Indicators of pretreatment suicidal ideation in adults with major depressive disorder

Transcription

1 Acta Psychiatr Scand 2010: 121: All rights reserved DOI: /j x Ó 2009 John Wiley & Sons A/S ACTA PSYCHIATRICA SCANDINAVICA Brief communication Indicators of pretreatment suicidal ideation in adults with major depressive disorder Morris DW, Trivedi MH, Husain MM, Fava M, Budhwar N, Wisniewski SR, Miyahara S, Gollan JK, Davis LL, Daly EJ, Rush AJ. Indicators of pretreatment suicidal ideation in adults with major depressive disorder. Objective: In order to evaluate the presence of treatment emergent suicidal ideation (SI), it becomes necessary to identify those patients with SI at the onset of treatment. The purpose of this report is to identify sociodemographic and clinical features that are associated with SI in major depressive disorder (MDD) patients prior to treatment with a selective serotonin reuptake inhibitor. Method: This multisite study enrolled 265 out-patients with nonpsychotic MDD. Sociodemographic and clinical features of participants with and without SI were compared post hoc. Results: Social phobia, bulimia nervosa, number of past depressive episodes, and race were independently associated with SI by one or more SI measure. Conclusion: Concurrent social phobia and bulimia nervosa may be potential risk factors for SI in patients with non-psychotic MDD. Additionally, patients with more than one past depressive episode may also be at increased risk of SI. D. W. Morris 1, M. H. Trivedi 1, M. M. Husain 1, M. Fava 2, N. Budhwar 3, S. R. Wisniewski 4, S. Miyahara 4, J. K. Gollan 5, L. L. Davis 6, E. J. Daly 1, A. J. Rush 7 1 Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, 2 Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, 3 Department of Family and Community Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, 4 Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 5 Asher Center for the Study and Treatment of Depressive Disorders, Northwestern University Feinberg School of Medicine, Chicago, IL, 6 VA Medical Center, University of Alabama at Birmingham, Tuscaloosa, AL and 7 Duke- National University of Singapore, Singapore Key words: suicidal ideation; suicide; depression; major depressive disorder; mood disorder David W. Morris, PhD, Mood Disorders Program & Clinic, Department of Psychiatry, University of Texas Southwestern Medical Center, 6363 Forest Park Road, Suite , Dallas, TX , USA. davidw.morris@utsouthwestern.edu Accepted for publication November 6, 2009 Significant outcomes Comorbid anxiety disorders may increase the risk of suicidal ideation. Patients with recurrent depression are at increased risk of suicidal ideation. Limitations Exploratory analysis. Per comparison error rates were used. The sample size was modest. Introduction The presence of suicidal ideation (SI) in adult patients treated with antidepressant medications for major depressive disorder (MDD), particularly selective serotonin reuptake inhibitors (SSRIs), has come to the forefront of clinical care subsequent to the warnings of treatment emergent SI issued by the American Food and Drug Administration (1). The occurrence of treatment emergent SI remains 480

