A. Benjamin Srivastava, MD

 

The opioid epidemic continues to devastate the United States across demographic and socioeconomic groups; two-thirds of the 63,632 Americans who died of drug overdoses¹ in 2016 died of prescription or illicit opioids.

In 2015, Theodore J. Cicero, PhD, professor of psychiatry at Washington University, St. Louis, reported on a fundamental change in the nature of the ongoing opioid epidemic: What started as prescription opioid overprescribing, leading to diversion, abuse, and opioid addiction, was transitioning to illicit heroin distribution and consumption. Prescription opioids, namely, extended-release oxycodone (Oxycontin), were perceived initially as pure and safe, as they were specifically dosed and physician prescribed. In addition, filling a prescription for opioids was not associated with the shame or stigma of buying illicit drugs off the street. Because those drugs were seen as therapeutic and pharmacologically “legitimate,” many clinicians and the lay public alike were surprised to see the surge of opioid addiction and overdoses.

Dr. Cicero and others noted² that prescription opioids, whether taken originally for analgesic or recreational purposes, became a “gateway” to heroin, which already was making its way into the United States from Mexico,³ as heroin was cheap and becoming cheaper, easier to find, easy to use, and “pure.” Prescription opioids, on the other hand, were becoming more expensive, and physicians were facing increased regulations in prescribing them. Thus, as prescription opioid use became more and more stigmatized, heroin use was seen, paradoxically, as a more practical alternative. The amount of opioids prescribed in the United States has peaked; physicians are prescribing opioids less often; and the averaged dose has dropped as well, according to the Centers for Disease Control and Prevention.⁴ The first wave of deaths was attributable to prescription opioids, and the second was tied to illicitly obtained potent fentanyl analogs (manufactured in China and smuggled primarily through Mexico), which is added to heroin and sold in the United States.⁵

Many addiction experts and health policy leaders were not surprised by the increases in HIV, TB, and hepatitis B and C that followed the increasing use of intravenous opioids. However, few had experience with previous opioid epidemics in the United States, the most recent being the heroin epidemic occurring in the 1960s-1970s in the aftermath of the Vietnam War. At that time, the notion that heroin was contaminated with other psychoactive drugs, medications, fillers, and other adulterants was a foregone conclusion – though in public health and treatment discussions, this issue is hardly ever raised. We believe this to be a significant lapse in policy and planning. Surveillance by the Drug Enforcement Administration shows that acetyl fentanyl–laced heroin costs a little more on the street than regular heroin. Yet it sells, because users believe its extreme potency produces a better high, thus worth the extra cost. This phenomenon underscores an important point: Opioid addicts often are in search of a better high and will go to any lengths – even risking their lives – to get it.

The “cutting” or “adulteration” of street drugs is common practice in the manufacturing, distribution, and selling of illicit drugs, and the motive is to increase profit. The term “adulterant” generally refers to addition of substances with some psychoactive effects, such as caffeine, ephedra, or even paracetamol. These substances are cheaper than the main substance, have similar or complementary effects when added, and thus help conceal the fact that the desired substance has been cut or diluted. Substances without psychoactive properties such as lactose, other sugars, or talc, are added to a drug primarily to increase the bulk or weight of the illicit substance, or for aesthetic purposes to fool the user. Some adulterants simply are the result of the particular manufacturing process used to make the drug. For example, illicitly manufactured methamphetamine frequently is contaminated by nonstimulant impurities such as lead or mercury (extremely toxic heavy metals), or from carcinogenic solvents used in the synthesis. The local anesthetic lidocaine often is added to cocaine, and the reasons are intuitive: Both drugs are fast-acting local anesthetics.

More intriguing is the story of the antiparasitic medication levamisole. The DEA has estimated that 60%-89% of the seized street cocaine contains levamisole. Levamisole appears to be partly metabolized into an amphetamine-like compound, which could increase dopamine concentration in the reward pathway and thus activate endogenous opioids: It can mimic the effects of cocaine at a fraction of the cost. Levamisole is associated with several types of severe blood disorders, including leukopenia, agranulocytosis, multifocal inflammatory leukoencephalopathy, and neutropenia; a common presentation is vasculitis resulting in loss of limbs. Thus, a real danger in adulterants such as levamisole is their toxicity beyond those of the drug to which they are added, causing numerous medical consequences – including death.

 

The consideration of adulterants is important in another, emerging problem: Cocaine, colloquially thought of as a drug of the 1980s, is making a comeback. A record amount of cocaine is coming across the Mexican border with increased seizures of drug. Also, the number of acres producing cocaine is increasing, the price per unit sold is decreasing, and the prevalence of use has increased. Unfortunately but predictably, cocaine-related deaths are up: National Vital Statistic Systems data indicate that cocaine-related deaths involving opioids climbed from 2000-2006 and 2012-2015. Opioids, primarily heroin and fentanyl, have been driving the recently reported increases in cocaine-related overdose deaths.⁶ At the March 12, 2018, Drug Enforcement Administration panel on the reemergence of cocaine and cocaine-related deaths, experts reported that adulterants, including fentanyl, were responsible for many cocaine-related deaths. Strikingly, the most recent data from the state of Florida suggest that fentanyl is found as a factor in nearly all cocaine-related deaths, and cocaine commonly is found in fentanyl and fentanyl analog-related deaths.

If stigmata of opioid overdose (for example, miotic pupils and respiratory depression) are present in a patient considered to have overdosed on cocaine, naloxone should be administered, as the clinical presentation may be tied to the presence of opioid adulterants. Then, the patient should be engaged in treatment in a long-term care model with evidenced-based therapies, including medication-assisted treatment and contingency management. An important point, however, as described by Thomas Kosten, MD, professor of psychiatry at Baylor University, Houston, is that while we have multiple pharmacologic treatments for opioid overdose and addiction, none exist for cocaine overdose, craving, addiction, or withdrawal.⁷ Dr. Kosten has pioneered novel treatments for cocaine addiction, including anti-cocaine vaccines, but none has been proven safe and effective as of 2018.

