1. Arch Suicide Res. 2016 Aug 16:1-15. [Epub ahead of print] Predictive Validity of the Columbia-Suicide Severity Rating Scale for Short-Term Suicidal Behavior: A Danish Study of Adolescents at a High Risk of Suicide. Conway PM, Erlangsen A, Teasdale TW, Jakobsen IS, Larsen KJ. Using the Columbia-Suicide Severity Rating Scale (C-SSRS), we examined the predictive and incremental predictive validity of past-month suicidal behavior and ideation for short-term suicidal behavior among adolescents at high risk of suicide. The study was conducted in 2014 on a sample of 85 adolescents (90.6% females) who participated at follow-up (85.9%) out of the 99 (49.7%) baseline respondents. All adolescents were recruited from a specialized suicide-prevention clinic in Denmark. Through multivariate logistic regression analyses, we examined whether baseline suicidal behavior predicted subsequent suicidal behavior (actual attempts and suicidal behavior of any type, including preparatory acts, aborted, interrupted and actual attempts; mean follow-up of 80.8 days, SD = 52.4). Furthermore, we examined whether suicidal ideation severity and intensity incrementally predicted suicidal behavior at follow-up over and above suicidal behavior at baseline. Actual suicide attempts at baseline strongly predicted suicide attempts at follow-up. Baseline suicidal ideation severity and intensity did not significantly predict future actual attempts over and above baseline attempts. The suicidal ideation intensity items deterrents and duration were significant predictors of subsequent actual attempts after adjustment for baseline suicide attempts and suicidal behavior of any type, respectively. Suicidal ideation severity and intensity, and the intensity items frequency, duration and deterrents, all significantly predicted any type of suicidal behavior at follow-up, also after adjusting for baseline suicidal behavior. The present study points to an incremental predictive validity of the C-SSRS suicidal ideation scales for short-term suicidal behavior of any type among high-risk adolescents. DOI: 10.1080/13811118.2016.1222318 PMID: 27602917 [PubMed - as supplied by publisher] 2. J Clin Psychiatry. 2016 Jul;77(7):e867-73. doi: 10.4088/JCP.15m10069. Psychometric Reevaluation of the Columbia-Suicide Severity Rating Scale: Findings From a Prospective, Inpatient Cohort of Severely Mentally Ill Adults. Madan A(1,)(2,)(3), Frueh BC(2,)(4), Allen JG(2,)(3), Ellis TE(2,)(3), Rufino KA(2,)(5), Oldham JM(2,)(3), Fowler JC(2,)(3). Author information: (1)12301 South Main St, Houston, TX 77035. amadan@menninger.edu. (2)The Menninger Clinic, Houston, Texas, USA. (3)Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA. (4)Department of Psychology, University of Hawaii, Hilo. (5)Department of Psychology, University of Houston-Downtown, Houston, Texas, USA. OBJECTIVE: Accurate prediction of suicide remains elusive due to lack of predictive measures. Given the Columbia-Suicide Severity Rating Scale's (C-SSRS) emerging "gold-standard" status for risk assessment, studies are needed to assess its psychometric properties, particularly predictive validity. The current study adds to the limited literature by assessing the C-SSRS's internal consistency, factor structure, concurrent validity, and predictive validity. METHODS: In this longitudinal study of 1,055 adults with DSM-IV diagnoses consecutively admitted to a specialized psychiatric hospital between July 1, 2012, and June 30, 2014, patients completed standardized assessments, including the C-SSRS, at admission and 2, 12, and 24 weeks postdischarge. RESULTS: The C-SSRS evidenced excellent internal consistency (ordinal α = .95). Principal components analysis (PCA) revealed a 2-factor solution, accounting for 65.3% of the variance across items. The severity of ideation and behavioral items loaded onto the first factor, and the intensity of ideation items loaded onto the second factor. The total score, factors, and the most severe ideation single item were moderately correlated with other measures of suicidality (0.27 ≤ r ≤ 0.58; P < .0001). The summary score from the ideation/behavior factor was found to be modestly correlated with any suicide-related behavior within the 6 months following hospitalization. Receiver operator characteristics indicated that the C-SSRS performed adequately in correctly classifying any suicide-related behavior within 6 months of discharge from the hospital (AUC = 0.757, P < .001) with the total score and summary score from the ideation/behavior factor providing the best balance between sensitivity (0.694) and specificity (0.652-0.674). CONCLUSIONS: This study is the first to assess the factor structure of the C-SSRS in a large, high-risk sample. The measure has solid psychometric properties and merits use as a suicide risk assessment measure. © Copyright 2016 Physicians Postgraduate Press, Inc. DOI: 10.4088/JCP.15m10069 PMID: 27464320 [PubMed - in process] 3. Actas Esp Psiquiatr. 2016 Jul;44(4):125-35. Epub 2016 Jul 1. Antipsychotic response in delusional disorder and schizophrenia: a prospective cohort study. González-Rodríguez A(1), Catalán R(2), Penadés R(2), Ruiz V(3), Torra M(4), Bernardo M(2). Author information: (1)Barcelona Clinic Schizophrenia Unit (BCSU). Neuroscience Institute. Hospital Clínic of Barcelona. Department of Psychiatry and Clinical Psychobiology. University of Barcelona. Barcelona, Spain. (2)Barcelona Clinic Schizophrenia Unit (BCSU). Neuroscience Institute. Hospital Clínic of Barcelona. University of Barcelona. CIBERSAM, IDIBAPS. Barcelona, Spain. (3)Neuroscience Institute. Hospital Clinic of Barcelona. Barcelona, Spain. (4)Biochemistry and Molecular Genetics Department. Hospital Clinic of Barcelona. University of Barcelona. Barcelona, Spain. INTRODUCTION: Scientific evidence focused on the treatment response in delusional disorder (DD) patients is scarce, and the findings are controversial. Our goal was to compare the antipsychotic response at the 12-week followup between patients diagnosed with DD and patients diagnosed with schizophrenia and to identify potential response dimensions. METHODS: A prospective, observational, cohort study with 12-week follow-up was conducted with DD and schizophrenia patients matched for sex, age and cumulative years of disease. The following scales were assessed: Positive and Negative Syndrome Scale (PANSS; 5-factors), Personal and Social Performance Scale (PSP), Clinical Global Impression Scale (CGI), and Columbia-Suicide Severity Rating Scale (C-SSRS). Treatment response was defined as a ≥30% reduction in the total PANSS score. Linear and logistic regression models were used to investigate the potential predictive value of psychopathological variables for the antipsychotic response. RESULTS: Response percentages in DD and schizophrenia were 61.5% and 69.2%, respectively. The duration of untreated psychosis, antipsychotic dosage, and diagnosis did not predict antipsychotic response. In the whole sample, improvement in positive symptoms was significantly associated with the clinical global improvement (p=0.006), explaining almost 20% of the variance in the model. Within the DD group, improvement in cognitive symptoms explained 30% of the variance in clinical global improvement. CONCLUSIONS: Both response percentages and required antipsychotic doses were similar between DD and schizophrenia. Changes in positive symptoms were associated with clinical global improvement in the entire sample, and improvement in cognitive symptoms was correlated with global improvement exclusively in DD. PMID: 27388104 [PubMed - in process] 4. J Clin Psychiatry. 2016 Jun;77(6):e719-25. doi: 10.4088/JCP.15m10056. Rapid and Sustained Reductions in Current Suicidal Ideation Following Repeated Doses of Intravenous Ketamine: Secondary Analysis of an Open-Label Study. Ionescu DF(1,)(2,)(3), Swee MB(2), Pavone KJ(2,)(4), Taylor N(4,)(3), Akeju O(4,)(5), Baer L(2,)(3), Nyer M(2,)(3), Cassano P(2,)(3), Mischoulon D(2,)(3), Alpert JE(2,)(3), Brown EN(4,)(3), Nock MK(5,)(3), Fava M(2,)(3), Cusin C(2,)(3). Author information: (1)Massachusetts General Hospital, Depression Clinical and Research Program, 1 Bowdoin Sq, 6th Floor, Boston, MA 02114. dionescu@partners.org. (2)Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston. (3)Harvard Medical School, Boston, Massachusetts, USA. (4)Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston. (5)Department of Psychology, Harvard University, Cambridge, Massachusetts, USA. BACKGROUND: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. METHODS: Between April 2012 and October 2013, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited for the presence of current, stable (≥ 3 months) suicidal thoughts. They received open-label ketamine infusions over 3 weeks (0.5 mg/kg over 45 minutes for the first 3 infusions; 0.75 mg/kg over 45 minutes for the last 3). In this secondary analysis, the primary outcome measures of suicidal ideation (Columbia-Suicide Severity Rating Scale [C-SSRS] and the Suicide Item of the 28-item Hamilton Depression Rating Scale [HDRS₂₈-SI]) were assessed at 240 minutes postinfusion and for 3 months thereafter in a naturalistic follow-up. RESULTS: Over the course of the infusions (acute treatment phase), 7 of 14 patients (50%) showed remission of suicidal ideation on the C-SSRS Ideation scale (even among patients whose depression did not remit). There was a significant linear decrease in this score over time (P < .001), which approached significance even after controlling for severity of 6-item Hamilton Depression Rating Scale (HDRS₆) core depression items (P = .05). Similarly, there were significant decreases in the C-SSRS Intensity (P < .01) and HDRS₂₈-SI (P < .001) scores during the acute treatment phase. Two of the 7 patients who achieved remission during the acute treatment phase (29%) maintained their remission throughout a 3-month naturalistic follow-up. CONCLUSIONS: In this preliminary study, repeated doses of open-label ketamine rapidly and robustly decreased suicidal ideation in pharmacologically treated outpatients with treatment-resistant depression with stable suicidal thoughts; this decrease was maintained for at least 3 months following the final ketamine infusion in 2 patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01582945. © Copyright 2016 Physicians Postgraduate Press, Inc. DOI: 10.4088/JCP.15m10056 PMID: 27232360 [PubMed - in process] 5. Schizophr Res. 2016 Aug;175(1-3):161-7. doi: 