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GME Research Review

GME Research Review is a monthly newsletter where internationally recognized experts select, summarize, and provide a clinical commentary on the latest published research in psychiatry.  Each summary has been derived from the relevant article’s abstract and the clinical commentary has been provided by our expert.

ISSUE 5, August 2012 — Guest Commentator: Philip R. Muskin, MD, Columbia University


Responsiveness of Hypochondriacal Patients with Chronic Low-Back Pain to Cognitive-Behavioral Therapy

Nakao M, Shinozaki Y, Nolido N, et al

Psychosomatics. 2012;53(2):139-147.

Background: Evidence has suggested that cognitive-behavioral therapy (CBT) is effective in reducing hypochondriacal symptoms, and another line of evidence has suggested that CBT is also effective in reducing pain and the psychological conditions associated with chronic low-back pain (CLBP). The purpose of this study was to examine the effectiveness of CBT among hypochondriacal patients with and without CLBP.

: A total of 182 hypochondriacal patients were randomly assigned to a CBT or control group. The Somatic Symptom Inventory was used to define CLBP, and the Symptom Checklist 90R (SCL90R) was used to assess psychological symptoms. The outcome measures for hypochondriasis, the Whiteley Index (WI), and the Health Anxiety Inventory (HAI) were administered before the intervention and at 6 and 12 months after completion of the intervention.

: In the total sample, both WI and HAI scores were significantly decreased after treatment in the CBT group compared with the control group. Ninety-three (51%) patients had CLBP; the SCL90R scores for somatization, depression, phobic anxiety, paranoid ideation, and general severity were significantly higher in the CLBP(+) group than in the CLBP(-) group at baseline. Although the WI and HAI scores were significantly decreased after treatment in the CLBP(-) group, such significant pre- to post-changes were not found in the CLBP(+) group.

: CBT was certainly effective among hypochondriacal patients without CLBP, but it appeared to be insufficient for hypochondriacal patients with CLBP. The core psychopathology of hypochondriacal CLBP should be clarified to contribute to the adequate management of hypochondriacal symptoms in CLBP patients.

Clinical Commentary
Patients with complaints of CLBP suffer from physical and psychological disability. In this study of CBT treatment, hypochondriacal patients who scored 4 or more on the low back pain item of the Somatic Symptom Inventory were compared to those who did not have that complaint. The patients did not receive medical treatment for CLBP as part of the study. CBT was effective for the hypochondriasis as measured by the Whiteley Index and the Health Anxiety Inventory in CLBP (-) patients but not those who were CLBP (+).  The CLBP (+) group was significantly different from the CLBP (-) group in terms of ethnicity, with a larger proportion of Caucasians in the CLBP (-) group. Controlling for ethnicity, Caucasian CLBP (+) patients did not respond to CBT compared to Caucasian CLBP (-) patients. A major limitation of the study is that a single item on a rating scale defined CLBP arbitrarily. In spite of the limitations, the study raises interesting questions regarding psychological approaches to patients who experience themselves as having low back pain. Their lives may be dramatically impaired by their health beliefs, and psychological treatments typically effective for hypochondriasis may not be beneficial. It is hoped that further research will identify modifications to CBT that will aid these patients.

Fertility Treatment Response: Is It Better to be More Optimistic or Less Pessimistic?

Bleil ME, Pasch LA, Gregorich SE, et al

Psychosom Med. 2012;74(2):193-199.

Objective: To evaluate the prospective relation between dispositional traits of optimism and pessimism and in vitro fertilization (IVF) treatment failure among women seeking medical intervention for infertility.

: Among 198 women (aged 24-45 years, mean [standard deviation]=35.1 [4.1] years; white, 77%), the outcome of each participant's first IVF treatment cycle was examined. Treatment outcome was classified as being successful (versus failed) if the woman either delivered a baby or was pregnant because of the cycle by the end of the 18-month study period. At baseline, optimism and pessimism were measured as a single bipolar dimension and as separate unipolar dimensions according to the Life Orientation Test total score and the optimism and pessimism subscale scores, respectively.

: Optimism/pessimism, measured as a single bipolar dimension, predicted IVF treatment failure initially (B=-0.09, p=.02, odds ratio [OR]=0.917, 95% confidence interval [CI]=0.851-0.988), but this association attenuated after statistical control for trait negative affect (B=-0.06, p=.13, OR=0.938, 95% CI=0.863-1.020). When examined as separate unipolar dimensions, pessimism (B=0.14, p=.04, OR=1.146, 95% CI=1.008-1.303), not optimism (B=-0.09, p=.12, OR=0.912, 95% CI=0.813-1.023), predicted IVF treatment failure independently of risk factors for poor IVF treatment response and trait negative affect.

Conclusions: Being pessimistic may be a risk factor for IVF treatment failure. Future research should attempt to delineate the biological and behavioral mechanisms by which pessimism may negatively affect treatment outcomes.

