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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)

[LETTER FROM THE EDITORS] Major Depressive Disorder and Suicide

Hales, D. J., Rapaport, M. H. — 2008-03-12

[LETTER FROM THE EDITORS] Performance in Practice in Maintenance of Certification

Faulkner, L. R. — 2008-03-12

[CLINICAL SYNTHESIS] Recent Findings in the Pathophysiology of Depression

Nemeroff, C. B. — 2008-03-12

[CLINICAL SYNTHESIS] Strategies for the Prevention and Treatment of Suicidal Behavior

Clayton, P., Auster, T. — 2008-03-12

This article discusses research-informed strategies for predicting and treating suicidal behavior. One of the most important approaches is to provide training to health professionals in recognizing and treating depression aggressively. An awareness of risk factors, such as certain psychiatric disorders, past suicide attempts, age, gender, other illnesses, and access to means, is essential to these strategies. Levels of treatment that include proper prescription of medication for depression, paired with psychotherapy, such as cognitive behavior therapy, and extensive communication between patient and health professional may be the best predictors of remission. Intervention plans should also include community education, simple interventions, and treatment of the underlying psychiatric disorders, including the use of lithium and electroconvulsive therapy.

[CLINICAL SYNTHESIS] Performance in Practice: Sample Tools for the Care of Patients with Major Depressive Disorder

Fochtmann, L. J., Duffy, F. F., West, J. C., Kunkle, R., Plovnick, R. M. — 2008-03-12

To facilitate continued clinical competence, the American Board of Medical Specialties and the American Board of Psychiatry and Neurology are implementing multi-faceted Maintenance of Certification programs, which include requirements for self-assessments of practice. Because psychiatrists may want to gain experience with self-assessment, two sample performance-in-practice tools are presented that are based on recommendations of the American Psychiatric Association's Practice Guideline for the Treatment of Patients with Major Depressive Disorder. One of these sample tools provides a traditional chart review approach to assessing care; the other sample tool presents a novel approach to real-time evaluation of practice. Both tools can be used as a foundation for subsequent performance improvement initiatives that are aimed at enhancing outcomes for patients with major depressive disorder.

[CLINICAL SYNTHESIS] Immune System Contributions to the Pathophysiology of Depression

Miller, A. H., Raison, C. L. — 2008-03-12

Major depression is a devastating disorder that represents a major public health concern. Of special relevance is the high percentage of patients whose depression does not respond to or who are unable to tolerate conventional antidepressant medications, which primarily target monoamine neurotransmission. Recent data indicate that the immune system may play a role in the pathophysiology of depression, representing a novel pathway for therapeutic development. Patients with major depression have been found to exhibit evidence of an activated innate immune response as reflected by increased biomarkers of inflammation, including innate immune cytokines, acute-phase proteins, chemokines, and adhesion molecules. In addition, administration of innate immune cytokines to laboratory animals and humans has been shown to induce behavioral changes that significantly overlap with the symptom criteria of major depression. Treatment of patients with inflammatory disorders using anticytokine therapies has also been found to reduce depressive symptoms. Interestingly, psychosocial stress, a well-known precipitant of depressive disorders, has been shown to activate the innate immune response. Finally, innate immune cytokines have been shown to influence virtually every pathophysiological domain relevant to depression including monoamine neurotransmission, neuroendocrine function, synaptic plasticity, and regional brain metabolism. Of note, a response to conventional antidepressant medications is associated with a decrease in inflammatory biomarkers, whereas patients with treatment-resistant depression are more likely to exhibit evidence of increased inflammation. Taken together, these data provide the foundation for considering an activated innate immune response as a potential target for further study and therapeutic development in mood disorders, especially in the context of treatment resistance.