Indeed, in the context of the opioid epidemic, the demand for opioid use treatment has increased, though the consequences of addiction, and thus areas requiring treatment in the opioid-addicted patient, are high in number and complexity.⁸ As we discussed previously, unfortunately, most management is aimed solely at reversing the overdose, stabilizing the patient medically, and discharge. We suggest that prior to discharge, the physician should determine whether the overdose was accidental, a suicide⁹ attempt, passive suicidality (for example, asking “Would you be better off dead?”),¹⁰ extreme risk-taking behavior (akin to playing Russian roulette,¹¹ or other causes. We have suggested that naloxone is similar to cardiopulmonary resuscitation: It is a critical life-saving intervention but not an end in itself. Rather, the need for naloxone should serve as a gateway to comprehensive evaluation, diagnosis, treatment, and long-term care.

 

 

Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health. Dr. Srivastava is a fourth-year resident in the department of psychiatry at Washington University.

References

1 NCHS Data Brief. No. 294. December 2017.

2 N Engl J Med. 2015;373:1789-90.

3 DEA Strategic Intelligence Section. 2017 National Drug Threat Assessment: Drug Enforcement Administration, U.S. Department of Justice, 2017.

4 Centers for Disease Control and Prevention, press release. Mar 29, 2018.

5 MMWR. 2018. Mar 30;67(12):349-58.

6 Am J Public Health. 2017 Mar;107(3):430-2.

7 “Q&A: Thomas Kosten, MD: Anti-drug vaccines.” RiverMend Health.

8 “Q&A: Stacy Seikel, MD. Opioid addiction.” RiverMend Health.

9 N Engl J Med. 2018 Apr 26;378:1567-9. doi: 10.1056/NEJMp1801417.

10 Innov Clin Neurosci. 2014 Sep;11(9-10):182-90.

11 Am J Psychiatry. 187 May;144(5):563-7.

 

The opioid epidemic continues to devastate the United States across demographic and socioeconomic groups; two-thirds of the 63,632 Americans who died of drug overdoses¹ in 2016 died of prescription or illicit opioids.

In 2015, Theodore J. Cicero, PhD, professor of psychiatry at Washington University, St. Louis, reported on a fundamental change in the nature of the ongoing opioid epidemic: What started as prescription opioid overprescribing, leading to diversion, abuse, and opioid addiction, was transitioning to illicit heroin distribution and consumption. Prescription opioids, namely, extended-release oxycodone (Oxycontin), were perceived initially as pure and safe, as they were specifically dosed and physician prescribed. In addition, filling a prescription for opioids was not associated with the shame or stigma of buying illicit drugs off the street. Because those drugs were seen as therapeutic and pharmacologically “legitimate,” many clinicians and the lay public alike were surprised to see the surge of opioid addiction and overdoses.

Dr. Cicero and others noted² that prescription opioids, whether taken originally for analgesic or recreational purposes, became a “gateway” to heroin, which already was making its way into the United States from Mexico,³ as heroin was cheap and becoming cheaper, easier to find, easy to use, and “pure.” Prescription opioids, on the other hand, were becoming more expensive, and physicians were facing increased regulations in prescribing them. Thus, as prescription opioid use became more and more stigmatized, heroin use was seen, paradoxically, as a more practical alternative. The amount of opioids prescribed in the United States has peaked; physicians are prescribing opioids less often; and the averaged dose has dropped as well, according to the Centers for Disease Control and Prevention.⁴ The first wave of deaths was attributable to prescription opioids, and the second was tied to illicitly obtained potent fentanyl analogs (manufactured in China and smuggled primarily through Mexico), which is added to heroin and sold in the United States.⁵

Many addiction experts and health policy leaders were not surprised by the increases in HIV, TB, and hepatitis B and C that followed the increasing use of intravenous opioids. However, few had experience with previous opioid epidemics in the United States, the most recent being the heroin epidemic occurring in the 1960s-1970s in the aftermath of the Vietnam War. At that time, the notion that heroin was contaminated with other psychoactive drugs, medications, fillers, and other adulterants was a foregone conclusion – though in public health and treatment discussions, this issue is hardly ever raised. We believe this to be a significant lapse in policy and planning. Surveillance by the Drug Enforcement Administration shows that acetyl fentanyl–laced heroin costs a little more on the street than regular heroin. Yet it sells, because users believe its extreme potency produces a better high, thus worth the extra cost. This phenomenon underscores an important point: Opioid addicts often are in search of a better high and will go to any lengths – even risking their lives – to get it.

The “cutting” or “adulteration” of street drugs is common practice in the manufacturing, distribution, and selling of illicit drugs, and the motive is to increase profit. The term “adulterant” generally refers to addition of substances with some psychoactive effects, such as caffeine, ephedra, or even paracetamol. These substances are cheaper than the main substance, have similar or complementary effects when added, and thus help conceal the fact that the desired substance has been cut or diluted. Substances without psychoactive properties such as lactose, other sugars, or talc, are added to a drug primarily to increase the bulk or weight of the illicit substance, or for aesthetic purposes to fool the user. Some adulterants simply are the result of the particular manufacturing process used to make the drug. For example, illicitly manufactured methamphetamine frequently is contaminated by nonstimulant impurities such as lead or mercury (extremely toxic heavy metals), or from carcinogenic solvents used in the synthesis. The local anesthetic lidocaine often is added to cocaine, and the reasons are intuitive: Both drugs are fast-acting local anesthetics.

More intriguing is the story of the antiparasitic medication levamisole. The DEA has estimated that 60%-89% of the seized street cocaine contains levamisole. Levamisole appears to be partly metabolized into an amphetamine-like compound, which could increase dopamine concentration in the reward pathway and thus activate endogenous opioids: It can mimic the effects of cocaine at a fraction of the cost. Levamisole is associated with several types of severe blood disorders, including leukopenia, agranulocytosis, multifocal inflammatory leukoencephalopathy, and neutropenia; a common presentation is vasculitis resulting in loss of limbs. Thus, a real danger in adulterants such as levamisole is their toxicity beyond those of the drug to which they are added, causing numerous medical consequences – including death.

