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Individual attitudes and behavior related to health and disease are major components of clinical encounters. These factors shape lifestyle, presentation of symptoms, access to patient care, interactions between patients and physicians, adherence to medical advice, and response to treatment. Health attitudes and behavior may range from anxiety and worry about illness to various forms of denial, such as delay of seeking care and lack of adherence to treatment. When attitudes result in health-damaging behavior, they may be particularly difficult to understand and become a source of frustration to both physicians and patients. Devising appropriate responses by health care providers may contribute to improving final outcomes and decrease health care costs. In particular, health behavior is likely to play a major role in the process of convalescence, in self-management of chronic conditions, in determining a state of recovery, and whenever a rehabilitation process is involved. Understanding the spectrum of health attitudes and behavior is also crucial for motivating people to make beneficial changes (lifestyle medicine), as well as for implementing safety procedures in the community.

There is growing awareness of the role of allostatic load (the cost of chronic exposure to fluctuating or heightened physiologic responses resulting from repeated or chronic stress) in the balance between health and disease. When environmental challenges exceed the individual ability to cope, allostatic overload ensues. The determination of allostatic load initially relied on measurements of biomarkers, and then it was expanded to clinimetric criteria for allostatic overload. It provides a characterization of the individual psychosocial environment that is missing from current clinical diagnostic formulations and has major implications for identifying syndromes that are not included in traditional diagnostic classifications. Healthy lifestyle behavior and euthymia may modulate the vulnerabilities induced by allostatic overload. Here, we present a staging system for the longitudinal development of allostatic load. Consideration of allostatic load allows clinicians to create individually tailored interventions to prevent or decrease the negative impact of environmental factors on health.

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.

BackgroundThe 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.MethodsA 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.ResultsA 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).ConclusionsThe 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.

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.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.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.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.

The evidence supporting the use of well-being therapy(WBT), a specific psychotherapeutic strategy for modulating psychological well-being, and its specific contribution when it is combined with other psychotherapeutic techniques is still limited. However, the insights gained by the use of WBT may unravel innovative approaches to assessment and treatment of mood and anxiety disorders. An important characteristic of WBT is self-observation of psychological well-being associated with specific homework. Another important feature of WBT is the assumption that imbalances in well-being and distress may vary from one illness to another, and from patient to patient. A final characteristic is its reference to the concept of euthymia, where lack of mood disturbances is associated with positive affect and psychological well-being (flexibility, consistency, and resilience). Progress can be achieved by modifying our clinical approach to mental disorders, and by promoting self-observation of psychological well-being and the pursuit of a state of euthymia.

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 clini­metric 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.

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.

Staging has been increasingly used in unipolar depression since its introduction in the nineties. Several models are available, but their differential features and implications are not completely clear. We systematically reviewed: (a) staging models of longitudinal development of unipolar depression; (b) staging models of treatment-resistant unipolar depression; (c) their applications. MEDLINE, PsycINFO, EMBASE, and Web of Science were examined according to PRISMA guidelines from inception to December 2021. Search terms were: ‘stage/staging’, combined using the Boolean ‘AND’ operator with ‘psychiatric disorder/mental disorder/depressive/mood disorder’. A total of 169 studies were identified for inclusion: 18 described staging models or applications, 151 described treatment-resistant staging models or applications. Staging models of longitudinal development were found to play a key role in formulating sequential treatment, with particular reference to the use of psychotherapy after pharmacotherapy. Staging methods based on treatment resistance played a crucial role in setting entry criteria for randomized clinical trials and neurobiological investigations. Staging is part of clinimetrics, the science of clinical measurements, and its role can be enhanced by its association with other clinimetric strategies, such as repeated assessments, organization of problematic areas, and evaluation of phenomena that may affect responsiveness. In research, it may allow to identify more homogeneous populations in terms of treatment history that may diminish the likelihood of spurious results in comparisons. In clinical practice, the use of staging in a clinimetric perspective allows clinicians to make full use of the information that is available for an individual patient at a specific time.

