Psychosomatics 2015:]:]]]–]]]

& 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Original Research Reports Updates in Psychosomatic Medicine: 2014 Oliver Freudenreich, M.D., Jeff C. Huffman, M.D., Michael Sharpe, M.D., Scott R. Beach, M.D., Christopher M. Celano, M.D., Lydia A. Chwastiak, M.D., M.P.H., Mary Ann Cohen, M.D., Anne Dickerman, M.D., Mary Joe Fitz-Gerald, M.D., Nicholas Kontos, M.D., Leena Mittal, M.D., Shamim H. Nejad, M.D., Shehzad Niazi, M.D., Marta Novak, M.D., Ph.D., med.habil., Kemuel Philbrick, M.D., Joseph J. Rasimas, M.D., Ph.D., Jewel Shim, M.D., Scott A. Simpson, M.D., M.P.H., Audrey Walker, M.D., Jane Walker, Ph.D., Christina L. Wichman, D.O., Paula Zimbrean, M.D., Wolfgang Söllner, M.D., Theodore A. Stern, M.D.

Background: The amount of literature published annually related to psychosomatic medicine is vast; this poses a challenge for practitioners to keep up-to-date in all but a small area of expertise. Objectives: To introduce how a group process using volunteer experts can be harnessed to provide clinicians with a manageable selection of important publications in psychosomatic medicine, organized by specialty area, for 2014. Methods: We used quarterly annotated abstracts selected by experts from the Academy of Psychosomatic Medicine and the European Association of

Psychosomatic Medicine in 15 subspecialties to create a list of important articles. Results: In 2014, subspecialty experts selected 88 articles of interest for practitioners of psychosomatic medicine. For this review, 14 articles were chosen. Conclusions: A group process can be used to whittle down the vast literature in psychosomatic medicine and compile a list of important articles for individual practitioners. Such an approach is consistent with the idea of physicians as lifelong learners and educators. (Psychosomatics 2015; ]:]]]–]]])

Received March 5, 2015; revised March 30, 2015; accepted March 31, 2015. From Department of Psychiatry, Massachusetts General Hospital, Boston, MA (OF, JCH, SRB, CMC, NK, SHN, TAS); Psychological Medicine Research, Department of Psychiatry, University of Oxford, Oxford, UK (MS, JW); Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA (LAC); Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, NY (MAC); Department of Psychiatry, Consultation-Liaison Service, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, NY (AD); Department of Psychiatry, Louisiana State University Health Sciences Center, Shreveport, LA (MJF-G.); Divisions of Medical Psychiatry and Women’s Mental Health, Department of Psychiatry, Brigham and Women’s Hospital, Boston, MA (LM); Department of Psychiatry & Psychology, Mayo Clinic, Jacksonville, FL (SN); Department of Psychiatry, University Health Network and University of Toronto, Toronto, Canada (MN); Institute of Behavioral Sciences, Semmelweis University, Budapest, Hungary (MN); Department of Psychiatry and

Psychology, Mayo Clinic, Rochester, MN (KP); HealthPartners/ Regions Hospital, St. Paul, MN (JJR); Department of Psychiatry, Kaiser Oakland Medical Center and the University of California, San Francisco, San Francisco, CA (JS); Denver Health Medical Center, University of Colorado School of Medicine, Denver, CO (SAS); Division of Child and Adolescent Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY (AW); Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI (CLW); Department of Psychiatry and Surgery (Transplant), Yale New Haven Hospital, New Haven, CT (PZ); Department of Psychosomatic Medicine and Psychotherapy, Paracelsus Medical University, Nuremberg General Hospital, Nuremberg, Germany (WS). Send correspondence and reprint requests to Oliver Freudenreich, M.D., MGH Schizophrenia Program, Erich Lindemann Mental Health Center, 25 Staniford Street, Boston, MA 02114; e-mail: ofreudenreich@ partners.org & 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Psychosomatics ]:], ] 2015

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Updates in Psychosomatic Medicine INTRODUCTION The sheer amount of literature published each year in medicine is overwhelming. Humankind’s collective knowledge is growing exponentially, and medical knowledge has been estimated in 2010 to double every 3.5 years and has been projected to double every 73 days by the year 2020.1 The area of psychosomatic medicine or consultationliaison psychiatry is no exception, and it has become all but impossible for practitioners to keep up-to-date on new developments across their field rather than just in a very narrow area of their expertise. Yet, our patients expect us to remain informed about new developments in medicine and practice based on current knowledge. To help practitioners of psychosomatic medicine keep updated (and to maintain their accreditation) the Academy of Psychosomatic Medicine (APM) in collaboration with its sister organization the European Association of Psychosomatic Medicine (EAPM) established a subcommittee of the APM Research and EvidenceBased Practice Committee, to publish annotated quarterly updates in the field of psychosomatic medicine. This article introduces the group process used to canvass the literature; it provides all references selected by the subcommittee for 2014; and in addition, it further distills the literature related to psychosomatic medicine to provide an overview of important developments in 2014.

