Well-Being Therapy and Lifestyle Intervention in Type 2 Diabetes: A Pilot Randomized Controlled Trial.

OBJECTIVE: This pilot randomized controlled trial evaluates the preliminary efficacy of a 4-month well-being therapy (WBT) and lifestyle intervention among adults with type 2 diabetes and overweight/obesity. METHODS: Fifty-eight patients were recruited from two outpatient clinics and randomized to receive the WBT-lifestyle intervention or the lifestyle intervention alone. Data were collected at baseline (T0), immediate postintervention (T1), 6-month follow-up (T2), and 12-month follow-up (T3). Primary efficacy outcomes included changes in weight, psychological distress, and well-being, whereas secondary efficacy outcomes included changes in lifestyle and physiological parameters. RESULTS: Compared with the lifestyle-alone intervention, the WBT-lifestyle intervention showed greater improvements in depression (p = .009, d = -0.6), hostility (p = .018, d = -0.6), and personal growth (p = .026, d = 0.5) at T1, in self-reported physical activity at T2 (p = .013, d = 0.7) and T3 (p = .040, d = 0.5), and in triglycerides (p = .019, d = -1.12) at T3. There were no differences between treatment groups in weight and other physiological parameters. CONCLUSIONS: These findings suggest that WBT may be a valuable addition to lifestyle interventions for improving short-term psychological outcomes and promoting long-term healthy changes in physical activity, with a potential impact on physiological outcomes.Trial Registration:ClinicalTrials.gov identifier: NCT03609463.

Appropriate controls for digital therapeutic clinical trials: A narrative review of control conditions in clinical trials of digital therapeutics (DTx) deploying psychosocial, cognitive, or behavioral content.

Digital therapeutics (DTx) are software programs that treat a disease or condition. Increasingly, DTx are part of medical care, and in the US healthcare system they are regulated by the FDA as Software as a Medical Device (SaMD). Randomized controlled trials (RCT) remain a key evidence generation step for most DTx. However, developing a unified approach to the design of appropriate control conditions has been a challenge for two main reasons: (1) inheriting control condition definitions from pharmacotherapy and medical device RCT that may not directly apply, and (2) challenges in establishing control conditions for psychosocial interventions that build the core of many DTx. In our critical review we summarize different approaches to control conditions and patient blinding in RCT evaluating DTx with psychosocial, cognitive or behavioral content. We identify control condition choices, ranging from very minimal digital controls to more complex and stringent digital applications that contain aspects of "fake" therapy, general wellness content or games. Our review of RCTs reveals room for improvement in describing and naming control conditions more consistently. We further discuss challenges in defining placebo controls for DTx and ways in which control choices may have a therapeutic effect. While no one-size-fits-all control conditions and study designs will apply to all DTx, we propose points to consider for defining appropriate digital control conditions. At the same time, given the rapid iterative development and optimization of DTx, treatments with low risk profile may be evaluated with minimal digital controls followed by extensive real-world effectiveness trials.

Clinical characterization of allostatic overload.

Allostatic load reflects the cumulative effects of stressful experiences in daily life and may lead to disease over time. When the cost of chronic exposure to fluctuating or heightened neural and systemic physiologic responses exceeds the coping resources of an individual, this is referred to as "toxic stress" and allostatic overload ensues. Its determination has initially relied on measurements of an interacting network of biomarkers. More recently, clinical criteria for the determination of allostatic overload, that provide information on the underlying individual experiential causes, have been developed and used in a number of investigations. These clinimetric tools can increase the number of people screened, while putting the use of biomarkers in a psychosocial context. The criteria allow the personalization of interventions to prevent or decrease the negative impact of toxic stress on health, with particular reference to lifestyle modifications and cognitive behavioral therapy.

Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review.

