Jenny Guidi

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.

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.

The Clinical Inadequacy of Evidence-Based Medicine and the Need for a Conceptual Framework Based on Clinical Judgment

Each therapeutic act may be seen as a result of multiple ingredients that may be specific or nonspecific [6] . Expectations, preferences, motivation, and patient-doctor interactions are examples of variables that may affect treatment outcome [6, 7] . The changed spectrum of medical disorders (shifted toward aging and chronicity) and the interindividual differences in health priorities make the focus on single diseases potentially misleading, whereas there is growing awareness that the aim of the treatment should refer to personal goals (from attainment of cure to prevention of recurrence, from removal of functional impairment to alleviation of symptoms) [8] . EBM does not do justice to the importance of these interactions and provides an oversimplified and reductionistic view of treatment. Finally, the presence of investigators with substantial financial conflicts of interest in panels concerned with clinical guidelines and the excessive reliance of metaanalyses on industry-funded studies constitute two major sources of bias in literature interpretation [1, 9] . Horwitz et al. [10] developed a method of clinical inquiry within RCT that can enhance the applicability of results to clinical decision making. Reanalyzing the BetaBlocker Heart Attack Trial, they found that propranolol reduced the risk of dying for the ‘average’ patient who survived an acute myocardial infarction, whereas it was harmful in a subgroup characterized by specific cotherapy histories. If we accept the possibility that a treatment The gap between clinical guidelines developed by evidence-based medicine (EBM) and the real world of clinicians and patients has been widely recognized. There is currently little evidence that EBM has actually improved patient care [1] . It is thus not surprising that most of the time clinicians rely more on their own experience and that of their colleagues (tacit knowledge or ‘mindlines’) than on explicit evidence from research [2] . Feinstein and Horwitz [3] were among the first to warn about excessive reliance on randomized controlled trials (RCT) and meta-analyses that were not intended to answer questions about the treatment of individual patients. The results of these types of trials may show comparative efficacy of treatments for the average randomized patient but not for those whose characteristics, such as severity of symptoms, comorbidity and other clinical features, depart from standard presentations [3] . In addition, meta-analyses often include highly heterogeneous studies and ascribe conflicting results to random variability, whereas different outcomes may reflect different patient populations, enrollment and protocol characteristics [4] . Even though personalized medicine, described as genomicsbased knowledge, has promised to approach each patient as the biological individual he/she is, the practical applications still have a long way to go and neglect of social and behavioral features may actually lead to ‘depersonalized’ medicine [5] . Other limitations have emerged over time. Received: July 11, 2014 Accepted after revision: July 21, 2014 Published online: December 24, 2014

Type A behaviour: a reappraisal of its characteristics in cardiovascular disease

Aims:u2002 The role of type A behaviour in cardiovascular disease is controversial and most of the research is based on self‐rating scales. The aim of this study was to assess the prevalence of type A behaviour in cardiology and in other medical settings using reliable interview methods that reflect its original description.

A cluster analysis-derived classification of psychological distress and illness behavior in the medically ill.

BACKGROUNDnThe classification of psychological distress and illness behavior in the setting of medical disease is still controversial. Current psychiatric nosology does not seem to cover the spectrum of disturbances. The aim of this investigation was to assess whether the joint use of DSM-IV categories and the Diagnostic Criteria for Psychosomatic Research (DCPR), that provide identification of syndromes related to somatization, abnormal illness behavior, irritable mood, type A behavior, demoralization and alexithymia, could yield subtyping of psychosocial variables in the medically ill.nnnMETHODnA cross-sectional assessment using both DSM-IV and the DCPR was conducted in eight medical centers in the Italian Health System. Data were submitted to cluster analysis. Participants were consecutive medical out-patients and in-patients for whom a psychiatric consultation was requested. A total of 1700 subjects met eligibility criteria and 1560 agreed to participate.nnnRESULTSnThree clusters were identified: non-specific psychological distress, irritability and affective disturbances with somatization.nnnCONCLUSIONSnTwo-step cluster analysis revealed clusters that were found to occur across clinical settings. The findings indicate the need of expanding clinical assessment in the medically ill to include the various manifestations of somatization, illness behavior and subclinical distress encompassed by the DCPR.

