Needs Assessment: Suicide remains an important public health problem, and suicide prevention is a major challenge. Primary care physicians treat numerous patients with known risk factors for suicide. Early detection, along with vigorous treatment of affective and substance use disorders—the two most common disorders found in people who commit suicide—is considered the most effective way to prevent suicide. However, advances in suicide prevention are hampered by lack of sensitive measures to evaluate the effect of specific interventions. In this article, evidence that toxicologic monitoring of suicide may provide valid ex vivo markers of treatment rate and substance abuse is discussed in the context of known risk factors and the recent black box warnings against antidepressants.
• Describe risk factors for suicide.
• Explain why the effects of most interventions on suicide prevention are unknown.
• Understand the value of postmortem toxicologic investigations in individual suicides.
• Identify the potential of ex vivo markers of treatment rate and substance abuse in suicides.
Target Audience: Primary care physicians and psychiatrists.
CME Accreditation Statement: This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the Mount Sinai School of Medicine and MBL Communications, Inc. The Mount Sinai School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.
Credit Designation: The Mount Sinai School of Medicine designates this educational activity for a maximum of 3 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Faculty Disclosure Policy Statement: It is the policy of the Mount Sinai School of Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. Presenters must also make a meaningful disclosure to the audience of their discussions of unlabeled or unapproved drugs or devices. This information will be available as part of the course material.
This activity has been peer-reviewed and approved by Eric Hollander, MD, chair and professor of psychiatry at the Mount Sinai School of Medicine, and Norman Sussman, MD, editor of Primary Psychiatry and professor of psychiatry at New York University School of Medicine. Review Date: October 24, 2007.
Drs. Hollander and Sussman report no affiliation with or financial interest in any organization that may pose a conflict of interest.
To receive credit for this activity: Read this article and the two CME-designated accompanying articles, reflect on the information presented, and then complete the CME posttest and evaluation. To obtain credits, you should score 70% or better. Early submission of this posttest is encouraged: please submit this posttest by November 1, 2009 to be eligible for credit. Release date: November 1, 2007. Termination date: November 30, 2009. The estimated time to complete all three articles and the posttest is 3 hours.
Dr. Dhossche is professor in the Department of Psychiatry and Human Behavior at the University of Mississippi Medical Center in Jackson.
Disclosure: Dr. Dhossche receives grant support from the American Foundation for Suicide Prevention.
Please direct all correspondence to: Dirk M. Dhossche, MD, PhD, Professor of Psychiatry, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216; Tel: 601-984-5805; Fax: 601-984-6965; E-mail: email@example.com.
Is surveillance of postmortem toxicology a useful way of evaluating the prior rate of psychiatric treatment and substance abuse in people who commit suicide? The question is an important public health issue given the lack of sensitive measures of suicide prevention and current controversy about the role of psychotherapeutic medications. This article reviews the literature on the toxicology of suicide. Although toxicologic investigations are considered an integral part of medical-forensic investigations in individual cases of suicide, very few states require comprehensive toxicology on all suicide victims. Instead, subjective determinations for toxicologic testing based on local policy and individual coroner or medical examiner preference are common practices. Systematic routine toxicologic monitoring in all suicides may serve as ex vivo markers of treatment rate and substance abuse patterns in suicides. The potential of such markers are noted in studies that evaluate risk factors of suicide, including the effects on suicide rates of changing prescription rates of psychotropic medications.
“Anatomy should be recalled from the dead.” —Andreas Vesalius (1514-1564)1
An important limitation of suicide research concerns the lack of access to the chief informant, ie, the deceased victim. Honoring Vesalius’ historic reappraisal of direct observation of anatomic structures over theory and speculation, the main tenet of this article concerns systematic toxicologic investigations of suicide, one of few objective pieces of information on the deceased victim, and its potential benefits both in individual cases and in epidemiologic research.