Reducing the risk of relapses is a critical component of major depressive disorders treatment. Guidelines suggest maintenance with antidepressant drugs in recurrent depression, but this solution has recently been questioned.The aim of this article is to provide a critical review of the literature of the main treatment options currently available to prevent relapse and recurrence in depression.We compared long-term antidepressant therapy (i.e., indefinite maintenance of antidepressant), intermittent antidepressant therapy (i.e., use of antidepressants mainly limited to the acute phases), use of psychotherapy in the sequential model (i.e., pharmacotherapy in the acute phase and psychotherapy in the residual phase).We argue that the same solution may not apply to all patients and question the feasibility of a single course of treatment in the setting of complex disorders that are encountered in practice. The clinician should weigh advantages and disadvantages in the individual case.The sequential model appears to be particularly indicated in recurrent depression. KEY POINTS Relapse is a major challenge of depressive disorders treatment Treatment options currently available include long-term antidepressants, intermittent antidepressants, addition of psychotherapy to pharmacotherapy in the sequential model Maintenance with antidepressants in recurrent depression has recently been questioned The sequential model appears to be particularly indicated in recurrent depression.

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.

Introduction Most people who seek treatment for depression experience relapse or recurrence, thus prevention represents a very important way to reduce suffering and burdens associated with this illness. Areas covered Preventive psychological interventions after depression remission include maintenance psychotherapy after an initial course of psychological treatment and the sequential model, i.e. the use of psychotherapy after pharmacotherapy or the application of drug treatment after a course of psychotherapy. Maintenance psychotherapy is aimed to prolong the effects obtained in the previous treatment course. The sequential model appeared to be more effective than monotherapy or the simultaneous combination of two different interventions. Expert opinion The patient should be informed about the prognosis of depressive illness and treatment options. One option would be to continue with an antidepressant drug indefinitely; however, loss of clinical effect may occur. The other option would be to start working on the prevention of the next episode. Thus, a sequential approach might be proposed. It includes antidepressants in the acute phase and a short-term course of cognitive-behavioral therapy in the residual phase. This approach has been specifically applied for its preventive effects. Completing the psychotherapy course with sessions of Well-Being Therapy would be optimal to enhance psychological well-being and euthymia.

Wahrend viele Psychosomatiker und Psychiater den positiven Eigenschaften, die Patienten ihrem klinischen Eindruck zufolge zeigen, Aufmerksamkeit widmen, betonen die heute ublichen Begutachtungs- und Behandlungsverfahren vor allem die psychischen Dysfunktionen. Euthymie ist ein transdiagnostisches Konstrukt, das sich auf das Vorliegen positiver Affekte und psychischen Wohlbefindens bezieht, d. h. auf Ausgeglichenheit und Integration psychischer Krafte (Flexibilitat), eine ganzheitliche Sicht des Lebens, an der sich die auf die Zukunft gerichteten Handlungen und Gefuhle orientieren (Bestandigkeit / Konsistenz), und eine Widerstandsfahigkeit gegenuber Stress (Resilienz und Angst- oder Frustrationstoleranz). Immer mehr Anhaltspunkte sprechen dafur, dass die Beurteilung der Euthymie und ihrer Komponenten bedeutsame Implikationen besitzt. Spezifische Instrumente (klinische Interviews und Fragebogen) konnen in eine klinimetrische Begutachtungsstrategie incl. Makroanalyse und Staging einbezogen werden. Das Streben nach Euthymie ist keine therapeutische Intervention fur spezifische psychische Storungen, sondern eine transdiagnostische Strategie, die in einen individualisierten Behandlungsplan integriert werden kann. Eine Reihe psychotherapeutischer Techniken, die auf die Unterstutzung der positiven Affekte und des psychischen Wohlbefindens zielen (z. B. die Well-Being Therapy oder die achtsamkeitsbasierte kognitive Therapie und die Akzeptanz- und Commitmenttherapie) wurden in randomisierten und kontrollierten klinischen Studien entwickelt und evaluiert. Die Ergebnisse zeigen, dass Wohlbefinden und Resilienz durch spezifische Interventionen gefordert werden konnen, die zu einer positiven Selbsteinschatzung fuhren sowie zu einem Gefuhl des Wachstums und der Weiterentwicklung, der Uberzeugung, dass das Leben sinnvoll und bedeutungshaltig ist, zur Zufriedenheit mit den eigenen zwischenmenschlichen Beziehungen, zu der Fahigkeit, das Leben erfolgreich zu bewaltigen, und zu einem Gefuhl der Selbstbestimmtheit.