10.1016/j.schres.2016.04.042. Epub 2016 May 18. Differential effects of childhood trauma and cannabis use disorders in patients suffering from schizophrenia. Baudin G(1), Godin O(2), Lajnef M(3), Aouizerate B(4), Berna F(5), Brunel L(6), Capdevielle D(7), Chereau I(8), Dorey JM(9), Dubertret C(10), Dubreucq J(11), Faget C(12), Fond G(6), Gabayet F(11), Laouamri H(13), Lancon C(12), Le Strat Y(10), Tronche AM(8), Misdrahi D(14), Rey R(9), Passerieux C(15), Schandrin A(7), Urbach M(15), Vidalhet P(16), Llorca PM(8), Schürhoff F(17); FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) Collaborators. Author information: (1)Fondation FondaMental, Créteil F94000, France; INSERM U955, Équipe de Psychiatrie Translationnelle, Créteil F94000, France; AP-HP, DHU Pe-PSY, Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor, Créteil F94000, France; Université François-Rabelais de Tours, PAV EA 2114, Tours F37000, France. (2)Fondation FondaMental, Créteil F94000, France; Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France. (3)INSERM U955, Équipe de Psychiatrie Translationnelle, Créteil F94000, France. (4)Fondation FondaMental, Créteil F94000, France; Centre Hospitalier Charles Perrens, F-33076, Bordeaux, France; Université de Bordeaux, France; Inserm, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000, Bordeaux, France. (5)Fondation FondaMental, Créteil F94000, France; Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France. (6)Fondation FondaMental, Créteil F94000, France; INSERM U955, Équipe de Psychiatrie Translationnelle, Créteil F94000, France; AP-HP, DHU Pe-PSY, Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor, Créteil F94000, France; Université Paris-Est Créteil F94000, France. (7)Fondation FondaMental, Créteil F94000, France; Service Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm 1061, Montpellier, France. (8)Fondation FondaMental, Créteil F94000, France; CMP B, CHU, EA 7280 Faculté de Médecine, Université d'Auvergne, BP 69, 63003 Clermont-Ferrand Cedex 1, France. (9)Fondation FondaMental, Créteil F94000, France; Université Claude Bernard Lyon 1, Centre Hospitalier Le Vinatier, Pole Est BP 300 39, 95 bd Pinel, 69678 Bron Cedex, France. (10)Fondation FondaMental, Créteil F94000, France; AP-HP, Department of Psychiatry, Louis Mourier Hospital, Colombes, Inserm U894, Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, France. (11)Fondation FondaMental, Créteil F94000, France; Centre Référent de Réhabilitation Psychosociale, CH Alpes Isère, Grenoble, France. (12)Fondation FondaMental, Créteil F94000, France; Assistance Publique des Hôpitaux de Marseille (AP-HM), Pôle Universitaire de Psychiatrie, Marseille, France. (13)Fondation FondaMental, Créteil F94000, France. (14)Fondation FondaMental, Créteil F94000, France; Université de Bordeaux, France; Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France; CNRS UMR 5287-INCIA, France. (15)Fondation FondaMental, Créteil F94000, France; Service de Psychiatrie d'Adulte, Centre Hospitalier de Versailles, UFR des Sciences de la Santé Simone Veil, Université Versailles Saint-Quentin en Yvelines, Versailles, France. (16)Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France. (17)Fondation FondaMental, Créteil F94000, France; INSERM U955, Équipe de Psychiatrie Translationnelle, Créteil F94000, France; AP-HP, DHU Pe-PSY, Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor, Créteil F94000, France; Université Paris-Est Créteil F94000, France. Electronic address: franck.schurhoff@inserm.fr. BACKGROUND: Childhood trauma (CT) and cannabis use are both environmental and modifier risk factors for schizophrenia. However, little is known about how they interact in schizophrenia. We examined the main effect of each of these two environmental factors on the clinical expression of the disease using a large set of variables, and we tested whether and how cannabis and CT interact to influence the course and the presentation of the illness. METHODS: A sample of 366 patients who met the DSM-IV-TR criteria for schizophrenia was recruited through the FACE-SCZ (Fondamental Advanced Centre of Expertise - Schizophrenia) network. Patients completed a large standardized clinical evaluation including Structured Clinical Interview for DSM Disorders-I (SCID-I), Positive and Negative Symptoms Scale (PANSS), Columbia-Suicide Severity Rating Scale (C-SSRS), Global Assessment of Functioning (GAF), Short-Quality of Life-18 (S-QoL-18), and Medication Adherence Rating Scale (MARS). We assessed CT with the Childhood Trauma Questionnaire and cannabis status with SCID-I. RESULTS: CT significantly predicted the number of hospitalizations, GAF, and S-QoL-18 scores, as well as the PANSS total, positive, excitement, and emotional distress scores. Cannabis use disorders significantly predicted age of onset, and MARS. There was no significant interaction between CT and cannabis use disorders. However, we found evidence of a correlation between these two risk factors. CONCLUSIONS: CT and cannabis both have differential deleterious effects on clinical and functional outcomes in patients with schizophrenia. Our results highlight the need to systematically assess the presence of these risk factors and adopt suitable therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved. DOI: 10.1016/j.schres.2016.04.042 PMID: 27209524 [PubMed - in process] 6. J Child Adolesc Psychopharmacol. 2016 May 16. [Epub ahead of print] Efficacy, Safety, and Tolerability of an Extended-Release Orally Disintegrating Methylphenidate Tablet in Children 6-12 Years of Age with Attention-Deficit/Hyperactivity Disorder in the Laboratory Classroom Setting. Childress AC(1), Kollins SH(2), Cutler AJ(3), Marraffino A(4), Sikes CR(5). Author information: (1)1 Center for Psychiatry and Behavioral Medicine , Las Vegas, Nevada. (2)2 Department of Psychiatry and Behavioral Science, Duke University , Durham, North Carolina. (3)3 Florida Clinical Research Center , Bradenton, Florida. (4)4 Florida Clinical Research Center , Orlando, Florida. (5)5 Neos Therapeutics, Inc. , Grand Prairie, Texas. OBJECTIVE: Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) represent a new technology for MPH delivery. ODTs disintegrate in the mouth without water and provide a pharmacokinetic profile that is consistent with once-daily dosing. This study sought to determine the efficacy, safety, and tolerability of this novel MPH XR-ODT formulation in school-age children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. METHODS: Children aged 6-12 years with ADHD (n = 87) were enrolled in this randomized, multicenter, double-blind, placebo-controlled, parallel, laboratory classroom study. The MPH XR-ODT dose was titrated to an optimized dose during a 4-week open-label period and maintained on that dose for 1 week. Participants (n = 85) were then randomized to receive their optimized dose of MPH XR-ODT or placebo once daily for 1 week (double blind), culminating in a laboratory classroom testing day. Efficacy was evaluated using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Attention, Deportment, and Combined scores along with Permanent Product Measure of Performance (PERMP; Attempted and Correct) assessments. Onset and duration of drug action were also evaluated as key secondary endpoints. Safety assessments included adverse events (AEs), physical examinations, electrocardiograms (ECGs), and the Columbia Suicide Severity Rating Scale (C-SSRS). RESULTS: The average SKAMP-Combined score on the classroom study day was significantly better for the MPH XR-ODT group (n = 43) than for the placebo group (n = 39; p < 0.0001). The effect was evident at 1 hour and lasted through 12 hours postdose. The average SKAMP-Attention, SKAMP-Deportment, PERMP-A, and PERMP-C scores were indicative of significantly greater ADHD symptom control for the MPH XR-ODT group. The most common AEs reported were decreased appetite, upper abdominal pain, headache, insomnia, upper respiratory tract infection, affect lability, irritability, cough, and vomiting. CONCLUSIONS: MPH XR-ODT was effective and well tolerated for the treatment of children with ADHD in a laboratory classroom setting. Clinical Trial Registry: NCT01835548 ( ClinicalTrials.gov ). DOI: 10.1089/cap.2016.0002 PMID: 27183299 [PubMed - as supplied by publisher] 7. Rev Psiquiatr Salud Ment. 2016 Jul-Sep;9(3):134-42. doi: 10.1016/j.rpsm.2016.02.002. Epub 2016 May 2. Validation of a Spanish version of the Columbia-Suicide Severity Rating Scale (C-SSRS). [Article in English, Spanish] Al-Halabí S(1), Sáiz PA(2), Burón P(1), Garrido M(3), Benabarre A(4), Jiménez E(5), Cervilla J(6), Navarrete MI(6), Díaz-Mesa EM(7), García-Álvarez L(7), Muñiz J(8), Posner K(9), Oquendo MA(9), García-Portilla MP(10), Bobes J(2). Author information: (1)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Oviedo, España; Instituto Universitario de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, España. (2)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Oviedo, España; Instituto Universitario de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, España; Departamento de Psiquiatría, Universidad de Oviedo, Oviedo, España. (3)Instituto Universitario de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, España. (4)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Oviedo, España; Unitat de Trastorn Bipolar, Hospital Clínic, Universitat de Barcelona, Institut d'Investigaciones Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España. (5)Unitat de Trastorn Bipolar, Hospital Clínic, Universitat de Barcelona, Institut d'Investigaciones Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España. (6)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Oviedo, España; Unidad de Salud Mental, Hospital Universitario San Cecilio, Departamento de Psiquiatría, Universidad de Granada, Granada, España. (7)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Oviedo, España; Departamento de Psiquiatría, Universidad de Oviedo, Oviedo, España. (8)Instituto Universitario de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, España; Departamento de Psicología, Universidad de Oviedo, Oviedo, España. (9)Departamento de Psiquiatría, New York State Psychiatric Institute, Columbia University, Nueva York, NY, Estados Unidos. (10)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Oviedo, España; Instituto Universitario de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, España; Departamento de Psiquiatría, Universidad de