Ideally, toxicologic analysis should be conducted in every suspected suicide and other types of unnatural death as an integral component in the investigation, requiring correlation with a detailed scene inspection, an extensive exploration into the decedent’s medical and social background, and both gross and microscopic findings, to uncover suicidal ideation or intent. The toxicologic procedures aim to detect all substances present in various body tissues and fluids. Items such as route of administration, acute versus chronic dose, and consistency between drug concentrations and behavioral effects may be critical factors in assessing the manner of death. Toxicologic results can be useful for reconstructing some events before a suicide, and may suggest impaired mental functioning due to intoxication with alcohol or other drugs either acutely, chronically, or both. The presence of prescription medication may indicate recent contact with a physician. Examination for prescribed psychoactive medications may also be useful to estimate the frequency and type of psychiatric treatment before suicide.
The role of toxicologic investigations has only recently received attention as a promising research tool.2 In this article, toxicologic studies in suicide are discussed in the context of known risk factors and the recent black box warnings against antidepressants. More effective suicide prevention will also be discussed. Future studies needed to establish the utility of systematic and comprehensive toxicologic monitoring of suicides for further understanding of suicide.
Systematic studies of consecutive suicides show that risk for suicide concentrates heavily in people with psychiatric illness,3 particularly depressive disorders and substance abuse. Postmortem psychiatric investigations4-14 show that a psychiatric disorder is diagnosable in most suicides. Any depressive disorder is present 47% to 89% of the time, any substance use disorder is present 19% to 51% of the time, and any schizophrenic disorder is present 2% to 16% of the time. No disorder was found in ≤19% of cases. In a study of adolescent suicide, the group with no apparent disorder still had more risk factors for suicide (eg, family history of suicide, past suicidal behavior, legal problems) than community controls.15
The lifetime risk of suicide is often quoted as 15% for affective disorders and alcoholism and 10% for schizophrenia. These rates mot likely apply to selected high-risk populations. Lower estimates on suicide rates in the group of affective disorders16,17 and substance use disorders17,18 (ie, approximately 2% to 7% in both groups), have been advanced. The general risk for suicide in schizophrenia is most likely closer to 4%.17
Facilitating Factors, Clinical Syndromes, and Psychopathology
Some risk factors for suicide, including clinical syndromes, are shown in Table 1. The list is not exhaustive. Severe emotional and cognitive turmoil is likely to precede suicide. Symptoms may be described as lowered mood, anxiety, rage, desire/impulse for self destruction, agitation, hopelessness, despair, guilt, or other cognitive distortions. Separating out these psychological states is difficult. Descriptors more often reflect the author’s frame of reference than a distinct abnormality. For example, in readings of Freud,19 it is speculated that anger and hatred can become self-directed, lead to depression, and be a motivating force in suicide. Recent psychodynamic formulations20,21 have stressed that in addition to affective states such as rage, hopelessness, despair, and guilt, it is also important to consider cognitive factors that lead people to view suicide as a permanent solution to their likely temporary predicament. Individuals can come to see suicide as a reunion, rebirth, retaliatory abandonment, revenge, or self-punishment.
Tendencies of suicidal people to engage in extreme aggression are illustrated in cases of murder followed by suicide. The incidence of murder-suicide has been relatively constant (and infrequent) over time across industrialized countries at approximately 0.2–0.3 per 100,000 people each year.22 In another report,23 violent behavior in the past year was approximately five times more frequent in suicides than accidental deaths. This finding was not explained by greater aggression in subjects with alcohol abuse. Reports conflict regarding the importance of aggressive personality traits as predictors of suicide.24,25 A link between suicide and violence is theoretically attractive as both have been associated with disturbances of central serotonin neurotransmission.26 However, further characterization of the type of aggression preceding suicide and further studies on psychological correlates of neurotransmitter disturbances are warranted before conclusions can be drawn.
