Rihmer Z, Akiskal H. Do antidepressants t(h)reat(en) depressives? Toward a clinically judicious formulation of the antidepressant-suicidality FDA advisory in light of declining national suicide statistics from many countries. J Affect Disord 94: 3-13

Department of Psychiatry, University of California, San Diego, San Diego, California, United States
Journal of Affective Disorders (Impact Factor: 3.38). 09/2006; 94(1-3):3-13. DOI: 10.1016/j.jad.2006.04.003
Source: PubMed


Given that suicidality is a well-known symptom and outcome of untreated or inadequately treated depressive illness, the United States (US) Food and Drug Administration (FDA) warning of emergent suicidality in children and adolescents based on the antidepressant arm of placebo-controlled randomized trials (RCTs) has created understandable concern in clinical practice. The issues involved are of broader public health importance for all age groups. As in other branches of medicine, psychiatrists must always be vigilant of the rare risk of iatrogenesis when prescribing potent agents like antidepressants for patients with depressive disorders where the risk of suicidality is inherent. The overall evidence we review suggests that the widespread use of antidepressants in the new "SSRI-era" appear to have actually led to highly significant decline in suicide rates in most countries with traditionally high baseline suicide rates. The decline is particularly striking for women who, compared with men, seek more help for depression. Recent clinical data on large samples in the US too have revealed a protective effect of antidepressant against suicide. We argue that the discrepancy between RCTs (in children) and national and clinical suicide statistics (in adults) may reside in new provocative data documenting high rates of unrecognized pseudo-unipolar mixed states particularly in juvenile, but also in adult, clinical populations. Such an interpretation accords well with equally provocative data that bipolar II (which is often "mixed" in nature) may well represent a particularly vulnerable clinical substrate for suicidality. In this respect, the widespread (at least in the psychiatric sector) augmentation of antidepressants with benzodiazepines, atypical antipsychotics or mood stabilizers may represent one situation where current practice is superior to evidence-based medicine. We conclude that rather than being a threat, the judicious clinical use of antidepressants actually does serve to effectively treat and indeed protect depressed patients from suicidal outcome. The fact of being in treatment with regular clinical follow-up appears beneficial as well.