Oviedo, Oviedo, España. Electronic address: albert@uniovi.es. OBJECTIVE: To examine the psychometric properties of a Spanish version of the C-SSRS (Sp-CSSRS). METHOD: Data are from a naturalistic, cross-sectional, multicentre, validation study, including 467 psychiatric outpatients, 242 of whom had a history of suicide attempt. The study measures were: C-SSRS; the Hamilton Depression Rating Scale (HDRS); the Beck Suicide Intent Scale; the Medical Damage Scale. RESULTS: Construct validity: Pearson coefficient between the C-SSRS severity (C-Sev) and intensity (C-Int) of ideation subscale scores was 0.44 (P<.000) for the total sample. Likewise, Pearson coefficient between C-Sev score and HDRS item 3 was 0.56 (P<.000). For the sub-sample of patients with suicide attempt, significant Pearson correlations were found between the C-Sev and the Beck Suicide Intent Scale scores (r=0.22; P=.001). Discriminant validity: Significant differences were found in C-Sev and C-Int scores between patients with and without suicide attempt (P<.000). The C-Sev score discriminated between patients based on HDRS item 3 (P<.009). Sensitivity to change: Linear regression showed that a one-unit decrease in HDRS item 3 corresponded to a decrease of 5.08 units in the C-Sev score (P=.141). A one-unit change in HDRS item 3 corresponded to a change of 13.51 on the C-Int assessments (P=.007). Cronbach's alpha was 0.53 for C-Int. The principal component analysis identified 2 components that explain 55.66% of the total variance (C-Int). CONCLUSION: The data support that the Sp-C-SSRS is a reliable and valid instrument for assessing suicidal ideation and behaviour in daily clinical practice and research settings. Copyright © 2016 SEP y SEPB. Published by Elsevier España. All rights reserved. DOI: 10.1016/j.rpsm.2016.02.002 PMID: 27158026 [PubMed - in process] 8. BMC Psychiatry. 2016 May 4;16:122. doi: 10.1186/s12888-016-0820-y. Predictive models for suicidal thoughts and behaviors among Spanish University students: rationale and methods of the UNIVERSAL (University & mental health) project. Blasco MJ(1,)(2,)(3), Castellví P(1,)(3), Almenara J(4), Lagares C(4), Roca M(5), Sesé A(5), Piqueras JA(6), Soto-Sanz V(6), Rodríguez-Marín J(6), Echeburúa E(7), Gabilondo A(8), Cebrià AI(9), Miranda-Mendizábal A(1), Vilagut G(1,)(2,)(3), Bruffaerts R(10), Auerbach RP(11,)(12), Kessler RC(13), Alonso J(14,)(15,)(16,)(17); UNIVERSAL study group. Collaborators: Alonso J, Almenara J, Barbaglia G, Blasco MJ, Castellví P, Cebrià AI, Echeburúa E, Gabilondo A, Iruin Á, Lagares C, Miranda-Mendizábal A, Parès-Badell O, Pérez-Vázquez MT, Piqueras JA, Roca M, Rodríguez-Marín J, Sesé A, Soto-Sanz V, Vilagut G, Vives M. Author information: (1)Health Services Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. (2)Pompeu Fabra University (UPF), Barcelona, Spain. (3)CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. (4)University of Cadiz (UCA), Cádiz, Spain. (5)Institut Universitari d'Investigació en Ciències de la Salut (IUNICS-IDISPA), University of Balearic Islands (UIB), Palma de Mallorca, Spain. (6)Miguel Hernandez University of Elche (UMH), Alicante, Spain. (7)University of the Basque Country (UPV-EHU), San Sebastian, Spain. (8)Outpatient Mental Health Care Network, Osakidetza-Basque Health Service. Biodonosti Health Research Institute, San Sebastian, Spain. (9)Department of Mental Health, Corporació Sanitaria Parc Taulí, Sabadell, Spain. (10)Universitair Psychiatrisch Centrum, KULeuven (UPC-KUL), Leuven, Belgium. (11)Department of Psychiatry, Harvard Medical School, Boston, MA, USA. (12)Center for Depression, Anxiety and Stress Research, McLean Hospital, Boston, MA, USA. (13)Department of Health Care Policy, Harvard Medical School, Boston, MA, USA. (14)Health Services Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. jalonso@imim.es. (15)Pompeu Fabra University (UPF), Barcelona, Spain. jalonso@imim.es. (16)CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. jalonso@imim.es. (17)IMIM (Hospital del Mar Medical Research Institute), PRBB Building, Doctor Aiguader 88, 08003, Barcelona, Spain. jalonso@imim.es. BACKGROUND: Suicide is a leading cause of death among young people. While suicide prevention is considered a research and intervention priority, longitudinal data is needed to identify risk and protective factors associate with suicidal thoughts and behaviors. Here we describe the UNIVERSAL (University and Mental Health) project which aims are to: (1) test prevalence and 36-month incidence of suicidal thoughts and behaviors; and (2) identify relevant risk and protective factors associated with the incidence of suicidal thoughts and behaviors among university students in Spain. METHODS: An ongoing multicenter, observational, prospective cohort study of first year university students in 5 Spanish universities. Students will be assessed annually during a 36 month follow-up. The surveys will be administered through an online, secure web-based platform. A clinical reappraisal will be completed among a subsample of respondents. Suicidal thoughts and behaviors will be assess with the Self-Injurious Thoughts and Behaviors Interview (SITBI) and the Columbia-Suicide Severity Rating Scale (C-SSRS). Risk and protective factors will include: mental disorders, measured with the Composite International Diagnostic Interview version 3.0 (CIDI 3.0) and Screening Scales (CIDI-SC), and the Epi-Q Screening Survey (EPI-Q-SS), socio-demographic variables, self-perceived health status, health behaviors, well-being, substance use disorders, service use and treatment. The UNIVERSAL project is part of the International College Surveys initiative, which is a core project within the World Mental Health consortium. Lifetime and the 12-month prevalence will be calculated for suicide ideation, plans and attempts. Cumulative incidence of suicidal thoughts and behaviors, and mental disorders will be measured using the actuarial method. Risk and protective factors of suicidal thoughts and behaviors will be analyzed by Cox proportional hazard models. DISCUSSION: The study will provide valid, innovative and useful data for developing prevention programs for youth suicide and for improving early identification for high-risk students. The longitudinal design of this study will improve causal interpretation of analyzed associations, needed for generating and validating predictive models. It will represent the first results about suicidal thoughts and behaviors in the Spanish university population. The World Mental Health Survey collaboration will permit accurate cross-national comparisons. DOI: 10.1186/s12888-016-0820-y PMCID: PMC4855708 PMID: 27142432 [PubMed - in process] 9. J Clin Psychiatry. 2015 Dec;76(12):1675. doi: 10.4088/JCP.15f10520. Suicidal behavior: measurement and mechanisms. Oquendo MA(1). Author information: (1)moquendo@psychiatrist.com. This issue of Focus on Suicide brings us new data about risk assessment, with 2 articles examining the utility of rating scales for assessment of suicidal behavior. Youngstrom et al conduct a careful comparison of 3 suicide rating scales: the Columbia Suicide Severity Rating Scale (C-SSRS), the Suicide Tracking Scale (STS), and the Sheehan Suicidality Tracking Scale (S-STS). While the scales did comparably in 2 broad categories, suicidal ideation and suicide attempts, the study suggests that some subtypes of suicidal behavior/ideation are not captured as well by the S-STS. © Copyright 2015 Physicians Postgraduate Press, Inc. DOI: 10.4088/JCP.15f10520 PMID: 26717527 [PubMed - indexed for MEDLINE] 10. J Clin Psychiatry. 2015 Dec;76(12):1676-82. doi: 10.4088/JCP.14m09353. Direct comparison of the psychometric properties of multiple interview and patient-rated assessments of suicidal ideation and behavior in an adult psychiatric inpatient sample. Youngstrom EA(1), Hameed A, Mitchell MA, Van Meter AR, Freeman AJ, Algorta GP, White AM, Clayton PJ, Gelenberg AJ, Meyer RE. Author information: (1)Department of Psychology, University of North Carolina at Chapel Hill, CB #3270, Davie Hall, Chapel Hill, NC 27599-3270 eay@unc.edu. OBJECTIVE: Compare the accuracy, agreement, internal consistency, and interrater reliability of 3 interviews to assess suicidal ideation and behavior in accordance with US Food and Drug Administration guidance about reporting categories. METHOD: Adults admitted to a psychiatric inpatient unit (N = 199) completed 3 assessments of past month and lifetime suicidal ideation and behavior-the Columbia Suicide Severity Rating Scale (C-SSRS), the Suicide Tracking Scale (STS), and the Sheehan Suicidality Tracking Scale (S-STS)-in randomized, counterbalanced order. "Missing gold standard" latent class analyses defined categories for ideation and behavior. Analyses also evaluated the S-STS mapping to C-SSRS categories. Three trained judges re-rated 89 randomly selected interview videotapes. Cohen κ, the primary outcome measure, quantified agreement above chance. Data were collected between November 2011 and June 2013. RESULTS: All 3 assessments showed excellent accuracy for suicidal ideation (κ = 0.72 to 1.00) and attempts (κ = 0.82 to 0.95) calibrated against latent classes. Interrater agreement ranged from κ = 0.52 to 1.00. Interrater agreement about more granular C-SSRS categories varied more widely (κ = 0.48 to 1.00), and the C-SSRS and S-STS assigned significantly different numbers of cases to many categories. Cronbach α was < 0.55 for the C-SSRS ideation and between 0.78 and 0.92 for the other scales. CONCLUSIONS: All 3 assessments showed good accuracy for broad categories of suicidal ideation and behavior. More granular, specific categories usually were rated reliably, but the C-SSRS and S-STS differed significantly in regard to which patients were assigned to these subcategories. Using any of these interviews would improve reliability over unstructured assessment in evaluating suicidal ideation and behavior. Clinical predictive validity of these interviews, and particularly the more granular categories, remains to be shown. © Copyright 2015 Physicians Postgraduate Press, Inc. DOI: 10.4088/JCP.14m09353 PMID: 26613136 [PubMed - indexed for MEDLINE] 11. Oncol Nurs Forum. 2015 Sep;42(5):E319-29. doi: 10.1188/15.ONF.42-05AP. Assessing Suicidal Ideation and Behaviors Among Survivors of Childhood Brain Tumors and Their Mothers During Sociobehavioral Research. Lucas MS(1), Brawner BM(2), Hardie TL(3), Beacham B(4), Paidipati C(5), Diaz M(3), Lauer A(6), Hobbie WL(7), Deatrick JA(3). Author information: (1)Temple University in Philadelphia, PA. (2)University of Pennsylvania in Philadelphia. (3)University of Pennsylvania. (4)Indiana University in Indianapolis. (5)University of Pennsylvania and Children's Hospital of Philadelphia. (6)Children's Hospital of Philadelphia. (7)The Children's Hospital, Philadelphia, PA. PURPOSE/OBJECTIVES: To describe the development and feasibility of a protocol for nonpsychiatric subspecialty research staff members to screen research participants who endorse suicidal ideations or behaviors during data collection