Psychiatrists often consider the positive characteristics displayed by a patient in their clinical judgment, yet current assessment and treatment strategies are shifted on the side of psychological dysfunction. Euthymia is a transdiagnostic construct referring to the presence of positive affects and psychological well‐being, i.e., balance and integration of psychic forces (flexibility), a unifying outlook on life which guides actions and feelings for shaping future accordingly (consistency), and resistance to stress (resilience and tolerance to anxiety or frustration). There is increasing evidence that the evaluation of euthymia and its components has major clinical implications. Specific instruments (clinical interviews and questionnaires) may be included in a clinimetric assessment strategy encompassing macro‐analysis and staging. The pursuit of euthymia cannot be conceived as a therapeutic intervention for specific mental disorders, but as a transdiagnostic strategy to be incorporated in an individualized therapeutic plan. A number of psychotherapeutic techniques aiming to enhance positive affects and psychological well‐being (such as well‐being therapy, mindfulness‐based cognitive therapy, and acceptance and commitment therapy) have been developed and validated in randomized controlled clinical trials. The findings indicate that flourishing and resilience can be promoted by specific interventions leading to a positive evaluation of one's self, a sense of continuing growth and development, the belief that life is purposeful and meaningful, satisfaction with one's relations with others, the capacity to manage effectively one's life, and a sense of self‐determination.

Introduction: Patient-reported outcomes (PROs) are of increasing importance in clinical medicine. However, their evaluation by classic psychometric methods carries considerable limitations. The clinimetric approach provides a viable framework for their assessment. Objective: The aim of this paper was to provide a systematic review of clinimetric properties of the Symptom Questionnaire (SQ), a simple, self-rated instrument for the assessment of psychological symptoms (depression, anxiety, hostility, and somatization) and well-being (contentment, relaxation, friendliness, and physical well-being). Methods: The PRISMA guidelines were used. Electronic databases were searched from inception up to March 2019. Only original research articles, published in English, reporting data about the clinimetric properties of the SQ, were included. Results: A total of 284 studies was selected. The SQ has been used in populations of adults, adolescents, and older individuals. The scale significantly discriminated between subgroups of subjects in both clinical and nonclinical settings, and differentiated medical and psychiatric patients from healthy controls. In longitudinal studies and in controlled pharmacological and psychotherapy trials, it was highly sensitive to symptoms and well-being changes and discriminated between the effects of psychotropic drugs and placebo. Conclusions: The SQ is a highly sensitive clinimetric index. It may yield clinical information that similar scales would fail to provide and has a unique position among the PROs that are available. Its use in clinical trials is strongly recommended.

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.

