Allostatic Load in Children and Adolescents: A Systematic Review.

INTRODUCTION: The concept of allostatic load encompasses the cumulative effects of both ordinary daily life events as well as major challenges, and also includes related health-damaging behavior. Allostatic overload ensues when environmental challenges exceed the individual's ability to cope. Identification of allostatic load is carried out through the use of biomarkers and clinimetric criteria. Studies are increasingly reported on allostatic load in younger populations, yet a systematic review is missing. OBJECTIVE: The aim of the present systematic review was to summarize the current knowledge on allostatic load/overload among children and adolescents. METHODS: PubMed, PsycINFO, Web of Science, and the Cochrane Library were searched from inception to April 2023. A manual search of the literature was also performed. We considered only studies in which allostatic load or overload were adequately described and assessed in either clinical or non-clinical populations younger than 18 years. RESULTS: A total of 38 original investigations were included in this systematic review. Studies reported an association between allostatic load and sociodemographic characteristics (e.g., poverty, ethnicity, perceived discrimination, adverse childhood experiences) and environmental factors, as well as consequences of allostatic load on both physical and mental health among children and adolescents. CONCLUSIONS: The findings indicate that greater allostatic load is associated with poorer health outcomes in both clinical and non-clinical pediatric populations, with possible enduring effects. The results support the clinical utility of the transdiagnostic identification of allostatic load and overload in children and adolescents across a variety of settings, with a number of potential clinical implications.

Allostatic Load and Endocrine Disorders.

The building of life stress, well expressed by the concept of allostatic load, plays an important part in all phases of endocrine illness. Allostatic load refers to the cumulative burden of both stressful life events and chronic stress. When environmental challenges exceed the individual ability to cope, allostatic overload ensues. Assessment of allostatic load/overload by clinical measurements including indices and rating scales, in addition to biomarkers, offers a characterization of the person's psychosocial environment that is missing from current formulations. Consideration of allostatic load in endocrinology may shed light on a number of clinical issues: interpretation of abnormal hormone values that lack explanations; coping with the various phases of illness; maladaptive illness behavior; response to treatment; presence of residual symptoms; health-damaging lifestyle habits. Addressing allostatic load calls for innovative models of endocrine outpatients with multidisciplinary organization of care, extended time for the interview, focus on rehabilitation. We provide an overview on the mechanisms of allostatic load, how it can be assessed, its potential role in endocrine disturbances, and how its consideration may lead to a needed innovation in patient care.

An innovative approach to the assessment of mood disturbances in patients with acute coronary syndrome.

BACKGROUND: The clinical value of the identification of mood disorders in patients with acute coronary syndrome (ACS) is well established. However, assessment based on DSM criteria presents some limitations. This study aimed to provide an innovative strategy for evaluating the spectrum of mood disturbances in ACS. METHODS: A total of 288 patients with a first episode of ACS underwent interviews based on DSM-IV-TR criteria (major depressive disorder, minor depression, and dysthymia), Diagnostic Criteria for Psychosomatic Research-DCPR (demoralization and type A behavior), and the Clinical Interview for Depression-CID. Additional self-report inventories (psychological well-being and distress) were administered. A total of 100 consecutive patients who satisfied criteria for DSM-IV-TR depression or DCPR demoralization were enrolled in a randomized controlled trial on a sequential combination of cognitive-behavioral and well-being therapy (CBT/WBT) vs clinical management (CM) and reassessed up to 30-month post-intervention. RESULTS: A total of 29.9% of patients showed a DSM-IV-TR depressive syndrome. Inclusion of demoralization and type A identified psychological distress in 58% of the sample. According to CID, reactivity to social environment, fatigue, depressed mood, and somatic anxiety were the most common symptoms. Somatic symptoms were significantly associated with DSM-IV-TR depression (fatigue and changes of appetite), whereas environmental reactivity with demoralization. Both depression and demoralization were associated with higher distress and lower well-being. Unlike CM, CBT/WBT was significantly associated with decrease of guilt, pessimism, fatigue, and early insomnia (CID). CONCLUSIONS: The findings indicate that standard psychiatric approach identifies only a narrow part of mood disturbances affecting ACS patients. A more articulated assessment unravels specific clinical configurations that may entail prognostic and therapeutic implications.