. DESIGN: Descriptive protocol development.
. SETTING: The Children's Hospital of Philadelphia and the University of Pennsylvania.
. SAMPLE: 186 mother caregivers and 134 adolescent or young adult survivors of childhood brain tumors, with the protocol implemented for 5 caregivers and 11 survivors. METHODS: During telephone- and home-based interviews, the interviewer assessed the participant using the Columbia-Suicide Severity Rating Scale (C-SSRS). MAIN RESEARCH VARIABLES: Expressed suicidal ideation or behavior
. FINDINGS: Implementation of the C-SSRS by nonpsychiatric subspecialty staff members was feasible and valid. Interviewers' conclusions based on this instrument matched those of the mental health professional who followed up with participants. Process notes contained themes about the participants, including anger and sadness in survivors and the physical and emotional demands of the survivor in caregivers. Progress notes for the interviewer included a reiteration of events, whether the assessment was successful, and whether the recommendation of the interviewer was in agreement with that of the mental health professional
. CONCLUSIONS: The protocol based on the C-SSRS was useful and feasible for nonpsychiatric subspecialty staff members to use in the collection of data from survivors of childhood brain tumors and their caregivers. IMPLICATIONS FOR NURSING: Survivors of childhood brain tumors and their caregivers may experience psychosocial distress. Nurses, as research assistants or in other roles, can use tools such as the C-SSRS to assist in front-line assessments. 
. DOI: 10.1188/15.ONF.42-05AP PMCID: PMC4548293 PMID: 26302289 [PubMed - indexed for MEDLINE] 12. Psychosomatics. 2015 Sep-Oct;56(5):460-9. doi: 10.1016/j.psym.2015.04.005. Epub 2015 May 8. Comparison of Electronic Screening for Suicidal Risk With the Patient Health Questionnaire Item 9 and the Columbia Suicide Severity Rating Scale in an Outpatient Psychiatric Clinic. Viguera AC(1), Milano N(2), Laurel R(3), Thompson NR(4), Griffith SD(4), Baldessarini RJ(5), Katzan IL(6). Author information: (1)Department of Psychiatry, Cleveland Clinic, Cleveland, OH; Neurological Institute Center for Outcomes Research & Evaluation, Cleveland Clinic, Cleveland, OH. Electronic address: viguera@ccf.org. (2)Department of Neurology, Cleveland Clinic, Cleveland, OH. (3)Department of Psychiatry, Cleveland Clinic, Cleveland, OH. (4)Neurological Institute Center for Outcomes Research & Evaluation, Cleveland Clinic, Cleveland, OH; Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH. (5)Department of Psychiatry, Harvard Medical School, and International Consortium for Bipolar & Psychotic Disorders Research, McLean Hospital, Boston, MA. (6)Neurological Institute Center for Outcomes Research & Evaluation, Cleveland Clinic, Cleveland, OH; Department of Neurology, Cleveland Clinic, Cleveland, OH. BACKGROUND: Patient-reported data can improve clinical care, including identifying patients who are at risk for suicide. METHODS: In a tertiary care, psychiatric outpatient clinic, we compared computerized self-assessments of suicidal risk based on item 9 of the Patient Health Questionnaire-9 and an electronic version of the Columbia Suicide Severity Rating Scale (C-SSRS), using retrospective medical record review of clinical psychiatric assessments as the reference standard. We also surveyed patients׳ attitudes about participating in the process. We compared prevalence of suicidal risk rates by the 3 assessment methods as well as their sensitivity, specificity, and predictive value. RESULTS: Observed prevalence of positive suicidal risk screenings differed significantly, ranking (1) Patient Health Questionnaire-9 item 9, 24% (343/1416; 95% CI: 22%-26%) < (2) C-SSRS, 6.0% (85/1416; 95% CI: 5.0%-7.4%) < (3) clinical assessment, 1.4% (20/1416; 95% CI: 0.9%-2.2%). The sensitivity of Patient Health Questionnaire-9 item 9 was 92% (78/85; 95% CI: 86%-98%) and the specificity was 81% (1107/1376; 95% CI: 78%-82%). The sensitivity of the C-SSRS was 95.0% (19/20; 95% CI: 75%-100%) and the specificity was 95% (1330/1396; 95% CI: 94%-96%). Of 100 patients surveyed, the screening was well accepted, with some concerns about confidentiality and adequate clinical follow-up. CONCLUSIONS: As expected, Patient Health Questionnaire-9 item 9 generated much higher rates of apparently false-positive findings than the C-SSRS did, when compared with clinical assessment. C-SSRS backed with timely clinical assessment may be a useful and efficient method of screening for suicidal risk, provided that adequate, immediate clinical follow-up is available. Copyright © 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.psym.2015.04.005 PMID: 26278339 [PubMed - indexed for MEDLINE] 13. J Clin Psychiatry. 2015 May;76(5):583-91. doi: 10.4088/JCP.14m09337. A randomized, double-blind, placebo-controlled study of the efficacy and safety of 2 doses of vortioxetine in adults with major depressive disorder. Mahableshwarkar AR(1), Jacobsen PL, Serenko M, Chen Y, Trivedi MH. Author information: (1)CNS Medicine, Takeda Development Center Americas, Deerfield, Illinois. Comment in J Clin Psychiatry. 2015 May;76(5):e657-9. BACKGROUND: This 8-week, randomized, double-blind, placebo-controlled study, conducted August 2010-May 2012 in the United States, evaluated the safety and efficacy of vortioxetine 10 mg and 15 mg in patients with major depressive disorder (MDD). The mechanism of action of vortioxetine is thought to be related to direct modulation of serotonin (5-HT) receptor activity and inhibition of the serotonin transporter. METHOD: Adults aged 18-75 years with MDD (DSM-IV-TR) and Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 26 were randomized (1:1:1) to receive vortioxetine 10 mg or 15 mg or placebo once daily, with the primary efficacy end point being change from baseline at week 8 in MADRS analyzed by mixed model for repeated measures. Adverse events were recorded during the study, suicidal ideation and behavior were assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), and sexual dysfunction was assessed using the Arizona Sexual Experience (ASEX) scale. RESULTS: Of the 1,111 subjects screened, 469 subjects were randomized: 160 to placebo, 157 to vortioxetine 10 mg, and 152 to vortioxetine 15 mg. Differences from placebo in the primary efficacy end point were not statistically significant for vortioxetine 10 mg or vortioxetine 15 mg. Nausea, headache, dry mouth, constipation, diarrhea, vomiting, dizziness, and flatulence were reported in ≥ 5% of subjects receiving vortioxetine. Discontinuation due to adverse events occurred in 7 subjects (4.4%) in the placebo group, 8 (5.2%) in the vortioxetine 10 mg group, and 12 (7.9%) in the vortioxetine 15 mg group. ASEX total scores were similar across groups. There were no clinically significant trends within or between treatment groups on the C-SSRS, laboratory values, electrocardiogram, or vital sign parameters. CONCLUSIONS: In this study, vortioxetine did not differ significantly from placebo on MADRS total score after 8 weeks of treatment in MDD subjects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01179516. © Copyright 2015 Physicians Postgraduate Press, Inc. DOI: 10.4088/JCP.14m09337 PMID: 26035186 [PubMed - indexed for MEDLINE] 14. Schizophr Res. 2015 Jul;165(2-3):152-6. doi: 10.1016/j.schres.2015.04.022. Epub 2015 May 7. Assessing suicidal ideation in individuals at clinical high risk for psychosis. Gill KE(1), Quintero JM(2), Poe SL(2), Moreira AD(2), Brucato G(2), Corcoran CM(2), Girgis RR(2). Author information: (1)Department of Psychiatry at Columbia University Medical Center, New York, NY, United States; Department of Psychology at The Catholic University of America, Washington, DC, United States. Electronic address: kegill13@gmail.com. (2)Department of Psychiatry at Columbia University Medical Center, New York, NY, United States. BACKGROUND: The majority of individuals with schizophrenia and other psychotic illnesses have had suicidal ideation at some point during the illness. However, little is known about the variation in level and intensity of suicidal ideation and symptoms in the attenuated stage of psychotic illness. Our aims were to assess prevalence of suicidal ideation in this at risk group, and to examine the severity and intensity of suicidal ideation, and their relation to symptoms. METHODS: Suicidal ideation was assessed in 42 clinical high-risk participants using the Columbia Suicide Severity Rating Scale (C-SSRS). We hypothesized that prevalence rates would be similar to what was found in previous studies, and individuals with suicidal ideation would have higher positive and negative symptoms, with poorer functioning. We assessed levels of severity and intensity of suicidal ideation related to these symptoms, and examined how depressive symptoms affected these relationships. RESULTS: Nearly half (42.9%) of participants reported having current suicidal ideation. We found no relationship to positive symptoms. However, severity and intensity of suicidal ideation were found to be related to negative symptoms and level of functioning. When controlling for depressive symptoms during exploratory analysis, this relationship still emerged. CONCLUSIONS: This study adds to the literature demonstrating the complex nature of suicidal ideation in psychotic illness. The C-SSRS has shown to be helpful in determining relationships between severity and intensity in suicidal ideation in relation to specific symptoms in a research setting. Published by Elsevier B.V. DOI: 10.1016/j.schres.2015.04.022 PMCID: PMC4457707 PMID: 25960038 [PubMed - indexed for MEDLINE] 15. J Am Acad Child Adolesc Psychiatry. 