 

The consideration of adulterants is important in another, emerging problem: Cocaine, colloquially thought of as a drug of the 1980s, is making a comeback. A record amount of cocaine is coming across the Mexican border with increased seizures of drug. Also, the number of acres producing cocaine is increasing, the price per unit sold is decreasing, and the prevalence of use has increased. Unfortunately but predictably, cocaine-related deaths are up: National Vital Statistic Systems data indicate that cocaine-related deaths involving opioids climbed from 2000-2006 and 2012-2015. Opioids, primarily heroin and fentanyl, have been driving the recently reported increases in cocaine-related overdose deaths.⁶ At the March 12, 2018, Drug Enforcement Administration panel on the reemergence of cocaine and cocaine-related deaths, experts reported that adulterants, including fentanyl, were responsible for many cocaine-related deaths. Strikingly, the most recent data from the state of Florida suggest that fentanyl is found as a factor in nearly all cocaine-related deaths, and cocaine commonly is found in fentanyl and fentanyl analog-related deaths.

If stigmata of opioid overdose (for example, miotic pupils and respiratory depression) are present in a patient considered to have overdosed on cocaine, naloxone should be administered, as the clinical presentation may be tied to the presence of opioid adulterants. Then, the patient should be engaged in treatment in a long-term care model with evidenced-based therapies, including medication-assisted treatment and contingency management. An important point, however, as described by Thomas Kosten, MD, professor of psychiatry at Baylor University, Houston, is that while we have multiple pharmacologic treatments for opioid overdose and addiction, none exist for cocaine overdose, craving, addiction, or withdrawal.⁷ Dr. Kosten has pioneered novel treatments for cocaine addiction, including anti-cocaine vaccines, but none has been proven safe and effective as of 2018.

Indeed, in the context of the opioid epidemic, the demand for opioid use treatment has increased, though the consequences of addiction, and thus areas requiring treatment in the opioid-addicted patient, are high in number and complexity.⁸ As we discussed previously, unfortunately, most management is aimed solely at reversing the overdose, stabilizing the patient medically, and discharge. We suggest that prior to discharge, the physician should determine whether the overdose was accidental, a suicide⁹ attempt, passive suicidality (for example, asking “Would you be better off dead?”),¹⁰ extreme risk-taking behavior (akin to playing Russian roulette,¹¹ or other causes. We have suggested that naloxone is similar to cardiopulmonary resuscitation: It is a critical life-saving intervention but not an end in itself. Rather, the need for naloxone should serve as a gateway to comprehensive evaluation, diagnosis, treatment, and long-term care.

 

 

Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health. Dr. Srivastava is a fourth-year resident in the department of psychiatry at Washington University.

References

1 NCHS Data Brief. No. 294. December 2017.

2 N Engl J Med. 2015;373:1789-90.

3 DEA Strategic Intelligence Section. 2017 National Drug Threat Assessment: Drug Enforcement Administration, U.S. Department of Justice, 2017.

4 Centers for Disease Control and Prevention, press release. Mar 29, 2018.

5 MMWR. 2018. Mar 30;67(12):349-58.

6 Am J Public Health. 2017 Mar;107(3):430-2.

7 “Q&A: Thomas Kosten, MD: Anti-drug vaccines.” RiverMend Health.

8 “Q&A: Stacy Seikel, MD. Opioid addiction.” RiverMend Health.

9 N Engl J Med. 2018 Apr 26;378:1567-9. doi: 10.1056/NEJMp1801417.

10 Innov Clin Neurosci. 2014 Sep;11(9-10):182-90.

11 Am J Psychiatry. 187 May;144(5):563-7.

 

The opioid epidemic continues to devastate the United States across demographic and socioeconomic groups; two-thirds of the 63,632 Americans who died of drug overdoses¹ in 2016 died of prescription or illicit opioids.

In 2015, Theodore J. Cicero, PhD, professor of psychiatry at Washington University, St. Louis, reported on a fundamental change in the nature of the ongoing opioid epidemic: What started as prescription opioid overprescribing, leading to diversion, abuse, and opioid addiction, was transitioning to illicit heroin distribution and consumption. Prescription opioids, namely, extended-release oxycodone (Oxycontin), were perceived initially as pure and safe, as they were specifically dosed and physician prescribed. In addition, filling a prescription for opioids was not associated with the shame or stigma of buying illicit drugs off the street. Because those drugs were seen as therapeutic and pharmacologically “legitimate,” many clinicians and the lay public alike were surprised to see the surge of opioid addiction and overdoses.

Dr. Cicero and others noted² that prescription opioids, whether taken originally for analgesic or recreational purposes, became a “gateway” to heroin, which already was making its way into the United States from Mexico,³ as heroin was cheap and becoming cheaper, easier to find, easy to use, and “pure.” Prescription opioids, on the other hand, were becoming more expensive, and physicians were facing increased regulations in prescribing them. Thus, as prescription opioid use became more and more stigmatized, heroin use was seen, paradoxically, as a more practical alternative. The amount of opioids prescribed in the United States has peaked; physicians are prescribing opioids less often; and the averaged dose has dropped as well, according to the Centers for Disease Control and Prevention.⁴ The first wave of deaths was attributable to prescription opioids, and the second was tied to illicitly obtained potent fentanyl analogs (manufactured in China and smuggled primarily through Mexico), which is added to heroin and sold in the United States.⁵

Many addiction experts and health policy leaders were not surprised by the increases in HIV, TB, and hepatitis B and C that followed the increasing use of intravenous opioids. However, few had experience with previous opioid epidemics in the United States, the most recent being the heroin epidemic occurring in the 1960s-1970s in the aftermath of the Vietnam War. At that time, the notion that heroin was contaminated with other psychoactive drugs, medications, fillers, and other adulterants was a foregone conclusion – though in public health and treatment discussions, this issue is hardly ever raised. We believe this to be a significant lapse in policy and planning. Surveillance by the Drug Enforcement Administration shows that acetyl fentanyl–laced heroin costs a little more on the street than regular heroin. Yet it sells, because users believe its extreme potency produces a better high, thus worth the extra cost. This phenomenon underscores an important point: Opioid addicts often are in search of a better high and will go to any lengths – even risking their lives – to get it.

