MHEI transcript 1 introduction


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The Mental Health Educational Initiative is an interactive program that utilizes a combination of formal and non-formal learning to provide a multidisciplinary group of health care providers with a unique model for the understanding, identification, and management of actual vs. perceived risk for suicidal ideation and related adverse events.

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MHEI transcript 1 introduction

  1. 1. PODCAST TRANSCRIPT: INTRODUCTION TO SUICIDAL RISK ASSOCIATED WITH THE USE OF MEDICATIONSNeubauer, David N., M.D.Associate ProfessorPsychiatry and Behavioral SciencesJohns Hopkins Bayview Medical CenterHello, my name is David Neubauer and I would like to welcome you to the first part in aseries of four podcasts focusing on the issues surrounding the suicide risk associated withthe use of medications, particularly antidepressant and antiepileptic agents, and particularlyamong children, adolescents and young adults.During this series we will discuss some of the background leading up to the FDA advisoriesand black box warnings and the research that has helped better define suicidality andsuicide risk. We will also consider strategies for the long-term monitoring of suicide risk inpatients taking these medications.In this first podcast we will consider the history of the concern about suicide risk withantidepressant use and some of the effects of the black box warnings in the US. Concernabout a potential heightened risk of suicide among people prescribed antidepressants datesback nearly to the introduction of these medications over a half century ago. It washypothesized that severely depressed individuals with strong suicidal intention whentreated with an antidepressant, most likely a tricyclic antidepressant in the distant past,early in treatment would experience some improvement in their energy while still verydepressed and tragically carry through with their plans to kill themselves. However, a newworry about suicide emerged following the introduction of the SSRI antidepressants and by1991 there was discussion in the literature about the possibility of an actual increased riskof suicide with SSRI use. Concern over this issue grew and by 2003 the FDA had issued astatement recommending that paroxetine not be prescribed for children and adolescents.Then just a few months later that same year following a preliminary review of clinical trialdata, the FDA issued a public health advisory regarding antidepressants in children andadolescents suggesting that they should be used with increased caution and withsupervision. The advisory specifically referred to the SSRIs, fluoxetine, paroxetine,sertraline, fluvoxamine and citalopram as well as nefazodone, mirtazapine, and venlafaxine. Register here to earn credit for this activity: Presented by The Johns Hopkins University School of Medicine Developed through a strategic educational facilitation by Medikly, LLC. Supported by an educational grant from Lilly USA, LLC.
  2. 2. By March 2004 the FDA warned that patients prescribed 10 antidepressants, the list nowalso including escitalopram and bupropion, should be monitored for suicidality. Finally, inOctober 2004 came the FDA black box requirement for all antidepressants prescribed forchildren and adolescents stating that the medications may be associated with increasedsuicidal thoughts and behaviors. That black box warning was extended to young adultsthrough age 24 in December 2006.What was the evidence that led to the FDA warning and the subsequent controversy andthe debate about whether the FDA did the right thing? The evidence initially was anecdotalcase reports, stories in the media, and the observation that the rate at whichantidepressants were prescribed for children and adolescents had risen rather dramatically.Where would be the quickest and easiest place to get a better handle on whether certainantidepressants actually increase suicidal thinking or behavior? Right, clinical trial data thatalready had been collected. The use of antidepressants had been evaluated for efficacy andsafety in children and adolescents in these placebo controlled studies with well organizeddata collection. There were many clinical trials to examine and they involved a variety ofSSRIs and other newer antidepressants, and they were for a variety of indications inaddition to major depression. The clinical trial approach should have provided clear andunambiguous evidence to answer the simple question, do antidepressants increasedsuicidal thinking or behavior in this population of young people. Here is what they found:quite a mess when it came to consistency of what constituted suicidality. There simply wasno standard definition or methods of inquiry, in fact, the studies tended to note suicidalityas an adverse event when it was reported. But it was not routinely assessed and the casesof thinking or behaviors that constituted suicidality in these studies varied widely. Whenthe data in the clinical trials ultimately was reviewed with consistent methods, it was foundthat some serious suicidal behavior had not been categorized as suicidal at all, and thatsome other very trivial behaviors were classed as suicidal.In the attempt to figure out what was really going on and so they could make educateddecisions about warnings and other clinical guidelines regarding antidepressants, the FDAcontracted with the Columbia University New York State Psychiatric Institute to develop asystematic approach to classify potential suicidal adverse events. This work, coordinated byKelly Posner, led to the creation of the Columbia Classification Algorithm of SuicideAssessment known as C-CASA. The C-CASA organization scheme uses three broad Register here to earn credit for this activity: Presented by The Johns Hopkins University School of Medicine Developed through a strategic educational facilitation by Medikly, LLC. Supported by an educational grant from Lilly USA, LLC.