Clinical Commentary
When a woman is unsuccessful in her attempts to conceive a child, there is often speculation about how psychological issues might have factored into the failure.  Meta-analyses have indicated that depression and anxiety do not predict the outcome of assisted reproductive technologies (ART), but that stress and state/trait anxiety do have an impact. In this study, optimism and pessimism were measured using the Life Orientation Test and, as the authors note, individuals can “embody traits of both optimism and pessimism concurrently.” They also measured negative trait affect using the 23-item neuroticism subscale of the Eysenck Personality Questionnaire.  Pessimism was negatively correlated with positive IVF treatment outcome, independent of negative trait affect and other risk factors for poor fertility treatment response.  Each 1-unit increase in the pessimism score increased the likelihood of IVF treatment failure by 17.8%. Optimism was not related to the IVF outcome. The authors speculate that pessimism reflects an accurate appraisal by women with poor prognosis; however, the women in the study were undergoing IVF for the first time and older age was related to less pessimism. Some data suggest that pessimism may be amenable to change. Results from this study might be incorporated into the evaluation of women in ART programs and into the psychiatric support provided to the patients.

Optimism, Response to Treatment of Depression, and Rehospitalization After Coronary Artery Bypass Graft Surgery

Tindle H, Belnap BH, Houck PR, et al

Psychosom Med. 2012;74(2):200-207.

Objective: Optimism has been associated with a lower risk of rehospitalization after coronary artery bypass graft (CABG) surgery, but little is known about how optimism affects treatment of depression in post-CABG patients.

: Using data from a collaborative care intervention trial for post-CABG depression, we conducted exploratory post hoc analyses of 284 depressed post-CABG patients (2-week posthospitalization score in the 9-item Patient Health Questionnaire ≥10) and 146 controls without depression who completed the Life Orientation Test-Revised (full scale and subscale) to assess dispositional optimism. We classified patients as optimists and pessimists based on the sample-specific Life Orientation Test-Revised distributions in each cohort (full sample, depressed, nondepressed). For 8 months, we assessed health-related quality of life (using the 36-item Short-Form Health Survey) and mood symptoms (using the Hamilton Rating Scale for Depression [HRSD]) and adjudicated all-cause rehospitalization. We defined treatment response as a 50% or higher decline in HRSD score from baseline.

: Compared with pessimists, optimists had lower baseline mean HRSD scores (8 versus 15, p=.001). Among depressed patients, optimists were more likely to respond to treatment at 8 months (58% versus 27%, odds ratio=3.02, 95% confidence interval=1.28-7.13, p=.01), a finding that was not sustained in the intervention group. The optimism subscale, but not the pessimism subscale, predicted treatment response. By 8 months, optimists were less likely to be rehospitalized (odds ratio=0.54, 95% confidence interval=0.32-0.93, p=.03).

: Among depressed post-CABG patients, optimists responded to depression treatment at higher rates. Independent of depression, optimists were less likely to be rehospitalized by 8 months after CABG. Further research should explore the impact of optimism on these and other important long-term post-CABG outcomes.

Clinical Commentary

Data indicate that optimistic postmenopausal women and older men have a lower risk of a first myocardial infarction, and optimistic people are at lower risk for cardiovascular disease progression. This paper investigates the role of optimism in post-CABG patients, suggesting that factors we do not usually measure may be operative in determining patients’ outcomes. The authors note that optimism and pessimism are not necessarily a bipolar trait and may independently contribute to health outcomes. They screened for depression in post-CABG patients using the PHQ-2 in the hospital, followed by the PHQ-9 via telephone 2 weeks after discharge. Those patients with a score of 10 or higher on the PHQ-9 (moderate depression) were included in the study. They were compared to a group of post-CABG patients who screened negative on the PHQ-2 and had a score of <5 on the follow-up questionnaire. Participants completed the Life Orientation Test-Revised (LOT-R) to measure their optimism/pessimism. Depressed patients were randomized to usual care (UC) or to a collaborative care intervention; however, the patients and their physicians in the UC group were informed of their depression status. After adjusting for intervention type, education level, physical functioning, perceived social support, and baseline depression severity, optimists were significantly more likely to respond to depression treatment. In the UC group the optimists were five times more likely to respond to treatment than the pessimists. Risk of rehospitalization was 46% lower in optimists overall (17% lower in the depressed patients and 65% lower in those not depressed). Optimism appeared to operate independently of pessimism in this study and pessimism was not correlated with outcomes, a finding that varies from other research. A limitation of the study is the failure to obtain LOT-R scores after treatment. Thus, we do not know if the LOT-R scores for depressed patients truly represent optimism/pessimism or depression. Nevertheless, this study points clinicians to investigate patients’ outlook as potentially modifiable factors in their health outcomes.