Alexithymia in the medically ill. Analysis of 1190 patients in gastroenterology, cardiology, oncology and dermatology

OBJECTIVEnTo use the Diagnostic Criteria for Psychosomatic Research (DCPR) for characterizing alexithymia in a large and heterogeneous medical population, in conjunction with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and other DCPR criteria.nnnMETHODnOf 1305 patients recruited from 4 medical centers in the Italian Health System, 1190 agreed to participate. They all underwent an assessment with DSM-IV and DCPR structured interviews. A total of 188 patients (15.8%) were defined as alexithymic by using the DCPR criteria. Data were submitted to cluster analysis.nnnRESULTSnFive clusters of patients with alexithymia were identified: (1) alexithymia with no psychiatric comorbidity (29.3% of cases); (2) depressed somatization with alexithymic features (23.4%); (3) alexithymic illness behavior (17.6%); (4) alexithymic somatization (17%) and (5) alexithymic anxiety (12.8%).nnnCONCLUSIONSnThe results indicate that DCPR alexithymia is associated with a comorbid mood or anxiety disorder in about one third of cases; it is related to various forms of somatization and abnormal illness behavior in another third and may occur without psychiatric comorbidity in another subgroup. Identification of alexithymic features may entail major prognostic and therapeutic differences among medical patients who otherwise seem to be deceptively similar since they share the same psychiatric and/or medical diagnosis.

Prevalence of hyperandrogenic states in late adolescent and young women: epidemiological survey on italian high-school students.

CONTEXTnMost of the estimates of the prevalence of hyperandrogenic states refer to the general adult population.nnnOBJECTIVEnThe objective of the study was to estimate the prevalence of hyperandrogenic states in late adolescence and youth and to evaluate potential independent predictors.nnnDESIGNnThis was a cross-sectional study.nnnSETTINGnThe study was conducted in high schools.nnnPATIENTSnPatients included female students, aged 16-19 years.nnnMAIN OUTCOME MEASURESnThe study protocol was designed with 3 possible levels of participation: the first level consisted of a self-compiled questionnaire; the second level added a medical examination; and the third level added a blood sample for laboratory testing. Liquid chromatography-tandem mass spectrometry was used to measure total testosterone, and a reference interval was established in-house.nnnRESULTSnWe offered participation to 2052 students, and 1469 of those compiled the questionnaire. Of these, 1038 were examined, and 519 also provided blood samples. Two hundred three of the 1038 examined students and 125 of the 519 students who provided blood samples were subsequently excluded because of treatment with oral contraceptives or because of endocrine disorders. In the sample of women with a questionnaire + a medical examination, 13% were affected by isolated menstrual irregularity, 16.1% by isolated clinical hyperandrogenism, and 3.8% by both states. A similar prevalence of isolated menstrual irregularity (10.2%) and isolated clinical hyperandrogenism (16.7%) was found in the subsample of women with laboratory tests; in addition, 6.6% showed isolated hyperandrogenemia, and 4.3% proved to be affected by polycystic ovary syndrome.nnnCONCLUSIONSnThis study provides for the first time a reliable assessment of the prevalence of hyperandrogenic states in late adolescent and young females and confirms that hyperandrogenic disorders originate at a young age.

Assessing psychological factors affecting medical conditions: comparison between different proposals.