2015 Apr;54(4):283-93. doi: 10.1016/j.jaac.2015.01.008. Epub 2015 Jan 29. A randomized, placebo-controlled study of duloxetine for the treatment of children and adolescents with generalized anxiety disorder. Strawn JR(1), Prakash A(2), Zhang Q(2), Pangallo BA(2), Stroud CE(2), Cai N(2), Findling RL(3). Author information: (1)University of Cincinnati, College of Medicine, and Cincinnati Children's Hospital Medical Center, Division of Child and Adolescent Psychiatry, Cincinnati. Electronic address: strawnjr@uc.edu. (2)Eli Lilly and Co., Indianapolis. (3)Johns Hopkins University/Kennedy Krieger Institute, Baltimore, MD. OBJECTIVE: To evaluate the efficacy, safety, and tolerability of the selective serotonin norepinephrine inhibitor duloxetine in children and adolescents with generalized anxiety disorder (GAD). METHOD: Youth aged 7 through 17 years with a primary diagnosis of GAD were treated with flexibly dosed duloxetine (30-120 mg daily, n = 135) or placebo (n = 137) for 10 weeks, followed by open-label duloxetine (30-120mg daily) for 18 weeks. Efficacy measures included the Pediatric Anxiety Rating Scale (PARS), Clinical Global Impression-Severity (CGI-Severity) scale, and Children's Global Assessment Scale (CGAS). Safety measures included the Columbia-Suicide Severity Rating Scale (C-SSRS) as well as vital signs and electrocardiographic and laboratory monitoring. RESULTS: On the primary efficacy measure (PARS severity for GAD), mean improvement from baseline to 10 weeks was statistically significantly greater for duloxetine (-9.7) compared with placebo (-7.1, p ≤ .001, Cohen's d: 0.5). Symptomatic response (50% improvement on the PARS severity for GAD), remission (PARS severity for GAD ≤8), and functional remission (CGAS >70) rates for the duloxetine group (59%, 50%, 37%, respectively) were statistically significantly greater than for the placebo group (42%, 34%, 24%, respectively, p ≤ .05) during acute treatment. Changes in systolic and diastolic blood pressure and discontinuation because of adverse events did not statistically differ between the duloxetine and placebo groups, although gastrointestinal-related adverse events, oropharyngeal pain, dizziness, cough, and palpitations were reported with a statistically significantly greater incidence for the duloxetine group compared with the placebo group. Mean changes in pulse and weight for the duloxetine group (+6.5 beats/min, -0.1 kg, respectively) were statistically different from the placebo group (+2.0 beats/min, +1.1 kg, respectively, p ≤ .01). CONCLUSION: In this study, duloxetine was superior to placebo on the primary efficacy analysis of mean change from baseline to week 10 on the PARS severity for GAD score, and safety results were consistent with the known safety profile of duloxetine in pediatric and adult patients. Clinical trial registration information-A Study in Pediatric Participants With Generalized Anxiety Disorder; http://clinicaltrials.gov; NCT01226511. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.jaac.2015.01.008 PMID: 25791145 [PubMed - in process] 16. Innov Clin Neurosci. 2014 Sep;11(9-10):182-90. Is There Value in Asking the Question "Do you think you would be better off dead?" in Assessing Suicidality? A Case Study. Giddens JM(1), Sheehan DV(1). Author information: (1)J. Giddens is the Co-founder of the Tampa Center for Research on Suicidality, Tampa, Florida; and Dr. Sheehan is Distinguished University Health Professor Emeritus, University of South Florida College of Medicine, Tampa, Florida. OBJECTIVE: The author of the widely used suicidality scale, the Columbia-Suicide Severity Rating Scale, has repeatedly made the claim that asking the question, "Do you think you would be better off dead?" in suicidality assessment delivers false positive results. This case study investigates the value of this question as an immediate antecedent to impulsive suicidality and as a correlate of functional impairment. METHOD: One subject with daily suicidality and frequent impulsive suicidality rated five passive suicidal ideation phenomena and impulsive suicidality daily on a 0 to 4 Likert scale and rated weekly functional impairment scores for 13 weeks on a 0 to 10 Discan metric. RESULTS: Each of the five passive suicidal ideation phenomena studied frequently occurred at a different severity level, and the five phenomena did not move in synchrony. Most passive suicidal ideation phenomena were very low on dates of impulsive suicidality. Thoughts of being better off dead were a frequent antecedent to impulsive suicidality and were related to an increase in functional impairment. CONCLUSION: The relationship to both functional impairment and impulsive suicidality suggest that it is potentially dangerous to ignore thoughts of being better off dead in suicidality assessment. PMCID: PMC4267794 PMID: 25520897 [PubMed] 17. Innov Clin Neurosci. 2014 Sep;11(9-10):172-8. Do the Five Combinations of Suicidal Ideation in the FDA 2012 Draft Guidance Document and the C-SSRS Adequately Cover All Suicidal Ideation Combinations in Practice? A Case Study. Giddens JM(1), Sheehan DV(1). Author information: (1)J. Giddens is Co-founder of the Tampa Center for Research on Suicidality, Tampa, Florida; and Dr. Sheehan is Distinguished University Health Professor Emeritus, University of South Florida College of Medicine, Tampa, Florida. OBJECTIVE: The United States Food and Drug Administration's newest classification system for suicidality assessment anchors suicidal ideation to various combinations of passive suicidal ideation, active suicidal ideation, method, intent, and plan. This is based upon the suicidal ideation categories in the Columbia-Suicide Severity Rating Scale. Although there are 32 possible combinations of these suicidal ideation phenomena, the Food and Drug Administration's 2012 system and the Columbia-Suicide Severity Rating Scale accommodate six combinations. We use a case study to explore the impact of possible type II errors on suicidality classification posed by not including remaining 26 possible categories. METHODS: A suicidal subject kept detailed daily records of her experience of suicidality over two separate intervals of eight-months' and nine-months' duration. These records permitted classification of individual events into each of the possible 32 suicidal ideation combinations. RESULTS: Although only a small percentage of all events of suicidality from either collection period fell outside of the Food and Drug Administration's classification system and the Columbia -Suicide Severity Rating Scale categories, those that were not so categorized constituted a large percentage of the time this subject experienced suicidality. When these two timeframes were aggregated, more than half of the subject's time spent experiencing suicidality fell into the suicidal ideation combinations not captured by the Food and Drug Administration's classification system and the Columbia-Suicide Severity Rating Scale categories. CONCLUSION: This case study suggests that type II errors in the Food and Drug Administration's classification system and in the Columbia-Suicide Severity Rating Scale categories for suicidal ideation may represent important omissions. PMCID: PMC4267792 PMID: 25520895 [PubMed] 18. Innov Clin Neurosci. 2014 Sep;11(9-10):66-80. The Columbia-Suicide Severity Rating Scale (C-SSRS): Has the "Gold Standard" Become a Liability? Giddens JM(1), Sheehan KH(1), Sheehan DV(1). Author information: (1)J. Giddens is the Co-founder of the Tampa Center for Research on Suicidality, Tampa, Florida; Dr. K. Sheehan is Associate Professor Emeritus at the University of South Florida College of Medicine, Tampa, Florida; and Dr. D. Sheehan is Distinguished University Health Professor Emeritus at the University of South Florida College of Medicine, Tampa, Florida. OBJECTIVE: The Columbia- Suicide Severity Rating Scale has become the gold standard for the assessment of suicidal ideation and behavior in clinical trials. Criticism of the instrument has been mounting. We examine whether the instrument meets widely accepted psychometric standards and maps to the United States Food and Drug Administration's most recent 2012 algorithm for assessment of suicidal phenomena. Our goal is to determine if the Columbia-Suicide Severity Rating Scale should be retained as the preferred instrument for assessment of suicidal ideation and behavior. METHOD: Standard psychometric criteria dictate that categorizations to avoid type I and type II errors should be comprehensive and address the full spectrum (i.e., all dimensions) of a phenomenon. The criteria should also be well defined and consistent, and the wording throughout should be unambiguous. We examine the Columbia-Suicide Severity Rating Scale in terms of these criteria. RESULTS: The Columbia-Suicide Severity Rating Scale does not address the full spectrum of suicidal ideation or behavior. As a result, it has the potential to miss many combinations of suicidal ideation and behavior that present to clinicians in practice (type II error). Potential misclassifications (type I and II errors) are compounded by flawed navigation instructions; mismatches in category titles, definitions, and probes; and wording that is susceptible to multiple interpretations. Further, the Columbia-Suicide Severity Rating Scale in its current form does not map to the 2012 Food and Drug Administration's draft classification algorithm for suicidal ideation and behavior. CONCLUSION: The evidence suggests that the Columbia-Suicide Severity Rating Scale is conceptually and psychometrically flawed and does not map to the Food and Drug Administration's new standards. A new gold standard for assessment of suicidality may be warranted. PMCID: PMC4267801 PMID: 25520890 [PubMed] 19. Innov Clin Neurosci. 