[CLINICAL SYNTHESIS] Ask the Expert: Major Depressive Disorder

Gabbard, G. O. — 2008-03-12

[PATIENT MANAGEMENT] Patient Management Exercise: Major Depressive Disorder and Suicide

Levine, B. H., Albucher, R. C. — 2008-03-12

[INFLUENTIAL PUBLICATIONS] Bibliography for Major Depressive Disorder and Suicide

2008-03-12

[INFLUENTIAL PUBLICATIONS] Abstracts For Major Depressive Disorder and Suicide

2008-03-12

[INFLUENTIAL PUBLICATIONS] Genetic Markers of Suicidal Ideation Emerging During Citalopram Treatment of Major Depression

2008-03-12

Objectives:

Suicidal ideation is an uncommon symptom than can emerge during antidepressant treatment. The biological basis of treatment-emergent suicidal ideation is unknown. Genetic markers may shed light on the causes of treatment-emergent suicidal ideation and help identify individuals at high risk who may benefit from closer monitoring, alternative treatments, or specialty care. Method: A clinically representative cohort of outpatients with major depressive disorder who enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were treated with citalopram under a standard protocol for up to 14 weeks. DNA samples from 1,915 participants were genotyped for 768 single-nucleotide polymorphisms in 68 candidate genes. Allele and genotype frequencies were compared between the 120 participants who developed treatment-emergent suicidal ideation and those who did not. Results: Two markers were significantly associated with treatment-emergent suicidal ideation in this sample (marker rs4825476, p = 0.0000784, odds ratio = 1.94; permutation p = 0.01; marker rs2518224, p = 0.0000243, odds ratio = 8.23; permutation p = 0.003). These markers reside within the genes GRIA3 and GRIK2, respectively, both of which encode ionotropic glutamate receptors. Conclusions: Markers within GRIK2 and GRIA3 were associated with treatment-emergent suicidal ideation during citalopram therapy. If replicated, these findings may shed light on the biological basis of this potentially dangerous adverse event and help identify patients at increased risk.

(Reprinted with permission from the American Journal of Psychiatry 2007; 164:1530–1538)

[INFLUENTIAL PUBLICATIONS] Suicide Attempts Among Patients Starting Depression Treatment With Medications or Psychotherapy

Simon, G. E., Savarino, J. — 2008-03-12

Objectives:

This study compared the time patterns of suicide attempts among outpatients starting depression treatment with medication or psychotherapy. Method: Outpatient claims from a prepaid health plan were used to identify new episodes of depression treatment beginning with an antidepressant prescription in primary care (N = 70,368), an antidepressant prescription from a psychiatrist (N = 7,297), or an initial psychotherapy visit (N = 54,123). Outpatient and inpatient claims were used to identify suicide attempts or possible suicide attempts during the 90 days before and 180 days after the start of treatment. Results: Overall incidence of suicide attempt was highest among patients receiving antidepressant prescriptions from psychiatrists (1,124 per 100,000), lower among those starting psychotherapy (778 per 100,000), and lowest among those receiving antidepressant prescriptions in primary care (301 per 100,000). The pattern of attempts over time was the same in all three groups: highest in the month before starting treatment, next highest in the month after starting treatment, and declining thereafter. Results were unchanged after eliminating patients receiving overlapping treatment with medication and psychotherapy. Overall incidence of suicide attempt was higher in adolescents and young adults, but the time pattern was the same across all three treatments. Conclusions: The pattern of suicide attempts before and after starting antidepressant treatment is not specific to medication. Differences between treatments and changes over time probably reflect referral patterns and the expected improvement in suicidal ideation after the start of treatment.

(Reprinted with permission from the American Journal of Psychiatry 2007; 164:1029–1034)

[INFLUENTIAL PUBLICATIONS] Treating Suicidality in Depressive Illness. Part 2: Does Treatment Cure or Cause Suicidality?

Sakinofsky, I. — 2008-03-12

Objectives:

To systematically review studies of treatment efficacy for suicidality in mood disorders. To consider the evidence for whether antidepressants may induce suicidality. Method: Systematic review of the literature. Results and Conclusions: There is fairly good evidence that lithium reduces completed suicide and attempt rates in people with bipolar disorder and recurrent unipolar depression. Antidepressants and psychological treatments may reduce suicidal ideation in depressed patients. Antidepressant trials do not, however, a priori target suicidality as an outcome, and inferences made are post hoc. For practical reasons, no adequate trials to date have tested the efficacy of treatment aimed at reducing completed suicide in people with depressive disorders. Antidepressants have been implicated in suicide in one metaanalysis (the elderly) and in one case-control study (youth), signalling the need for caution. However, most metaanalyses have found no significant excess of completed suicide among antidepressant users, compared with placebo groups, in adults and juveniles, but excess nonfatal suicidality is found more often in children and adolescents who take antidepressants (except fluoxetine). The controversy is ongoing.