METHODS Beginning in 2013, the evidence-based practice subcommittee of the APM, in collaboration with members from the EAPM, began publishing annotated updates of important articles on the APM website (in the Education section) quarterly.2 The quarterly updates are accessible to anyone and not restricted to the APM members. In 2014, these quarterly updates covered 15 subspecialties or sections of psychosomatic medicine. Each quarterly update contained up to 3 articles per subspecialty area that were published during that quarter (Epub ahead of print or published in the journal) and were selected by a designated section expert from the APM or the EAPM who volunteered to participate in this educational endeavor in his or her area of expertise. In addition to the PubMed article abstract, section experts annotated the articles using a structured format (Table 1). For many subspecialty areas, although 1 expert author was the designated point person and primary 2

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contributing expert, 2 or more authors were responsible for canvassing the literature in their assigned topic area and selecting articles of importance; in addition, the primary experts were encouraged to use outside consultants (i.e., colleagues with relevant expertise) and APM special interest groups for article suggestions. Experts were instructed to preferentially select high-quality articles. Consistent with the grading scheme for the critical appraisal of literature that was developed by the Oxford Centre for Evidencebased Medicine, we operationalized high-quality articles as those that used a randomized controlled trial design, represented a cohort study, or reported a meta-analysis.3 Table 2 summarizes the selection criteria for other types of articles that experts could include in their updates because of high educational value. Authors were instructed to limit themselves to 3 articles per quarter to avoid an uncritical inclusion of articles; if no articles were deemed high quality or educationally valuable, none were selected for the quarter. For this 2014 update in psychosomatic medicine, 2 authors (O. F. and T. A. S.) created a consensus list of articles that they judged to be of particular relevance for general practitioners of psychosomatic medicine who want to educate themselves about major findings in psychosomatic medicine in 2014. One of the authors (O. F.) is the chairperson of the subcommittee, who in this function had collected and read all submitted articles and annotations before posting on the website; the other author (T. A. S.) functioned as a neutral judge, as he had not been involved in the quarterly updates. For the annual update, articles were given preference if they reported on innovations, investigated a clinical topic using high-quality research methodology, represented consensus documents from important medical bodies, or educated helpfully about an area of psychosomatic medicine. The number of final articles was not limited initially but evolved during the consensus building. The overall process of selecting articles for the quarterly and the annual update is depicted in the Figure. RESULTS A total of 88 articles had been selected in 2014 by the contributing APM/EAPM experts for annotation and publication on the APM website. The articles were Psychosomatics ]:], ] 2015

Freudenreich et al.

TABLE 1.

Annotation Format for APM Quarterly Updates

The finding Concise summary of the study This should include the (one) main finding in the topic expert's own words This should include the population studied, the study design used, and the main outcome variable Strength and weaknesses Comments regarding the appropriateness of the study's methodology This should include patient selection and measurement issues such as rating scales used This should include the study's power and generalizability Relevance Background and the larger context of the study that illustrates why it is important This should include applicability for psychosomatic medicine

APM ¼ Academy of Psychosomatic Medicine.

related to 15 subspecialties: cardiac psychiatry,4–9 collaborative care/integrated behavioral health,10,11 emergency psychiatry,12,13 HIV psychiatry,14–20 neuropsychiatry,21–31 pediatric psychosomatic medicine,32–36 psychodermatology,37–45 psychonephrology,46–55 psycho-oncology and palliative care,56–64 serious mental illness,65–72 somatic symptom disorders,73 suicide,74–78 transplant psychiatry,79–85 trauma and critical care psychiatry,86,87 and women’s mental health.11,88–91 In addition, 14 articles with substantial educational value for general practitioners of psychosomatic medicine psychiatry were selected as described earlier. The full annotations for those articles (as provided by the original authors, with some editing for uniformity) are provided later, and their main findings are summarized in Table 3. Cardiac Psychiatry Depression As a Risk Factor for Poor Prognosis Among Patients With Acute Coronary Syndrome: Systematic Review and Recommendations: A Scientific Statement From the American Heart Association Lichtman JH, Froelicher ES, Blumenthal JA, Carney RM, Doering LV, Frasure-Smith N, et al: Circulation 2014; 129:1350–1369 The Finding: Despite moderate heterogeneity of individual studies, this comprehensive systematic Psychosomatics ]:], ] 2015

review found clear connections between depression and adverse outcomes after acute coronary syndrome (ACS). Based on this review and additional aspects of this association (e.g., a plausible mechanism connecting depression and adverse outcomes), the committee concluded that depression should be considered a risk factor for adverse events after ACS. Strengths and Weaknesses: The strengths included a careful and comprehensive systematic review and consideration of multiple criteria required to reach risk factor status. The authors also carefully outlined and discussed sources of heterogeneity. The weaknesses of the review included incorporation only of articles written in English, only considering post-ACS outcomes (rather than onset of cardiac illness or other conditions), and the inherent limitations and heterogeneity of the reviewed studies. Regarding the assignment as a risk factor, an important weakness was that the authors did not include the criterion that treatment/reduction of the risk factor leads to improved prognosis (not yet proven) and that it includes only a very specific condition rather than coronary artery disease overall. Relevance: This article may prove controversial for the reasons listed earlier. However, there is little doubt that depression is linked with cardiac mortality after ACS. Although there has not yet been an adequately powered study proving that treatment of depression leads to a reduction in mortality, there have been several studies showing that management of depression in patients with cardiac disease leads to improved health-related quality of life and function. Whether one considers depression a “risk factor,” it is clearly important to address in patients post-ACS.

TABLE 2.

Selection Criteria for Articles Included in the APM Quarterly Updates

High-quality evidence Randomized, controlled trial Cohort study Meta-analysis Publications in high-impact journals that practitioners should be aware of Novel findings or approaches that might change practice Summary statements or expert guidelines by large organizations Articles with high educational value APM ¼ Academy of Psychosomatic Medicine.

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Updates in Psychosomatic Medicine FIGURE.