BACKGROUND: Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim of this paper is to identify the occurrence, frequency, and features of withdrawal symptoms after SNRI discontinuation. METHODS: PRISMA guidelines were followed to conduct a systematic review. Electronic databases included PubMed, the Cochrane Library, Web of Science, and MEDLINE from the inception of each database to June 2017. Titles, abstracts, and topics were searched using a combination of the following terms: "duloxetine" OR "venlafaxine" OR "desvenlafaxine" OR "milnacipran" OR "levomilnacipran" OR "SNRI" OR "second generation antidepressant" OR "serotonin norepinephrine reuptake inhibitor" AND "discontinuation" OR "withdrawal" OR "rebound." Only published trials in the English language were included. RESULTS: Sixty-one reports met the criteria for inclusion. There were 22 double-blind randomized controlled trials, 6 studies where patients were treated in an open fashion and then randomized to a double-blind controlled phase, 8 open trials, 1 prospective naturalistic study, 1 retrospective study, and 23 case reports. Withdrawal symptoms occurred after discontinuation of any type of SNRI. The prevalence of withdrawal symptoms varied across reports and appeared to be higher with venlafaxine. Symptoms typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well. CONCLUSIONS: Clinicians need to add SNRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with other types of psychotropic drugs. The results of this study challenge the use of SNRI as first-line treatment for mood and anxiety disorders.

Benzodiazepines as a Monotherapy in Depressive Disorders: A Systematic Review.

BACKGROUND: The aim of this paper was to perform a systematic review and, when feasible, a meta-analysis of randomized controlled trials (RCT) which used benzodiazepines (BZD) as a monotherapy versus placebo, antidepressant drugs (AD), or both. METHODS: Keyword searches were conducted for identifying RCT comparing BZD and AD, and/or placebo in the treatment of depression, using electronic databases from their inception up to April 2017. We selected reports of RCT in which BZD were compared to AD and/or placebo in the treatment of adult patients with a primary diagnosis of depressive disorder or anxious depression. When feasible, data were subjected to meta-analysis. RESULTS: A total of 38 studies met the criteria for inclusion and were then included in the systematic review. Only 1 study concerned a newer AD, fluvoxamine. For the meta-analysis, we submitted data on response rate from 22 RCT, considering BZD versus placebo (8 comparisons) and BZD versus tricyclic antidepressants (TCA) (20 comparisons). There was a lack of significant differences as to response rate between BZD and placebo, as well as between BZD and TCA. Analysis of individual studies disclosed that, in more than half of the studies comparing BZD to TCA and/or placebo, BZD were significantly more effective than placebo and as effective as TCA. CONCLUSIONS: BZD are a therapeutic option in anxious depression and there are no indications that AD are preferable. There is a pressing need for RCT of adequate methodological quality and follow-up comparing BZD to second-generation AD and placebo in anxious depression.

Impact of Depression and Demoralization on Blood Pressure Control in African Americans with Hypertension: Findings from the TRIUMPH Trial.

BACKGROUND: African Americans develop hypertension earlier and have worse cardiovascular outcomes than Caucasians. Accumulating evidence suggests that psychological distress may play a role in the observed racial differences in hypertension. Several studies have investigated the relationship between depression and hypertension while little is still known about the role of demoralization. METHODS: Using data from the Trial Using Motivational Interviewing, Positive Affect, and Self-affirmation in African Americans with Hypertension (TRIUMPH), logistic regression models were used to estimate differences in blood pressure control at 12 months among participants with demoralization, depression, and both conditions. RESULTS: Our logistic models showed that reported psychosocial symptoms significantly differed in predicting success in blood pressure control at 12 months. Contrast analyses showed that, after adjusting for sociodemographic, clinical, and psychosocial variables, demoralized patients were less likely to achieve blood pressure control than participants without affective conditions (p = 0.020). Similar results emerged for patients with depression (p = 0.042) and both conditions (p = 0.022). CONCLUSIONS: Depression can be extremely debilitating and has serious health consequence. Our findings confirm this result and show that, even though depression and demoralization share common features, they are two distinct clinical phenomena with similar negative impact on blood pressure control in African Americans.

Stress and Response to Treatment: Insights From a Pilot Study Using a 4-week Contemplative Self-Healing Meditation Intervention for Posttraumatic Stress in Breast Cancer.