(Reprinted with permission from the Canadian Journal of Psychiatry, 2007; 52 (6 Suppl 1): 85S–191S; full text of the article available online at http://publications.cpa-apc.org/media.php?mid=425)

[INFLUENTIAL PUBLICATIONS] Cognitive Therapy Versus Medication in Augmentation and Switch Strategies as Second-Step Treatments: A STAR*D Report

2008-03-12

Objectives:

The authors compared the effectiveness of cognitive therapy and pharmacotherapy as second-step strategies for outpatients with major depressive disorder who had received inadequate benefit from an initial trial of citalopram. Cognitive therapy was compared with medication augmentation and switch strategies. Method: An equipoise-stratified randomization strategy was used to assign participants to either augmentation of citalopram with cognitive therapy (N = 65) or medication (N = 117; either sustained-release bupropion [N = 56] or buspirone [N = 61]) or switch to cognitive therapy (N = 36) or another antidepressant (N = 86; sertraline [N = 27], sustained-release bupropion [N = 28], or extended-release venlafaxine [N = 31]). Treatment outcomes and the frequency of adverse events were compared. Results: Less than one-third of participants consented to randomization strata that permitted comparison of cognitive therapy and pharmacotherapy. Among participants who were assigned to second-step treatment, those who received cognitive therapy (either alone or in combination with citalopram) had similar response and remission rates to those assigned to medication strategies. For those who continued on citalopram, medication augmentation resulted in significantly more rapid remission than augmentation with cognitive therapy. Among those who discontinued citalopram, there were no significant differences in outcome, although those who switched to a different antidepressant reported significantly more side effects than those who received cognitive therapy alone. Conclusions: After an unsatisfactory response to citalopram, patients who consented to random assignment to either cognitive therapy or alternative pharmacologic strategies had generally comparable outcomes. Pharmacologic augmentation was more rapidly effective than cognitive therapy augmentation of citalopram, whereas switching to cognitive therapy was better tolerated than switching to a different antidepressant.

(Reprinted with permission from the American Journal of Psychiatry 2007; 164:739–752)

[INFLUENTIAL PUBLICATIONS] Randomized Trial of Weekly, Twice-Monthly, and Monthly Interpersonal Psychotherapy as Maintenance Treatment for Women With Recurrent Depression

2008-03-12

Objectives:

The authors sought to determine whether a greater frequency of interpersonal psychotherapy (IPT) sessions during maintenance treatment has a greater prophylactic effect than a previously validated once-a-month treatment. Method: A total of 233 women 20–60 years of age with recurrent unipolar depression were treated in an outpatient research clinic. After participants had achieved remission with weekly IPT or, if required, with weekly IPT plus antidepressant pharmacotherapy, they were randomly assigned to weekly, twice-monthly, or monthly maintenance IPT monotherapy for 2 years or until a recurrence of their depression occurred. Results: Among participants who remitted with IPT alone and entered maintenance treatment (N = 99), 19 (26%) of the 74 who remained in the study throughout the 2-year maintenance phase experienced a recurrence of depression. Among participants who required the addition of a selective serotonin reuptake inhibitor to achieve remission (N = 90), 32 (36%) sustained that remission through continuation treatment and drug discontinuation and began maintenance treatment; of these, 13 (50%) of the 26 who remained in the study throughout the maintenance phase experienced a recurrence. Survival analysis of time to recurrence by randomized treatment frequency showed no effect on recurrence-free survival in either treatment subgroup. Conclusions: These results suggest that maintenance IPT, even at a frequency of only one visit per month, is a good method of prophylaxis for women who can achieve remission with IPT alone. In contrast, among those who require the addition of pharmacotherapy, IPT monotherapy represents a significantly less efficacious approach to maintenance treatment.

(Reprinted with permission from the American Journal of Psychiatry 2007; 164:761–767)

[INFLUENTIAL PUBLICATIONS] Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report

2008-03-12

Objective:

This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N = 3,671) to four (N = 123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of ≤5 on the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR₁₆) (equivalent to ≤7 on the 17-item Hamilton Rating Scale for Depression [HRSD₁₇]) defined remission; a QIDS-SR₁₆ total score of ≥11 (HRSD₁₇≥14) defined relapse. Results: The QIDS-SR₁₆ remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. Conclusions: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed.