Pregnancy Outcome After Exposure to Antidepressants and the Role of Maternal Depression: Results From the Norwegian Mother and Child Cohort Study

Nordeng H, van Gelder MM, Spigset O, et al

J Clin Psychopharmacol. 2012;32(2):186-194.

Objective: Results of previous studies on the safety of antidepressants during pregnancy have been conflicting. The primary objective of this study was to investigate whether first-trimester exposure to antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs), was associated with increased risk of congenital malformations. The secondary objective was to examine the effects of exposure to antidepressants during pregnancy on birth weight and gestational age.

: We included 63,395 women from the Norwegian Mother and Child Cohort Study. The women had completed 2 self-administered questionnaires at gestational weeks 17 and 30 on medication use and medical, sociodemographic, and psychological factors. Data on pregnancy outcome were retrieved from the Medical Birth Registry of Norway.

: Of the 63,395 women, 699 (1.1%) reported using antidepressants during pregnancy, most frequently SSRIs (0.9%). Exposure to SSRIs during the first trimester was not associated with increased risk of congenital malformations in general (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 0.81-1.84) or cardiovascular malformations (adjusted OR, 1.51; 95% CI, 0.67-3.43). Exposure to antidepressants during pregnancy was not associated with increased risk of preterm birth (adjusted OR, 1.21; 95% CI, 0.87-1.69) or low birth weight (adjusted OR, 0.62; 95% CI, 0.33-1.16).

: This study does not suggest a strongly increased risk of malformations, preterm birth, or low birth weight following prenatal exposure to antidepressants. Without adjustments for level of maternal depression and various sociodemographic and lifestyle factors, antidepressant use during pregnancy would wrongly have been associated with an increased risk of preterm birth.

Clinical Commentary

Safe treatment for depression during pregnancy remains an unsolved problem. Both treating and not treating a depressed pregnant woman exposes the woman and her fetus to risks. Each study contributes something to our knowledge base. In this large study (N=63,395) from the Norwegian Mother and Child Cohort Study, 1.1% reported antidepressant use, with SSRIs being the most frequently used class of medication. There was no increase in risk of congenital malformations in general or cardiovascular malformations associated with first trimester antidepressant use. Antidepressant use was not associated with preterm birth or low birth weight. Women who used antidepressants were also more likely to use benzodiazepines, opioids, hypnotics, and antipsychotics during pregnancy. A major strength of the study is the prospective collection of data; however, major limitations of the study come from how the data were obtained, i.e., self-report, the low response rate (38%), the lack of data obtained about alcohol use, and the lack of data regarding antidepressant dose or duration of exposure. Nevertheless, this study adds to the information we can share with women who are pregnant and in need of treatment for their depression. Ideally, a study will be performed where women are interviewed to obtain accurate information regarding medication use, adherence to treatment, substance use, and outcome of pregnancy. While such a study will not resolve all of the safety issues, it would solve some of the methodological problems of research done to date.

Myocardial Infarction and Generalized Anxiety Disorder: 10-Year Follow-Up

Roest AM, Zuidersma M, de Jonge P

Br J Psychiatry. 2012;200:324-329.

Background: Few studies have addressed the relationship between generalized anxiety disorder (GAD) and cardiovascular prognosis using a diagnostic interview.

: To assess the association between GAD and adverse outcomes in patients with myocardial infarction.

: Patients with acute myocardial infarction (n=438) were recruited between 1997 and 2000 and were followed up until 2007. Current GAD and post-myocardial infarction depression were assessed with the Composite International Diagnostic Interview. The end-point consisted of all-cause mortality and cardiovascular-related readmissions.

: During the follow-up period, 198 patients had an adverse event. GAD was associated with an increased rate of adverse events after adjustment for age and gender (hazard ratio: 1.94; 95% confidence interval: 1.14-3.30; P=.01). Additional adjustment for measures of cardiac disease severity and depression did not change the results.

: GAD was associated with an almost twofold increased risk of adverse outcomes independent demographic and clinical variables and depression.

Clinical Commentary

Most studies investigating the impact of psychological factors on coronary artery disease (CAD) have looked at the role of depression. Depression is a risk factor for both the development of CAD and morbidity and mortality in patients with CAD. This group looked at the prognostic role of GAD over a 10-year period in patients who experienced a myocardial infarction. GAD was associated with an increased risk of cardiovascular events and mortality. Post-myocardial infarction depression was not a significant predictor of adverse outcome in this study. Patients with GAD were two times more likely to have an adverse prognosis even after adjustment for age, gender, and cardiac disease severity. One strength of this study is that the diagnosis was made by a standardized diagnostic interview. The study is also of long duration. It is not known if the patients were treated for their psychiatric disorders and thus we do not have information as to whether interventions would impact on the outcomes. This study does guide us to both inquire ourselves and teach our colleagues to assess patients for both anxiety and depression after a myocardial infarction.