The Clinical Science of Euthymia: A Conceptual Map.

Euthymia is a trans-diagnostic construct characterized by lack of mood disturbances; presence of positive affect; balance of psychological well-being dimensions, flexibility, consistency, and resistance to stress. The aim of this critical review is to draw a conceptual map of euthymia. Relationships with other constructs, continuum between euthymia and dysthymia with discomfort as an intermediate area, associations with lifestyle, clinimetric assessment, role of psychotherapeutic interventions, establishment of therapeutic targets, and neurobiological mechanisms are discussed. The model is based on the bipolar nature of well-being dimensions. Euthymia means using allostasis optimally and maintaining a healthy balance that promotes positive aspects of brain and body health through health-promoting behaviors. It may provide a framework for a renewed definition of recovery, for measuring treatment outcome and for targeting interventions, including the sequential administration of therapeutic components. Clinical assessment requires a clinimetric approach encompassing a broad range of aspects, such as allostatic load and lifestyle behaviors, all interacting with each other and contributing to the euthymia/dysthymia balance. Clinimetric indices for assessing euthymia (the Clinical Interview for Euthymia and the Euthymia Scale) and related constructs (the Clinical Interview for Dysthymia and the Semi-Structured Interview for the Diagnostic Criteria for Psychosomatic Research) are presented here. Well-Being Therapy, a psychotherapeutic strategy specifically aimed at pursuing euthymia, relies on self-observation of well-being episodes using a structured diary as a distinct therapeutic ingredient. The clinical science of euthymia may unravel innovative approaches to assessment and treatment of psychiatric and medical disorders, according to a unitary conceptual framework.

Charlson Comorbidity Index: A Critical Review of Clinimetric Properties.

The present critical review was conducted to evaluate the clinimetric properties of the Charlson Comorbidity Index (CCI), an assessment tool designed specifically to predict long-term mortality, with regard to its reliability, concurrent validity, sensitivity, incremental and predictive validity. The original version of the CCI has been adapted for use with different sources of data, ICD-9 and ICD-10 codes. The inter-rater reliability of the CCI was found to be excellent, with extremely high agreement between self-report and medical charts. The CCI has also been shown either to have concurrent validity with a number of other prognostic scales or to result in concordant predictions. Importantly, the clinimetric sensitivity of the CCI has been demonstrated in a variety of medical conditions, with stepwise increases in the CCI associated with stepwise increases in mortality. The CCI is also characterized by the clinimetric property of incremental validity, whereby adding the CCI to other measures increases the overall predictive accuracy. It has been shown to predict long-term mortality in different clinical populations, including medical, surgical, intensive care unit (ICU), trauma, and cancer patients. It may also predict in-hospital mortality, although in some instances, such as ICU or trauma patients, the CCI did not perform as well as other instruments designed specifically for that purpose. The CCI thus appears to be clinically useful not only to provide a valid assessment of the patient's unique clinical situation, but also to demarcate major diagnostic and prognostic differences among subgroups of patients sharing the same medical diagnosis.

Prodromal Symptoms in Depression: A Systematic Review.

