness of the medication change on clinical outcomes were also reported. Methods: Psychiatrists participating in a nationally representative mailed survey (N = 209) reported on the clinical features, management, and response to the change in antipsychotic medication (added versus switched) of one adult patient with treatment-refractory schizophrenia under their care for at least one year. Results: Thirty-three percent of patients were treated with an added antipsychotic medication. Compared with patients whose antipsychotic medications were switched, those with an added antipsychotic medication were more likely to be female, to have received care from the same psychiatrist for more than two years, and to have been recently prescribed an antidepressant. Compared with psychiatrists who switched antipsychotic prescriptions, those who added an antipsychotic reported that the change was less likely to reduce positive symptoms, improve functioning, and prevent hospitalization. Psychiatrists who added rather than switched antipsychotics reported more frequent attendance at educational programs sponsored by a pharmaceutical company. Conclusions: Consistent with other lines of research and practice guideline recommendations, psychiatrists perceive antipsychotic polypharmacy to be a generally ineffective strategy for treatment-resistant positive psychotic symptoms. In light of these findings, efforts to identify and implement more effective evidence-based pharmacologic approaches should be undertaken.

(Reprinted with permission by Psychiatric Services 2007; 58:983–990)

[INFLUENTIAL PUBLICATIONS] Deconstructing Schizophrenia: An Overview of the Use of Endophenotypes in Order to Understand a Complex Disorder

Braff, D. L., Freedman, R., Schork, N. J., Gottesman, I. I. — 2008-05-15

(Reprinted with permission from the Schizophrenia Bulletin 2007; 3(1):21–32)

[INFLUENTIAL PUBLICATIONS] Sexual Dysfunction in Schizophrenia

Malik, P. — 2008-05-15

Purpose of review Sexual dysfunctions have been described as being common in schizophrenia patients. The pathophysiology behind their development remains unclear. They can be secondary to the disease itself or an adverse event of antipsychotic medication. Therapeutic interventions are also not well studied. Recent findings Earlier work has suggested that second-generation antipsychotics bear fewer risks for developing sexual dysfunction because of a lower propensity to elevate prolactin levels, although the latter does not apply to amisulpride and risperidone. Only a few controlled trials with larger patient samples have been performed in the past. Summary The review covers studies published from March 2005 to June 2006 focusing on sexual dysfunctions in schizophrenia patients, as well as their possible causes. Treatment options and the impact of sexual dysfunction on quality of life are also covered. The reviewed papers show no clear consistency regarding potential advantages of one drug over another. Many trials suffer from small sample sizes. The field badly needs more and larger studies on this topic.

(Reprinted with permission from Curr Opin Psychiatry 20:138–142)

[INFLUENTIAL PUBLICATIONS] Mortality and Medical Comorbidity Among Patients With Serious Mental Illness

Miller, B. J., Paschall, C. B., Svendsen, D. P. — 2008-05-15

Objectives:

This study examined mortality and medical comorbidity among patients with serious mental illness in Ohio. Methods: Data for 20,018 patients admitted to an Ohio public mental health hospital between 1998 and 2002 were matched against state death records, and 608 deaths were identified. Leading causes of death and medical comorbidities, years of potential life lost (YPLL), and standardized mortality ratios were calculated for this population. Results: Heart disease (126 persons, or 21 percent) and suicides (108 persons, or 18 percent) were the leading causes of death. The mean ± SD number of YPLL was 32.0 ± 12.6 years. The highest cause-specific mean YPLL was for suicides (41.7 ± 10.3 years). Deaths from unnatural causes had higher mean YPLL than deaths from any other causes. Cause-specific mean YPLL were higher for women than for men, except for homicides, pneumonia and influenza, and heart disease. The aggregated standardized mortality ratio from all causes of death was 3.2, corresponding to 417 excess deaths (p < .001). Obesity (144 persons, or 24 percent) and hypertension (136 persons, or 22 percent) were the most prevalent medical comorbidities. Conclusions: This study demonstrated excess mortality among patients in Ohio with serious mental illness. Results highlight the need to integrate delivery of currently fragmented mental and physical health services and to target interventions that improve quality-of-life outcomes for this population.