APM/EAPM Quarterly and Annual Updates in Psychosomatic Medicine. The 2014 Topic Areas and Article Selection. APM ¼ Academy of Psychosomatic Medicine, EAPM ¼ European Association of Psychosomatic Medicine, SSS ¼ Somatic Symptom Disorder, SMI ¼ Serious Mental Illness. *APM website (education section, annotated abstracts): http://www.apm.org/library/articles/ index.shtml.

APM and EAPM Members

Psychosomac Medicine Topic Area Experts

TOPIC AREAS

Cardiopsychiatry

Neuropsychiatry

Psychonephrology

Transplant psychiatry

Emergency psych

Ped psychosom med

Psychooncology

Trauma

HIV psychiatry

Psychodermatology

Suicide; SSS; SMI

Women’s mental health

QUARTERLY UPDATES (APM Website*) ANNUAL UPDATE (Psychosomacs)

Q1

Q2

Asymptomatic HIV-Associated Neurocognitive Impairment Increases Risk for Symptomatic Decline Grant I, Franklin DR, Jr., Deutsch R, Woods SP, Vaida F, Ellis RJ, et al: Neurology 2014; 82:2055– 2062 The Finding: In this longitudinal cohort study (the CHARTER cohort), a diagnosis of “asymptomatic neurocognitive impairment” (ANI) at the beginning of the study predicted, over a median follow-up of 45.2 months, progression to problems in everyday functioning. Combining self-report and performance-based measure, the presence of ANI conferred a relative risk (RR) of 3.0 (CI: 2.1–4.4) when compared with patients without impairment at baseline. Strength and Weaknesses: This is an important longitudinal study (as opposed to a cross-sectional www.psychosomaticsjournal.org

Q3

Q4

Updates in Psychosomac Medicine

HIV Psychiatry

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Outside Consultants

study) with a sufficiently large sample (N ¼ 121) of patients diagnosed as having ANI and 226 diagnosed as being cognitively intact. The CHARTER cohort’s longitudinal design might be biased toward those who can commit to participating in a longitudinal study (i.e., removing people at the extremes of function: those who work and those who are impaired). Relevance: In patients with HIV infection, preserving cognition remains elusive for some, in whom, despite seemingly effective HIV treatment, functional impairments from HIV-associated neurocognitive disorder develop. It is a high priority to develop treatment strategies (either new drugs or optimizing current regimens for central nervous system protection) for patients who are labeled as having “ANI” (most patients with HIV-associated neurocognitive disorder) using the Frascati criteria. In this scheme, ANI indicates measurable cognitive impairment that is Psychosomatics ]:], ] 2015

Freudenreich et al. TABLE 3.

Updates in Psychosomatic Medicine 2014: 14 Key Findings

Subspecialty Domain Cardiac psychiatry HIV psychiatry

Reference No. 4

17

18

Neuropsychiatry

23

31

Major Finding/Relevance The American Heart Association officially concluded that depression should be considered a risk factor for adverse events after an acute coronary syndrome (ACS). Depression in post-ACS patients is ignored to the detriment of the patient and must be addressed. An asymptomatic form of HIV-associated neurocognitive disorder termed asymptomatic neurocognitive impairment (ANI) increases the risk for cognitive decline that becomes symptomatic. Patients with HIV infection who have ANI have to be identified, and attempts should be made to protect cognition. The old standby first-generation NNRTI antiretroviral agent efavirenz, which is a component of standard treatment for HIV infection, is associated with an increased risk of suicidality. It remains yet to be seen if next-generation NNRTIs have a lower risk for neuropsychiatric complications. Cognitive deficits 6 months after a stroke were common. After a stroke (regardless of location), serial testing including formal neuropsychologic testing where there is a discrepancy between subjective complaints and “bedside” screening is needed. A simple bedside test of attention (months of year backward) was both sensitive and specific for delirium in hospitalized (but not in intensive care) patients. Quality initiatives in hospitals should pay attention to this simple test.

Psychodermatology

39

Psychotropic medications can cause a variety of dermatologic side effects. Consultation psychiatrists would benefit from this review that details reported reactions for all major medications and has a small section on treatment and prevention.

Psycho-oncology and palliative care

60

The investigators failed to recruit to a placebo-controlled trial for depression in patients with cancer. Given the importance of clinical psychiatric research in medical settings, the experience of the authors and the discussion are informative for any C-L psychiatrist who works in academic settings or who considers conducting a clinical trial in a medical setting. Patients with cancer with major depression had substantially greater improvement in depression when treated with manualized depression care when compared with usual treatment. This large, randomized effectiveness trial convincingly showed the power of intensive and integrated collaborative care to address depression in patients with cancer. Such coordinated and interdisciplinary treatment sets the standard for care.

63

Serious mental illness

68

Patients with serious mental illness admitted for diabetes had an increased risk for (a costly) early rehospitalization. This finding points to need for better coordinated and integrated medicalpsychiatry care for patients with serious mental illness and diabetes.

Suicide

75

A 41-year longitudinal study established traumatic brain injury as a risk factor for suicide (and also for other violent deaths). This is an important clinical finding that clinicians should keep in mind when assessing post-TBI patients, be it returning veterans, people with sports-related head injuries, or other groups where head injuries are likely (e.g., patients who are homeless). The US Preventive Services Task Force concluded that there was no clear evidence for benefit from routinely screening asymptomatic primary care patients for suicide risk. This is an important reminder that indiscriminant, broad screening (in this case for suicidality) can lead to wasted resources with little to show for it.