Evaluation of Suicide Prevention
Suicide is thought to be preventable, although there is currently no foolproof evidence for efficacy of any preventive action. Theoretically, quick and effective treatment of emerging depression or other mental disorders in every person at any time would most likely be most effective (but practically difficult to implement) in reducing suicide rates given the fact that suicide does not or rarely occurs without psychiatric impairment. General approaches such as efforts to educate physicians about diagnosing and treating depressive disorders and to restrict access to lethal means have been supported as most promising ways to reduce suicides while other methods including public education, screening programs, and media education are equivocal and require more testing.27
Lack of sensitive measures poses major methodologic problems to evaluate the success or failure of suicide prevention. This important shortcoming has been discussed in the evaluation of the world’s first comprehensive suicide prevention program in Finland.28 After program implementation, a 20% reduction of the suicide rate was observed until 1996. Since then, the suicide rate has remained stable at 9% below pre-project levels. However, it is unclear which component, if any, of the prevention program was effective, as not enough data to control for confounding variables and to evaluate outcome were included in the program’s design. Reviews of other suicide prevention programs have concluded similarly.29
The two most important obstacles for progress in suicide research are the low base rate of suicide and ethical concerns of studying suicidal people in controlled trials of medications or psychotherapy. The low base-rate of suicide requires the study of large populations to yield meaningful and significant results. These costly and lengthy studies have not been done yet. It is difficult to know if anything actually prevents a suicide because of statistical constraints of the prediction of infrequent events. The issue has been summarized by Murphy,30 who stated that “if suicide is difficult to predict, its prevention is even more difficult to detect.”
Tackling the other problem of including suicidal people in clinical trials of drug or psychotherapy treatment would require acceptance by ethics committees that suicide is at times an unfortunate but difficult-to-avoid outcome of psychiatric illness in some people. Any studies that enroll people with suicidal behaviors should have sufficient safeguards to protect participants from unnecessary risk.
The literature supports a strong association between chronic substance abuse, suicide attempts,31 and suicide.32-34 A recent analysis found the highest standardized mortality rates (SMR) for suicide for mixed drug use (SMR 1,685; 95% CI 1,473–1,920), followed by intravenous drug use (SMR 1,373; 95% CI 1,029–1,796), opioid-use disorders (SMR 1,351; 95% CI 1,047–1,715), and alcohol-use disorders (SMR 979; 95% CI 898–1,065).35 In these calculations, an SMR of 100 indicates that the observed number of suicides is the same as the expected number of suicides, whereas an SMR of 1,000 indicates a 10-fold greater number of observed (in substance users) compared to expected (in the general population) suicides.
Antidepressants, lithium, and clozapine have been ascribed anti-suicide properties for selected patient groups, but there are conflicting results mostly due to methodologic problems. The problem of assessing the impact of psychotropic medications on suicide has long been anticipated by Murphy30:
It is important to realize that the absence of a suicide generates no data. Thus, we can never prove what has been accomplished. Yet, we can hardly doubt that it occurs. This argument would be more satisfying if there had been a gradual reduction in the national suicide rate since studies of the late 1950s clearly linked suicide to psychiatric illness or if it had paralleled the growing use of antidepressants. It might then be concluded that physicians had learned from these studies and were more alert to the indicators of risk, at least that they were recognizing and treating more depressions. In fact, the suicide rate has risen during that period. But it has not done so uniformly. It has actually fallen among the older age groups, those most likely to see a physician. It has risen most—and considerably—among adolescents and young adults. Evidence that is fragmentary at present suggests that this group is far less likely to have been under a physician’s care. Thus, the opportunity to treat may not have occurred in many of these cases.30
Recent studies confirm that approximately 25% to 33% of suicides received psychiatric care in the year before committing suicide.36-38
The evidence that the use of psychotropic medications can prevent suicides is considerable.39-44 The effect is logically stronger if the medication is prescribed appropriately, in sufficient dose, together with other psychotherapeutic and psychosocial interventions, and continually in people at high risk.45,46 Prospective studies providing definitive evidence for anti-suicide effects of psychotropic medications face great methodologic problems and may never be done. In contrast, the evidence that the use of antidepressants increases suicide is equivocal,47,48 although it is possible that in some patients, antidepressant treatment increases suicidal ideas and attempts.49,50
Toxicology of Suicide
Systematic, comprehensive toxicologic studies in suicides and other violent deaths have been infrequently conducted. There is only one study with comprehensive toxicologic data on suicides in the literature that has examined all suicides in a geographically defined area. This study was done in 1,348 suicides from Finland during 1987–1988, representing 97% of all suicides during that period.51 There were 1,032 men (77%) and 316 women (23%) in the sample. The most frequent methods in men were hanging (34%), firearms (26%), and overdose (13%). In women, overdose was the most frequently used method (41%), followed by hanging (29%) and drowning (14%). More than 150 commonly prescribed and/or abused drugs were toxicologically detected. Drugs were found in 42% of cases, in 67% of women, and 34% of men. Alcohol was detected more frequently in men (41%) than in women (20%). Benzodiazepines were the most frequently detected specific prescription drug in both sexes (23% of all cases), followed by neuroleptics (13%) and antidepressants (8%). In cases with overdose, a single drug was found in 29%, two drugs in 30%, three drugs in 23%, four drugs in 15%, and five or more drugs in 4%. The relative risk (RR) of suicide was calculated for different drugs relating the number of suicides committed by use of each drug to its national sales. The highest risk was found for barbiturates (RR=105), followed by imipramine (RR=18), maprotiline (RR=12), doxepin (RR=12), and dextropropoxyphene (RR=10). The lowest risk was found for benzodiazepines (RR=0.33).