The “cutting” or “adulteration” of street drugs is common practice in the manufacturing, distribution, and selling of illicit drugs, and the motive is to increase profit. The term “adulterant” generally refers to addition of substances with some psychoactive effects, such as caffeine, ephedra, or even paracetamol. These substances are cheaper than the main substance, have similar or complementary effects when added, and thus help conceal the fact that the desired substance has been cut or diluted. Substances without psychoactive properties such as lactose, other sugars, or talc, are added to a drug primarily to increase the bulk or weight of the illicit substance, or for aesthetic purposes to fool the user. Some adulterants simply are the result of the particular manufacturing process used to make the drug. For example, illicitly manufactured methamphetamine frequently is contaminated by nonstimulant impurities such as lead or mercury (extremely toxic heavy metals), or from carcinogenic solvents used in the synthesis. The local anesthetic lidocaine often is added to cocaine, and the reasons are intuitive: Both drugs are fast-acting local anesthetics.

More intriguing is the story of the antiparasitic medication levamisole. The DEA has estimated that 60%-89% of the seized street cocaine contains levamisole. Levamisole appears to be partly metabolized into an amphetamine-like compound, which could increase dopamine concentration in the reward pathway and thus activate endogenous opioids: It can mimic the effects of cocaine at a fraction of the cost. Levamisole is associated with several types of severe blood disorders, including leukopenia, agranulocytosis, multifocal inflammatory leukoencephalopathy, and neutropenia; a common presentation is vasculitis resulting in loss of limbs. Thus, a real danger in adulterants such as levamisole is their toxicity beyond those of the drug to which they are added, causing numerous medical consequences – including death.

 

The consideration of adulterants is important in another, emerging problem: Cocaine, colloquially thought of as a drug of the 1980s, is making a comeback. A record amount of cocaine is coming across the Mexican border with increased seizures of drug. Also, the number of acres producing cocaine is increasing, the price per unit sold is decreasing, and the prevalence of use has increased. Unfortunately but predictably, cocaine-related deaths are up: National Vital Statistic Systems data indicate that cocaine-related deaths involving opioids climbed from 2000-2006 and 2012-2015. Opioids, primarily heroin and fentanyl, have been driving the recently reported increases in cocaine-related overdose deaths.⁶ At the March 12, 2018, Drug Enforcement Administration panel on the reemergence of cocaine and cocaine-related deaths, experts reported that adulterants, including fentanyl, were responsible for many cocaine-related deaths. Strikingly, the most recent data from the state of Florida suggest that fentanyl is found as a factor in nearly all cocaine-related deaths, and cocaine commonly is found in fentanyl and fentanyl analog-related deaths.

If stigmata of opioid overdose (for example, miotic pupils and respiratory depression) are present in a patient considered to have overdosed on cocaine, naloxone should be administered, as the clinical presentation may be tied to the presence of opioid adulterants. Then, the patient should be engaged in treatment in a long-term care model with evidenced-based therapies, including medication-assisted treatment and contingency management. An important point, however, as described by Thomas Kosten, MD, professor of psychiatry at Baylor University, Houston, is that while we have multiple pharmacologic treatments for opioid overdose and addiction, none exist for cocaine overdose, craving, addiction, or withdrawal.⁷ Dr. Kosten has pioneered novel treatments for cocaine addiction, including anti-cocaine vaccines, but none has been proven safe and effective as of 2018.

Indeed, in the context of the opioid epidemic, the demand for opioid use treatment has increased, though the consequences of addiction, and thus areas requiring treatment in the opioid-addicted patient, are high in number and complexity.⁸ As we discussed previously, unfortunately, most management is aimed solely at reversing the overdose, stabilizing the patient medically, and discharge. We suggest that prior to discharge, the physician should determine whether the overdose was accidental, a suicide⁹ attempt, passive suicidality (for example, asking “Would you be better off dead?”),¹⁰ extreme risk-taking behavior (akin to playing Russian roulette,¹¹ or other causes. We have suggested that naloxone is similar to cardiopulmonary resuscitation: It is a critical life-saving intervention but not an end in itself. Rather, the need for naloxone should serve as a gateway to comprehensive evaluation, diagnosis, treatment, and long-term care.

 

 

Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University in St. Louis. He also serves as chairman of the scientific advisory boards for RiverMend Health. Dr. Srivastava is a fourth-year resident in the department of psychiatry at Washington University.

References

1 NCHS Data Brief. No. 294. December 2017.

2 N Engl J Med. 2015;373:1789-90.

3 DEA Strategic Intelligence Section. 2017 National Drug Threat Assessment: Drug Enforcement Administration, U.S. Department of Justice, 2017.

4 Centers for Disease Control and Prevention, press release. Mar 29, 2018.

5 MMWR. 2018. Mar 30;67(12):349-58.

6 Am J Public Health. 2017 Mar;107(3):430-2.

7 “Q&A: Thomas Kosten, MD: Anti-drug vaccines.” RiverMend Health.

8 “Q&A: Stacy Seikel, MD. Opioid addiction.” RiverMend Health.