76

Transplant psychiatry

80

In this prospective study, cognitive decline developed in patients after liver transplantation even though hepatic encephalopathy resolved after transplantation. Not all cognitive dysfunction seen in patients after liver transplantation is thus explained by hepatic encephalopathy.

Trauma and critical care psychiatry

86

This randomized trial found ramelteon to be an effective prevention of delirium in hospitalized patients. Replication is needed before ramelteon can become standard delirium prophylaxis. Whether ramelteon is safer and more effective than melatonin in this setting is also unknown.

Women's mental health

90

In this cohort study, antidepressants were not associated with an increased risk for cardiac malformations once cofounders (e.g., depression severity) were taken into account. This study adds to the large body of literature suggesting that either antidepressants are not teratogenic or the absolute risk is very low.

C-L ¼ consultation liaison; NNRTI ¼ non–nucleoside reverse transcriptase inhibitors; traumatic brain injury.

Psychosomatics ]:], ] 2015

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Updates in Psychosomatic Medicine clinically silent and has no functional relevance. There is still value in diagnosing ANI: “Asymptomatic” might not sound alarming but, as shown in the study, it is a risk factor for cognitive deterioration, and those patients need to be identified even when they are “asymptomatic.” Association Between Efavirenz as Initial Therapy for HIV-1 Infection and Increased Risk for Suicidal Ideation or Attempted or Completed Suicide: An Analysis of Trial Data Mollan KR, Smurzynski M, Eron JJ, Daar ES, Campbell TB, Sax PE, et al: Ann Intern Med 2014; 161:1–10 The Finding: Using data from 4 AIDS Clinical Trials Group studies of treatment-naive patients with HIV infection who were started with treatment on randomized antiretroviral treatment regimens, it was found that the risk of suicidality (defined as suicidal ideation or attempted or completed suicide) was twice as high for patients randomly assigned to an efavirenzcontaining regimen when compared with those assigned to efavirenz-free regimens. Of the observed 9 suicides, 8 were in the efavirenz group. Strength and Weaknesses: This is the first analysis using data about suicidality from random assignment to treatment regimens with or without efavirenz. Still, 3 of the 4 trials were open label; with suicide already listed in the prescribing information as a complication, reporting bias is possible. In addition, suicidality was not assessed with a standard rating scale, and patients who were deemed to be at a higher risk for suicidality might not have been referred to these 4 trials to begin with. Finally, efavirenz was not compared with regimens containing other non–nucleoside reverse transcriptase inhibitors or integrase inhibitors. Relevance: The non–nucleoside reverse transcriptase inhibitors efavirenz (Sustiva) has been an important cornerstone medication for the treatment of HIV/AIDS because of its excellent antiretroviral efficacy. It is also included in the most widely used single-pill regimen (Atripla). However, its use has always been complicated by a higher rate of neuropsychiatric side effects and by anecdotal observations of serious events (such as thoughts of suicide). This analysis, using data from randomized trials, provides the best evidence yet that these clinical observations are true and that there is some risk of suicidal 6

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thinking (and death from suicide) owing to use of efavirenz. Thus, careful clinical monitoring for psychiatric problems is needed for patients starting with the treatment with efavirenz. It remains yet to be seen if next-generation non–nucleoside reverse transcriptase inhibitorss have a lower risk for neuropsychiatric complications. Neuropsychiatry The Cognitive Burden of Stroke Emerges Even With an Intact National Institutes of Health Stroke Scale Score: A Cohort Study Kauranen T, Laari S, Turunen K, Mustanoja S, Baumann P, Poutiainen E: J Neurol Neurosurg Psychiatry 2014; 85:295–299 The Finding: Cognitive deficits at 6 months after stroke (without regard for localization) were common in a working-age cohort. Further, a screening instrument used at the time of discharge was of limited use in predicting this. Strengths and Weaknesses: Strict definitions for cognitive impairment were used; along with the relatively young sample, this makes the study’s findings striking. However, the baseline cognitive status of the patients was unknown, and although presumed to be buoyed by age, relative youth plus stroke suggests unfavorable CNS vasculopathy burden; thus, mitigating assumptions about baseline cognition. Relevance: This study highlights the need for serial cognitive screening in persons with acute, subacute, and remote stroke. The importance of formal neuropsychologic testing when subjective functioning and “bedside” screening are incongruent is suggested. Attention! A Good Bedside Test for Delirium? O’Regan NA, Ryan DJ, Boland E, Connolly W, McGlade C, Leonard M, et al: J Neurol Neurosurg Psychiatry 2014; 85:1122–1131 The Finding: Simple attention screening (months of year backward) is a sensitive and surprisingly specific detector of delirium in hospitalized (nonintensive care) populations. It is enhanced by combining it with screens for subjective confusion or a visuospatial attention task or both. Strengths and Weaknesses: This article highlighted the continued problems that exist in delirium detection in the general hospital setting, reviewed proposed Psychosomatics ]:], ] 2015