Along with symptoms of anxiety and depression, many breast cancer survivors experience symptoms of posttraumatic stress disorder (PTSD) that may worsen in the setting of other stressful life events. The aim of this pilot study was to evaluate whether a 4-week version of our Contemplative Self-Healing program would have different effects in reducing PTSD symptoms between breast cancer survivors with or without chronic stress at baseline. PTSD symptoms were measured using the Impact of Events scale (IES). A linear mixed model analysis was used to evaluate within patients changes in IES score. Results showed that breast cancer patients who were experiencing chronic stress reported greater improvement in IES score than those without chronic stress. Our preliminary findings shed light on the need to evaluate life stressors in breast cancer patients. Evaluating chronic stress may be essential in predicting which cancer patients may benefit most from a psychological intervention.

Experiences of patients undergoing dialysis who are from ethnic and racial minorities.

BACKGROUND: Approximately 500,000 people in the United States are affected by end-stage kidney disease (ESKD), 53% of whom are Black or Latino. ESKD significantly impacts psychosocial health and quality of life. However, few studies address the psychosocial aspects of ESKD, especially among black and Latino adults. This study sought to understand the psychosocial context of living with ESKD among black and Latino adults who reside in a medically underserved community. STUDY DESIGN: A qualitative study. SETTING AND PARTICIPANTS: Participants were recruited from a dialysis centre in East New York, Brooklyn, a medically underserved community. METHODOLOGY: Descriptive phenomenology was used as a qualitative approach for capturing the experiences of patients who received dialysis in this community. ANALYTICAL APPROACH: Open-ended interviews were audio-taped, transcribed, coded and analysed using standard qualitative techniques. RESULTS: Data saturation was achieved at 36 participants. The following five themes emerged: the transition to dialysis is abrupt and unexpected; denial is often an initial response; dialysis is the new normal and in order to survive one must forget the past and press forward; dialysis changes everything and impacts the entire family; strength was often found in faith and family. LIMITATIONS: This study was conducted in one setting and may need to be expanded to other sites to capture the experiences of patients cared for in other settings. CONCLUSION: These findings have practical implications for informing patient-centered models of care that are more responsive to the psychosocial needs of patients with ESKD living in medically underserved communities.

Use of the Psychosocial Index: A Sensitive Tool in Research and Practice.

BACKGROUND: The Psychosocial Index (PSI) is a self-rating scale based on clinimetric principles that is simple to use in a busy clinical setting. It can be integrated by observer-rated clinical judgment, providing a first-line, comprehensive assessment of stress, well-being, distress, illness behavior, and quality of life. By calculation of scores, it can be used for conventional psychological measurements. Its clinical applications and clinimetric properties are reviewed. The present version of the PSI has been slightly revised. In addition, a modified version for use in adolescents and young adults (PSI-Young; PSI-Y) is also included. METHODS: Articles that involved the use of the PSI were identified by searching the Web of Science database from 1998 to February 2016 and by a manual search of the literature. RESULTS: A total of 20 studies reporting results from the use of PSI were included. The PSI has been employed in various clinical populations in different countries and showed high sensitivity. It significantly discriminated varying degrees of psychosocial impairment in different populations. When subjects were identified by categorical criteria (presence of allostatic overload, psychosomatic syndromes, psychiatric disorders), the PSI scores were significantly different across subgroups. CONCLUSIONS: In clinical practice, scanning the list of symptoms allows clinicians to assess rapidly which symptoms and problems are perceived as most troublesome. In research settings, the use of scores makes the PSI a valid and sensitive tool in differentiating levels of psychosocial variables among groups.

Behavioral Toxicity Revisited: Iatrogenic Comorbidity in Psychiatric Evaluation and Treatment.