9 N Engl J Med. 2018 Apr 26;378:1567-9. doi: 10.1056/NEJMp1801417.

10 Innov Clin Neurosci. 2014 Sep;11(9-10):182-90.

11 Am J Psychiatry. 187 May;144(5):563-7.

 

The current opioid epidemic in the United States has been universally recognized as one of the most important public health issues to date. This crisis has cost nearly $80 billion in lost productivity, treatment (including emergency, medical, psychiatric, and addiction-specific care), and criminal justice involvement.¹ Opioid overdoses have increased by 200% since 2000, with more than 33,000 individuals dying from opioid overdoses in 2015 alone.^2,3

Devonyu/Thinkstock

Because of the surge in opioid overdose–related mortality, resources have been devoted to the widespread dissemination of the mu-opioid receptor antagonist naloxone, which is deemed a “rescue” medication administered by emergency departments, health professionals, the lay public, and/or first responders.⁴ Naloxone use has been successful in saving lives. However, it has not seemed to reduce recidivism, and overdose prevalence continues to increase.^5,6 It is best viewed as an intervention analogous to CPR or cardioversion in acute cardiovascular compromise. CPR and cardioversion provide acute rescue and are lifesaving – but do not contribute to the diagnosis and understanding of the chronic, underlying (cardiovascular) pathology that led to the acute event in the first place. Similarly, while naloxone is an essential rescue medication, it is not a treatment for the opioid addiction or the frequently occurring psychiatric comorbidities. In addition, naloxone rescue does not assist with diagnosis or help the physician understand why the opioid overdose occurred. Still, naloxone remains important.

Currently, overdoses are considered accidental in origin until proved otherwise, and that assumption has become an acceptable hypothesis for the many parties involved: This hypothesis permits the patient to receive the much-needed overdose treatment, the physicians to discharge the patient from the emergency department after resuscitation and medical stabilization, the hospital to collect reimbursement, the pharmaceutical companies to continue to raise prices – and the health system to ignore recidivism and/or long-term outcomes.

However, while well accepted, the accidental overdose hypothesis might not tell the entire story. A recent, competing etiological hypothesis is that many opioid overdoses may, in fact, be misdiagnosed suicide attempts.⁷ National suicide prevalence has been increasing since 1999, and both all-cause mortality generally and suicides specifically have been increasing in white, male, and middle-aged patients, which encompass the same demographic groups affected by the opioid epidemic.^8,9

Also, more than 50% of patients with opioid use disorder have histories of major depressive disorder,which, when untreated, may further drive suicidal thoughts and behavior.^10,11Maria A. Oquendo, MD, PHD, immediate past president of the American Psychiatric Association, wrote in a guest post on the blog of Nora D. Volkow, MD, director of the National Institute on Drug Abuse, about the strong link between opioid use disorders and suicidal thoughts and behavior Furthermore, a 2004 literature review on substance use disorders and suicide found that individuals with opioid use disorders had a 13 times greater risk of completed suicide, compared with the general population.¹²

Additional associations

A recent study of nearly 5 million veterans enrolled in the Veterans Health Administration demonstrated that, even when adjusted for age and comorbid psychiatric diagnoses, opioid use disorder was associated with an increased risk for suicide; particularly striking was that this risk was doubled in women.¹³

A survey of 40,000 subjects from the 2014 National Survey on Drug Use and Health demonstrated that prescription opioid misuse was associated with an increased risk of suicidal ideation, and weekly misuse was associated with increased suicide planning and attempts.

The data regarding the prevalence of suicidal ideation in patients who have overdosed are limited, although recent evidence from the National Vital Statistics System on adolescent (aged 15-19 years) drug overdose is concerning, with 772 drug overdoses occurring in this age demographic in 2015 alone. Opioids were involved in the vast majority of fatal drug overdoses among this group, and the prevalence of death from opioid overdoses increased during 1999-2007 (0.8/100,000 to 2.7/100,000), stabilized during 2007-2011, declined during 2012-2014 (down to 2.0/100,000) then increased in 2015 (up to 2.4/100,000). While 80.4% of all drug overdoses in this group (including opioids) were considered unintentional, 13.5% were most likely completed suicides.¹⁴

These results suggest that, at the very least, some proportion of opioid overdoses are suicide attempts, and the actual prevalence may be much larger. All of this is difficult to discern as these data come from an epidemiological survey with data input as International Classification of Diseases, 10th revision, codes. Thus, the real-life and real-time quality of the psychiatric and postmortem evaluation that led to the determination of a suicide attempt is unknown. More explicitly, because a thorough evaluation and collateral history may have been lacking, this study may have underestimated the prevalence of overdoses that were actual suicide attempts.

 

Lessons for physicians

Given the epidemiological evidence linking suicidal thoughts and behavior with opioid use disorders, the frequency of overdoses, demographic factors, and recidivism with naloxone rescue, we should be very concerned that many overdoses are unrecognized suicide attempts. Many physicians can recount giving naloxone to a patient – reversing his or her overdose and simultaneously saving his or her life – only to be confronted with anger and combativeness on the part of the patient. When this response occurs, many physicians may attribute the behavioral dysregulation to the patient’s lack of experience with or tolerance to the drug (especially among naive users) or may disregard the emotional response altogether. The danger in physicians’ reacting like this to such behavior is that substantial ambiguity regarding the patient’s motives still remains: Did the patient intentionally use intravenously thinking he or she would die? Was the patient ambivalent about death? Did the patient wish he or she would die – or not wake up? Or was the patient just was playing a version of “Russian roulette” with needles and lethal quantities of opioids?

When considering logical next steps after naloxone reversal to ensure appropriate diagnosis of and treatment for the patient, a psychiatric consultation and thorough evaluation may be indispensable. This is particularly important given that those who attempt suicide or have active suicidal ideation often are evasive about their behavior and current state of mind.¹⁵ Thus, these individuals may be unwilling to disclose active suicidal ideation, intent, and/or plans when interviewed. A psychiatrist, however, has the skill set to evaluate risk and protective factors, assess for other psychiatric comorbidities carefully, and make recommendations for safe disposition and comprehensive treatment. Just as a comprehensive cardiovascular evaluation, formulation of a differential diagnosis, and treatment of chronic cardiovascular disease is the standard of care after a cardiac emergency intervention, we suggest quite similar practice standards for an opioid overdose intervention.