2 Pretreatment suicidal ideation an ongoing concern despite evidence that patients treated with antidepressant medications have a decreased rate of suicide compared with community controls (2, 3). While suicidal behavior can occur in the absence of overt psychopathology, depression has been found to be strongly associated with suicidal behavior and SI (4). A significant number of patients experience SI during the course of a major depressive episode (MDE), but only a fraction of these individuals attempt suicide. While not all suicide attempts are believed to be preceded by significant SI, a 20 years prospective study of 6891 psychiatric out-patients found that SI is a risk factor for suicide (5). Further, Fu et al. (6) found that 91.4% of men who reported a lifetime history of suicide attempts also reported a lifetime history of SI. In patients with MDD, Sokero et al. (7) found that 95% of those patients who attempted suicide had SI. Therefore, for many patients, SI appears to be an important consideration in determining risk of suicidal behavior. In order to evaluate the presence of treatment emergent SI, it becomes necessary to identify those patients with SI at the onset of treatment. Aims of the study The purpose of this report is to identify sociodemographic and clinical features associated with suicidal ideation in major depressive disorder patients prior to treatment with selective serotonin reuptake inhibitors (SSRIs). the use of any SSRI. Participants were not followed if they had a primary Axis I diagnosis other than non-psychotic MDD or required inpatient hospitalization for suicidality. Patients were also not included if they were pregnant, breastfeeding, or had taken an antipsychotic medication within 4 months of study entry. Assessments At the screening baseline visit, clinical research coordinators (CRCs) collected sociodemographic and clinical information and completed the HRSD 17. Additionally, participants were screened for DSM-IV Axis I psychiatric disorders with the Psychiatric Diagnostic Screening Questionnaire (PDSQ) (9); and for medical comorbidities using the Self-administered Comorbidity Questionnaire (SCQ) (10). Depressive symptoms were measured using the 16-item Quick Inventory of Depressive Symptomatology Clinician-rated (QIDS-C 16 ) (11). Suicidal ideation was assessed using the QIDS- C 16, as well as the Concise Health Risk Tracking Scale Self-Report (CHRT-SR) and Clinicianrated (CHRT-C) versions. The CHRT-SR and CHRT-C are newly developed scales consisting of 12 clinician-rated or patient self-report items that assess active and passive SI as well as feelings of hopelessness, helplessness, and lack of social support. There are three items on the CHRT-SR and CHRT-C that assess active SI, and one item on the QIDS-C which assesses active and passive suicidal ideation. Material and methods Study population The study enrolled 265 adult out-patient participants from six primary care and nine psychiatric clinical care sites across the United States. Participants were years of age and were diagnosed with non-psychotic MDD. The clinical diagnosis of non-psychotic MDD was established using a MDD checklist based upon the Diagnostic and Statistical Manual of Mental Disorders fourth edition text revision (DSM-IV-TR). Investigators evaluated MDD patients for the first 8 weeks of open label treatment with SSRI monotherapy. Participants were included in this observational study if they had a baseline score 14 on the 17-item Hamilton Rating Scale for Depression (HRSD 17 ) (8), and were medically appropriate for treatment with an SSRI. Participants with general medical conditions (GMCs) were included as long as their current treatment did not contraindicate Analytic methods Chi-square analyses and logistic regression models were used to assess the bivariate association of baseline sociodemographic and clinical characteristics with the presence of SI. Stepwise logistic regression models were used to identify features independently associated with SI. Per comparison error rates were used and alpha was set at Results Suicide items There was 86% agreement between the QIDS-C 16 and CHRT (clinician-rated and patient self-report) items, with all three measures classifying 8% of participants as having frank SI, and 78% reporting no SI. Of the remaining 14%, there was 8% disagreement between the QIDS-C 16 and the CHRT, and another 6% represented inconsistencies between the clinician-rated and participant 481

