The Best of Pill Pushing - The pharmacology of death by suicide - (8/1/2021)

By Dr. Ron Gasbarro

A disclaimer right off the bat: There is nothing good about suicide. It solves no problems but creates many. It pleases no one but saddens everyone. Suicide is free but it is not freeing. It is not a crime but how it impacts its survivors is criminal. Yet, suicide has been with us since antiquity and beyond. This blog is about the pharmaceuticals currently used to die by suicide with a look back at which drugs were used in the past for this reason. In no way does this blog condone, endorse, or glorify this ultimate sin against life.

Is there romance in death by suicide?
There was romance for William Shakespeare. In his 1597 tragedy Romeo and Juliet, forbidden love tempts and destroys a young couple. In this play, Juliet Capulet must choose between her family and her star-crossed lover Romeo Montague. The feud between the Capulets and the Montagues made the relationship between Romeo and Juliet doomed from the start. The Capulet’s wanted their daughter to marry Count Paris as he was handsome, rich, established. Yet, she was already secretly married to young Romeo. So she concocted a scheme whereby she would drink a potion that would temporarily make her appear dead so that Paris would find her, believing that she was actually poisoned. While Paris and her family went off to plan for Juliet’s funeral, she and Romeo could run away together. Ah, but the fates foiled this scheme. Romeo found the sleeping Juliet and believing she was dead, obtained poison from the town apothecary, drank it and died next to Juliet’s body. When she finally regained consciousness, she saw that Romeo was dead and impaled herself on his sword and died. The curtain falls. The audience weeps.

The not-so-romantic side of suicide
This is one of the biggest urban legends of Hollywood and was highlighted in Kenneth Anger’s book Hollywood Babylon. Lupe Vélez was a popular actress in the 1930’s and 1940’s, who was known for fiery personality and, thus, The Mexican Spitfire became her nickname. But while her career was doing well, her personal life was a bit messy and by 1944 she found herself pregnant and unwed. The relationship with the father of her child was rocky and she was so upset that she decided to end her life. According to the story, Lupe planned to stage a beautiful suicide scene. She did her hair and make-up, put on a stunning nightgown, arranged fresh flowers and lit scented candles in her bedroom. On her bed, she took an overdose of the barbiturate, Seconal, but it did not mix well with the spicy Mexican with food she had eaten to celebrate her last supper. She started to vomit and stumbled to the adjoining bathroom. There, she went headfirst into the toilet and subsequently drowned. Her housekeeper Juanita found her the next morning, still in the same position. 

Hence, for Romeo, Juliet, and Lupe, the best-laid plans of mice and men oft go awry.

Suicide by the numbers – The demographics
According to the American Foundation for Suicide Prevention (afsp.org), suicide is the tenth leading cause of death in the US. Each year, almost 45,000 Americans die by suicide. For every completed suicide, there are 25 attempts to die by suicide. Many suicide attempts, however, go unreported or untreated. Surveys suggest that at least one million people in the US engage in intentionally inflicted self-harm each year.

Females attempt suicide twice as often as males, states the AFSP. As with suicide deaths, rates of attempted suicide vary considerably among demographic groups. Males are 4 times more likely than females to die by suicide. The ratio of suicide attempts to suicide death in youth is estimated to be about 25:1, compared to about 4:1 in the elderly.

The Centers for Disease Control and Prevention (CDC) has observed that suicide rates are higher in rural America than in urban America. The gap in suicide rates between rural and urban areas grew steadily from 1999 to 2015. Since 2007, the gap began widening more quickly. 

According to the Suicide Prevention Resource Center (sprc.org), suicide rates vary by race and ethnicity. In 2016, the rate of suicide among American Indians/Alaska Natives was 21.39 per 100,000 and among whites, 18.15. In contrast, the suicide rate among Asian/Pacific Islanders was 7.00; the rate for blacks was 6.35; the rate among Hispanics was 6.38.

Copycat suicides
A 10% increase in suicides - nearly 2,000 additional deaths - was recorded in the US in the 4 months after actor/comedian Robin Williams took his own life in 2014, according to research published in 2018 in the journal PLOS ONE [Fink, 2018]. The "celebrity-suicide effect" – in which copycat suicides follow that of someone famous – has been documented in previous research [Niederkrotenthaler, 2012; Stack, 2005; Cheng, 2007]. The increase following Williams’ death was especially large among men ages 30 to 44, whose suicide rate rose almost 13% [Fink, 2018]. This is not a new phenomenon. The media has had an impact on copycat suicides. Marilyn Monroe’s barbiturate overdose death on August 5, 1962, was followed by a 12% increase of suicides in the weeks following her demise [Phillips, 1996]. 

In recent years, satellite television and the internet have increased the global range of the mass media; celebrities such as film actors and pop singers are being assigned increasing importance relative to politicians and intellectuals whose suicides do not elicit copycat suicide attempts. The number of reality TV programs is skyrocketing along with the number of celebrities to which society is exposed. 

Upon learning of someone else's suicide, the more vulnerable of us may decide that suicide may be appropriate for them as well, especially if the publicized suicide was of someone in a similar situation as them, situations such as failing relationships, faltering careers, or financial woes. How does the media accelerate the increases in copycat suicides? 1) Publishing the methods of suicides, 2) Romanticized and sensationalized reporting, particularly about celebrities, 3) Suggestions that there is an epidemic of suicides, 4) Glorifying the deceased, and 5) Simplifying the reasons for the suicide. Indeed, people may see suicide as a glamorous ending, with the person getting much attention, plenty of sympathy, and lots of concern that they never got in life [Mesoudi, 2009]. Another possible factor is that vulnerable youth may feel like, "If they couldn't cut it, neither can I".