Clearly, better data are needed. We recommend high-quality, prospective studies examining the overall prevalence of suicidal ideation with intent and plan in patients who overdose on opioids. These studies should include thorough psychiatric evaluations performed by experts, using evidence-based scales for suicide, substance use disorders, and other psychiatric comorbidities. Research of this nature should make significant strides toward creating standards of care in the management of patients presenting with opioid overdoses that allow for appropriate assessment, disposition, treatment, and, ultimately, sustained recovery and wellness.
 

Dr. Srivastava is a fourth-year psychiatry resident at Washington University in St. Louis. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University. He also serves as chairman of the scientific advisory boards for RiverMend Health.

References

1. Med Care. 2016 Oct;54:901-6.

2. MMWR Morb Mortal Wkly Rep. 2016 Dec 30;65(5051):1445-52.

3. MMWR Morb Mortal Wkly Rep. 2016 Jan 1;64(50-51):1378-82.

4. N Engl J Med. 2016 Dec 8;375(23):2213-15.

5. Drug Alcohol Depend. 2017 Sep 1;178:176-87.

6. BMJ. 2013 Jan 30;346:f174.

7. Nora’s Blog. 2017 Apr 20. https://www.drugabuse.gov/about-nida/noras-blog/2017/04/opioid-use-disorders-suicide-hidden-tragedy-guest-blog

8. NCHS Data Brief. 2016 Apr;(241):1-8.

9. Proc Natl Acad Sci U S A. 2015 Dec 8;112(49):15078-83.

10. Addict Behav. 2009 Jun-Jul;34(6-7):498-504.

11. J Affect Disord. 2013 May;147(1-3):17-28.

12. Drug Alcohol Depend. 2004 Dec 7;76 Suppl:S11-9.

13. Addiction. 2017 Jul;112(7):1193-1201.

14. NCHS Data Brief. 2017 Aug;282:1-7.

15. Am J Psychiatry. 2003 Nov;160(11 Suppl):1-60.

 

The current opioid epidemic in the United States has been universally recognized as one of the most important public health issues to date. This crisis has cost nearly $80 billion in lost productivity, treatment (including emergency, medical, psychiatric, and addiction-specific care), and criminal justice involvement.¹ Opioid overdoses have increased by 200% since 2000, with more than 33,000 individuals dying from opioid overdoses in 2015 alone.^2,3

Devonyu/Thinkstock

Because of the surge in opioid overdose–related mortality, resources have been devoted to the widespread dissemination of the mu-opioid receptor antagonist naloxone, which is deemed a “rescue” medication administered by emergency departments, health professionals, the lay public, and/or first responders.⁴ Naloxone use has been successful in saving lives. However, it has not seemed to reduce recidivism, and overdose prevalence continues to increase.^5,6 It is best viewed as an intervention analogous to CPR or cardioversion in acute cardiovascular compromise. CPR and cardioversion provide acute rescue and are lifesaving – but do not contribute to the diagnosis and understanding of the chronic, underlying (cardiovascular) pathology that led to the acute event in the first place. Similarly, while naloxone is an essential rescue medication, it is not a treatment for the opioid addiction or the frequently occurring psychiatric comorbidities. In addition, naloxone rescue does not assist with diagnosis or help the physician understand why the opioid overdose occurred. Still, naloxone remains important.

Currently, overdoses are considered accidental in origin until proved otherwise, and that assumption has become an acceptable hypothesis for the many parties involved: This hypothesis permits the patient to receive the much-needed overdose treatment, the physicians to discharge the patient from the emergency department after resuscitation and medical stabilization, the hospital to collect reimbursement, the pharmaceutical companies to continue to raise prices – and the health system to ignore recidivism and/or long-term outcomes.

However, while well accepted, the accidental overdose hypothesis might not tell the entire story. A recent, competing etiological hypothesis is that many opioid overdoses may, in fact, be misdiagnosed suicide attempts.⁷ National suicide prevalence has been increasing since 1999, and both all-cause mortality generally and suicides specifically have been increasing in white, male, and middle-aged patients, which encompass the same demographic groups affected by the opioid epidemic.^8,9

Also, more than 50% of patients with opioid use disorder have histories of major depressive disorder,which, when untreated, may further drive suicidal thoughts and behavior.^10,11Maria A. Oquendo, MD, PHD, immediate past president of the American Psychiatric Association, wrote in a guest post on the blog of Nora D. Volkow, MD, director of the National Institute on Drug Abuse, about the strong link between opioid use disorders and suicidal thoughts and behavior Furthermore, a 2004 literature review on substance use disorders and suicide found that individuals with opioid use disorders had a 13 times greater risk of completed suicide, compared with the general population.¹²

Additional associations

A recent study of nearly 5 million veterans enrolled in the Veterans Health Administration demonstrated that, even when adjusted for age and comorbid psychiatric diagnoses, opioid use disorder was associated with an increased risk for suicide; particularly striking was that this risk was doubled in women.¹³

A survey of 40,000 subjects from the 2014 National Survey on Drug Use and Health demonstrated that prescription opioid misuse was associated with an increased risk of suicidal ideation, and weekly misuse was associated with increased suicide planning and attempts.

The data regarding the prevalence of suicidal ideation in patients who have overdosed are limited, although recent evidence from the National Vital Statistics System on adolescent (aged 15-19 years) drug overdose is concerning, with 772 drug overdoses occurring in this age demographic in 2015 alone. Opioids were involved in the vast majority of fatal drug overdoses among this group, and the prevalence of death from opioid overdoses increased during 1999-2007 (0.8/100,000 to 2.7/100,000), stabilized during 2007-2011, declined during 2012-2014 (down to 2.0/100,000) then increased in 2015 (up to 2.4/100,000). While 80.4% of all drug overdoses in this group (including opioids) were considered unintentional, 13.5% were most likely completed suicides.¹⁴

These results suggest that, at the very least, some proportion of opioid overdoses are suicide attempts, and the actual prevalence may be much larger. All of this is difficult to discern as these data come from an epidemiological survey with data input as International Classification of Diseases, 10th revision, codes. Thus, the real-life and real-time quality of the psychiatric and postmortem evaluation that led to the determination of a suicide attempt is unknown. More explicitly, because a thorough evaluation and collateral history may have been lacking, this study may have underestimated the prevalence of overdoses that were actual suicide attempts.