3 Morris et al. self-report versions of the CHRT. Twenty-three observations were not included because of missing data. Sociodemographic and clinical features Several sociodemographic and clinical features distinguished participants with baseline, pretreatment SI from those without. The most prominent difference was found in participants that screened positive for social phobia, of whom 20 26% reported SI, a rate more than twice that seen in participants without social phobia (8 13%). Additionally, participants with a positive screen for bulimia nervosa reported SI at a rate of 16 30% compared to the rate of 9 15% found in those without bulimia nervosa. Participants with a greater number of past depressive episodes also reported more SI (12 18%) than those without (4 11%). Isolated differences were also found in race, age of onset, early-morning insomnia, hypersomnia, education, depressive severity, and GMC severity. Of these characteristics, the following variables were independently associated with SI using one or more of the three measures: social phobia, bulimia nervosa, number of depressive episodes, and race (Table 1). No suicide attempts or suicidal gestures were reported during the study period. Discussion Given the exploratory nature of the analysis, and the large number of variables evaluated, the results must be interpreted conservatively. The findings suggest that social phobia, and possibly bulimia nervosa, may be indicators of an increased risk of SI for patients with MDD. There was also evidence, albeit limited, to support the hypothesis that white patients are at greater risk of SI than Table 1. Baseline characteristics independently associated with suicidal ideation Measure of SI Baseline characteristic OR P-value QIDS-C 16 Race Black (vs. White) 0.54 Other (vs. White) 3.18 CHRT-SR Social phobia CHRT-C Social phobia Number of depressive episodes* Bulimia Nervosa P < 0.05 indicates statistically significant difference. *Binary variable (1 = more than or equal to 2 depressive episodes, 0 = less than 2 depressive episodes). QIDS-C 16, 16-item Quick Inventory of Depressive Symptomatology Clinician-rated; CHRT-SR, Concise Health Risk Tracking-Self Report; CHRT-C, Concise Health Risk Tracking-Clinician rated; OR, odds ratio. black patients, and that patients with more than one past MDE are at increased risk of SI. Several other factors (age of onset of the current MDE, sleep disturbance, education, severity of general medical conditions, and current depressive severity) were found to be significantly, but not independently, related to SI. Consistent with our findings, there is a significant amount of research indicating the presence of anxiety disorders is associated with SI. Sareen et al. (12) found that patients with social phobia were 3.9 times more likely to have new onset SI, and 4.0 times more likely to have a new onset suicide attempt. In the current study, the odds ratios (ORs) for SI found in participants with MDD and comorbid social phobia were consistent with those found in earlier studies of patients with bipolar disorder who had comorbid social phobia (13), as well as those found in patients with social phobia alone. While the current studyõs finding of an increased vulnerability to SI in patients with depression and comorbid social phobia hardly appears unique given the literature supporting an increased vulnerability to SI in patients with bipolar disorder and comorbid social phobia, the finding is novel in patients with unipolar depression. In the STAR*D sample, 16% of the patients qualifying for a provisional diagnosis of bulimia nervosa reported a past suicide attempt (14). In the current study, we found that in participants with MDD, bulimia nervosa was associated with a significant increase in risk of SI. Participants with MDD and comorbid bulimia nervosa had a 3.7-fold greater chance (OR) of having SI than those without comorbid bulimia nervosa when directly queried on the CHRT-C. Increased rates of SI were also seen in participants with bulimia nervosa using the QIDS-C 16 and CHRT-SR, but these findings were not statistically significant. In a recent article, Favaro et al. (15) found that in patients with bulimia nervosa (purging type), the presence of social phobia was associated with a lifetime history of suicide attempts. Clearly, clinicians should be mindful of the potentially greater risk of SI and or suicidal behavior in MDD patients who have concurrent bulimia nervosa or social phobia. Overall, there was good agreement between the three measures of suicidality (QIDS-C 16, CHRT-C, and CHRT-SR). Given the slightly different queries used to evaluate SI found on the QIDS-C 16 and the CHRT scales, it is not unanticipated that some disagreement will occur between the measures. It is difficult to determine if such a difference is because of random chance or if there is response 482