(Reprinted with permission from the American Journal of Psychiatry 2006; 163:1905–1917)

[INFLUENTIAL PUBLICATIONS] Deep Brain Stimulation for Treatment-Resistant Depression

2008-03-12

Treatment-resistant depression is a severely disabling disorder with no proven treatment options once multiple medications, psychotherapy, and electroconvulsive therapy have failed. Based on our preliminary observation that the subgenual cingulate region (Brodmann area 25) is metabolically overactive in treatment-resistant depression, we studied whether the application of chronic deep brain stimulation to modulate BA25 could reduce this elevated activity and produce clinical benefit in six patients with refractory depression. Chronic stimulation of white matter tracts adjacent to the subgenual cingulate gyrus was associated with a striking and sustained remission of depression in four of six patients. Antidepressant effects were associated with a marked reduction in local cerebral blood flow as well as changes in downstream limbic and cortical sites, measured using positron emission tomography. These results suggest that disrupting focal pathological activity in limbic-cortical circuits using electrical stimulation of the subgenual cingulate white matter can effectively reverse symptoms in otherwise treatment-resistant depression.

(Reprinted with permission by Neuron, 2005; (45):651–660)

[INFLUENTIAL PUBLICATIONS] Efficacy of ECT in Depression: A Meta-Analytic Review

Pagnin, D., de Queiroz, V., Pini, S., Cassano, G. B. — 2008-03-12

This study analyzed the efficacy of electroconvulsive therapy (ECT) in depression by means a meta-analytic review of randomized controlled trials that compared ECT with simulated ECT or placebo or antidepressant drugs and by a complementary meta-analytic review of nonrandomized controlled trials that compared ECT with antidepressants drugs. The review revealed a significant superiority of ECT in all comparisons: ECT versus simulated ECT, ECT versus placebo, ECT versus antidepressants in general, ECT versus TCAs and ECT versus MAOIs. The nonrandomized controlled trials also revealed a significant statistical difference in favor of ECT when confronted with antidepressants drugs. Data analyzed suggest that ECT is a valid therapeutic tool for treatment of depression, including severe and resistant forms.

(Reprinted with permission by J ECT 2004; 20:13–20)

[FROM THE GUEST EDITOR] Medical Ethics: Ageless Issues that Will Not Go Away

Jibson, M. D. — 2007-11-09

[CLINICAL SYNTHESIS] Clinical and Ethical Issues in Palliative Care

Block, S. D. — 2007-11-09

Over the past 15 years, in response to widely-recognized gaps in the care of patients at the end of life, palliative care has emerged as a recognized subspecialty, focused on the care of patients with advanced, progressive, life-threatening illness. The aim of palliative care is to optimize the quality of life for the patient and family through the provision of expert interdisciplinary care, including symptom assessment and treatment, psychosocial and spiritual support to the patient and family, help with complex decisions about treatment options, coordination of care in the community, and bereavement care for families. A growing evidence base demonstrates the effectiveness of palliative care clinical programs in improving symptoms, quality of life, communication, concordance between patient wishes and care received, family satisfaction, and bereavement outcomes and in reducing costs. There are many opportunities for psychiatrists to contribute to care for patients at the end of life through enhanced involvement in palliative care teams.

[CLINICAL SYNTHESIS] Interactions Between Physicians and Industry: A Guide for Clinicians

Jibson, M. D. — 2007-11-09

Physicians and the pharmaceutical industry share a convergence of interest in providing safe and effective medications to patients, but differ in their practices and ethical standards. Interactions between them are inevitable and desirable, but may create conflicts of interest for physicians. Marketing and medical education are fundamentally different and must not be confused with one another. Studies show that marketing affects physician practice, that information from industry is biased in favor of the manufacturer, and that physicians are not skilled in identifying the impact of marketing on their clinical decisions. Self-serving bias is pervasive in these interactions and is particularly difficult to detect in oneself. Guidelines regarding gifts are based on studies demonstrating their impact and generally recommend that they be limited or avoided altogether. Free samples may be of benefit to patients, but must be used with caution to avoid inappropriate drug choice. Contract services, such as research or speakers bureaus, require strict conformity to ethical and regulatory standards. Disclosure, peer review, adherence to policies and guidelines, and frank self-examination are essential to ensure the objectivity of physicians engaged in clinical care, research, and teaching.