Most other studies have typically focused on a particular substance, eg, alcohol and/or cocaine52,53 or one class of substances, eg, prescription psychotropics.54 In most studies, the most frequent substance detected is alcohol. The proportions of alcohol-positive suicides have varied in the 30% to 40% range.51,55-57 Several studies have reported the rates of alcohol detection for various methods of suicide in cases of all ages (Table 2).51,56,58-61 Alcohol detection among suicides by gunshot in these reports tends to be toward the high end of the 30% to 40% range.51,56,58-61 The same is true, however, for overdoses and carbon monoxide poisoning. These findings suggest that, in general, the presence of alcohol is not preferentially associated with any particular suicide method.
Prescription psychotropic medications were the focus of a New York City study.54 Among 1,970 certified suicides from 1990–1992, 1,635 (83%) of cases had valid toxicology findings. Overdose was the method of suicide in 293 cases (18%). Antidepressants and neuroleptic medications were detected in 268 (16%) of 1,635 suicides studied. There were more detections in women and whites. Age was not associated with detection of these medications. In approximately 50% of cases that died by overdose, a prescription psychotropic medication was found. Conversely, approximately 50% of those with positive detection of an antidepressant or neuroleptic drug overdosed. The other 50% used a method other than poisoning, such as guns or fall from height. From this study, it seems that only a small proportion of suicide victims took antidepressants or neuroleptics in the days before their death. The authors of the study54 comment that it is unknown if wider use of psychotropic medication in people with psychiatric conditions can reduce the number of suicide, but that the null hypothesis (ie, that use of psychotropic medications does not affect suicide rates) requires that individuals who commit suicide have been prescribed and have taken those medications. Findings suggest that this is not the case in most suicides.
The Centers for Disease Control and Prevention62 reported that 13 states collected data for the National Violent Death Reporting System (NVDRS) in 2004. None of the states conducted comprehensive alcohol and drug screenings on all suicide victims, despite evidence of substance use among substantial numbers of suicide victims. Descriptions of cases selected for toxicology screening suggest subjective determinations for testing on the basis of local policy and individual coroner or medical examiner preference.63 It was found that the percentage of suicide victims tested varied among states, ranging from 25.9% to 97.7%. Among all suicide victims with positive test results, the greatest percentage tested positive for alcohol (33.3%), followed by opiates (16.4%), cocaine (9.4%), marijuana (7.7%), and amphetamines (3.9%). A similar percentage of poisoning suicide (ie, suspected intentional overdose) and non-poisoning suicide victims tested positive for alcohol or other drugs, with the exception of opiates. Overall, these findings emphasize the need to continue monitoring toxicology test results of suicide victims, which might identify geographic and temporal patterns of substance use that can help guide development of effective suicide interventions. Uniform, comprehensive, toxicology testing practices on a state and national basis should be adopted for better understanding of suicide and development of effective interventions.
Ex Vivo Marker of Treatment Rate
Several studies support that toxicologic monitoring is a promising marker of treatment rate in suicides. For example, in a study of toxicologic data in 333 consecutive suicides occurring in Mobile County, Alabama, between 1990 and 1998,64 it was found that detection rates of antidepressants were low (ie, 20%) in suicides. This suggests undertreatment of depressive disorders in people who commit suicide. Alcohol was detected in 33% of cases. Extensive overlap in detections of prescribed psychotropics and abusable substances suggests that patients at risk for suicide should be advised not to use abusable substances.