4 Pretreatment suicidal ideation bias whereby patients with SI are less comfortable disclosing it to a clinician as opposed to endorsing it through self-report. The current study has several limitations. Given the exploratory nature of this post hoc analysis, per comparison error rates were used. Therefore, the results must be interpreted accordingly. Additionally, the study would benefit from a larger sample size. Eleven to fifteen per cent of the study patients reported thoughts of suicide at baseline, prior to treatment. Few sociodemographic and clinical variables distinguished participants with pretreatment SI. However, the results of the analysis did indicate that among participants with MDD, suicidal thinking is much more common in those with comorbid social phobia or bulimia nervosa than in those without either of these disorders. Previous studies have demonstrated increased rates of SI in MDD patients who lack social support or have comorbid anxiety disorders, but the current study is the first to specifically find an association between social phobia and increased rates of SI. Additionally, patients with more than one past depressive episode may also be at increased risk of SI. There was also limited evidence to suggest white patients are at greater risk of SI than black patients. Further work needs to be done in this area to confirm our findings and to continue identifying sociodemographic and clinical characteristics associated with increased risk of SI in patients with MDD in order to enable clinicians to identify and assist these at-risk patients. Acknowledgements This project was funded by the National Institute of Mental Health under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (PI, Trivedi MH). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The NIMH approved of the design of the overall study and reviewed its conduct, but performed no role in the collection, management, and interpretation of the data analyzed in this manuscript, nor in the preparation, review, or approval of the manuscript. Declaration of interest Some of the authors received educational grants, received honoraries, or had otherwise associations to the National Institute of Mental Health, the Robert Wood Johnson Foundation, and the Stanley Medical Research Institute, Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra- Zeneca; Bristol-Myers Squibb Company; Cephalon; Cyberonics, Inc., Neuronetics, Inc., Magstim, and Advanced Neuromodulation Systems, Forest Pharmaceuticals Inc.; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Eli Lilly & Company; Lorex Pharmaceuticals; Novartis; Organon Inc.; PamLab, LLC; Pfizer Inc.; Pharmavite; Roche; Sanofi Synthelabo; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories, Aspect Medical Systems; Astra- Zeneca; Bayer AG; Biovail Pharmaceuticals, Inc.; BrainCells, Inc.; Bristol-Myers Squibb Company; Cephalon; Compellis; Cypress Pharmaceuticals; Dov Pharmaceuticals; EPIX Pharmaceuticals; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals Inc.; GlaxoSmithKline; Grunenthal GmBH; J & J Pharmaceuticals; Janssen Pharmaceutica; Jazz Pharmaceuticals; Knoll Pharmaceutical Company; Eli Lilly & Company; Lundbeck; MedAvante, Inc.; Novartis; Nutrition 21; Organon Inc.; PamLab, LLC; Pfizer Inc.; PharmaStar; Pharmavite; Roche; Sanofi Synthelabo; Sepracor; Solvay Pharmaceuticals, Inc.; Somerset Pharmaceuticals; Wyeth-Ayerst Laboratories. He has been on speaking bureaus for Astra- Zeneca; Bristol-Myers Squibb Company; Cephalon; Forest Pharmaceuticals Inc.; GlaxoSmithKline; Eli Lilly & Company; Novartis; Organon Inc.; Pfizer Inc.; PharmaStar; Wyeth- Ayerst Laboratories, American Foundation of Suicide Prevention, and Brain Research Foundation, the American Psychological Association, the US Department of VeteransÕ Affairs. Trial registry name Assessing Treatment Emergent Suicidal Ideation in Patients With Major Depression (SAMS), Identification # NCT , References 1. Food and Drug Administration. FDA Public Health Advisory: suicidality in adults being treated with antidepressant medications. [online]. Available at: Last updated: 2005; Accessed: Isacsson G, Holmgren A, Osby U, Ahlner J. Decrease in suicide among the individuals treated with antidepressants: a controlled study of antidepressants in suicide, Sweden Acta Psychiatr Scand 2009;120: Sondergard L, Kvist K, Lopez AG, Andersen PK, Kessing LV. Temporal changes in suicide rates for persons treated and not treated with antidepressants in Denmark during Acta Psychiatr Scand 2006;114: Goldney RD, Dal Grande E, Fisher LJ, Wilson D. Population attributable risk of major depression for suicidal ideation in a random and representative community sample. J Affect Disord 2003;74: Brown GK, Beck AT, Steer RA, Grisham JR. Risk factors for suicide in psychiatric outpatients: a 20 year prospective study. J Consult Clin Psychol 2000;68: Fu Q, Heath AC, Bucholz KK et al. A twin study of genetic and environmental influences on suicidality in men. Psychol Med 2002;32: Sokero TP, Melartin TK, Rytsala HJ, Leskela US, Lestela- Mielonen PS, Isometsa ET. Suicidal ideation and attempts among psychiatric patients with major depressive disorder. J Clin Psychiatry 2003;64: Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23: Zimmerman M, Mattia JI. A self-report scale to help make psychiatric diagnoses: the Psychiatric Diagnostic Screening Questionnaire. Arch Gen Psychiatry 2001;58: Sangha O, Stucki G, Liang MH, Fossel AH, Katz JN. The Self-Administered Comorbidity Questionnaire: a new 483

5 Morris et al. method to assess comorbidity for clinical and health services research. Arthritis Rheum 2003;49: Rush AJ, Trivedi MH, Ibrahim HM et al. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 2003;54: Erratum p Sareen J, Cox BJ, Afifi TO et al. Anxiety disorders and risk for suicidal ideation and suicide attempts: a populationbased longitudinal study of adults. Arch Gen Psychiatry 2005;62: Perroud N, Baud P, Preisig M et al. Social phobia is associated with suicide attempt history in bipolar inpatients. Bipolar Disord 2007;9: Claassen CA, Trivedi MH, Rush AJ et al. Clinical differences among depressed patients with and without a history of suicide attempts: findings from the STAR*D trial. J Affect Disord 2007;97: Favaro A, Santonastaso P, Monteleone P et al. Self-injurious behavior and attempted suicide in purging bulimia nervosa: associations with psychiatric comorbidity. J Affect Disord 2008;105:

6 Copyright of Acta Psychiatrica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or ed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or articles for individual use.