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      Behavioral Toxicity Revisited : Iatrogenic Comorbidity in Psychiatric Evaluation and Treatment

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          Abstract

          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.

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          Most cited references27

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          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.
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            Staging of mental disorders: systematic review.

            The staging method, whereby a disorder is characterized according to its seriousness, extension, development and features, is attracting increasing attention in clinical psychology and psychiatry. The aim of this systematic review was to critically summarize the tools that are available for reproducing and standardizing the clinical intuitions that are involved in a staging formulation. A comprehensive research was conducted on the MEDLINE, PsycINFO, EMBASE and Cochrane databases from inception to May 2012. The following search terms were used: 'stage/staging' AND 'psychiatric disorder/mental disorder/schizophrenia/mood disorder/anxiety disorder/substance use disorder/eating disorder'. A total of 78 studies were identified for inclusion in the review. We discussed studies addressing or related to the issue of staging in a number of mental disorders (schizophrenia, unipolar depression, bipolar disorder, panic disorder, substance use disorders, anorexia and bulimia nervosa). The literature indicates that disorders have a longitudinal development or a treatment history that can be categorized according to stages. We proposed staging formulations for the above-mentioned psychiatric disorders. Staging models offer innovative assessment tools for clinical psychologists and psychiatrists. Characterizing each stage of an illness demarcates major prognostic and therapeutic differences among patients who otherwise seem to be deceptively similar since they share the same psychiatric diagnosis. A stage 0 to denote an at-risk condition does not appear to be warranted at the current state of research. Copyright © 2012 S. Karger AG, Basel.
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              Mania associated with antidepressant treatment: comprehensive meta-analytic review.

              To review available data pertaining to risk of mania-hypomania among bipolar (BPD) and major depressive disorder (MDD) patients with vs. without exposure to antidepressant drugs (ADs) and consider effects of mood stabilizers. Computerized searching yielded 73 reports (109 trials, 114 521 adult patients); 35 were suitable for random effects meta-analysis, and multivariate-regression modeling included all available trials to test for effects of trial design, AD type, and mood-stabilizer use. The overall risk of mania with/without ADs averaged 12.5%/7.5%. The AD-associated mania was more frequent in BPD than MDD patients, but increased more in MDD cases. Tricyclic antidepressants were riskier than serotonin-reuptake inhibitors (SRIs); data for other types of ADs were inconclusive. Mood stabilizers had minor effects probably confounded by their preferential use in mania-prone patients. Use of ADs in adults with BPD or MDD was highly prevalent and moderately increased the risk of mania overall, with little protection by mood stabilizers.
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                Author and article information

                Journal
                Journal of Clinical Psychopharmacology
                Journal of Clinical Psychopharmacology
                Ovid Technologies (Wolters Kluwer Health)
                0271-0749
                2016
                December 2016
                : 36
                : 6
                : 550-553
                Article
                10.1097/JCP.0000000000000570
                27631576
                e4e0f6d8-3b2c-4a9e-a7b7-56e4d1fdf44d
                © 2016
                History

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