Update on the Toxicology of Suicide — (Primary Psychiatry)

SSRI Ed note: Biased analysis starts with assumption that psychotropic drugs reduce suicides, findings show opposite but reviewers fail to notice.

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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.

Learning Objectives:
• 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: dr6340451@pol.net.


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.

Psychiatric Impairment

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.

Substance Abuse

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.

Psychotropic Medications

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.