Freudenreich et al. remedies, and made a convincing argument for a much simpler solution than has been proffered previously. The study design was ambitious (all assessments of the 4200 patients took place on the same day; this included screening followed by a second screening with the Confusion Assessment Method, followed by psychiatric assessment) but it appears to have been carried out rigorously. The authors did an excellent job of identifying the potential limiting factors of the study. The biggest quibble is that attention is far from a specific delirium finding and probably ought not be taken as such in a cross-sectional assessment. However, as noted by the authors, very, very few patients with documented dementia in this study did not have delirium. The fact that patients with cognitive impairment were more susceptible to delirium may have mitigated the usual insensitivity of attention impairment as a diagnostic screen. In addition, technically, months of the year backward is not a pure test of attention, as it uses working memory as well. Relevance: Delirium detection in the general hospital remains poor and is often thought to require significant investment in time and effort. This article may have quality improvement implications as it offers a straightforward and brief bedside method of detecting delirium. Psychodermatology Dermatologic Side Effects of Psychotropic Medications Mitkov MV, Trowbridge RM, Lockshin BN, Caplan JP: Psychosomatics 2014; 55:1–20 The Finding: The authors presented a broad overview of the most common dermatologic side effects associated with psychotropic medications. In general, dermatologic symptoms are most commonly associated with antiepileptic medications; the most serious dermatologic adverse effects are also due to this class of medications. The authors described the most common dermatologic conditions, their onset and clinical course, risk factors for cutaneous drug reactions, as well as recommendations on how to diagnose these problems. Strengths and Weaknesses: The primary strength of this article was that it presented a comprehensive overview of the most common dermatologic side Psychosomatics ]:], ] 2015

effects of psychotropic medication and served as good resource for psychiatrists for information and guidance on recognition, diagnosis, and evaluation of these conditions. A weakness was that a significant amount of the data on cutaneous drug reactions and psychotropic medications were based on case reports or retrospective data, which limited the quality of the evidence. Relevance: Dermatologic side effects are not uncommonly associated with psychotropic medications, and it is important for practitioners of psychosomatic medicine to be aware of the potential for dermatologic adverse effects, particularly with certain medications (i.e., mood stabilizers) and in higher risk groups. Risk mitigation is already possible for some medications (e.g., HLA genotyping before carbamazepine use).

Psycho-Oncology and Palliative Care Conducting an Antidepressant Clinical Trial in Oncology: Challenges and Strategies to Address Them Park EM, Raddin RS, Nelson KM, Hamer RM, Mayer DK, Bernard SA, et al: Gen Hosp Psychiatry 2014; 36:474–476 The Finding: The researchers planned a 4-arm clinical trial to compare the efficacy of citalopram with placebo and mirtazapine with placebo for depressed patients with cancer (participants were to be stratified according to their symptom profile). They were unable to recruit any participants and, after removing the placebo arms, were still unable to recruit sufficient numbers. They described the reasons for poor recruitment (summarized in 4 categories: diagnostic ambiguity, participant recruitment and retention, practical barriers, and placebo concerns) and the possible solutions. Strengths and Weaknesses: This article’s strength was that it was one of only a few that described the practical aspects of conducting a real clinical research study in psycho-oncology. Its weakness was that the researchers were not able to put their potential solutions to the test. Relevance: This description of the challenges of doing clinical research in psychiatry in a medical setting is relevant to all consultation-liaison psychiatrists. www.psychosomaticsjournal.org

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Updates in Psychosomatic Medicine Integrated Collaborative Care for Comorbid Major Depression in Patients With Cancer (SMaRT Oncology-2): A Multicentre Randomised Controlled Effectiveness Trial Sharpe M, Walker J, Holm Hansen C, Martin P, Symeonides S, Gourley C, et al: Lancet 2014; 384:1099–1108 The Finding: An integrated, systematic, multicomponent collaborative care–based treatment program for major depression was significantly better than usual care in achieving a treatment response in patients with cancer. The treatment program was relatively inexpensive. Strengths and Weaknesses: The strengths of this trial included its rigorous methods, recruitment by screening, and high follow-up rate. The main weakness was that, as is usually the case with such trials, the participants could not be masked to intervention allocation. Relevance: The findings suggested that systematic and intensive integrated collaborative care treatment programs could achieve striking results for patients with comorbid depression.

between 2010 and 2011 with any discharge diagnosis indicating diabetes mellitus. The study sample was representative of patients in Washington State with diabetes, as data were obtained from all community hospitals in the state. The study limitations were related to the use of administrative data. First, there may have been misclassification of patients with serious mental illness disorders, resulting in their inclusion in the reference group. Moreover, the administrative data set used for these analyses did not include information about health behaviors (such as smoking, sedentary lifestyle, and poor diet) or laboratory or pharmacy data—so the effect of these important factors could not be evaluated. Relevance: These findings may indicate poor quality of medical care for patients with diabetes who also have comorbid serious mental illness, or maybe further evidence that patients with serious mental illness interact with the health care system differently, and have unique barriers to adherence with medical care and follow-up. Improving the coordination or integration of outpatient medical and psychiatric care for these complex patients may decrease the risk of early rehospitalizations.