[CLINICAL SYNTHESIS] A Cautionary Tale About Boundary Violations in Psychodynamic Psychotherapy and Psychoanalysis

Procci, W. R. — 2007-11-09

[CLINICAL SYNTHESIS] Ask the Expert: Exploring the Clinician's Concern About Physician-Assisted Suicide

Muskin, P. R. — 2007-11-09

[CLINICAL SYNTHESIS] Ask the Expert: Ethics and Professionalism

Jibson, M. D. — 2007-11-09

[INFLUENTIAL PUBLICATIONS] Bibliography for Ethics, Professionalism, and End of Life Care

2007-11-09

[INFLUENTIAL PUBLICATIONS] Abstracts for Ethics, Professionalism, and End of Life Care

2007-11-09

[ERRATUM] Errata Fall 2007

2007-11-09

[INFLUENTIAL PUBLICATIONS] The Doctor-Patient Relationship

Simon, R.I., Shuman, D.W. — 2007-11-09

(Reprinted with permission from Simon RI, Shuman DW: The doctor-patient relationship, in Clinical Manual of Psychiatry and Law. Arlington VA, American Psychiatric Publishing Inc. 2007; 17–36)

[INFLUENTIAL PUBLICATIONS] Overview of Psychiatric Ethics I: Professional Ethics and Psychiatry

Robertson, M., Walter, G. — 2007-11-09

Objectives:

The aim of this paper is to describe the current status of psychiatric ethics as a form of professional ethics and apply this approach to a common clinical situation. Conclusion: Psychiatry is a profession and, like all professions, comprises a set of specific skills and knowledge that are applied for the ‘common good’ of society. Such a proposition places the psychiatrist in a position of tension between contractarian and Hippocratic ideals of ethical conduct, in that there is an assumption of moral equivalence between the law and ethics. The supposition that legally defensible behaviours are the same as ethically defensible behaviours is integral to the definition of professional ethics. This frequently places psychiatrists at odds with the ‘do no harm’ principle.

(Reprinted with permission from Australasian Psychiatry 2007; 15(3):201–206; full text of article available online at www.informaworld.com/10.1080/10398560701308274)

[INFLUENTIAL PUBLICATIONS] Involuntary Hospitalization of Medical Patients Who Lack Decisional Capacity: An Unresolved Issue

Byatt, N., Pinals, D., Arikan, R. — 2007-11-09

(Reprinted with permission from Psychosomatics 2006; 47(5):443–448)

[INFLUENTIAL PUBLICATIONS] Ethical Issues in the Use of Genetic Information in the Workplace: A Review of Recent Developments

Geppert, C. M.A., Roberts, L. W. — 2007-11-09

Purpose of review:

In the wake of the Human Genome Project, the pace of genetic discovery has quickened. New genetic tests and other molecular technology have had immediate and wide relevance to American and European workers. These tests have the potential to provide improved workplace safety and protect workers' health, but they also carry the risk of genetic discrimination including loss of employment, promotion, insurance and health care. Ethical safeguards are necessary if the benefits are to outweigh the adverse consequences of genetics in the workplace. Recent findings: This review examines the major policy statements issued in Europe and the USA from 2000 to 2005 pertaining to genetic issues in occupational health. Recent findings stress that genetic testing can only be utilized with worker consent and that the workers should control access to genetic information. Such testing is only justified when the information is required to protect the safety of the worker or a third party. The progress of occupational genetic technology should not be permitted to shift the responsibility for a safe working environment from the employer to the employee. Genetic discrimination in all forms is neither supported scientifically nor warranted ethically. Summary: Increasingly, occupational physicians and clinicians treating workers will be faced with potentially stigmatizing genetic information and there is an urgent need for education and research to expand and implement the recommendations of major governmental and professional policy statements.