Behavioural lifestyle interventions focused on diet and physical activity are a cornerstone for the treatment of obesity. However, their effects vary substantially across individuals in terms of magnitude and durability. Personalized approaches that target psychological well-being may be promising to facilitate healthy behaviours and sustained weight loss. This preliminary study aimed to explore whether the sequential combination of behavioural lifestyle intervention (BLI) and well-being therapy (WBT) may result in more favourable outcomes than BLI alone in promoting weight loss (primary outcome) and improving psychological well-being, distress, dietary behaviours and physical activity (secondary outcomes). A total of 83 patients with obesity were randomly assigned to BLI/WBT (N = 38) or BLI group (N = 45). The BLI group received a 12-week behavioural weight loss programme, whereas the BLI/WBT group received the same programme followed by an additional 4-week WBT, adapted for group interventions. Data were collected at pretreatment (baseline, T1), at the end of BLI/WBT (T2), at 6-month (T3) and 12-month (T4) follow-ups. There was a significant weight loss in both treatment groups at T2, T3 and T4. The BLI/WBT group showed greater improvements in depressive symptoms at T3 and T4, in autonomy at T2, in personal growth at T4 and in global well-being at T4 compared with BLI group. WBT yielded no additional effect on weight loss. However, the secondary outcomes indicate that WBT may have enduring effects that reduce vulnerability to psychological distress in patients with obesity. In order to confirm these preliminary findings and explore whether a more intensive and individualized WBT can foster sustained weight loss, future studies are needed.

Many individuals with posttraumatic stress disorder (PTSD) continue to have substantial residual symptoms after completing psychological treatment. Well‐being therapy (WBT) has been developed to treat the residual phase of mental disorders, prevent relapse, and promote a full recovery. The present study aimed to compare treatment as usual (TAU) with the long‐term effects of WBT as a rehabilitation therapy in adults who successfully completed psychological treatment for PTSD. Participants who did not meet PTSD diagnostic criteria after completing treatment were randomized to WBT (n = 29) or TAU (n = 35) groups. Assessments of well‐being, residual PTSD symptoms, and posttraumatic growth were conducted at baseline (T0) and again after 3 months (T1), 6 months (T2), and 1 year (T3). The results of the multilevel analysis revealed that WBT was not more effective than TAU in increasing levels of well‐being, γ = 0.02 (SE = 0.11) or posttraumatic growth, γ = 0.10 (SE = 0.13) nor in decreasing PTSD symptoms, γ = −0.04 (SE = 0.05). However, for participants with low levels of well‐being at baseline (Mental Health Continuum‐Short Form score < 2.6), WBT was more effective than TAU in increasing ratings of well‐being, γ = −0.41 (SE = 0.19) and posttraumatic growth, γ = −0.55 (SE = 0.24); this effect was most evident at T3 for posttraumatic growth, d = 1.23. Future research should assess clinically relevant individual characteristics that to optimize the effectiveness and utility of WBT.

The chapter describes how the problem of withdrawal syndromes during tapering and/or after discontinuation of antidepressant medications emerged in the literature and clinical practice. Withdrawal reactions were promptly renamed as discontinuation syndromes, unlike with other psychotropic drugs, to avoid any inference to issues of dependence. Both physicians and patients were taught that the problem manifests itself only with abrupt discontinuation of antidepressant medications and that, if symptoms arise, they have to be considered signs of relapse, with prompt re-administration of the antidepressant. The chapter outlines how the author’s findings of the persistence of withdrawal symptoms were in sharp contrast to key opinion of the time.

The first psychotherapeutic module is based on Kellner’s explanatory therapy—a psychotherapeutic approach for improving illness behavior (an important factor in modulating the individual response to the emergence and persistence of new withdrawal symptoms) and treating hypochondriacal fears and beliefs. It consists of providing accurate information, clarification, teaching of the principles of selective perception (i.e., attention to one part of the body makes the patient more aware of sensations in that part of the body than in other parts), reassurance, and repetition. The protocol was devised to increase endurance to withdrawal symptoms during tapering and after discontinuation of antidepressants.

The treatment strategy for discontinuing antidepressant medications is presented in this chapter. The various pharmacological options are reviewed as to their advantages and disadvantages, with particular reference to staging and methods of discontinuation. Rapid and slow taperings are compared; and potential interactions with other medications are reviewed. There is a lack of appropriate randomized controlled studies comparing different methods. Treatment choices are based entirely on clinical judgment and decision sharing with the patient. In this chapter, the author outlines the dilemmas and potential solutions that the clinician encounters, referring to both the literature that is available on various aspects of antidepressant medications and his own clinical and conceptual appraisal of the problem.