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    • "The highest annual suicide rates are reported from Eastern Europe (13–42 suicides per 100,000 persons) followed by Western/Nordic European countries (8–21 suicides per 100,000 persons) and North America and Australia (11–13 suicides per 100,000 persons). Latin America, as well as ‘Latin Europe’ (Greece, Spain, Italy), and Central Asian countries report annual suicide rates less than 10 [1,9,10]. Reasons for these great differences between national/regional suicide rates have not been fully explained. "
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    ABSTRACT: Annual suicide rates of Hungary were unexpectedly high in the previous century. In our narrative review, we try to depict, with presentation of the raw data, the main descriptive epidemiological features of the Hungarian suicide scene of the past decades. Accordingly, we present the annual suicide rates of the period mentioned and also data on how they varied by gender, age, urban vs. rural living, seasons, marital status, etc. Furthermore, the overview of trends of other factors that may have influenced suicidal behavior (e.g., alcohol and tobacco consumption, antidepressant prescription, unemployment rate) in the past decades is appended as well. Based on raw data and also on results of the relevant papers of Hungarian suicidology we tried to explain the observable trends of the Hungarian suicide rate. Eventually, we discuss the results, the possibilities, and the future tasks of suicide prevention in Hungary.
    Full-text · Article · Jun 2013 · Annals of General Psychiatry
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    • "This state has also recently drawn attention as one of the strongest risk factors for suicidality (Balázs et al., 2006; Undurraga et al., 2012; Valtonen et al., 2008). In line with the phenomenological similarities between AS and DMX, Akiskal and Benazzi (2006) and Rihmer and Akiskal (2006) argued that AS could be understood as antidepressant-induced DMX. Faedda et al. (2004) retrospectively analyzed 57 patients with juvenile BP who had been given an antidepressant or psychostimulant and reported that 33 of the 57 (58%) patients so exposed developed mania with a median latency of 14 days. "
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    ABSTRACT: Activation syndrome (AS) is a cluster of symptoms listed by the US Food and Drug Administration as possible suicidality precursors during antidepressant treatment. We aimed to clarify whether AS is associated with bipolar II disorder (BP-II) and its related disorder, i.e., bipolar disorder not otherwise specified (BP-NOS), which are often mistreated as major depressive disorder (MDD), as well as bipolar suggestive features in outpatients with depression. The frequency of AS, bipolar suggestive features, and background variables in consecutive outpatients with a major depressive episode (MDE) due to BP-II/BP-NOS or MDD, who were naturalistically treated with antidepressants, were investigated and analyzed retrospectively. Of 157 evaluable patients (46 BP-II/BP-NOS, 111 MDD), 39 (24.8%) experienced AS. Patients with BP-II/BP-NOS experienced AS significantly more frequently than patients with MDD (52.2% of BP-II/BP-NOS vs. 13.5% of MDD, p<0.01). Univariate analysis revealed that BP-II/BP-NOS diagnosis, cyclothymic temperament, early age at onset of first MDE, psychiatric comorbidities, and depressive mixed state (DMX) were significantly associated with AS development in the entire sample. Multivariate analysis revealed that BP-II/BP-NOS diagnosis and DMX were independent risk factors for AS. This is a retrospective and naturalistic study; therefore, patient selection bias could have occurred. Cautious monitoring of AS is needed during antidepressant trials in patients with BP-II/BP-NOS. Clinicians should re-evaluate underlying bipolarity when they confront AS. Antidepressants should be avoided for treating a current DMX beyond the unipolar-bipolar dichotomy. Prospective studies are needed to confirm these results.
    Full-text · Article · Jun 2013 · Journal of Affective Disorders
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    • "The traditional categorical paradigm of the bipolar disorder spectrum (manic, depressive, and mixed states) has been recently completed by a dimensional paradigm with the description of a range of intermediate states (e.g., dysphoric mania and hypomania, mixed depression) which belong to a broad spectrum of mixed states [1,2]. One of the major issues in clinical practice is the accurate differential diagnosis between mixed states and depression, often leading to inappropriate prescriptions of antidepressants in mixed states, and as a consequence, increasing the risk of manic switch and suicide [3,4]. In order to better define the spectrum of mixed states, it may be useful to develop a dimensional approach. "
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    ABSTRACT: One of the major issues in clinical practice is the accurate differential diagnosis between mixed states and depression, often leading to inappropriate prescriptions of antidepressants in mixed states, and as a consequence, increasing the risk of manic switch and suicide. In order to better define the spectrum of mixed states, it may be useful to develop a dimensional approach. In this context, the MAThyS (Multidimensional Assessment of Thymic States) scale was built to assess activation/inhibition levels in all bipolar mood episodes, and to determine whether a clinical description in terms of activation/inhibition can help better define bipolar states with which both manic and depressive symptoms are associated. The aim of this paper is the validation of the MAThyS scale in 141 bipolar patients in acute states (manic, hypomanic, mixed, or depressive). The validation of the MAThyS scale was the primary outcome of this 24-week, phase III, open-label, olanzapine single-arm clinical trial. Principal component, factorial analysis, and Cronbach's coefficient calculation (internal consistency) were performed. Concurrent validity (correlations with 17-item Hamilton Depression Rating Scale [HAMD-17], Hamilton Anxiety Rating Scale [HAMA], and Young Mania Rating Scale [YMRS]) and responsiveness to the clinical intervention were assessed (change in MAThyS scale and effect size) at 6 and 24 weeks. Scree plot of eigenvalues identified a 2-dimension structure ("activation/inhibition level" and "emotional component"). Psychometric properties were good: Cronbach's coefficient was >0.9. Concurrent validity was good with low correlation (-0.19) with the HAMA scale and a higher correlation at baseline with the YMRS (0.72) and HAMD-17(-0.43). As expected, the activation state was predominant in manic, hypomanic, and mixed states while inhibition was predominant in depressive states. MAThyS score improvement was observed (effect size: -0.3 at 6 and 24 weeks). The MAThyS demonstrated good psychometric properties. The MAThyS scale may help clinicians to better discriminate and follow bipolar episodes, especially the broad spectrum of mixed episodes. registration identification number: NCT#002592722.
    Full-text · Article · Mar 2013 · BMC Psychiatry
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