2014 Sep;11(9-10):32-46. Comparative Validation of the S-STS, the ISST-Plus, and the C-SSRS for Assessing the Suicidal Thinking and Behavior FDA 2012 Suicidality Categories. Sheehan DV(1), Alphs LD(1), Mao L(1), Li Q(1), May RS(1), Bruer EH(1), Mccullumsmith CB(1), Gray CR(1), Li X(1), Williamson DJ(1). Author information: (1)Dr. Sheehan is Distinguished University Health Professor Emeritus, University of South Florida College of Medicine, Tampa, Florida; Dr. Alphs is with Janssen Medical Affairs, LLC, Titusville, New Jersey; Dr. Mao is with Janssen Research & Development, LLC, Titusville, New Jersey; Mr. Q. Li is Director, Statistical Programming, Regeneron Pharmaceuticals, Inc., Basking Ridge, New Jersey; Ms. May is with the University of Alabama, Birmingham, Alabama; Ms Bruer is with the University of Alabama, Department of Psychiatry and Behavioral Neurobiology, Birmingham, Alabama; Dr. McCullumsmith is with the University of Cincinnati Department of Psychiatry and Behavioral Neuroscience, Cincinnati, Ohio; Mr. Gray is with Medical Outcomes Systems, Jacksonville, Florida; Mr. X. Li is with St. Vincent East Hospital, St. Vincent Health System, Birmingham, Alabama; and Dr. Williamson is with the University of South Alabama College of Medicine, Departments of Psychiatry and Neurology, Birmingham, Alabama, and Janssen Medical Affairs, LLC, Titusville, New Jersey. OBJECTIVE: This exploratory study examines the concurrent validity for mapping symptoms of suicidal ideation, self-harm, and suicidal behavior as recorded on the InterSePT Scale for Suicidal Thinking-Plus, the Sheehan-Suicidality Tracking Scale (clinician- and patient-rated and reconciled patient/clinician versions), and the Columbia-Suicide Severity Rating Scale to the 11 United States Food and Drug Administration-Classification Algorithm of Suicide Assessment (September 2012) categories. METHOD: Forty subjects with varying degrees of suicidal ideation and behavior severity (from not present to extremely severe) were recruited from inpatient, outpatient, and emergency room settings. Each patient was interviewed using all three scales (InterSePT Scale for Suicidal Thinking-Plus, the Sheehan-Suicidality Tracking Scale, and the Columbia-Suicide Severity Rating Scale) on the same day. The scales were administered in a random sequence by three independent raters who were blind to the ratings on the other scales. RESULTS: The Sheehan-Suicidality Tracking Scale and the InterSePT Scale for Suicidal Thinking-Plus show acceptable agreement with the Columbia-Suicide Severity Rating Scale in detecting the presence or absence of the 2012 Food and Drug Administration-Classification Algorithm of Suicide Assessment categories 1, 5, 6, 10, and 11 (passive ideation; active ideation with method, intent, and plan; completed suicide; preparatory actions; and self-injurious behavior) but not of categories 2, 3, and 4 (3 other active suicidal ideation combination categories) or to 8 and 9 (aborted and interrupted attempt). Despite the significant disagreement between the Columbia-Suicide Severity Rating Scale on the one side and the InterSePT Scale for Suicidal Thinking-Plus and the Sheehan-Suicidality Tracking Scale on the other in the ability to accurately map to the 2012 Food and Drug Administration-Classification Algorithm of Suicide Assessment categories on some items, there was close agreement between the InterSePT Scale for Suicidal Thinking-Plus and the Sheehan-Suicidality Tracking Scale on these categories. CONCLUSION: The results of this exploratory study invite discussion and debate about the validity of the Columbia-Suicide Severity Rating Scale and its ability to accurately assess key active suicidal ideation categories, since it disagrees so much with the other two standardized scales that agree so closely with each other. PMCID: PMC4267798 PMID: 25520887 [PubMed] 20. Innov Clin Neurosci. 2014 Sep;11(9-10):14-22. Prospective assessment of suicidal ideation and behavior: an internet survey of pharmaceutical sponsor practices. ISCTM SUICIDAL IDEATION AND BEHAVIOR ASSESSMENT WORKGROUP:, Chappell PB(1), Mahableshwarkar AR(1), Alphs LD(1), Bangs ME(1), Butler A(1), DuBrava SJ(1), Greist JH(1), Lenderking WR(1), Mundt JC(1), Stewart M(1). Author information: (1)Dr. Chappell is with Pfizer, Inc., Groton, Connecticut; Dr. Mahableshwarkar is with Takeda Pharmaceutical Company, Deerfield, Illinois; Dr. Alphs is with Janssen Scientific Affairs, Titusville, New Jersey; Dr. Bangs is with Eli Lilly and Company, Indianapolis, Indiana; Mr. Butler is with Bracket Global, Wayne, Pennsylvania; Ms. DuBrava is with Pfizer, Inc., Groton, Connecticut; Dr. Greist is Clinical Adjunct Professor of Psychiatry at University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Dr. Lenderking is with Evidera, Bethesda, Maryland; Dr. Mundt is with Center for Telepsychology, Madison, Wisconsin; and Dr. Stewart is with Pfizer, Groton, Connecticut. OBJECTIVE: To survey the current approaches of clinical trial sponsors in prospective suicidal ideation and behavior assessments and challenges encountered. DESIGN: An internet-based survey. SETTING: Inclusion of prospective assessments of suicidal ideation and behavior in industry-sponsored clinical studies were required following the release of the September 2010 United States Federal Drug Administration draft guidance. The International Society for CNS Clinical Trials and Methodology Suicidal Ideation and Behavior Assessment Workgroup conducted an online survey to understand industry practices and experiences in implementing suicidal ideation and behavior assessments in clinical trials. PARTICIPANTS: The survey was sent to 1,447 industry employees at 178 pharmaceutical companies. A total of 89 evaluable responses, representing 39 companies, were obtained. MEASUREMENTS: A 30-item internet survey was developed asking about potential challenges and issues in implementing prospective suicidal ideation and behavior assessments. RESULTS: Common factors in deciding whether to include suicidal ideation and behavior assessments in a clinical trial were psychiatric or neurologic drug product (95%); central nervous system activity (78%); disease (74%) and patient population (71%); and regulatory announcements and policies (74%). The most common challenges in implementing suicidal ideation and behavior assessments included cross-cultural differences in acceptance of SIB assessments (40%); obtaining adequate baseline history (36.8%); obtaining translations (35%); investigator/rater discomfort with asking about suicidal ideation and behavior (32%); and inadequate training of raters to administer suicidal ideation and behavior ratings (30%). CONCLUSION: Among sponsors surveyed, the implementation rate of suicidal ideation and behavior assessment in central nervous systems studies is very high. Most have used the Columbia-Suicide Severity Rating Scale. Challenges regarding standardization of retrospective assessment timeframes and differing approaches to summarizing and analyzing suicidal ideation and behavior-related study data were frequently reported. These results suggest that inconsistent reports of suicidal ideation and behavior within study datasets may occur and that integration of data across studies remains a concern. PMCID: PMC4267789 PMID: 25520885 [PubMed] 21. Pediatr Emerg Care. 2015 Feb;31(2):88-94. doi: 10.1097/PEC.0000000000000225. Columbia-suicide severity rating scale: predictive validity with adolescent psychiatric emergency patients. Gipson PY(1), Agarwala P, Opperman KJ, Horwitz A, King CA. Author information: (1)From the *Department of Psychiatry, †Depression Center, and ‡Departments of Psychiatry and Psychology, University of Michigan, Ann Arbor, MI. OBJECTIVE: Despite the high prevalence of psychiatric emergency (PE) visits for attempted suicide and nonsuicidal self-injury (NSSI) among adolescents, we have limited information about assessment tools that are helpful in predicting subsequent risk for suicide attempts among adolescents in PE settings. This study examined the predictive validity of a highly promising instrument, the Columbia-Suicide Severity Rating Scale (C-SSRS). METHOD: Participants were 178 adolescents (44.4% male; ages 13-17 years) seeking PE services. The C-SSRS interview and selected medical chart data were collected for the index visit and subsequent visits during a 1-year follow-up. RESULTS: A suicide risk concern was the most common chief complaint (50.6%) in this sample, and nearly one third of the adolescents (30.4%) reported a lifetime history of suicide attempt at index visit. Sixty-two adolescents (34.8%) had at least one return PE visit during follow-up. Lifetime history of NSSI predicted both return PE visits and a suicide attempt at return visit. The C-SSRS intensity scale score was a significant predictor of a suicide attempt at return visit for both the full sample of adolescents and the subsample who reported suicidal ideation at their index visit. In this subsample, one specific item on the intensity scale, duration, was also a significant predictor of both a return PE visit and a suicide attempt at return visit. CONCLUSIONS: The C-SSRS intensity scale and NSSI had predictive validity for suicide attempts at return visit. Results also suggest that duration of adolescents' suicidal thoughts may be particularly important to risk for suicidal behavior, warranting further study. DOI: 10.1097/PEC.0000000000000225 PMID: 25285389 [PubMed - indexed for MEDLINE] 22. J Child Adolesc Psychopharmacol. 2014 May;24(4):170-9. doi: 10.1089/cap.2013.0096. Epub 2014 May 9. A double-blind efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder. Emslie GJ(1), Prakash A, Zhang Q, Pangallo BA, Bangs ME, March JS. Author information: (1)1 Child and Adolescent Psychiatry Division, University of Texas Southwestern and Children's Medical Center , Dallas, Texas. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of duloxetine fixed dose in the treatment of children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD). METHODS: Patients (n=463) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine 60 mg QD (n=108), duloxetine 30 mg QD (n=116), fluoxetine 20 mg QD (n=117, active control), or placebo (n=122). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. Total TEAEs and discontinuation for AEs were significantly (p<0.05) higher only for the duloxetine 60 mg group versus the placebo group during acute treatment. No clinically significant electrocardiogram (ECG) or laboratory abnormalities were observed, and no completed suicides or deaths occurred during the study. A total of 7 (6.7%) duloxetine 60 mg, 6 (5.2%) duloxetine 30 mg, 9 (8.0%) fluoxetine, and 11 (9.4%) placebo patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 13/16 (81%) duloxetine 60 mg, 16/17 (94%) duloxetine 30 mg, 11/16 (69%) fluoxetine, and 13/15 (87%) placebo had improvement in suicidal ideation at end-point during acute treatment. One fluoxetine, one placebo, and six duloxetine patients had treatment-emergent suicidal behavior during the 36 week study. CONCLUSIONS: Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number ( www.ClinicalTrials.gov ): NCT00849693. DOI: 10.1089/cap.2013.0096 PMCID: PMC4026396 PMID: 24815533 [PubMed - indexed for MEDLINE] 23. J Child Adolesc Psychopharmacol. 