Coping Flexibility and Complicated Grief: A Comparison of American and Chinese Samples

Burton CL, Yan OH, Pat-Horenczyk R, et al

Depress Anxiety. 2012;29(1):16-22.

Background: The ability to process a death and the ability to remain optimistic and look beyond the loss are both thought to be effective means of coping with loss and other aversive events. Recently, these seemingly contrary dimensions have been integrated into the idea of coping flexibility.

: In this study, we assessed the ability of married and bereaved individuals in the United States and Hong Kong to use both coping approaches as operationalized by the trauma-focused and forward-focused coping scales of a previously validated questionnaire. We also calculated a single flexibility score.

: Bereaved participants reported greater trauma-focused coping ability than did married participants. However, bereaved participants meeting criteria for complicated grief (CG) reported less forward-focused coping than both asymptomatic bereaved and married participants. The CG group also showed less overall coping flexibility than the asymptomatic bereaved and married groups. Country was not a factor.

: Findings suggest that deficits in coping flexibility are indicative of pathology in bereaved individuals, and that this relationship extends across cultures. Limitations of the study and directions for future research are discussed.

Clinical Commentary

Freud wrote that the “work” of mourning involved the intense processing of personal meanings and emotions associated with the loss of a loved one. Avoiding this process has been seen as pathological and putting the individual at risk for delayed grief syndromes. Emerging research suggests that flexibility in coping may be a better predictor of grief outcome. This study used a structured clinical interview for DSM-IV-TR for depression comparing married individuals and a group of conjugally bereaved individuals in the United States and Hong Kong. The bereaved participants were questioned about symptoms of complicated grief. Despite the cultural differences between the countries, the ability of bereaved individuals to use flexible coping strategies was more important in distinguishing pathological grief reactions than using a particular coping strategy. While the asymptomatic bereaved and complicated grief groups reported high trauma-focused coping than the married controls, the complicated grief group used less forward-focused coping. The complicated grief group was less flexible than either of the other groups. These results suggest that individuals who can focus on their loss and also move beyond the loss are less likely to develop complicated grief. The therapeutic implications are interesting and suggest how we might work with patients who have suffered a loss both to treat complicated grief and to possibly prevent the occurrence of this painful state.

Cardiac Transplantation in Adult Patients with Mental Retardation: Do Outcomes Support Consensus Guidelines?

Samelson-Jones E, Mancini DM, Shapiro PA

Psychosomatics. 2012;53(2):133-138.

Background: Selection criteria guidelines list mental retardation as a relative contraindication to heart transplantation, but not to kidney transplantation.

: The authors present a case series of adults with mental retardation or comparable acquired intellectual disability who underwent heart transplantation. They discuss the literature on heart and kidney transplantation in people with mental retardation and the ethical reasoning that guides how recipients of solid organ grafts are chosen.

: Literature review and retrospective review of long-term outcomes for five adult patients with mental retardation or comparable disability who received heart transplants.

: Among these cases, survival times to date ranged from 4 to 16 years, with a median survival of greater than 12 years. Medical non-adherence was a significant factor in only 1 of the 5 cases. In that case, the patient's medical non-adherence was due to a functional decline in the primary caretaker.

: People with mental retardation can receive long-term benefit from heart transplantation when they have the cognitive and social support necessary to ensure adherence to post-transplant regimens. There is no ethical or medical reason for guidelines to consider mental retardation, in and of itself, a contraindication to heart transplantation. The totality of the individual patient's circumstances should be considered in assessing transplant candidacy.

Clinical Commentary

Psychosocial factors are assessed as part of a pre-transplantation evaluation. Mental retardation is a relative contraindication to cardiac transplantation and concerns regarding adherence in these patients may limit their ability to be listed for transplantation. The authors reviewed the cases of four patients with mental retardation and one case of acquired intellectual disability (anoxic brain injury) out of the 2,199 heart transplantations performed at New York-Presbyterian hospital from 1978 to 2010.  They note that contraindications for transplantation have been modified over the decades since renal transplantation was first begun. For example, age limitations for transplantation have progressively increased. They note that patients with mental retardation are less frequently referred to transplantation centers and are less frequently listed for transplantation; however, the evidence from renal transplantation indicates that the outcome for these patients is comparable to patients without mental retardation. The survival time in the five patients reviewed ranged from four to fourteen years, with a mean survival time >12 years. Only one case demonstrated medical non-adherence and that was secondary to a functional decline in the patient’s caregiver. As they note, “Patients with mental retardation should not be held to a higher standard than other patients.”  Reviews such as this one inform how we as psychiatrists can contribute with our non-psychiatric colleagues in the decisions regarding this life-saving but extremely limited procedure.  

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