In 1968, DiMascio and Shader provided a conceptual framework for behavioral toxicity of psychotropic drugs (ie, the pharmacological actions of a drug that, within the dose range in which it has been found to possess clinical utility, may produce alterations in mood, perceptual, cognitive, and psychomotor functions that limit the capacity of the individual or constitute a hazard to one's well-being). A drug effect such as sedation or motor stimulation may be considered adverse for one patient and yet therapeutic and desired for another patient; within the same patient, it may be of value at one stage of one's illness and adverse at a later stage. The concept of behavioral toxicity encompasses adverse events that may be limited to the period of drug administration and/or persist long after their discontinuation. These latter phenomena can be subsumed under the rubric of iatrogenic comorbidity. Behavioral toxicity may ensue with any type of medical drug. Examples related to antidepressant drug use (onset of suicidality and aggression, switching from unipolar to bipolar course, withdrawal phenomena upon discontinuation, postwithdrawal persistent disorders) are discussed. Consideration of potential vulnerability to adverse events including behavioral toxicity should be placed in the context of the benefits that treatment may entail.

Discriminating the Presence of Psychological Distress in Patients Suffering from Psoriasis: An Application of the Clinimetric Approach in Dermatology.

Psoriasis is a chronic dermatologic disease that negatively impacts physical and mental health of patients as well as their social and work life. The aim of this study is to illustrate, by a clinimetric approach the differences in psychological distress and well-being between patients with mild and moderate to severe psoriasis. Seventy patients with psoriasis were evaluated using the Structured Clinical Interview for DSM-IV (SCID-I), the Diagnostic Criteria for Psychosomatic Research (DCPR), along with the following self-report instruments: the Symptoms Questionnaire (SQ), the Psychological Well-being scales (PWB) and the Temperament and Character Inventory (TCI). Illness severity was evaluated using the Psoriasis Area and Severity Index (PASI). While no differences were reported between groups in terms of psychiatric diagnoses, patients with greater severity (PASI <10) presented higher rates of demoralization (61.5%) and Type A behavior (53.8%) than subjects with mild severity (17.5% and 21.1%, respectively). Patients with moderate/severe psoriasis also reported impaired levels of psychological well-being in terms of lower autonomy, environmental mastery, personal growth and purpose in life. Furthermore, according to TCI, patients with severe psoriasis reported greater harm avoidance and lower self-directness than individuals with milder psoriasis levels. Overall results highlighted the need in psoriasis care of a more comprehensive psychological and psychosomatic assessment not limited to the customary psychiatric diagnostic criteria.

Results from the Trial Using Motivational Interviewing, Positive Affect, and Self-Affirmation in African Americans with Hypertension (TRIUMPH).

OBJECTIVE: Our objective was to determine the effectiveness of combining positive affect and self-affirmation strategies with motivational interviewing in achieving blood pressure control among hypertensive African Americans (AA) compared with AA hypertensives in an education-only control group. DESIGN: Randomized trial. SETTING: Ambulatory practices in the South Bronx and Harlem, New York City. PARTICIPANTS: African American adults with uncontrolled hypertension. INTERVENTIONS: Participants were randomized to a positive affect and self-affirmation intervention or an education control group. The positive affect and self-affirmation intervention involved having participants think about things that made them happy and that reminded them of their core values on a daily basis. These strategies were reinforced every two months through motivational interviewing. The control arm received a workbook of strategies on blood pressure control. All participants were called every two months for one year. MAIN OUTCOMES: Blood pressure control rate. RESULTS: A total of 238 participants were randomized. The average age was 56 ± 11 years, approximately 70% were female, 80% were not married, and up to 70% had completed high school. There was no difference in control rates between the intervention and the control group. However, at one year, female participants were more likely to be controlled. Participants with high depressive symptoms or high perceived stress at baseline were less likely to be controlled. CONCLUSIONS: While this study did not demonstrate an intervention effect, it does provide important insight into the psychosocial factors that may underlie blood pressure control in African Americans. Implications for future behavioral intervention trials are discussed.

The Assessment of Allostatic Overload in Patients with Congestive Heart Failure by Clinimetric Criteria.