  3. 3. categories and a total of eight specific definitions associated with events that may or maynot be regarded as representing suicidal thinking or behavior.The three major categories are:1. Events regarded as suicidal.2. Nonsuicidal events.3. Intermediate or potentially suicidal events.The cases are individually assessed with a detailed narrative that involves past history ofsuicide attempts or self-injurious behavior as well as family history. There was strong focuson attempting to determine the presence of the intention to commit suicide and on thelethality of the means. All of the categories are well-defined with published trainingexamples.The broad suicidal events category has four subcategories:1. Completed suicide.2. Suicide attempt.3. Preparatory acts toward imminent suicidal behavior.4. Suicidal ideation.The C-CASA definition of complete suicide is “a self-injurious behavior that resulted infatality and was associated with at least some intent to die as a result of the act.” A suicideattempt is a potentially self-injurious behavior associated with at least some intent to die asa result of the act. The intent may have to be inferred from the person’s behavior orcircumstances. The suicide attempt does not necessarily result in actual injury. Thepreparatory acts toward imminent suicidal behavior category represents situations wherepeople have taken steps to injure themselves, but have stopped on their own or beenprevented by others from performing the harmful acts. Examples would includecircumstances where people plan suicide and were acquiring means to end their livesperhaps by using a gun, knife, rope, poison or excessive medication doses.The C-CASA suicidal ideation definition is “passive thoughts about wanting to be dead oractive thoughts about killing oneself not accompanied by preparatory behavior.” Thereforethis label would be appropriate when the person expresses the suicidal intention andperhaps a specific plan or passively where he or she states a desire to be dead withoutacting on the feelings. Register here to earn credit for this activity: Presented by The Johns Hopkins University School of Medicine Developed through a strategic educational facilitation by Medikly, LLC. Supported by an educational grant from Lilly USA, LLC.