INTRODUCTION: Appraisal of prodromal symptoms of unipolar depression may complement the traditional cross-sectional approach and provide a longitudinal perspective, according to a staging model of the illness. OBJECTIVE: To provide an updated systematic review of clinical studies concerned with prodromal symptoms of unipolar depression, according to PRISMA guidelines. METHODS: Keyword searches were conducted in PubMed, Scopus, and Web of Science. Longitudinal studies on prodromal symptoms and signs in adult patients primarily diagnosed with unipolar depression were selected. Findings were examined separately according to study design (i.e., retrospective or prospective). RESULTS: Twenty-five studies met the criteria for inclusion in this systematic review. Findings indicate that a distinct prodromal symptomatology - commonly characterized by anxiety, tension, irritability, and somatic complaints - exists before the onset of unipolar depression. The duration of the prodromal phase was highly variable across studies, ranging from less than a month to several years. Prodromal symptoms profile and duration were consistent within individuals across depressive episodes. There was a close relationship between prodromal and residual symptoms of the same depressive episode. CONCLUSIONS: The present systematic review addresses an important, and yet relatively neglected, clinical issue that deserves further investigation and may be of immediate practical value. The findings provide challenging insights into the pathogenesis and course of unipolar depression, which may result in more timely and effective treatment of recurrences. The definition of a prodromal phase in depression would benefit from the joint use of symptom identification, biomarkers, and neuroimaging.

Allostatic Load and Its Impact on Health: A Systematic Review.

INTRODUCTION: Allostatic load refers to the cumulative burden of chronic stress and life events. It involves the interaction of different physiological systems at varying degrees of activity. When environmental challenges exceed the individual ability to cope, then allostatic overload ensues. Allostatic load is identified by the use of biomarkers and clinical criteria. OBJECTIVE: To summarize the current knowledge on allostatic load and overload and its clinical implications based on a systematic review of the literature. METHODS: PubMed, PsycINFO, Web of Science, and the Cochrane Library were searched from inception to December 2019. A manual search of the literature was also performed, and reference lists of the retrieved articles were examined.We considered only studies in which allostatic load or overload were adequately described and assessed in either clinical or non-clinical adult populations. RESULTS: A total of 267 original investigations were included. They encompassed general population studies, as well as clinical studies on consequences of allostatic load/overload on both physical and mental health across a variety of settings. CONCLUSIONS: The findings indicate that allostatic load and overload are associated with poorer health outcomes. Assessment of allostatic load provides support to the understanding of psychosocial determinants of health and lifestyle medicine. An integrated approach that includes both biological markers and clinimetric criteria is recommended.

Clinimetric Criteria for Patient-Reported Outcome Measures.

Patient-reported outcome measures (PROMs) are self-rated scales and indices developed to improve the detection of the patients' subjective experience. Given that a considerable number of PROMs are available, it is important to evaluate their validity and usefulness in a specific research or clinical setting. Published guidelines, based on psychometric criteria, do not fit in with the complexity of clinical challenges, because of their quest for homogeneity of components and inadequate attention to sensitivity. Psychometric theory has stifled the field and led to the routine use of scales widely accepted yet with a history of poor performance. Clinimetrics, the science of clinical measurements, may provide a more suitable conceptual and methodological framework. The aims of this paper are to outline the major limitations of the psychometric model and to provide criteria for clinimetric patient-reported outcome measures (CLIPROMs). The characteristics related to reliability, sensitivity, validity, and clinical utility of instruments are critically reviewed, with particular reference to the differences between clinimetric and psychometric approaches. Of note is the fact that PROMs, rating scales, and indices developed according to psychometric criteria may display relevant clinimetric properties. The present paper underpins the importance of the clini-metric methodology in choosing the appropriate PROMs. CLIPROM criteria may also guide the development of new indices and the validation of existing PROMs to be employed in clinical settings.

Mental pain and pain-proneness in patients with migraine: results from the PAINMIG cohort-study.