The precipitating role of emotional stress in the development of congestive heart failure (CHF) is a long-standing clinical observation. We employed new clinimetric criteria for the assessment of allostatic overload (AO) in a sample of CHF patients, with regard to its associations with psychological distress and health status. Allostatic overload was assessed by a semi-structured interview based on clinimetric criteria in 70 consecutive outpatients with CHF. One observer-rated scale and two self-rating questionnaires for psychological distress were administered. Cardiac variables were also collected at intake. Twenty-three patients (32.9%) were classified as having AO according to clinimetric criteria. Significant differences were found with regard to gender, with women being more likely to report AO than men (23.5% versus 57.9%). Patients with AO presented significantly higher levels of psychological distress (based on scales administered) compared with those who did not. Among cardiac risk factors, hyperglycaemia was found to be significantly associated with the presence of AO. The use of the clinimetric criteria provides a global index for identifying distress that might adversely influence the course and progression of CHF. It may be of use in clinical practice, leading to therapeutic suggestions such as lifestyle modifications and psychotherapy to help patients deal with their difficulties.

Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review.

Background: Selective serotonin reuptake inhibitors (SSRI) are widely used in medical practice. They have been associated with a broad range of symptoms, whose clinical meaning has not been fully appreciated. Methods: The PRISMA guidelines were followed to conduct a systematic review of the literature. Titles, abstracts, and topics were searched using the following terms: 'withdrawal symptoms' OR 'withdrawal syndrome' OR 'discontinuation syndrome' OR 'discontinuation symptoms', AND 'SSRI' OR 'serotonin' OR 'antidepressant' OR 'paroxetine' OR 'fluoxetine' OR 'sertraline' OR 'fluvoxamine' OR 'citalopram' OR 'escitalopram'. The electronic research literature databases included CINAHL, the Cochrane Library, PubMed and Web-of-Science from inception of each database to July 2014. Results: There were 15 randomized controlled studies, 4 open trials, 4 retrospective investigations, and 38 case reports. The prevalence of the syndrome was variable, and its estimation was hindered by a lack of case identification in many studies. Symptoms typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering. However, many variations are possible, including late onset and/or longer persistence of disturbances. Symptoms may be easily misidentified as signs of impending relapse. Conclusions: Clinicians need to add SSRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs. The term 'discontinuation syndrome' that is currently used minimizes the potential vulnerabilities induced by SSRI and should be replaced by 'withdrawal syndrome'. © 2015 S. Karger AG, Basel.

Iatrogenic comorbidity in childhood and adolescence: new insights from the use of antidepressant drugs.

The term "iatrogenic comorbidity" refers to unfavorable modifications in the course of an illness, with regard to its characteristics and responsiveness, which may be related to previous treatments. Some iatrogenic adverse events arising from either pharmacotherapy or psychotherapy cannot be subsumed under the traditional rubric of adverse effects and require careful evaluation. Children and adolescents are generally more likely to experience adverse health consequences after drug treatment. The use of antidepressant drugs in this age group may cause potential long-term detrimental effects, such as mood elevation that does not subside when drugs are discontinued and may predispose to the development of a bipolar disorder. The concept of iatrogenic comorbidity in children and adolescents has heuristic value in weighing potential benefits and risks associated particularly with psychotropic treatments.

Five-factor model personality traits as predictors of incident coronary heart disease in the community: a 10.5-year cohort study based on the Baltimore epidemiologic catchment area follow-up study.