(Reprint with permission from Curr Opin Psychiatry 2005; 18:518–524)

[INFLUENTIAL PUBLICATIONS] Psychotherapeutic Interventions at the End of Life: A Focus on Meaning and Spirituality

Breitbart, W., Gibson, C., Poppito, S. R., Berg, A. — 2007-11-09

Medical and psychological discourse on end-of-life care has steadily shifted over the years from focusing primarily on symptom control and pain management to incorporating more person-centred approaches to patient care. Such approaches underscore the significance of spirituality and meaning making as important resources for coping with emotional and existential suffering as one nears death. Though existential themes are omnipresent in end-of-life care, little has been written about their foundations or import for palliative care practitioners and patients in need. In this article, we explore the existential foundations of meaning and spirituality in light of terminal illness and palliative care. We discuss existential themes in terms of patients' awareness of death and search for meaning and practitioners' promotion of personal agency and responsibility as patients face life-and-death issues. Viktor Frankl's existential logotherapy is discussed in light of emerging psychotherapeutic interventions. Meaning-centred group therapy is one such novel modality that has successfully integrated themes of meaning and spirituality into end-of-life care. We further explore spiritual and existential themes through this meaning-oriented approach that encourages dying patients to find meaning and purpose in living until their death.

Reprinted with permission from Canadian Journal of Psychiatry 2004; 49:366–372; full text of article available online at http://ww1.cpa-apc.org:8080/Publications/Archives/CJP/2004/june/breitbart.pdf and http://ww1.cpa-apc.org:8080/Publications/Archives/CJP/2004/june/breitbart.asp)

[INFLUENTIAL PUBLICATIONS] End-of-Life Care: Issues Relevant to the Geriatric Psychiatrist

Lyness, J. M. — 2007-11-09

Most deaths in the United States occur in the context of chronic diseases in later life and are too often accompanied by potentially remediable emotional or physical suffering. Geriatric psychiatrists and other mental health professionals can contribute meaningfully to the provision of optimal care during the final phases of life. This review provides an overview of end-of-life care, focusing on issues most relevant to the geriatric psychiatrist. The author examined palliative care textbooks and review papers to determine the topics to be included in this article, and searched computerized literature databases on these topics. Many of the recommendations provided herein stem from experts' clinical experience; however empirical evidence is also incorporated and critiqued. Topics covered include conversations with patients and families about end-of-life care; the evaluation and treatment of suffering, including pain, depression, suicidality, anxiety, and delirium; the role of individual and family therapies in caring for dying patients; capacity determination; advance care planning; withholding life-sustaining treatments; and "last resort" (and, in some cases, quite controversial) options, such as terminal sedation, assisted suicide, and euthanasia. The author also notes the relevance of such end-of-life-care considerations to patients with dementia. Geriatric psychiatrists' skills across these multiple domains are of particular usefulness. Through such clinical skills and the application of empirical research tools to the many unanswered questions in the care of dying patients, geriatric psychiatry can make increasingly valuable and visible contributions to improving quality of life for people suffering from life-threatening illnesses.

(Reprinted with permission from Am J Geriatr Psychiatry 2004; 12:457–472)

[INFLUENTIAL PUBLICATIONS] Caring for People at End of Life

Roberts, L.W., Dyer, A.R. — 2007-11-09

(Reprinted with permission from Roberts LW, Dyer AR: Caring for people at end of life, in Concise Guide to Ethics in Mental Health Care. American Psychiatric Publishing, Inc, 2004, 185–195. Please refer to the original source for appended material cited in text.)

[INFLUENTIAL PUBLICATIONS] This Couldn't Happen to Me: Boundary Problems and Sexual Misconduct in the Psychotherapy Relationship

Norris, D. M., Gutheil, T. G., Strasburger, L. H. — 2007-11-09

Drawing on their own consultative experience illustrated by case vignettes and with support from the professional literature, the authors discuss the perennial problematic issue of boundary violations and sexual misconduct, aiming at an audience of both experienced and novice clinicians. The authors review the difference between boundary crossings and boundary violations and stress the therapist's responsibility to maintain boundaries. Therapist risk factors for violations include the therapist's own life crises, a tendency to idealize a "special" patient or an inability to set limits, and denial about the possibility of boundary problems. Factors exacerbating patient vulnerability, such as overdependence on the therapist, seeking therapy to find an intense relationship or even "true love," and the acceptance by childhood abuse victims of an abusive therapy relationship, are discussed. Consultation and education—for students and for clinicians at all levels of experience—and effective supervision are reviewed as approaches to boundary problems.