Serious Mental Illness The Effect of Serious Mental Illness on the Risk of Rehospitalization Among Patients With Diabetes Chwastiak LA, Davydow DS, McKibbin CL, Schur E, Burley M, McDonell MG, et al: Psychosomatics 2014; 55:134–143 The Finding: Among Medicare beneficiaries, rehospitalization within 30 days of discharge occurs in almost 20% of patients, costing the health care system an estimated $17.4 billion. A key component of the comprehensive strategy of the Centers for Medicare and Medicaid Services to reduce costs focuses on reducing 30-day rehospitalizations for heart failure, acute myocardial infarction, and pneumonia. In this study, of all admissions to community hospitals in Washington State for diabetes between 2010 and 2011, a diagnosis of serious mental illness was independently associated with an increased risk of early medical rehospitalization. Strength and Weaknesses: This observational cohort study comprised a very large (82,060 adults in Washington State), population-based sample of patients who had a medical-surgical hospitalization 8

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Suicide Suicide, Fatal Injuries, and Other Causes of Premature Mortality in Patients With Traumatic Brain Injury: A 41-Year Swedish Population Study Fazel S, Wolf A, Pillas D, Lichtenstein P, Langstrom N: JAMA Psychiatry 2014; 71:326–333 The Finding: Drawing on an extended longitudinal follow-up (4 to 440 y) of more than 218,000 Swedish individuals who had a traumatic brain injury (TBI), this study showed that people who survived 6 months or more beyond a TBI were 3 times more likely to die prematurely of suicide, assault, or other injuries. Of particular interest to psychiatrists, post-TBI patients were twice as likely to die of suicide as compared with their uninjured siblings. Strengths and Weaknesses: This study relied on impressive numbers and on extensive longitudinal data, taking advantage of comprehensive nationwide population-based registers in Sweden that also allowed for comparison with general population controls and a substantial number (4237,000) of uninjured siblings; this extensive database enabled Psychosomatics ]:], ] 2015

Freudenreich et al. uncommon statistical power to examine relatively infrequent events. Unfortunately, the study was not able to either specify the type of TBI or quantify the severity of the TBI. Relevance: This study underscored the utility of regarding post-TBI patients as having chronic medical problems that deserve ongoing attention, perhaps particularly those who are also prone to impulsivity, risk-taking behaviors, or substance abuse. Returning veterans, youth involved in contact sports, and individuals who live in environments where assaults were more common comprised a population that was at an increased risk of having a TBI and may invite psychiatric attention when they pursue medical attention. Screening for Suicide Risk in Adolescents, Adults, and Older Adults in Primary Care: U.S. Preventive Services Task Force Recommendation Statement LeFevre ML: Ann Intern Med 2014; 160:719–726 The Finding: Although the United States Preventive Services Task Force recommended that primary care clinicians should remain attentive to screening patients in high-risk groups (such as immediately following dismissal from an emergency department visit for a suicidal act or following a psychiatric hospitalization), there was insufficient evidence of benefit to support routine screening for suicide risk in primary care. The American Academy of Family Physicians and the Canadian Task Force on Preventive Health Care reached similar conclusions. The United States Preventive Services Task Force continues to support screening for depression in primary care, provided such screening is coupled with adequate resources to ensure accurate diagnosis, treatment, and follow-up. However, the United States Preventive Services Task Force concluded that there was no clear evidence that screening for suicide risk in asymptomatic primary care patients yielded improved health outcomes. Strengths and Weaknesses: Given that suicide was the 10th leading cause of death in the United States in 2010, this update of the 2004 United States Preventive Services Task Force recommendations is timely. Unfortunately, available studies for review were sparse, the accuracy of the screening instruments used varied widely, and no 2 studies used the same instrument. Psychosomatics ]:], ] 2015

Relevance: Recent emphases on patient safety and the recognition of the potential adverse effects of depression in select groups of medical and surgical patients have increased the attention given to suicide screening in and out of the hospital. Awareness of the paucity of evidence for benefit from routine screening for suicide risk in primary care patients may enable consultation psychiatrists to inform these efforts, such that the energy and work invested are directed toward high-risk individuals where intervention may favorably influence outcome. Transplant Psychiatry New-Onset Cognitive Dysfunction Impairs the Quality of Life in Patients After Liver Transplantation Tryc AB, Pflugrad H, Goldbecker A, Barg-Hock H, Strassburg CP, Hecker H, et al: Liver Transpl 2014; 20:807–814 The Finding: A total of 50 patients were investigated prospectively before orthotopic liver transplantation (OLT), at 6 months, and at 12 months after OLT. A battery of psychometric tests was used: the psychometric hepatic encephalopathy score, the inhibitory control test, the critical flicker frequency, and the Repeatable Battery for the Assessment of Neuropsychological Status. The hepatic encephalopathy group performed significantly worse on all tests in comparison with the nonhepatic encephalopathy group before OLT (psychometric hepatic encephalopathy score, p o 0.01; inhibitory control test, p o 0.04; and critical flicker frequency, p o 0.01). At 6 months after OLT, the hepatic encephalopathy group still had lower mean scores for critical flicker frequency (p o 0.04) and psychometric hepatic encephalopathy score (p o 0.09) in comparison with the nonhepatic encephalopathy group. Over time, the patients in the hepatic encephalopathy group improved on the Repeatable Battery for the Assessment of Neuropsychological Status (T1 vs T3, p o 0.06), whereas a cognitive decline was measured with Repeatable Battery for the Assessment of Neuropsychological Status for the nonhepatic encephalopathy group (T1 vs T2, p o 0.02, and T1 vs T3, p o 0.02). At 12 months after OLT, no significant differences between the groups were detectable. Approximately 70% of the patients showed a decline in cognition, exceeding 10% in www.psychosomaticsjournal.org