(Reprinted with permission by Psychiatric Services 2006; 57:1482–1487)

[INFLUENTIAL PUBLICATIONS] Medication-Induced Weight Gain and Dyslipidemia in Patients With Schizophrenia

Fenton, W. S., Chavez, M. R. — 2008-05-15

"Mr. P," a 40-year-old unmarried man, sought treatment after a move to live closer to his sister. He had attended a first-rate university and worked as a legal researcher before suffering a psychotic episode in 1994 as a first-year law student at age 28. With thiothixene treatment, he improved quickly and returned to school after a brief hospitalization. Mr. P soon stopped his medication, and in 1995 police found him attempting to break into a professor's office to "collect evidence." He was rehospitalized and treated with 6 mg/day of risperidone. After several weeks of treatment, he realized that his delusions were implausible. He was discharged after 1 month and returned home to live with his parents. On admission, he had appeared emaciated and disheveled; during his hospitalization he gained 14 lbs., and at discharge he weighed 145 lbs. Now, at age 40, Mr. P was taking 1.5 mg of risperidone daily and no other medications. Working alone at home, he had published two articles in a local law newsletter. He was reconciled to being a lone scholar and had abandoned dreams of having a girlfriend or getting married. He spent his days reading, writing, or watching television. Over time he had gained weight, and when ziprasidone and quetiapine became available, Mr. P had attempted to switch to these new medications, hoping to lose weight and have more energy. Despite careful cross-titration during these trials, each attempt ended with the reemergence of psychotic symptoms. After these frightening near-relapse experiences, by the time aripiprazole became available in 2003, Mr. P did not want to take a chance with another new medication. At initial assessment, Mr. P weighed 203 lbs. at 5 ft. 8 in. tall (body mass index [BMI] = 30.9) and had a waist circumference of 44 in. His blood pressure was 135/85 mm Hg. His total cholesterol was 211 mg/dl; triglycerides, 225 mg/dl (low-density lipoprotein [LDL] cholesterol, 148 mg/dl, high-density lipoprotein [HDL] cholesterol = 32 mg/dl), fasting plasma glucose, 102 mg/ dl. Thyroid function tests, blood chemistry, and urinalysis were unremarkable. Mr. P does not smoke and rarely consumes alcohol. His sister and his previous doctor encouraged him to exercise and diet, but he was unable to sustain efforts in either. Mr. P's family history was significant for a paternal aunt who had a psychotic disorder and a maternal grandmother who had died at age 50 from complications of diabetes. His father had died at age 55 of a myocardial infarction. Mr. P was free of psychotic symptoms, but despite a keen intelligence, he felt too fatigued to work. He wanted to take a class at a local college but felt humiliated because he could not fit into the lecture hall desk and chair. Does this patient have the metabolic syndrome? What is his risk of developing diabetes or heart disease? What treatment or prevention strategies should be considered?

(Reprinted with permission from the American Journal of Psychiatry 2006; 163:1697–1704)

[INFLUENTIAL PUBLICATIONS] Prenatal Infection as a Risk Factor for Schizophrenia

Brown, A. S. — 2008-05-15

(Reprinted with permission from the Schizophrenia Bulletin 2006; 32(2):200–202)

[INFLUENTIAL PUBLICATIONS] Cognitive Behavior Therapy for Schizophrenia

Turkington, D., Kingdon, D., Weiden, P. J. — 2008-05-15

Objective:

A growing body of evidence supports the use of cognitive behavior therapy for the treatment of schizophrenia. A course of cognitive behavior therapy, added to the antipsychotic regimen, is now considered to be an appropriate standard of care in the United Kingdom. The objective of this article is to offer a broad perspective on the subject of cognitive behavior therapy for schizophrenia for the American reader. Method: The authors summarize current practice and data supporting the use of cognitive behavior therapy for schizophrenia. Results: Five aspects of cognitive behavior therapy for schizophrenia are addressed: 1) evidence from randomized clinical trials, 2) currently accepted core techniques, 3) similarities to and differences from other psychosocial interventions for schizophrenia, 4) differences between the United States and United Kingdom in implementation, and 5) current directions of research. Conclusions: The strength of the evidence supporting cognitive behavior therapy for schizophrenia suggests that this technique should have more attention and support in the United States.

(Reprinted with permission by the American Journal of Psychiatry 2006; 163:365–373)