(Reprinted with permission from Psychiatric Services 2003; 54(4):517–522)

[INFLUENTIAL PUBLICATIONS] Analysts Who Commit Sexual Boundary Violations: A Lost Cause?

Celenza, A., Gabbard, G. O. — 2007-11-09

The causes of sexual misconduct by analysts are discussed, as is the viability of rehabilitation for different types of transgressors. Common misunderstandings about the transgressor (such as the assumption of psychopathy and the likelihood of multiple offenses) are countered with a summary of data derived from the evaluation and/or treatment of over two hundred cases, most of them one-time transgressors. The typical characteristics of the analyst or therapist who engages in sexual misconduct are presented and discussed as qualities that are to some extent present in analysts generally. The temptation to deny this universal vulnerability is viewed as effectively replicating the kind of vertical splitting or compartmentalization that makes one vulnerable to sexual misconduct in the first place.

(Reprinted with permission from J Am Psychoanal Assoc 2003; 51(2):617–636)

[FROM THE GUEST EDITORS] From the Guest Editors: First, Do No Harm; Second, Do Something Helpful

Greist, J. H., Jefferson, J. W. — 2007-08-10

[CLINICAL SYNTHESIS] Obsessive-Compulsive Disorder

Greist, J. H., Jefferson, J. W. — 2007-08-10

OCD, a surprisingly common disorder, is often hidden by patients who have insight into the inappropriateness of their obsessional concerns and the excessive rituals they feel compelled to perform to ward off exceedingly low risk danger or more vague feelings of discomfort. Onset in childhood is common and many suffer lifelong with a few becoming incapacitated by incessant demands of their disorder.

Diagnosis is straightforward once obsessions and rituals are admitted. Once recognized, treatment with cognitive behavior therapy (CBT) and potent serotonin reuptake inhibitors (SRIs) is often helpful, alone or in combination. For those with disorders unresponsive to these standard treatments, somatic treatment with multiple medications and rarely, deep brain stimulation or neurosurgical lesions may be helpful. The largest obstacle to effective treatment of OCD at present is the difficulty obtaining effective CBT which is twice as beneficial, on average, as SRIs.

[REVIEW] Obsessive-Compulsive Disorder: An Update for the Clinician

Koran, L. M. — 2007-08-10

[PATIENT MANAGEMENT] Ask the Expert: Obsessive-Compulsive Disorder

Pato, M. T. — 2007-08-10

[PATIENT MANAGEMENT] Patient Management Exercise for Obsessive-Compulsive Disorder

Levine, B. H., Albucher, R. C. — 2007-08-10

[INFLUENTIAL PUBLICATIONS] Bibliography for Obsessive-Compulsive Disorder

2007-08-10

[INFLUENTIAL PUBLICATIONS] Abstracts for Obsessive-Compulsive Disorder

2007-08-10

[INFLUENTIAL PUBLICATIONS] Is Compulsive Hoarding a Genetically and Neurobiologically Discrete Syndrome? Implications for Diagnostic Classification

Saxena, S. — 2007-08-10

(Reprinted with permission from American Journal of Psychiatry 2007; 164:380–384)

[INFLUENTIAL PUBLICATIONS] Telephone Administered Cognitive Behaviour Therapy for Treatment of Obsessive Compulsive Disorder: Randomised Controlled Non-inferiority Trial

2007-08-10

OBJECTIVES:

To compare the effectiveness of cognitive behaviour therapy delivered by telephone with the same therapy given face to face in the treatment of obsessive compulsive disorder. Design: Randomised controlled non-inferiority trial. Setting: Two psychology outpatient departments in the United Kingdom. Participants: 72 patients with obsessive compulsive disorder. Intervention: 10 weekly sessions of exposure therapy and response prevention delivered by telephone or face to face. Main outcome measures: Yale Brown obsessive compulsive disorder scale, Beck depression inventory, and client satisfaction questionnaire. Results: Difference in the Yale Brown obsessive compulsive disorder checklist score between the two treatments at six months was –0.55 (95% confidence interval –4.26 to 3.15). Patient satisfaction was high for both forms of treatment. Conclusion: The clinical outcome of cognitive behaviour therapy delivered by telephone was equivalent to treatment delivered face to face and similar levels of satisfaction were reported.