OBJECTIVEnWe compared the provisional Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for Somatic Symptom Disorders (SSD) and an alternative classification based on the Diagnostic Criteria for Psychosomatic Research (DCPR) as to prevalence and associations with dimensional measures of psychological distress and functioning in a population of medical patients.nnnMETHODnSeventy consecutive outpatients with congestive heart failure were administered an ad hoc structured clinical interview for the identification of DSM-5 SSD, the section concerning hypochondriasis of the Structured Clinical Interview for DSM-IV, the Structured Interview for DCPR and Paykels Clinical Interview for Depression. Subjects also completed the Symptom Questionnaire and the Psychosocial Index. Global assessment of functioning was performed with the DSM-IV Axis V.nnnRESULTSnA diagnosis within DSM-5 SSD was found in 13 patients (18.5%): 61.5% of them were diagnosed with the Psychological Factors Affecting Medical Condition category. Twenty-nine patients (41.4%) were classified according to the DCPR-based proposal: illness denial, demoralization and irritable mood were the most frequent specifiers. The DCPR-based classification showed a greater number of significant associations with dimensional measures of psychological distress, global functioning and stress.nnnCONCLUSIONnCompared to DSM-5 SSD, the DCPR-based proposal was more sensitive in detecting psychological factors relevant to illness course and provided a better characterization of such factors. The DCPR-based proposal was also superior in identifying patients with increased psychological distress and poor psychosocial functioning.

The Missing Link between Clinical States and Biomarkers in Mental Disorders

Current diagnostic definitions of psychiatric disorders based on collections of symptoms encompass very heterogeneous populations and are thus likely to yield spurious results when exploring biological correlates of mental disturbances. It has been suggested that large studies of biomarkers across diagnostic entities may yield improved clinical information. Such a view is based on the concept of assessment as a collection of symptoms devoid of any clinical judgment and interpretation. Yet, important advances have been made in recent years in clinimetrics, the science of clinical judgment. The current clinical taxonomy in psychiatry, which emphasizes reliability at the cost of clinical validity, does not include effects of comorbid conditions, timing of phenomena, rate of progression of an illness, responses to previous treatments, and other clinical distinctions that demarcate major prognostic and therapeutic differences among patients who otherwise seem to be deceptively similar since they share the same psychiatric diagnosis. Clinimetrics may provide the missing link between clinical states and biomarkers in psychiatry, building pathophysiological bridges from clinical manifestations to their neurobiological counterparts.

Clinical configuration of cyclothymic disturbances

OBJECTIVEnWhile there is an increasing recognition of the role of subthreshold symptomatology in bipolar disorder, little attention has been dedicated to its only formally acknowledged subtype, cyclothymic disorder. The aim of this investigation was to provide a controlled evaluation of DSM-IV cyclothymic disorder by using a broad assessment strategy geared to subclinical signs.nnnMETHODSnSixty-two patients who met the DSM-IV criteria for cyclothymic disorder and did not present comorbidity with other mood disorders, alcohol and drug abuse, and borderline personality disorder and 62 control subjects matched for sociodemographic variables were administered the Structured Interview for Diagnostic Criteria for Psychosomatic Research (DCPR), the Clinical Interview for Depression (CID) and the Mania Scale (MAS).nnnRESULTSnIn DSM-IV terms, there was an overlap with anxiety disorders in more than half of the cases. About 3 patients out of 4 were found to present with at least one DCPR syndrome (particularly demoralization and irritable mood). Cyclothymic patients displayed significantly higher levels of depressive and anxiety disturbances on the CID, with particular reference to reactivity to social environment. They also had significantly higher scores on the MAS.nnnLIMITATIONSnThe study was cross-sectional and the sample, because of the exclusion criteria, may not be representative of the clinical populations in psychiatric settings.nnnCONCLUSIONnIn our patients with cyclothymia, without comorbidity with major mood disorders, DSM-IV anxiety disorders, psychosomatic clinical syndromes (irritable mood, demoralization) and subclinical symptoms such as reactivity to social environment resulted to be more frequent than in controls. The use of a broad assessment strategy aimed at subclinical symptomatology may help identifying clinical phenomena that cut across the current definition of subthreshold forms of bipolar disorder.