2014 May;24(4):180-9. doi: 10.1089/cap.2013.0146. Epub 2014 May 9. A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder. Atkinson SD(1), Prakash A, Zhang Q, Pangallo BA, Bangs ME, Emslie GJ, March JS. Author information: (1)1 Finger Lakes Clinical Research , Rochester, New York. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD). METHODS: Patients (n=337) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine (60-120 mg once daily [QD], n=117), fluoxetine (20-40 mg QD, n=117), or placebo (n=103). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs (SAEs), total TEAEs, or discontinuation for AE during acute treatment. There were no completed suicides or deaths, and no clinically significant electrocardiogram (ECG) abnormalities observed during the study. One fluoxetine and one duloxetine patient experienced alanine aminotransferase (ALT) three or more times the upper limit of normal, which resolved during the study. A total of 8 (7.1%) duloxetine patients, 7 (6.8%) placebo patients, and 9 (8.0%) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 15/19 (79%) duloxetine, 19/19 (100%) placebo, and 16/19 (84%) fluoxetine had improvement in suicidal ideation at end-point during acute treatment. One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study. CONCLUSION: Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number: NCT00849901. DOI: 10.1089/cap.2013.0146 PMID: 24813026 [PubMed - indexed for MEDLINE] 24. J Child Adolesc Psychopharmacol. 2014 May;24(4):201-9. doi: 10.1089/cap.2012.0126. Epub 2014 Mar 10. Safety and tolerability of desvenlafaxine in children and adolescents with major depressive disorder. Findling RL(1), Groark J, Chiles D, Ramaker S, Yang L, Tourian KA. Author information: (1)1 Johns Hopkins University , Baltimore, Maryland. OBJECTIVE: The purpose of this study was to assess long-term safety and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) in children and adolescents with major depressive disorder (MDD). METHODS: An 8 week, multicenter, open-label, fixed-dose study of children (ages 7-11 years) and adolescents (ages 12-17 years) with MDD was followed by a 6 month, flexible-dose extension study. Patients were administered desvenlafaxine 10-100 mg/day (children) or 25-200 mg/day (adolescents) for a total of 8 months. Treatment-emergent adverse events (AEs), withdrawals because of AEs, laboratory tests, vital signs, and the Columbia Suicide-Severity Rating Scale (C-SSRS) were collected. Eight month safety results from the lead-in plus extension studies are reported for extension study participants, using lead-in study day -1 as baseline. RESULTS: Forty patients were enrolled in both studies (20 children; 20 adolescents). Of those, four children and three adolescents withdrew because of AEs. Treatment-emergent AEs reported by three or more patients were upper abdominal pain (15%) and headache (15%) in children, and somnolence (30%), nausea (20%), upper abdominal pain (15%), and headache (15%) in adolescents. Negativism (oppositional behavior) in a child was the single serious AE reported. No deaths occurred during the lead-in or extension studies. Mean pulse rates demonstrated statistically significant increases from lead-in study baseline to final evaluation (children, +5.2 bpm; adolescents, +5.9 bpm; p≤0.05). No statistically significant change in blood pressure was observed at final evaluation. Two adolescents (0 children) reported suicidal ideation on the C-SSRS at screening assessment and during the lead-in and/or extension trials; one adolescent reported suicidal ideation after screening only. CONCLUSIONS: Long-term (8 month) treatment with desvenlafaxine was generally safe and well tolerated in depressed children and adolescents. DOI: 10.1089/cap.2012.0126 PMCID: PMC4026302 PMID: 24611442 [PubMed - indexed for MEDLINE] 25. Suicide Life Threat Behav. 2014 Apr;44(2):113-29. doi: 10.1111/sltb.12072. Epub 2014 Jan 22. Young adult follow-up of adolescent girls in juvenile justice using the Columbia suicide severity rating scale. Kerr DC(1), Gibson B, Leve LD, Degarmo DS. Author information: (1)Oregon Social Learning Center, Oregon State University, Corvallis, OR, USA. This study focused on the reliability and validity of the Columbia Suicide Severity Scale (C-SSRS). Severely delinquent adolescent girls (n = 166) participated in a treatment trial and repeated assessments over time. Lifetime suicide attempt history was measured using the C-SSRS in early adulthood (n = 144; 7-12 years postbaseline). Nonclinician raters showed strong interrater reliability using the C-SSRS. Self-reports, caseworker reports, and caregiver reports of girls' suicide attempt histories collected at baseline correlated with adult participants' recollections of their baseline attempt histories. Suicidal ideation measured prospectively across a 7- to -12-year period was associated with retrospectively reported suicide attempt across the same period. © 2014 The American Association of Suicidology. DOI: 10.1111/sltb.12072 PMCID: PMC3989504 PMID: 24446880 [PubMed - indexed for MEDLINE] 26. Dement Geriatr Cogn Disord. 2014;37(3-4):232-45. doi: 10.1159/000355373. Epub 2013 Nov 14. Phase II crossover trial of varenicline in mild-to-moderate Alzheimer's disease. Kim SY(1), Choi SH, Rollema H, Schwam EM, McRae T, Dubrava S, Jacobsen J. Author information: (1)Department of Psychiatry, Asan Medical Center, Seoul, South Korea. BACKGROUND: Evidence supports a role of α4β2 receptors in Alzheimer's disease (AD). METHODS: This Korean, multicenter, double-blind, two-period (6 weeks each), crossover study randomized participants to the order in which they received varenicline (1 mg twice daily) and placebo. Assessments included AD Assessment Scale-Cognitive Subscale (ADAS-Cog) 75, Neuropsychiatric Inventory (NPI), adverse events (AEs) and Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: For varenicline versus placebo (n = 66 randomized), there was no significant difference in the week 6 least square (LS) mean ADAS-Cog 75 total score (primary endpoint; 18.07 vs. 18.49; p = 0.3873) and a slight worsening in the week 6 LS mean NPI (3.82 vs. 2.55; p = 0.0468), primarily driven by decreased appetite/eating. Common treatment-related AEs were nausea (23.3; 3.4%), vomiting (15.0%; 0) and decreased appetite (15.0; 6.8%). CONCLUSIONS: Varenicline did not improve cognition, behavior or global change in this population. The most frequent varenicline-associated AEs were gastrointestinal; psychiatric AEs were rare and similar between the groups. DOI: 10.1159/000355373 PMID: 24247022 [PubMed - indexed for MEDLINE] 27. Trials. 2013 Oct 17;14:338. doi: 10.1186/1745-6215-14-338. Efficacy of repetitive transcranial magnetic stimulation in the prevention of relapse of depression: study protocol for a randomized controlled trial. Wang H, Xue Y, Chen Y, Zhang R, Wang H, Zhang Y, Gan J, Zhang L, Tan Q(1). Author information: (1)Department of Psychiatry, Xijing Hospital, The Fourth Military Medical University, 15 Changle Road, 710032, Xi'an, China. tanqingr@fmmu.edu.cn. BACKGROUND: Depression is a chronic illness that generally requires lifelong therapy. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique with few side effects that has been reported to be useful in the treatment of depression. However, no studies to date have evaluated in a randomized controlled trial (RCT) the efficacy of rTMS for maintenance treatment of depression. METHODS/DESIGN: In this article, we report the design and protocol of a randomized, single-blind, placebo-controlled, parallel-group, multicenter study in China to evaluate the efficacy of rTMS in the prevention of relapse of depressive symptoms. In total, 540 patients, aged 18 to 60 years, diagnosed with depression and experiencing an acute exacerbation of depressive symptoms, will be enrolled. The study will consist of four phases: a screening/tolerability phase of up to 7 days; an open-label, flexible-dose lead-in phase of 8 weeks; an open-label, fixed-dose stabilization phase of 6 weeks; and a single-blind relapse prevention phase of 12 months. During the open-label phase, all patients will be treated with venlafaxine. Remitters with Hamilton Rating Scale for Depression (HAM-D₁₇) score ≤7 will be eligible to enter the single-blind phase and will be randomly assigned to one of three groups: group 1 on active rTMS and venlafaxine; group 2 on sham rTMS and venlafaxine; and group 3 on venlafaxine alone. Efficacy will be evaluated during the study using relapse assessment (time between subject randomization to treatment and the first occurrence of relapse). Secondary outcome measures will include: symptom changes, measured by the HAM-D₁₇; illness severity changes, measured by the Clinical Global Impression of Severity for Depression (CGI-S-DEP); and changes in subject functioning, assessed with the Personal and Social Performance (PSP)scale. Safety will be assessed throughout the study by monitoring of adverse events, clinical laboratory tests, electrocardiography (ECG), and measurements of vital signs (temperature, pulse, and blood pressure) and weight. Suicidality will be assessed by the Columbia Suicide Severity Rating Scale (C-SSRS). DISCUSSION: The result of this trial will assess the efficacy of rTMS in the prevention of relapse of symptoms of depression by determining whether rTMS in combination with an antidepressant is more efficacious than the antidepressant alone for maintenance of the clinical response. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01516931. DOI: 10.1186/1745-6215-14-338 PMCID: PMC4016597 PMID: 24135054 [PubMed - indexed for MEDLINE] 28. J Child Adolesc Psychopharmacol. 2013 Sep;23(7):468-80. doi: 10.1089/cap.2012.0023. Escitalopram in the treatment of adolescent depression: a randomized, double-blind, placebo-controlled extension trial. Findling RL(1), Robb A, Bose A. Author information: (1)1 Johns Hopkins University and the Kennedy Krieger Institute , Baltimore, Maryland. OBJECTIVE: The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). METHODS: Adolescents (12-17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10-20 mg versus placebo could enroll in a 16-24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥ 40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤ 2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤ 28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥ 5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were mild/moderate and not related to the study drug. AEs suggestive of self-harm occurred in 5.7% and 7.1% of placebo and escitalopram patients. Occurrence of suicidal behavior and/or suicidal ideation assessed by C-SSRS was 10.9% (14/128) for placebo and 14.5% (19/131) for escitalopram. CONCLUSIONS: Extended use of escitalopram was generally safe and resulted in modest improvement in efficacy in adolescents with MDD. DOI: 10.1089/cap.2012.0023 PMCID: PMC3779002 PMID: 24041408 [PubMed - indexed for MEDLINE] 29. Epilepsia. 