 

Lessons for physicians

Given the epidemiological evidence linking suicidal thoughts and behavior with opioid use disorders, the frequency of overdoses, demographic factors, and recidivism with naloxone rescue, we should be very concerned that many overdoses are unrecognized suicide attempts. Many physicians can recount giving naloxone to a patient – reversing his or her overdose and simultaneously saving his or her life – only to be confronted with anger and combativeness on the part of the patient. When this response occurs, many physicians may attribute the behavioral dysregulation to the patient’s lack of experience with or tolerance to the drug (especially among naive users) or may disregard the emotional response altogether. The danger in physicians’ reacting like this to such behavior is that substantial ambiguity regarding the patient’s motives still remains: Did the patient intentionally use intravenously thinking he or she would die? Was the patient ambivalent about death? Did the patient wish he or she would die – or not wake up? Or was the patient just was playing a version of “Russian roulette” with needles and lethal quantities of opioids?

When considering logical next steps after naloxone reversal to ensure appropriate diagnosis of and treatment for the patient, a psychiatric consultation and thorough evaluation may be indispensable. This is particularly important given that those who attempt suicide or have active suicidal ideation often are evasive about their behavior and current state of mind.¹⁵ Thus, these individuals may be unwilling to disclose active suicidal ideation, intent, and/or plans when interviewed. A psychiatrist, however, has the skill set to evaluate risk and protective factors, assess for other psychiatric comorbidities carefully, and make recommendations for safe disposition and comprehensive treatment. Just as a comprehensive cardiovascular evaluation, formulation of a differential diagnosis, and treatment of chronic cardiovascular disease is the standard of care after a cardiac emergency intervention, we suggest quite similar practice standards for an opioid overdose intervention.

Clearly, better data are needed. We recommend high-quality, prospective studies examining the overall prevalence of suicidal ideation with intent and plan in patients who overdose on opioids. These studies should include thorough psychiatric evaluations performed by experts, using evidence-based scales for suicide, substance use disorders, and other psychiatric comorbidities. Research of this nature should make significant strides toward creating standards of care in the management of patients presenting with opioid overdoses that allow for appropriate assessment, disposition, treatment, and, ultimately, sustained recovery and wellness.
 

Dr. Srivastava is a fourth-year psychiatry resident at Washington University in St. Louis. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University. He also serves as chairman of the scientific advisory boards for RiverMend Health.

References

1. Med Care. 2016 Oct;54:901-6.

2. MMWR Morb Mortal Wkly Rep. 2016 Dec 30;65(5051):1445-52.

3. MMWR Morb Mortal Wkly Rep. 2016 Jan 1;64(50-51):1378-82.

4. N Engl J Med. 2016 Dec 8;375(23):2213-15.

5. Drug Alcohol Depend. 2017 Sep 1;178:176-87.

6. BMJ. 2013 Jan 30;346:f174.

7. Nora’s Blog. 2017 Apr 20. https://www.drugabuse.gov/about-nida/noras-blog/2017/04/opioid-use-disorders-suicide-hidden-tragedy-guest-blog

8. NCHS Data Brief. 2016 Apr;(241):1-8.

9. Proc Natl Acad Sci U S A. 2015 Dec 8;112(49):15078-83.

10. Addict Behav. 2009 Jun-Jul;34(6-7):498-504.

11. J Affect Disord. 2013 May;147(1-3):17-28.

12. Drug Alcohol Depend. 2004 Dec 7;76 Suppl:S11-9.

13. Addiction. 2017 Jul;112(7):1193-1201.

14. NCHS Data Brief. 2017 Aug;282:1-7.

15. Am J Psychiatry. 2003 Nov;160(11 Suppl):1-60.

 

The current opioid epidemic in the United States has been universally recognized as one of the most important public health issues to date. This crisis has cost nearly $80 billion in lost productivity, treatment (including emergency, medical, psychiatric, and addiction-specific care), and criminal justice involvement.¹ Opioid overdoses have increased by 200% since 2000, with more than 33,000 individuals dying from opioid overdoses in 2015 alone.^2,3

Devonyu/Thinkstock

Because of the surge in opioid overdose–related mortality, resources have been devoted to the widespread dissemination of the mu-opioid receptor antagonist naloxone, which is deemed a “rescue” medication administered by emergency departments, health professionals, the lay public, and/or first responders.⁴ Naloxone use has been successful in saving lives. However, it has not seemed to reduce recidivism, and overdose prevalence continues to increase.^5,6 It is best viewed as an intervention analogous to CPR or cardioversion in acute cardiovascular compromise. CPR and cardioversion provide acute rescue and are lifesaving – but do not contribute to the diagnosis and understanding of the chronic, underlying (cardiovascular) pathology that led to the acute event in the first place. Similarly, while naloxone is an essential rescue medication, it is not a treatment for the opioid addiction or the frequently occurring psychiatric comorbidities. In addition, naloxone rescue does not assist with diagnosis or help the physician understand why the opioid overdose occurred. Still, naloxone remains important.

Currently, overdoses are considered accidental in origin until proved otherwise, and that assumption has become an acceptable hypothesis for the many parties involved: This hypothesis permits the patient to receive the much-needed overdose treatment, the physicians to discharge the patient from the emergency department after resuscitation and medical stabilization, the hospital to collect reimbursement, the pharmaceutical companies to continue to raise prices – and the health system to ignore recidivism and/or long-term outcomes.