Continued drug treatment with antidepressant medications may stimulate processes that run counter to the initial acute effects of a drug. The oppositional model of tolerance may explain loss of treatment efficacy during maintenance treatment and the fact that some side effects tend to occur only after a certain time. These processes may also direct the illness into a treatment-unresponsive course, including manifestations of bipolar disorder or paradoxical reactions. When drug treatment ends, oppositional processes no longer encounter resistance, resulting in the potential onset of new withdrawal symptoms, persistent postwithdrawal disorders, hypomania, resistance to treatment if it is reinstituted, and refractoriness.

Tapering and discontinuation of antidepressant medications are associated with a variety of clinical manifestations that, in many cases, reach the threshold of a withdrawal syndrome. Selective serotonin reuptake inhibitors (SSRI) and serotonin-noradrenaline reuptake inhibitors (SNRI) are the antidepressants that appear to be mostly associated with these manifestations. The clinical manifestations of withdrawal following discontinuation of antidepressant medications, and the findings of a number of systematic reviews on such manifestations, are discussed in this chapter. The definition of clinical phenomena following such discontinuation, the diagnostic criteria for withdrawal syndromes and persistent postwithdrawal disorders, and the qualitative experience of withdrawal are all described.

The problems and difficulties that patients encounter in discontinuing antidepressant medications, and the increasing awareness of their long-term complications, alert us to the need of preventing the occurrence of dependence, with its ensuing problems of withdrawal symptomatology. Prevention of the dependence and withdrawal caused by antidepressants basically depends on their rational use. Antidepressant medications are life-saving drugs, but clinicians need to target their application only to the most severe and persistent cases of depression, limiting their use to the shortest possible time, and reducing their utilization in anxiety disorders, unless a major depressive disorder is present or other treatments have been ineffective. The importance of a psychotherapeutic approach for addressing symptoms with enduring effects is emphasized in this chapter.

Guided antidepressant discontinuation requires a revision of the current model of the outpatient clinic in a direction that maximizes the expertise of the specialist as well as of other clinicians in the healthcare team. The basic unit would consist of a psychiatrist (with an adequate background both in psychopharmacology and psychotherapy), an internist, and four clinical psychotherapists, who may provide evidence-based treatment after the initial evaluation of the psychiatrist. Its functioning emphasizes repeated assessments, sequential combination of treatments, and close coordination of team members. An alternative setting could be that of a clinical pharmacopsychology service specifically tailored to the problems produced by psychotropic drug discontinuation.

The third psychotherapeutic module introduces Well-Being Therapy (WBT)—a short-term psychotherapeutic strategy that emphasizes self-observation of psychological well-being, with the use of a structured diary, cognitive restructuring of interfering thoughts and/or behaviors through cognitive-behavioral techniques, and homework assignments (such as pursuing optimal experiences). WBT may have an important role in counteracting psychological vulnerabilities that may ensue with discontinuation of antidepressant medications. Through the use of WBT, flourishing and resilience can be promoted, leading to a positive evaluation of one’s self, a sense of continuous growth and development, the belief that life is purposeful and meaningful, quality relations with others, the capacity to manage effectively one’s life, and a sense of self-determination.

Discontinuation of antidepressant medications is a complex medical decision that should consider the detailed clinical history of the patient and is essentially based on clinical judgment. It should take into account a number of specific clinical situations, such as the presence of side effects from treatment, insufficient response to the antidepressant drug, and manifestations of behavioral toxicity. The physician’s clinical judgment, and particularly the notion that each therapeutic act has advantages and disadvantages, is the ideal ground for sharing decisions with the patient, who has then the opportunity of expressing opinions and preferences.