2013 May;54(5):879-87. doi: 10.1111/epi.12128. Epub 2013 Feb 28. Suicidal ideation and behavior screening in intractable focal epilepsy eligible for drug trials. Hesdorffer DC(1), French JA, Posner K, DiVentura B, Pollard JR, Sperling MR, Harden CL, Krauss GL, Kanner AM. Author information: (1)GH Sergievsky Center and Department of Epidemiology, Columbia University, New York, New York 10032, USA. dch5@columbia.edu PURPOSE: Three suicidal ideation and suicidal behavior instruments were used to assess the prevalence of lifetime and recent suicidal ideation and suicidal behavior in patients with frequent treatment-resistant focal seizures who would be eligible for randomized clinical trials. This was done to determine which instrument was optimal for use in epilepsy. METHODS: In a cross-sectional study, we compared lifetime and recent suicidal ideation and suicide attempt on the MINI International Neuropsychiatric Interview (MINI), Columbia Suicide Severity Rating Scale (C-SSRS), and Interactive Voice Response System CSSRS (E-CSSRS). A safety algorithm determined treatment referral. Coordinators and participants evaluated experiences with the C-SSRS. The proportion of participants that baseline assessment would exclude from clinical trial enrollment was determined. KEY FINDINGS: Among 208 participants, 1.6-3.9% had recent high risk suicidal ideation and 1.0-4.7% had a recent suicide attempt across all instruments. Lifetime high-risk suicidal ideation occurred in 12.1-14.1%. Lifetime suicide attempt occurred in 10.2-13.1% of participants. Of those with recent suicide attempt, 31.1% required referral to a health professional, and 3.9% needed urgent referral. Lifetime suicidal behavior (including aborted suicide attempt, interrupted suicide attempt, suicide attempt, preparatory acts or behavior, and nonsuicidal self-injurious behavior) was found in 21.1% on the E-CSSRS and 15.5% on the C-SSRS. Agreement (Kappa) was good to excellent for comparisons of all instruments. Fifty-two percent of subjects preferred either the CSSRS or E-CSSRS, whereas the rest had no preference; of those having a preference, 87.5% favored the CSSRS. Of the 18.9% of participants who might have been excluded from trials based on suicidal ideation and suicide attempt, the CSSRS identified high-risk suicidal ideation or suicide attempt in the preceding 2 years in only 4.4%. SIGNIFICANCE: Suicidality screening is feasible in people with epilepsy. Slightly more suicidal behavior is reported with the E-CSSRS than C-SSRS, suggesting the E-CSSRS may be optimal. The proportion of patients who may be excluded from clinical trials based on worrisome suicidal ideation or suicide attempt is small, suggesting that it is possible to enroll most eligible individuals. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy. DOI: 10.1111/epi.12128 PMID: 23448169 [PubMed - indexed for MEDLINE] 30. J Child Adolesc Psychopharmacol. 2012 Feb;22(1):48-55. doi: 10.1089/cap.2011.0072. Epub 2012 Jan 17. An open-label safety and pharmacokinetics study of duloxetine in pediatric patients with major depression. Prakash A(1), Lobo E, Kratochvil CJ, Tamura RN, Pangallo BA, Bullok KE, Quinlan T, Emslie GJ, March JS. Author information: (1)Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. prakash@lilly.com OBJECTIVE: This preliminary, 32-week study assessed the safety, tolerability, and pharmacokinetics of duloxetine in pediatric patients (aged 7-17 years) with major depressive disorder. METHODS: Patients received flexible duloxetine doses of 20-120 mg once daily, with dose changes made based on clinical improvement and tolerability. Pharmacokinetic samples were collected across all duloxetine doses, and data were analyzed using population modeling. Primary outcome measures included treatment-emergent adverse events (TEAEs), vital signs, and Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: Of the 72 enrolled patients, 48 (66.7%) completed acute treatment (18 weeks) and 42 (58.3%) completed extended treatment. Most patients (55/72; 76%) required doses ≥ 60 mg once daily to optimize efficacy based on investigator judgment and Clinical Global Impressions-Severity score. Body weight and age did not significantly affect duloxetine pharmacokinetic parameters. Typical duloxetine clearance in pediatric patients was ≈ 42%-60% higher than that in adults. Four patients (5.6%) discontinued due to TEAEs. Many (36/72, 50%) patients experienced potentially clinically significant (PCS) elevations in blood pressure, with most cases (21/36, 58%) being transient. As assessed via C-SSRS, one nonfatal suicidal attempt occurred, two patients (2.8%) experienced worsening of suicidal ideation, and among the 19 patients reporting suicidal ideation at baseline, 17 (90%) reported improvement in suicidal ideation. CONCLUSION: Results suggested that pediatric patients generally tolerated duloxetine doses of 30 to 120 mg once daily, although transient PCS elevations in blood pressure were observed in many patients. Pharmacokinetic results suggested that adjustment of total daily dose based on body weight or age is not warranted for pediatric patients and different total daily doses may not be warranted for pediatric patients relative to adults. DOI: 10.1089/cap.2011.0072 PMID: 22251023 [PubMed - indexed for MEDLINE] 31. Am J Psychiatry. 2011 Dec;168(12):1266-77. doi: 10.1176/appi.ajp.2011.10111704. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Posner K(1), Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. Author information: (1)Department of Psychiatry, Division of Child and Adolescent Psychiatry, Columbia University, College of Physicians and Surgeons, New York, USA. posnerk@nyspi.columbia.edu Comment in Am J Psychiatry. 2011 Dec;168(12):1233-4. Am J Psychiatry. 2012 Jun;169(6):662-3; author reply 663. Am J Psychiatry. 2012 Jun;169(6):662; author reply 663. OBJECTIVE: Research on suicide prevention and interventions requires a standard method for assessing both suicidal ideation and behavior to identify those at risk and to track treatment response. The Columbia-Suicide Severity Rating Scale (C-SSRS) was designed to quantify the severity of suicidal ideation and behavior. The authors examined the psychometric properties of the scale. METHOD: The C-SSRS's validity relative to other measures of suicidal ideation and behavior and the internal consistency of its intensity of ideation subscale were analyzed in three multisite studies: a treatment study of adolescent suicide attempters (N=124); a medication efficacy trial with depressed adolescents (N=312); and a study of adults presenting to an emergency department for psychiatric reasons (N=237). RESULTS: The C-SSRS demonstrated good convergent and divergent validity with other multi-informant suicidal ideation and behavior scales and had high sensitivity and specificity for suicidal behavior classifications compared with another behavior scale and an independent suicide evaluation board. Both the ideation and behavior subscales were sensitive to change over time. The intensity of ideation subscale demonstrated moderate to strong internal consistency. In the adolescent suicide attempters study, worst-point lifetime suicidal ideation on the C-SSRS predicted suicide attempts during the study, whereas the Scale for Suicide Ideation did not. Participants with the two highest levels of ideation severity (intent or intent with plan) at baseline had higher odds for attempting suicide during the study. CONCLUSIONS: These findings suggest that the C-SSRS is suitable for assessment of suicidal ideation and behavior in clinical and research settings. DOI: 10.1176/appi.ajp.2011.10111704 PMCID: PMC3893686 PMID: 22193671 [PubMed - indexed for MEDLINE] 32. J Psychiatr Res. 2010 Dec;44(16):1224-8. doi: 10.1016/j.jpsychires.2010.04.025. Epub 2010 Jun 2. Feasibility and validation of a computer-automated Columbia-Suicide Severity Rating Scale using interactive voice response technology. Mundt JC(1), Greist JH, Gelenberg AJ, Katzelnick DJ, Jefferson JW, Modell JG. Author information: (1)Healthcare Technology Systems, Inc., 7617 Mineral Point Road, Ste. 300, Madison, WI 53717, USA. OBJECTIVE: To evaluate a computer-automated version of the Columbia-Suicide Severity Rating Scale (C-SSRS) using interactive voice response technology (eC-SSRS™). The eC-SSRS assesses "Lifetime" ideations and behaviors at baseline and monitors suicidality prospectively thereafter. Ten control volunteers and ten psychiatric inpatients participated and were administered the C-SSRS at baseline and 4-8 days later by two experienced clinical trial raters. Study participants also completed the eC-SSRS using touch-tone telephones. Kappa measures of agreement compared inter-rater reliability of the C-SSRS administrations and the C-SSRS administrations with the eC-SSRS. Convergent validity with the Beck Scale for Suicide Ideation BSS and patient feedback forms were also evaluated. Twenty baseline and nineteen follow-up assessments were completed. In general, agreement between the eC-SSRS and each rater was comparable or superior to the agreement between both raters. Subject feedback and personal preferences varied across individuals, but were generally supportive of the feasibility and validity of the eC-SSRS. The reliability and validity of the C-SSRS and eC-SSRS for assessing suicidal ideation and behaviors were comparable in this first study comparing the methods. These data were obtained from relatively small patient samples recruited from a single investigational site over a relatively short follow-up period. They support the feasibility and validity of the eC-SSRS for prospective monitoring of suicidality for use in clinical trials or clinical care, but further research with larger samples, other patient populations, and longer follow-up periods is needed. Copyright © 2010 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.jpsychires.2010.04.025 PMID: 20553851 [PubMed - indexed for MEDLINE]