OBJECTIVE: Certain personality and behavioral traits (e.g., type A and type D) have been reported to be associated with development and progression of coronary heart disease (CHD), but few have examined the relationship using a comprehensive assessment of personality along with a structured assessment of psychiatric disorders. METHODS: Based on participants (age: 47.3 ± 12.8; female: 62.6%) of the Baltimore Epidemiologic Catchment Area follow-up study, we examined the relationship between the 5 major domains of personality traits (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and incident CHD between Wave III (1993-1996) and Wave IV (2004-2005). RESULTS: Incident CHD developed in 65 participants during the follow-up. Those with incident CHD had lower on openness (44.06 ± 9.29 vs. 47.18 ± 8.80; p = 0.007) and extraversion (45.98 ± 9.25 vs. 49.12 ± 8.92; p = 0.007) scores than those without. Logistic regression models revealed an inverse association (OR = 0.73; 95% CI = 0.54-0.98) between openness factor z-scores and incident CHD after adjusting for putative confounding factors, including DSM III-R Major Depressive Disorder. CONCLUSION: High openness appears to be an independent protective factor for incident CHD in the community. Future studies should examine behavioral and pathophysiologic mechanisms underlying this association.

Psychological well-being in out-patients with eating disorders: a controlled study.

OBJECTIVE: Positive functioning is widely neglected in research on eating disorders (EDs). The aim of this exploratory study was to assess psychological well-being (PWB) in out-patients with ED and in controls. METHOD: The authors assessed PWB in 245 out-patients with EDs [105 with bulimia nervosa (BN), 57 with anorexia nervosa (AN), and 83 with binge eating disorder (BED) who met DSM-IV-TR] and 60 controls. They tested whether PWB was associated with eating attitude test (EAT) scores and if such associations differed among ED groups while taking into account confounding variables. RESULTS: Significant differences between groups in all PWB scales were found. While individuals with BN reported significantly lower scores in all PWB dimensions than healthy controls, patients with BED scored significantly lower than controls in PWB autonomy, environmental mastery, and self-acceptance scales. Patients with AN showed similar scores to controls in all PWB dimensions, except for positive relationships and self-acceptance. In all ED groups, most PWB dimensions resulted significantly and negatively associated with EAT scales, except for AN where oral control was found to positively correlate with a high sense of purpose in life. All results were maintained even after adjusting for possible confounding variables. DISCUSSION: Patients with EDs reported an impairment in PWB. The paucity of PWB was not necessarily dependent on the presence of high levels of psychological distress and on the severity of the disorder. Such assessments may therefore yield a more comprehensive evaluation in this clinical population.

Efficacy and tolerability of benzodiazepines versus antidepressants in anxiety disorders: a systematic review and meta-analysis.

BACKGROUND: Placebo-controlled trials showed that both benzodiazepines (BDZ) and antidepressant drugs (AD) are effective in treating anxiety disorders. However, in the last years a progressive shift in the prescribing pattern from BDZ to newer AD has taken place. The aim of this systematic review and meta-analysis is to analyze whether controlled comparisons support such a shift. METHODS: CINHAL, the Cochrane Library, MEDLINE, PubMed and Web of Science were searched from inception up to December 2012. A total of 22 studies met the criteria for inclusion. They were mostly concerned with tricyclic antidepressants (TCA; 18/22) and involved different anxiety disorders. In order to reduce clinical heterogeneity, only the 10 investigations that dealt with the comparison between TCA and BDZ in panic disorder were submitted to meta-analysis, whereas the remaining papers were individually summarized and critically examined. RESULTS: According to the systematic review, no consistent evidence emerged supporting the advantage of using TCA over BDZ in treating generalized anxiety disorder (GAD), complex phobias and mixed anxiety-depressive disorders. Indeed, BDZ showed fewer treatment withdrawals and adverse events than AD. In panic disorder with and without agoraphobia our meta-analysis found BDZ treatments more effective in reducing the number of panic attacks than TCA (risk ratio, RR = 1.13; 95% CI = 1.01-1.27). Furthermore, BDZ medications were significantly better tolerated than TCA drugs, causing less discontinuation (RR = 0.40; 95% CI = 0.20-0.57) and side effects (RR = 0.41; 95% CI = 0.34-0.50). As to newer AD, BDZ trials resulted in comparable or greater improvements and fewer adverse events in patients suffering from GAD or panic disorder. CONCLUSIONS: The change in the prescribing pattern favoring newer AD over BDZ in the treatment of anxiety disorders has occurred without supporting evidence. Indeed, the role and usefulness of BDZ need to be reappraised.