In another study,65 toxicologic findings were compared between 179 suicides in San Diego County, California, from 1981–1982,8 and 333 suicides in Mobile County, Alabama, from 1990–1998. Toxicologic detection rates were similar for most categories of psychoactive substances in suicides from Mobile, Alabama (1990–1998) and San Diego, California (1981–1983). Higher detection rates of antidepressants in Mobile suicides (20% versus 8% in San Diego) suggest higher treatment rates of depression in recent samples. Toxicologic detection rates of neuroleptics in suicides vary greatly between studies, occuring from 2% to 7% in United States suicide samples (Mobile County suicide sample,64 San Diego suicide sample,65 1995 New York City suicide sample54), 7% in a Swedish study,66 and 23% in a Finnish study.51 In the Mobile sample, detection rates of neuroleptics increased from ≤1% to 6% over an 8-year period.64
In order to make maximum use of systematic toxicologic monitoring, future study designs need to collect and correlate three pieces of information. First, all suicides in a defined geographic area need be recorded over a period of time. Second, comprehensive toxicologic findings need to be done in all cases. Last, prescription medication data in the years preceding suicide need to gathered. This design will allow for testing the hypothesis that, first, positive detection rate of prescription psychotropic medications will be higher in suicide victims who have been prescribed psychotropic medications the last year before death than in suicide victims who have not been prescribed psychotropic medications; and second, positive detection rate of alcohol, cocaine, and cannabis will be higher in suicide victims who have not been prescribed psychotropic medications during the year before death than in suicide victims who have been prescribed such medications. Such an ideal study has not been conducted as of yet, but would be necessary to provide further support for routine toxicologic monitoring in all suicides as an important ex vivo measure of treatment rate in suicides.
Ex Vivo Marker of Substance Abuse
Toxicologic monitoring of suicide is also a promising marker for rates of substance use in people at risk for suicide. If interventions to decrease substance abuse in people at risk for suicide are successful, one would like to see a decrease in detection of alcohol, cocaine, and/or cannabis as well as other street drugs. In a review of suicide studies with both comprehensive toxicologic and diagnostic data,67 the sensitivity of alcohol detection to diagnose alcohol and substance use disorders in suicides was low in all studies (range=39% to 42%). The specificity was between 80% and 95%. It was concluded that most suicides with positive alcohol detection seem to suffer from chronic substance abuse problems, although the high rate of false negatives limit the sensitivity of the testing.
Black Box Warnings
In 2003, the US Food and Drug Administration issued a public health advisory about the risk of suicidality in pediatric patients taking selective serotonin reuptake inhibitors (SSRIs) for depression. In 2005, the agency mandated a black box warning and medication guide indicating that pediatric and adult patients may be at risk. Recent studies have reported that the FDA advisory was associated with significant reductions in aggregate rates of diagnosis and treatment of pediatric depression. Evaluation of a large pediatric cohort with newly diagnosed episodes of depression68 showed that from 1999 to 2004 pediatric diagnoses of depression increased from 3 to 5 per 1,000. After the FDA advisory was issued, the national rate decreased to levels observed in 1999, a significant deviation from the historic trend. Pediatricians and nonpediatrician primary care physicians accounted for the largest reductions in new diagnoses. Among patients with depression, the proportion receiving no antidepressant increased to three times the rate predicted by the pre-advisory trend, and SSRI prescription fills were 58% lower than predicted by the trend. Similar findings were presented in analyses of another database.69
Despite the focus of the policy on pediatric patients, the FDA advisory had significant effects on the treatment for adults with depression.70 In a large cohort (1998–2005) with newly diagnosed episodes of depression, the rate of diagnosed depression was significantly lower after the advisory than would have been expected on the basis of the pre-advisory historic trend. The average percentage of adults with new (versus recurrent) depressive episodes was 88.6% in the pre-advisory period (declining at an annual rate of 1.69%), and it decreased significantly to 77.5% (declining more rapidly, at an annual rate of 7.7%). The percentage of adults with depression who did not receive an antidepressant increased from an average of 20% (declining at 0.45% annually) before the policy action to an average of 30% (increasing at an annual rate of 20.6%). The data did not show any compensatory increases in psychotherapy or prescription of atypical antipsychotics or anxiolytics. Specific criticisms of analytic procedures and inferences leading to these black box warnings have been articulated,71 emphasizing that no suicide occurred in clinical trials of approximately 4,400 children and that the composite variable labeled “suicidality” is an unvalidated and inappropriate surrogate.