However, while well accepted, the accidental overdose hypothesis might not tell the entire story. A recent, competing etiological hypothesis is that many opioid overdoses may, in fact, be misdiagnosed suicide attempts.⁷ National suicide prevalence has been increasing since 1999, and both all-cause mortality generally and suicides specifically have been increasing in white, male, and middle-aged patients, which encompass the same demographic groups affected by the opioid epidemic.^8,9

Also, more than 50% of patients with opioid use disorder have histories of major depressive disorder,which, when untreated, may further drive suicidal thoughts and behavior.^10,11Maria A. Oquendo, MD, PHD, immediate past president of the American Psychiatric Association, wrote in a guest post on the blog of Nora D. Volkow, MD, director of the National Institute on Drug Abuse, about the strong link between opioid use disorders and suicidal thoughts and behavior Furthermore, a 2004 literature review on substance use disorders and suicide found that individuals with opioid use disorders had a 13 times greater risk of completed suicide, compared with the general population.¹²

Additional associations

A recent study of nearly 5 million veterans enrolled in the Veterans Health Administration demonstrated that, even when adjusted for age and comorbid psychiatric diagnoses, opioid use disorder was associated with an increased risk for suicide; particularly striking was that this risk was doubled in women.¹³

A survey of 40,000 subjects from the 2014 National Survey on Drug Use and Health demonstrated that prescription opioid misuse was associated with an increased risk of suicidal ideation, and weekly misuse was associated with increased suicide planning and attempts.

The data regarding the prevalence of suicidal ideation in patients who have overdosed are limited, although recent evidence from the National Vital Statistics System on adolescent (aged 15-19 years) drug overdose is concerning, with 772 drug overdoses occurring in this age demographic in 2015 alone. Opioids were involved in the vast majority of fatal drug overdoses among this group, and the prevalence of death from opioid overdoses increased during 1999-2007 (0.8/100,000 to 2.7/100,000), stabilized during 2007-2011, declined during 2012-2014 (down to 2.0/100,000) then increased in 2015 (up to 2.4/100,000). While 80.4% of all drug overdoses in this group (including opioids) were considered unintentional, 13.5% were most likely completed suicides.¹⁴

These results suggest that, at the very least, some proportion of opioid overdoses are suicide attempts, and the actual prevalence may be much larger. All of this is difficult to discern as these data come from an epidemiological survey with data input as International Classification of Diseases, 10th revision, codes. Thus, the real-life and real-time quality of the psychiatric and postmortem evaluation that led to the determination of a suicide attempt is unknown. More explicitly, because a thorough evaluation and collateral history may have been lacking, this study may have underestimated the prevalence of overdoses that were actual suicide attempts.

 

Lessons for physicians

Given the epidemiological evidence linking suicidal thoughts and behavior with opioid use disorders, the frequency of overdoses, demographic factors, and recidivism with naloxone rescue, we should be very concerned that many overdoses are unrecognized suicide attempts. Many physicians can recount giving naloxone to a patient – reversing his or her overdose and simultaneously saving his or her life – only to be confronted with anger and combativeness on the part of the patient. When this response occurs, many physicians may attribute the behavioral dysregulation to the patient’s lack of experience with or tolerance to the drug (especially among naive users) or may disregard the emotional response altogether. The danger in physicians’ reacting like this to such behavior is that substantial ambiguity regarding the patient’s motives still remains: Did the patient intentionally use intravenously thinking he or she would die? Was the patient ambivalent about death? Did the patient wish he or she would die – or not wake up? Or was the patient just was playing a version of “Russian roulette” with needles and lethal quantities of opioids?

When considering logical next steps after naloxone reversal to ensure appropriate diagnosis of and treatment for the patient, a psychiatric consultation and thorough evaluation may be indispensable. This is particularly important given that those who attempt suicide or have active suicidal ideation often are evasive about their behavior and current state of mind.¹⁵ Thus, these individuals may be unwilling to disclose active suicidal ideation, intent, and/or plans when interviewed. A psychiatrist, however, has the skill set to evaluate risk and protective factors, assess for other psychiatric comorbidities carefully, and make recommendations for safe disposition and comprehensive treatment. Just as a comprehensive cardiovascular evaluation, formulation of a differential diagnosis, and treatment of chronic cardiovascular disease is the standard of care after a cardiac emergency intervention, we suggest quite similar practice standards for an opioid overdose intervention.

Clearly, better data are needed. We recommend high-quality, prospective studies examining the overall prevalence of suicidal ideation with intent and plan in patients who overdose on opioids. These studies should include thorough psychiatric evaluations performed by experts, using evidence-based scales for suicide, substance use disorders, and other psychiatric comorbidities. Research of this nature should make significant strides toward creating standards of care in the management of patients presenting with opioid overdoses that allow for appropriate assessment, disposition, treatment, and, ultimately, sustained recovery and wellness.
 

Dr. Srivastava is a fourth-year psychiatry resident at Washington University in St. Louis. Dr. Gold is the 17th Distinguished Alumni Professor at the University of Florida, Gainesville, and professor of psychiatry (adjunct) at Washington University. He also serves as chairman of the scientific advisory boards for RiverMend Health.

References

1. Med Care. 2016 Oct;54:901-6.

2. MMWR Morb Mortal Wkly Rep. 2016 Dec 30;65(5051):1445-52.

3. MMWR Morb Mortal Wkly Rep. 2016 Jan 1;64(50-51):1378-82.

4. N Engl J Med. 2016 Dec 8;375(23):2213-15.

5. Drug Alcohol Depend. 2017 Sep 1;178:176-87.

6. BMJ. 2013 Jan 30;346:f174.

7. Nora’s Blog. 2017 Apr 20. https://www.drugabuse.gov/about-nida/noras-blog/2017/04/opioid-use-disorders-suicide-hidden-tragedy-guest-blog

8. NCHS Data Brief. 2016 Apr;(241):1-8.

9. Proc Natl Acad Sci U S A. 2015 Dec 8;112(49):15078-83.

10. Addict Behav. 2009 Jun-Jul;34(6-7):498-504.

11. J Affect Disord. 2013 May;147(1-3):17-28.

12. Drug Alcohol Depend. 2004 Dec 7;76 Suppl:S11-9.

13. Addiction. 2017 Jul;112(7):1193-1201.

14. NCHS Data Brief. 2017 Aug;282:1-7.

15. Am J Psychiatry. 2003 Nov;160(11 Suppl):1-60.