A 6 Week Randomized Double-Blind Placebo-Controlled Trial of Ziprasidone for the Acute Depressive Mixed State

OBJECTIVE: To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD). METHODS: 73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d) or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE), while also meeting 2 or 3 (but not more nor less) DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery-Åsberg Depression Rating Scale (MADRS) scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo. RESULTS: The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038). Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036). Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms. CONCLUSIONS: There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state. TRIAL REGISTRATION: Clinicaltrials.gov NCT00490542

Koukopoulos׳ diagnostic criteria for mixed depression: A validation study

Artículo de publicación ISIBackground Mixed depression (MxD) is one subtype of depressive experiences within the depressive spectrum. MxD definition is debated among experts. Koukopoulos׳ proposed diagnostic criteria focused primarily on psychic agitation, marked irritability, and intense mood lability as markers of a mixed depressive episode. The present study validates Koukopoulos׳ criteria as diagnostic for MxD. Methods A sample of 435 patients from the International Mood Network (IMN), multi-center, international network of sites, and the Centro LucioBini of Rome was analyzed. Koukopoulos׳ criteria were assessed in all patients. Results The most prevalent MxD criteria were “absence of psychomotor retardation” (84%), “mood lability or marked reactivity” (78%), and “psychic agitation or inner tension” (75%). Multivariable predictors of a MxD (+) diagnosis were: higher current CGI (OR=1.23, 95% CI 1.23, 2.84), lower rates of previous bipolar type I diagnosis (OR=0.54, 95% CI −3.28, −0.13), mixed symptoms on the index episode (OR=10.02, 95% CI 2.32, 24.12), rapid cycling course (OR=2.6 95% CI 1.45, 3.56), past substance abuse (OR=3.02, 95% CI 2.01, 5.67) and lower education status (OR=0.44, 95% CI −3.23, −0.98). This model showed a sensitivity of 76.4%, specificity of 86.3%, negative predictive value of 75%, and positive predictive value of 86%. Limitations An external validation of these criteria in an independent sample is warranted. Conclusion A broad definition of mixed depression was internally validated with multiple diagnostic validators and was sensitively and specifically predicted. Contrary to DSM-5, Koukopoulos׳ broad criteria include agitation, irritability and mood lability as core features

Koukopoulos' diagnostic criteria for mixed depression: A validation study

Background: Mixed depression (MxD) is one subtype of depressive experiences within the depressive spectrum. MxD definition is debated among experts. Koukopoulos proposed diagnostic criteria focused primarily on psychic agitation, marked irritability, and intense mood lability as markers of a mixed depressive episode. The present study vandal:es Koukopoulos' criteria as diagnostic for MxD. Methods: A sample of 435 patients from the International Mood Network (IMN), multi center. infernational network of sites, and the Centro LucioBini of Rome was analyzed. Koukopoulos' criteria were assessed in all patients. Results: The most prevalent MxD criteria were "absence of psychomotor retardation" (84%), "mood lability or marked reactivity" (78%), and "psychic agitation or inner tension" (75%). Multivariable predictors of a MxD (+) diagnosis were: higher current CGI (OR=1.23, 95% CI 123, 2.84), lower rates of previous bipolar type I diagnosis (OR=0.54, 95% Cl 3.28, -0.13), mixed symptoms on the index episode (OR=10.02, 95% Cl 2.32, 24.12), rapid cycling course (OR=2.6 95% Cl 1.45, 3.56), past substance abuse (OR=3.02, 95% Cl 2.01, 5.67) and lower education status (OR=0.44, 95% Cl - 3.23, 0.98). This model showed a sensitivity of 76.4%, specificity of 86.3%, negative predictive value of 75%, and positive predictive value of 86%. Limitations: An external validation of these criteria in an independent sample is warranted. Conclusion: A broad definition of mixed depression was internally validated with multiple diagnostic vandators and was sensitively and specifically predicted. Contrary to DSM-5, Koukopoulos' broad criteria include agitation, irritability and mood lability as core features. (C) 2014 Elsevier B.V. All rights reserve

Antidepressants worsen rapid-cycling course in bipolar depression: A STEP-BD randomized clinical trial.

Artículo de publicación ISIBackground: The use of antidepressants in rapid-cycling bipolar disorder has been controversial. We report the first randomized clinical trial with modern antidepressants on this topic. Methods: As part of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we analyzed, as an a priori secondary outcome, rapid cycling as a predictor of response in 68 patients randomized to continue vs. discontinue antidepressant treatment, after initial response for an acute major depressive episode. Outcomes assessed were percent time well and total number of episodes. All patients received standard mood stabilizers. Results: In those continued on antidepressants (AD), rapid cycling (RC) subjects experienced 268% (3.14/1.17) more total mood episodes/year, and 293% (1.29/0.44) more depressive episodes/year, compared with non-rapid cycling (NRC) subjects (mean difference in depressive episodes per year RC vs. NRC was 0.85 +/- 0.37 (SE), df=28, p=0.03). In the AD continuation group, RC patients also had 28.8% less time in remission than NRC patients (95% confidence intervals (9.9%, 46.5%), p=0.004). No such differences between RC and NRC subjects were seen in the AD discontinuation group (Table 1). Analyses within the rapid-cycling subgroup alone were consistent with the above comparisons between RC and NRC subjects, stratified by maintenance antidepressant treatment, though limited by sample size. Conclusions: In an a priori analysis, despite preselection for good antidepressant response and concurrent mood stabilizer treatment, antidepressant continuation in rapid-cycling was associated with worsened maintenance outcomes, especially for depressive morbidity, vs. antidepressant discontinuation.NIMH, United State

Detecting mood disorder in resource-limited primary care settings: Comparison of a self-administered screening tool to general practitioner assessment

Objectives: Although efficacious treatments for mood disorders are available in primary care, under-diagnosis is associated with under-treatment and poorer outcomes. This study compares the accuracy of self-administered screening tests with routine general practitioner (GP) assessment for detection of current mood disorder. Methods: 197 consecutive patients attending primary care centres in Santiago, Chile enrolled in this cross-sectional study, filling out the Patients Health Questionnaire-9 (PHQ-9) for depression and the Mood Disorder Questionnaire (MDQ) for bipolar disorder, after routine GP assessment. Diagnostic accuracy of these self-administered tools was compared with GP assessment, with gold standard diagnosis established by a structured diagnostic interview with trained clinicians (SCID-I). Results: The sample was 75% female, with a mean age of 48.5 (SD 16.8); 37% had a current mood disorder (positive SCID-I result for depression or bipolar disorder). Sensitivity of the scre

Ziprasidone vs Placebo: 6 week change in MADRS (SD) from baseline.

<p>Ziprasidone vs Placebo: 6 week change in MADRS (SD) from baseline.</p