  4. 4. The second C-CASA broad category nonsuicidal events is important to avoid confusion andto help researchers better determine actual future suicide risk. The first of the twononsuicidal events sub-categories is labeled, “self-injurious behavior, no suicidal intent” andis appropriate for the circumstances where individuals have harmed themselves in somemanner, but where it is clear that they had no desire to end their lives. Examples wouldinclude superficial lacerations or burns. The second nonsuicidal events sub-category isdescribed as “other non-deliberate self-harm.” This label would be appropriate foraccidental injury or in relation to any psychiatric behavioral or medical symptoms, wherethere was no evidence of suicidal ideation or intent and no deliberate self-harm.The final C-CASA major category is “indeterminate or potentially suicidal events.” The firstoption here is “self-injurious behavior suicidal intent unknown”. Here there is clear actualor potential injury, but whether suicidal intent was present cannot be determined basedupon available information. The other sub-category is simply labeled “not enoughinformation” and is applicable for situations where there is suspicion but insufficientevidence to determine whether there was suicidal behavior or ideation.It is important to remember that C-CASA initially was developed to aid with retrospectivereviews of clinical trial data, where the level of detail varied considerably; however, thecategories provided the foundation for the suicide severity rating scale that we will discusslater.So back to the FDA and the evidence for the black box warnings. With C-CASA all thatclinical trial data now could be re-analyzed in a systematic manner. Data from 25 child oradolescent antidepressant clinical trials involving over 4500 patients were examined andcompared with the original 427 adverse event reports. The new C-CASA analysis found 38discrepancies that included 26 new possible suicidal events including a suicide attempt,preparatory act and several cases of suicidal ideation. There also were 12 cases originallylisted as potentially suicidal that were re-classified as not potentially suicidal. Overall the C-CASA study found more potentially suicidal events, but a lower rate of specific suicideattempts. While there was a greater rate of suicidal thinking and behavior among thechildren and adolescents taking the antidepressants compared with the placebo controlsubjects, it should be remembered that there were zero, no actual completed suicides inthese clinical trials and therefore in the data set driving the FDA warnings. But completedsuicides are rare and limited clinical trial data could not be expected to provide an accurateprediction. Register here to earn credit for this activity: Presented by The Johns Hopkins University School of Medicine Developed through a strategic educational facilitation by Medikly, LLC. Supported by an educational grant from Lilly USA, LLC.
  5. 5. Since it is well established that past suicide attempts are a major risk factor for completedsuicide, the concern certainly is appropriate. The ultimate answer must be appropriatelytreating patients including children and adolescents who have well-defined disorders withevidence based therapies and of course for mood and anxiety disorders that often meansantidepressants. Although the benefits of treatment far outweigh the risks, those risksassociated with suicidal thinking and behavior, need to be understood and appropriatelymanaged.What was the result of the black box warnings about prescribing antidepressants to childrenand adolescents? Initially, there was great concern that the warnings would makephysicians and other providers much less likely to treat patients with these medications,and that as a result there would be under treatment and an increase in the suicide rate inyoung people. Several research studies have made before and after comparisons with largedatabases focusing on psychiatric diagnoses for children and adolescents andantidepressant prescriptions. One recent example by Chen and Toh was published inPsychiatric Services in 2011. They analyzed centers for disease control and prevention CDCdata collected annually between 1998 and 2007. The available data included children ages5 to 17 years old and included information on patient visits where depression diagnoseswere coded on any visits where antidepressants were prescribed and where depression wascoded and an antidepressant was prescribed.They found a gradual increase in depression coded visits among children leading up to theFDA advisories followed by a decline. In contrast, there was not a decline among adults.For the children, the peak was 4.3 million visits in the 2002 to 2003 years and a 26%decrease to 3.2 million in the 2006 to 2007 years. Similarly there was a decline in visits forchildren when antidepressants were prescribed following the advisories and again therewas no significant decline during those periods for adults. However, the findings were morerevealing when Chen and Toh examined the visits where a depression diagnosis was codedand an antidepressant was prescribed. Although the total number of visits has declined, theproportion of children specifically diagnosed with major depression and subsequentlyprescribed an antidepressant did not decline. Other studies have found an increase inpsychotherapy treatment for children with depressive disorders following the FDAadvisories. Register here to earn credit for this activity: Presented by The Johns Hopkins University School of Medicine Developed through a strategic educational facilitation by Medikly, LLC. Supported by an educational grant from Lilly USA, LLC.
  6. 6. And what about the youth suicide rate? A 2007 CDC report highlighted a recent sharp rise inthe suicide rate among 10 to 24 years olds following the years of decline. It was notpossible to assign any specific causality.In future podcasts, we will have a closer look at the antiepileptic medication black box storyand will further explore the impact of the FDA warnings and we will discuss strategies formonitoring suicidality in patients taking these medications. Register here to earn credit for this activity: Presented by The Johns Hopkins University School of Medicine Developed through a strategic educational facilitation by Medikly, LLC. Supported by an educational grant from Lilly USA, LLC.