BACKGROUND: Pain has been qualified under four categories: nociception, perception of pain, suffering, and pain behaviors. Most of the literature on migraine has devoted attention to the first two. The aim of the present cohort study was to investigate patients with migraine enrolled at a tertiary care unit to study suffering and mental pain and identify potential risk factors for migraine. METHODS: An observational cross-sectional study was carried out on patients with chronic migraine (CM) and episodic migraine (EM), and healthy subjects (HS). The three groups were matched for age and sex. A comprehensive assessment of migraine disability, pain, psychiatric disorders, psychosomatic syndromes, depressive and anxious symptoms, euthymia, psychosocial variables, mental pain, and pain-proneness (PP) was performed. RESULTS: Three hundred subjects were enrolled (100 CM, 100 EM, and 100 HS). Based on the multiple regression analyses, those presenting PP (social impairment: odds ratio [OR] = 3.59, 95% confidence interval [CI] = 1.14-11.29; depressive symptoms: OR = 3.82, 95% CI = 1.74-8.41) were more likely to be CM than HS. Those with higher levels of PP (social impairment: OR = 4.04, 95% CI = 1.60-10.22; depressive symptoms: OR = 2.02, 95% CI = 1.26-3.24) were more likely to be EM than HS. Those presenting higher levels of mental pain were more likely to be CM than EM (OR = 1.45, 95% CI = 1.02-2.07). CONCLUSION: Migraine is an unpleasant sensory and emotional experience associated with psychosocial manifestations that might contribute to the level of suffering of the individuals. Mental pain resulted to be the variable that most differentiated patients with CM from EM.

When the Label Does Not Match the Content of a Trial: "Well-Being Therapy" in Posttraumatic Stress Disorder: Commentary on Radstaak et al. (2020).

Radstaak, Hüning, and Bohlmeijer (2020) reported on a randomized controlled trial (RCT) of well-being therapy (WBT) compared to treatment as usual (TAU) in the treatment of residual posttraumatic stress disorder (PTSD) symptoms. No significant differences emerged between treatment conditions. However, our view is that what the authors labeled as WBT did not match the manualized psychotherapeutic strategy, and what was defined as TAU was actually an active control group. Further methodological limitations hinder the interpretation of results and make it difficult to draw conclusions from the study. Radstaak et al. (2020) deserve credit for addressing the vexing and neglected problem of residual symptoms in PTSD. However, the role of WBT in PTSD treatment still needs to be explored via an effectively designed RCT. Given that WBT does not require exposure to a patient's index traumatic event as a means of alleviating PTSD symptoms, WBT may represent a promising alternative to current treatments of PTSD.

The Hamilton Rating Scales for Depression: A Critical Review of Clinimetric Properties of Different Versions.

The format of the original Hamilton Rating Scale for Depression (HAM-D) was unstructured: only general instructions were provided for rating individual items. Over the years, a number of modified versions of the HAM-D have been proposed. They differ not only in the number of items, but also in modalities of administration. Structured versions, including item definitions, anchor points and semi-structured or structured interview questions, were developed. This comprehensive review was conducted to examine the clinimetric properties of the different versions of the HAM-D. The aim was to identify the HAM-D versions that best display the clinimetric properties of reliability, validity, and sensitivity to change. The search was conducted on MEDLINE, Scopus, Web of Science, and PubMed, and yielded a total of 35,473 citations, but only the most representative studies were included. The structured versions of the HAM-D were found to display the highest inter-rater and test-retest reliability. The Clinical Interview for Depression and the 6-item HAM-D showed the highest sensitivity in differentiating active treatment from placebo. The findings indicate that the HAM-D is a valid and sensitive clinimetric index, which should not be discarded in view of obsolete and not clinically relevant psychometric criteria. The HAM-D, however, requires an informed use: unstructured forms should be avoided and the type of HAM-D version that is selected should be specified in the registration of the study protocol and in the methods of the trial.

Sequential Combination of Cognitive-Behavioral Treatment and Well-Being Therapy in Depressed Patients with Acute Coronary Syndromes: A Randomized Controlled Trial (TREATED-ACS Study).