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Updates in Psychosomatic Medicine at least one cognitive domain. Hepatic encephalopathy–related cognitive dysfunction was mostly resolved within the first 6 months after OLT, and no patient was diagnosed with minimal hepatic encephalopathy according to psychometric hepatic encephalopathy score and inhibitory control test targets 12 months after OLT. Strength and Weaknesses: The strengths of the study involved its prospective design, extensive cognitive battery, and length of follow-up (12 mo). All patients received a standard triple-immunosuppression regimen after OLT, which took away 1 possible confounding factor. The main limitation of the study was its lack of information about the possible causes of cognitive decline posttransplantation. Relevance: This study addressed the important topic of cognitive impairment after liver transplantation. Patients with liver transplant often have cognitive impairment related to hepatic encephalopathy while on the transplant waiting list; however, they often have significant risk factors for other cognitive disorders: long history of alcohol abuse, cardiovascular disease, medications, and age. Differentiating reversible from progressive cognitive decline before and after liver transplantation is often extremely difficult. This study brings valuable information regarding the evolution of the hepatic encephalopathy after liver transplantation and raises attention to the cognitive decline posttransplantation, which is not related to hepatic encephalopathy. The findings of the study suggested that 1 year after OLT, cognitive dysfunctions should not be interpreted as residual symptoms but instead be viewed as new-onset cognitive disturbances.

a lower incidence of delirium (p ¼ 0.01; odds ratio ¼ 0.07 [95% CI: 0.008–0.54]. Strength and Weaknesses: The primary strength of this study was its randomized, placebo-controlled design. Despite a relatively low number of patients in the trial, both the groups were reasonably similar concerning risk factors for development of delirium. The limitations of the study included that this was not a double-blind study but was rater-blinded. In addition, although the number of patients enrolled was more than that needed for power analysis, the study had a relatively small sample size. Other weaknesses include the exclusion of patients with hepatic dysfunction, diagnoses of mood disorders (including bipolar mood disorder and depression), and those with psychotic disorders. These groups represented not only those patients who often have sleep/wake dysfunction and circadian rhythm disturbances but also those who have also been shown to be at a higher risk for the development of delirium in the intensive care unit setting; their exclusion from the study deviates from real clinical practice. Relevance: During the last several years, varying strategies regarding delirium prevention, particularly in intensive care unit patients, have been studied, including use of dopamine antagonists, cholinesterase inhibitors, and even benzodiazepines, all with varying results. This particular study, despite its limitations, was one that is the first to show a significant prophylactic effect on the incidence of delirium in elderly intensive care unit patients with the use of the melatonin analogue ramelteon. Interestingly, no published studies exist to show if ramelteon is more effective (or if more safe) than melatonin is in clinical trials with human subjects. Women’s Mental Health

Trauma and Critical Care Psychiatry Preventative Effects of Ramelteon on Delirium: A Randomized Placebo-Controlled Trial Hatta K, Kishi Y, Wada K, Takeuchi T, Odawara T, Usui C, et al: JAMA Psychiatry 2014; 71:397–403 The Finding: In a randomized rater-blinded placebo-controlled trial that was conducted in 4 university hospitals and 1 general hospital involving 67 patients (24 patients in intensive care units and 43 admitted to regular acute care wards) between the ages of 65 and 89 years, ramelteon was associated with a lower risk of delirium (3% vs 32%; p ¼ 0.003). After risk factors were controlled for, ramelteon was still associated with 10

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Antidepressant Use in Pregnancy and the Risk of Cardiac Defects Huybrechts KF, Palmsten K, Avorn J, Cohen LS, Holmes LB, Franklin JM, et al: N Engl J Med 2014; 370:2397–2407 The Finding: This cohort study of 64,389 women nested within a large population-based cohort study of women enrolled in the nationwide Medicaid Analytic eXtract found no substantial increase in risk of cardiac malformations in infants of women with depression who use antidepressants (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, bupropion, and tricyclic antidepressants) in the Psychosomatics ]:], ] 2015

Freudenreich et al. first trimester when compared with women with depression without antidepressant use. This association was further attenuated by adjusting for a variety of factors including severity of depression, other indications for antidepressant use, sociodemographic factors, and health care use factors. In the unadjusted analysis, the RR of any cardiac defect with the use of a selective serotonin reuptake inhibitor was 1.25 (CI: 1.13–1.38). However, these findings were attenuated by adjustment for women with depression only (RR ¼ 1.12, with CI: 1.00–1.26) and a cohort that was fully adjusted for depression, depression severity, and other confounders (RR ¼ 1.06; 95% CI: 0.93–1.22). Strength and Weaknesses: The strengths of this study included its large sample size within a national database of Medicaid enrollees with the ability to link maternal and infant records as well as the use of propensity score matching to adjust for a large set of potential confounders. All major antidepressants were included. Additionally, this study controlled for the presence and severity of depression. Although epidemiologic studies have often been challenged by defining exposure and the timing of that exposure during pregnancy, these investigators enlisted secondary analyses limiting exposure to the first trimester and required women to have a filled prescription or refilled prescription that did not alter the findings substantially. The findings were further bolstered by the replication of prior reports’ findings of associations between well-known risk factors for cardiac malformation, such as diabetes, use of anticonvulsant, and multifetal pregnancy. Some of the limitations of this study included its use of a Medicaid population that is younger and more racially diverse than populations in prior studies were, though the authors found no effect related to age or race. The data also included only live births, thus excluding pregnancies resulting in stillbirth, termination, or spontaneous abortion that could have been the result of more severe cardiac malformation. Additionally, the information on important lifestyle factors (such as smoking, alcohol use, and obesity) was limited or absent. Relevance: The use of psychotropics, especially antidepressants, during pregnancy is still the focus of much scrutiny. Additionally, the role of untreated or unremitted symptoms of mental illness on pregnancy outcomes and infant outcomes has a growing body of literature. The decision about whether to initiate or Psychosomatics ]:], ] 2015