(Reprinted with permission from the BMJ Publishing Group Ltd., 2006; 333(7574):883–887)

[INFLUENTIAL PUBLICATIONS] The Psychological Treatment of Obsessive-Compulsive Disorder

Abramowitz, J. S. — 2007-08-10

[INFLUENTIAL PUBLICATIONS] A Review of Antipsychotics in the Treatment of Obsessive Compulsive Disorder

Fineberg, N. A., Gale, T. M., Sivakumaran, T. — 2007-08-10

(Reprinted with permission from the Journal of Psychopharmacology 2006; 20(1):97–103)

[INFLUENTIAL PUBLICATIONS] Tic or Compulsion? It's Tourettic OCD

Mansueto, C. S., Keuler, D. J. — 2007-08-10

A subgroup of individuals suffering from obsessive-compulsive disorder (OCD) frequently present to treatment with an atypical yet distinguishable array of symptoms akin to both Tourette's disorder (TD) and OCD. These individuals often receive standard treatments for OCD (or less likely, TD) that fail to address the blended features of their presentation. It is argued that these individuals would be better served, both psychotherapeutically and pharmacologically, by the adoption of a Tourettic OCD (TOCD) conceptual framework.

(Reprinted with permission from Behavioral Modification 2005; 29(5):784–799)

[INFLUENTIAL PUBLICATIONS] Randomized, Placebo-Controlled Trial of Exposure and Ritual Prevention, Clomipramine, and Their Combination in the Treatment of Obsessive-Compulsive Disorder

2007-08-10

Objective:

The purpose of the study was to test the relative and combined efficacy of clomipramine and exposure and ritual prevention in the treatment of obsessive-compulsive disorder (OCD) in adults. Serotonin reuptake inhibitors (SRIs) and cognitive behavior therapy by exposure and ritual prevention are both established treatments for OCD, yet their relative and combined efficacy have not been demonstrated conclusively. Method: A double-blind, randomized, placebo-controlled trial comparing exposure and ritual prevention, clomipramine, their combination (exposure and ritual prevention plus clomipramine), and pill placebo was conducted at one center expert in pharmacotherapy, another with expertise in exposure and ritual prevention, and a third with expertise in both modalities. Participants were adult outpatients (N=122 entrants) with OCD. Interventions included intensive exposure and ritual prevention for 4 weeks, followed by eight weekly maintenance sessions, and/ or clomipramine administered for 12 weeks, with a maximum dose of 250 mg/ day. The main outcome measures were the Yale-Brown Obsessive Compulsive Scale total score and response rates determined by the Clinical Global Impression improvement scale. Results: At week 12, the effects of all active treatments were superior to placebo. The effect of exposure and ritual prevention did not differ from that of exposure and ritual prevention plus clomipramine, and both were superior to clomipramine only. Treated and completer response rates were, respectively, 62% and 86% for exposure and ritual prevention, 42% and 48% for clomipramine, 70% and 79% for exposure and ritual prevention plus clomipramine, and 8% and 10% for placebo. Conclusions: Clomipramine, exposure and ritual prevention, and their combination are all efficacious treatments for OCD. Intensive exposure and ritual prevention may be superior to clomipramine and, by implication, to monotherapy with the other SRIs.

(Reprinted with permission from the American Journal of Psychiatry 2005; 162:151–161)

[INFLUENTIAL PUBLICATIONS] Treatment of Compulsive Hoarding

Saxena, S., Maidment, K. M. — 2007-08-10

Compulsive hoarding and saving symptoms, found in many patients who have obsessive-compulsive disorder (OCD), are part of a clinical syndrome that has been associated with poor response to antiobsessional medications and cognitive-behavioral therapy (CBT). Specific CBT strategies targeting the characteristic features of the compulsive hoarding syndrome have had better results. This article provides an overview of the compulsive hoarding syndrome, a review of treatment approaches and their efficacy, a case presentation, and a detailed discussion of intensive, multimodal CBT for compulsive hoarding. New insights into the neurobiological characteristics of compulsive hoarding that might direct future treatment development are also presented.

(Reprinted with permission from the Journal of Clinical Psychology 2004; 60(11): 1143–1154)