INTRODUCTION: Randomized controlled trials (RCT) of psychotherapeutic interventions have addressed depression and demoralization associated with acute coronary syndromes (ACS). The present trial introduces psychological well-being, an increasingly recognized factor in cardiovascular health, as a therapeutic target. OBJECTIVE: This study was designed to determine whether the sequential combination of cognitive-behavioral therapy (CBT) and well-being therapy (WBT) may yield more favorable outcomes than an active control group (clinical management; CM) and to identify subgroups of patients at greater risk for cardiac negative outcomes. METHODS: This multicenter RCT comparedCBT/WBT sequential combination versus CM, with up to 30 months of follow-up. One hundred consecutive depressed and/or demoralized patients (out of 740 initially screened by cardiologists after a first episode of ACS) were randomized to CBT/WBT associated with lifestyle suggestions (n = 50) and CM (n = 50). The main outcome measures included: severity of depressive symptoms according to the Clinical Interview for Depression, changes in subclinical psychological distress, well-being, and biomarkers, and medical complications and events. RESULTS: CBT/WBT sequential combination was associated with a significant improvement in depressive symptoms compared to CM. In both groups, the benefits persisted at follow-up, even though the differences faded. Treatment was also related to a significant amelioration of biomarkers (platelet count, HDL, and D-dimer), whereas the 2 groups showed similar frequencies of adverse cardiac events. CONCLUSIONS: Addressing psychological well-being in the psychotherapeutic approach to ACS patients with depressive symptoms was found to entail important clinical benefits. It is argued that lifestyle changes geared toward cardiovascular health may be facilitated by a personalized approach that targets well-being.

A Trial Integrating Different Methods to Assess Psychosocial Problems in Primary Care.

BACKGROUND: A number of studies have documented psychosocial problems, psychiatric morbidity and impaired quality of life in primary care patients. OBJECTIVE: The aim of this trial was to test the usefulness of the joint use of different diagnostic interviews and self-rated questionnaires. METHODS: Two hundred consecutive patients in a primary care practice in Italy underwent the Structured Clinical Interview for DSM-5 and the Semi-Structured Interview for the Diagnostic Criteria for Psychosomatic Research (DCPR) in its recently revised form. As self-rated evaluations, the PsychoSocial Index, the Short-Form Health Survey and the Illness Attitude Scales were administered. RESULTS: There were 46 patients (23%) with at least 1 DSM-5 diagnosis. Eighty-eight patients (44%) had at least 1 DCPR diagnosis, mainly maladaptive illness behavior (26.5%), allostatic overload (15.5%) and demoralization (15%). There were 47 (23.5%) patients who had a DCPR diagnosis only; 5 subjects (2.5%) had a DSM diagnosis only. Patients with DCPR syndromes displayed significantly higher self-rated levels of stress, psychological distress and maladaptive illness behavior and significantly lower levels of quality of life and well-being than patients with no diagnoses. CONCLUSIONS: In a busy clinical setting, a simple self-rated questionnaire such as the PsychoSocial Index may afford a useful tool to unveil patient current distress. The DCPR can provide clinical information for a substantial number of patients who do not satisfy DSM-5 classification criteria and yet present with psychosocial problems, as measured by self-rated scales. The DCPR may improve the assessment and treatment plan of primary care psychologists or consulting psychiatrists.

Mental Pain as a Transdiagnostic Patient-Reported Outcome Measure.

Patient-reported outcomes (PROs) refer to any report coming directly from patients about how they function or feel in relation to a health condition or its therapy. PROs have been applied in medicine for the assessment of the impact of clinical phenomena. Self-report scales and procedures for assessing physical pain in adults have been developed and used in clinical trials. However, insufficient attention has been dedicated to the assessment of mental pain. The aim of this paper is to outline the implications that assessment of mental pain may entail in psychiatry and medicine, with particular reference to a clinimetric index. A simple 10-item self-rating questionnaire, the Mental Pain Questionnaire (MPQ), encompasses the specific clinical features of mental pain and shows good clinimetric properties (i.e., sensitivity, discriminant and incremental validity). The preliminary data suggest that the MPQ may qualify as a PRO measure to be included in clinical trials. Assessment of mental pain may have important clinical implications in intervention research, both in psychopharmacology and psychotherapy. The transdiagnostic features of mental pain are supported by its association with a number of psychiatric disorders, such as depression, anxiety, eating disorders, as well as borderline personality disorder. Further, addressing mental pain may be an important pathway to prevent and diminish the opioid epidemic. The data summarized here indicate that mental pain can be incorporated into current psychiatric assessment and included as a PRO measure in treatment outcome studies.

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.