It is striking that toxicologic studies of suicide have not featured in the discussion of the alleged increased urge for suicide by antidepressants. In fact, the hypothesis that treatment of depressed individuals with SSRIs leads to an increased risk of suicide was rejected in several studies using toxicologic data from adult and youth suicide.72-76 For example, in a Utah study72 of 151 consecutive youth suicides in individuals 13–21 years of age between August 1, 1996, and June 6, 1999, toxicologic studies were completed for 91% (N=137) of subjects. Fifteen percent screened positive for alcohol. Medications were found in 18%, but common psychotropic medications (antidepressants, antipsychotics, and mood stabilizers) were found only in 3% (4 of 137). Studies of youth suicide in New York City reported that in the years 1993 through 1998,73 there were 66 suicides among youths <18 years of age. Toxicology was tested in 58 (87.9%) of the 66 suicides. None of the victims had paroxetine detected in their blood obtained at the time of autopsy. Imipramine was detected in two victims and fluoxetine in another two. The same group found that, from 1999 through 2002, there were 41 individuals in New York City <8 years of age who committed suicide.75 Thirty-six (87.8%) had a serum toxicologic analysis. There was one (2.8%) suicide in which both bupropion and sertraline were detected at the time of autopsy. Antidepressants were not detected in any of the other youth suicides.
Isacsson and colleagues74 compared detections of different antidepressants in the forensic toxicologic screening of 14,857 suicides and 26,422 cases of deaths by accident or natural causes in Sweden between 1992 and 2000. There were 3,411 (20%) detections of antidepressants in the suicide victims and 1,538 in the controls. SSRIs had lower odds ratios than the other antidepressants. In the 52 suicide victims <15 years of age, no SSRIs were detected. Among the victims 15–19 years of age, antidepressants were detected in 13 (4%) of 326 cases. SSRIs had lower relative risk in suicides compared with non-SSRIs. Taken together, these studies support undertreatment of depression and other psychiatric conditions in youths at risk for suicide, rather than supporting antidepressant use as an important risk factor for suicide in this age group. A similar argument applies to adult populations.39-44
In conclusion, evidence obtained from toxicologic studies in adult and youth suicide victims, which goes against the hypothesis that treatment of depressed individuals with SSRIs and other types of antidepressants leads to an increased risk of suicide, was not considered in the FDA advisory and black box warnings. Future toxicologic studies comparing detection rates of antidepressants in suicide victims should be informative as to the extent of decreased rates of depression treatment, especially in the younger age groups.
The routine use of comprehensive toxicologic evaluation of suicide and other violent deaths is a cost-effective tool to ensure completeness of forensic evaluations. Although toxicologic investigation is considered an integral part of medical-forensic investigations in individual cases of suicide, very few states require comprehensive toxicology on all suicide victims. Instead, subjective determination for toxicologic testing based on local policy and individual coroner or medical examiner preference is a common practice. Toxicologic monitoring of suicide should be more widespread. Systematic toxicologic monitoring of suicides have largely confirmed known problems in suicide prevention (ie, the undertreatment of psychiatric disorders, particularly depression, and the deleterious effect of alcohol abuse and other abusable substances on propensity for suicide). Future studies over time and in different areas should assess changes in medical treatment rates of people at risk for suicide as suggested by changes in detection rates of prescription psychotropic substances. In addition, changes in substance use patterns of alcohol and street drugs can be monitored this way. Further research should seek to strengthen the evidence that toxicologic measures are valid ex vivo markers of treatment rate and substance use. PP
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