The notion of psychiatric disease is not in line with the changed spectrum of health and the complex interplay of biological and psychosocial factors. Pharmaceutical reductionism leads to overtreatment or mistreatment, and does not offer solutions to the complexity of clinical situations, such as the problems related to discontinuation of antidepressant medications. A different psychiatric approach is outlined. Psychiatrists have the potential to move from their traditionally assigned position as marginal components of the medical profession to leaders in multidisciplinary medicine, favoring the role of clinical judgment. It is possible to practice highly effective precision psychiatry now.

Withdrawal syndromes and persistent postwithdrawal disorders may be associated with loss of antidepressant efficacy, paradoxical effects, switching to bipolar course, resistance, and refractoriness. All these manifestations appear to be interrelated and may be subsumed under the rubric of behavioral toxicity. Each of these clinical events is discussed in the chapter, preceded by a case illustration from the author’s Affective Disorders Program. The concept of iatrogenic comorbidity refers to the unfavorable modifications in the course, characteristics, and responsiveness to treatment of an illness that may be related to previously administered therapies. Such vulnerabilities may manifest themselves during treatment administration and/or after its discontinuation.

Depressive and anxiety disorders are frequently associated. Depression may be a complication of anxiety and anxiety can complicate depression. The nature of their relationship has been a source of controversy. Reviews generally base their conclusions on randomized controlled trials and meta-analyses that refer to the average patient and often clash with the variety of clinical presentations that may occur when anxiety and depression coexist. The aim of this review was to examine the literature according to profiling of subgroups of patients based on clinimetric criteria, in line with the recently developed concept of medicine-based evidence. We critically reviewed the literature pertaining to the specific presentations of anxiety and depression, outlining the advantages and disadvantages of each treatment approach. The following prototypic cases were presented: depression secondary to an active anxiety disorder, depression in patients with anxiety disorders under treatment, anxious depression, anxiety as a residual component of depression, and demoralization secondary to anxiety disorder. We argue that the selection of treatment when anxiety and depression coexist should take into account the modalities of presentation and be filtered by clinical judgment. Very different indications may ensue when the literature is examined according to this perspective.

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.

La Well-Being Therapy (WBT) e una strategia psicoterapeutica breve che incoraggia l’autosservazione del benessere psicologico per mezzo di un diario strutturato, di tecniche cognitivo-comportamentali per la ristrutturazione cognitiva di pensieri e/o comportamenti che interferiscono con il raggiungimento del benessere, e l’assegnazione di compiti a casa (ovvero, perseguendo esperienze ottimali). La WBT si fonda su un modello multidimensionale di benessere psicologico, che e stato originariamente sviluppato da Marie Jahoda, e il cui obiettivo e quello di raggiungere uno stato di eutimia. Un’importante caratteristica della terapia e l’autosservazione del benessere psicologico associata alla messa in atto di specifici compiti. Tale prospettiva e diversa da quella di interventi psicologici che vengono classificati come "positivi" ma che in realta si focalizzano sulla sofferenza. La WBT e stata validata in diversi studi randomizzati e controllati riguardanti la prevenzione delle ricadute nella depressione e il miglioramento dei livelli di guarigione nei disturbi affettivi. Un aspetto importante della WBT e l’assunzione che gli squilibri nei livelli di benessere e sofferenza possano variare da paziente a paziente e necessitino di strategie di valutazione specifiche. L’obiettivo di questo articolo e quello di fornire una rassegna aggiornata della WBT e di illustrare come le intuizioni cliniche ottenute con l’utilizzo della WBT possano svelare modalita di approccio innovative nell’ambito delle condizioni mediche. Viene inoltre presentato un caso clinico che esemplifica l’applicazione e il ruolo potenziale della WBT nel produrre cambiamenti nello stile di vita nella sindrome metabolica. Si sostiene che i cambiamenti nello stile di vita possono essere ottenuti solo attraverso un approccio personalizzato rivolto al benessere psicologico.