continue treatment with an antidepressant during pregnancy should be made with careful consideration that balances the risk of that medication with the risk of the untreated symptoms, and this study adds to this discussion by carefully analyzing the risks of cardiac malformation associated with antidepressants. This study calls into question previous findings from earlier epidemiologic studies that implicated paroxetine with a higher risk of right ventricular outflow tract obstructions in infants exposed in utero, which resulted in the Food and Drug Administration eventually reclassifying the drug to Category D. Similarly, sertraline, one of the most commonly prescribed selective serotonin reuptake inhibitors used in pregnancy, was previously associated with ventricular septal defects. Given the increasing prevalence of antidepressant use (among other psychotropics) during pregnancy, this study adds to the large body of literature suggesting low absolute and RR of antidepressant use during pregnancy and specifically argued against teratogenic effects associated with common antidepressants. CONCLUSION A concerted effort by members of the APM and the EAPM identified important findings in psychosomatic medicine that should be of interest for all psychosomatic medicine psychiatrists, even if some content lies outside the main thrust of the consultative work for individual practitioners. The group process for canvassing the vast medical literature and creating annotated versions of relevant articles by experts (further condensed in our list of 14 key findings for 2014) is one approach to synthesize medical information. The utility is 2-fold: one, clinicians and experts alike remain engaged as students and life-long learners and two, experts function as peer educators and serve an important professional function. The strengths of our selection approach lies in a group effort by experts to find the most relevant articles. Our approach for selecting the quarterly update articles also had weaknesses. Although the work group covered many topics in psychosomatic medicine, not all topics were covered (e.g., gastroenterology and hepatology; chronic pain), and the selection of only a few articles favors small areas of psychosomatic medicine (HIV psychiatry) over larger www.psychosomaticsjournal.org

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Updates in Psychosomatic Medicine areas (e.g., cardiopsychiatry) that are underrepresented. However, articles were also selected based on quality, and some areas did not have high-quality publications this past year and were noncompetitive. Further, even though key principles of article selection were outlined, the experts had leeway in making their ultimate article selections, and some selections may appear idiosyncratic. Last, limiting the number of selected articles per quarter to 3 main articles forced experts to make choices. In addition, any attempt to further reduce the number of relevant articles to 14 in this review for the whole field would omit some articles that could very reasonably have been considered. Our final selection attempts to provide practitioners of psychosomatic medicine with articles that capture current trends in the various subspecialties and practical articles to inform their clinical practice and help prepare for board examinations. Still, although our approach is not the best or only approach, it is a possible approach that uses a group process and the wisdom of a group of experts to make lifelong learning possible as a physician. The APM’s approach of eliciting quarterly, annotated updates from area experts could in principle be adopted by groups of clinicians (at a hospital or practice or

organization) who come together voluntarily and divvy up the literature. Without an attempt to synthesize the literature, individual clinicians would drown in the sea of information. This group of clinicians plans on continuing the quarterly updates and make the annual updates a regular feature in psychosomatics. Acknowledgment: We would like to thank other APM and EAPM members who have contributed articles for consideration but who were not listed as authors. We particularly want to thank APM’s web person Grace Bachmann who developed the overall layout for the web-based updates and who carefully read, edited, and put the abstracts and annotations on the APM website each quarter. Disclosure: Oliver Freudenreich has received grant support from Psychogenics and Forum, has received honoraria from Global Medical Education and the MGH Psychiatry Academy, has received consultant fees from Beacon Health Strategies and Optimal Medicine, and has received royalties from UpToDate. Theodore A. Stern is an employee of the Academy of Psychosomatic Medicine for serving as the editor in chief of Psychosomatics. The other authors had no disclosures.

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82. Fox KR, Posluszny DM, DiMartini AF, et al: Predictors of post-traumatic psychological growth in the late years after lung transplantation. Clin Transplant 2014; 28:384–393 83. Burkhalter H, Wirz-Justice A, Denhaerynck K, et al: The effect of bright light therapy on sleep and circadian rhythms in renal transplant recipients: a pilot randomized, multicentre wait-list controlled trial. Transpl Int 2015; 28:59–70 84. Ladner DP, Dew MA, Forney S, et al: Long-term quality of life after liver donation in the adult to adult living donor liver transplantation cohort study (A2ALL). J Hepatol 2015; 62:346–353 85. Sanchez R, Bailles E, Peri JM, et al: Cross-sectional psychosocial evaluation of heart transplantation candidates. Gen Hosp Psychiatry 2014; 36:680–685 86. Hatta K, Kishi Y, Wada K, et al: Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial. JAMA Psychiatry 2014; 71:397–403 87. Gacouin A, Tadie JM, Uhel F, et al: At-risk drinking is independently associated with ICU and one-year mortality in critically ill nontrauma patientsn. Crit Care Med 2014; 42:860–867 88. Freeman EW, Sammel MD, Boorman DW, Zhang R: Longitudinal pattern of depressive symptoms around natural menopause. JAMA Psychiatry 2014; 71:36–43 89. Joffe H, Guthrie KA, LaCroix AZ, et al: Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor venlafaxine for vasomotor symptoms: a randomized clinical trial. JAMA Intern Med 2014; 174:1058–1066 90. Huybrechts KF, Palmsten K, Avorn J, et al: Antidepressant use in pregnancy and the risk of cardiac defects. N Engl J Med 2014; 370:2397–2407 91. Bech BH, Kjaersgaard MI, Pedersen HS, et al: Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study. Br Med J 2014; 349:g5159

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