How do Americans die by suicide?
Men use guns; women use pills
Males take their own lives at nearly 4 times the rate of females and represent 78% of all suicides [CDC, 2018]. Females are more likely than males to have suicidal thoughts [SAMHSA, 2014]. Suicide is the seventh leading cause of death for males and the fourteenth leading cause for females [CDC, 2018]. Firearms are the most commonly used method of suicide among males (56.9%) [CDC, 2018]. Poisoning is the most common method of suicide for females (34.8%). 

The popularity of the methods used also varies between the sexes. While for men, firearms are by far the most commonly used method (57%), followed by suffocation/hanging and poisoning, women poisoning as their most common method (35%), followed by firearms then suffocation/hanging. A firearm is the most reliable method of ending one’s life, and given the accessibility of guns in the US, relative to other countries, the most easily obtainable [CDC, 2018]. Drug poisoning one of the least successful because the chances of revival are high. Thus, these factors may account for some of the differences in actual suicide rates between the genders.

What is a drug overdose?
Says the National Council on Alcoholism and Drug Dependence, drug overdoses can be accidental or intentional. They occur through the misuse of illicit drugs, used to get high, or when a person takes more than the medically recommended dose of a prescription or over-the-counter drug and cannot detoxify the drug fast enough to avoid dangerous side effects. This may occur suddenly when a large amount of the drug is taken at one time, or gradually, as a drug builds up in the body over a longer period of time.

The drugs used in death by suicide
According to the CDC, 81% of intentional poisoning suicides were caused by drugs - both legal and illegal [CDC, 2018]. The most commonly used drugs identified in drug-related suicides were psychoactive drugs, such as sedatives and antidepressants, followed by opiates and prescription pain medications. 
• Alcohol – Evidence suggests that alcohol had been ingested in around a third of people who died by suicide and in 29% of those admitted to ED departments. In nearly two-thirds of cases, more than one drug was involved.
• Analgesics – Pain relievers were found to be involved in 38% of drug-related suicide attempts. Narcotic pain relievers were involved in over a third of that number, and acetaminophen products were involved in just under a third.
• Benzodiazepines – These anti-anxiety drugs (anxiolytics) were found to be involved in 29.3% of drug-related suicide attempts. Alprazolam (Xanax) and clonazepam (Klonopin) each accounted for about a third.
• Antidepressants – This drug class was found to be used in 19.6% of visits. About half of those visits involved an SSRI (selective serotonin reuptake inhibitor) antidepressant such as citalopram (Celexa), sertraline (Zoloft), or fluoxetine (Prozac). Trazodone, a SARI (serotonin antagonist and reuptake inhibitor) antidepressant, was involved in about a quarter.
• Antipsychotics – These drugs, as a whole, appeared in 12.9% of visits, with the vast majority being the newer types of atypical antipsychotics such as quetiapine (Seroquel), olanzapine (Zyprexa), or clozapine (Clozaril).
• Other drugs – Miscellaneous cardiovascular drugs were associated with suicide deaths in 14.1% of cases, opioids in 8.9%, acetaminophen in combination with an opioid in 8.9%, miscellaneous stimulants, street drugs in 6.4%, and acetaminophen only in 6.1% of cases.  

Why barbiturates were – and still are – the perfect suicide drugs
Barbiturates once enjoyed a central place in the world of recreational drugs throughout much of the 20th century. They were used for a wide range of conditions including general anesthesia, epilepsy, treatment of acute migraines or cluster headaches, euthanasia, capital punishment, and assisted suicide. However, their liability for abuse led to an extensive number of barbiturate poisoning cases in the 1950s and 1960s. 

Pentobarbital (Nembutal®) and secobarbital (Seconal®) are barbiturates used as sedatives, hypnotics and anti-anxiety agents. Pentobarbital was widely used during the 1940s, 50s, and 60s. However, pentobarbital is highly lethal in overdose. When combined with alcohol, death can ensue via respiratory failure. Actress Marilyn Monroe supposedly used pentobarbital to end her life in 1962, while singer/actress Judy Garland apparently overdosed on the same drug in 1969.

Since it was so easy to overdose on pentobarbital – whether accidentally or intentionally – it was almost universally taken off the market by the 1970s. The drug was replaced by relatively safer sedative in the benzodiazepine class (e.g., temazepam, triazolam, flurazepam), followed by zolpidem (Ambien®) and eszopiclone (Lunesta®). However, pentobarbital remains in use by veterinary surgeons to euthanize bigger animals; many people are successful in obtaining veterinary pentobarbital for their suicide. 

Today, barbiturates are commonly used in geriatric suicide involving medication overdose. In one 2010 New York City study, 27.2% of fatal overdose suicide cases in elderly persons were due to barbiturates. Because pentobarbital is very reliable and brings about a peaceful death, it is one of the drugs of choice for assisted suicide and capital punishment. Pentobarbital is used by euthanasia organizations in the US (Oregon Death with Dignity Act), Switzerland (Dignitas) and The Netherlands. In the US, the drug has been used for executions of convicted criminals. Today, many manufacturers do not permit its sale to prisons or corrections departments to carry out the death penalty. Since its virtual unavailability due to protests regarding its use in capital punishment, secobarbital has become the most widely used drug to cause death.

Physician-assisted suicide
Secobarbital is the medication most commonly prescribed for physician-assisted suicide, followed by pentobarbital [Oregon, 2010]. According to Oregon’s February 2017 official report, deaths occurring during the first 19 years under that state’s Death with Dignity Act (DWDA) took place after patients took the following drugs: secobarbital – 59.3%; pentobarbital – 34.3%; other – 6.5% [Oregon, 2017]. The lethal dose prescribed is typically 9 grams (9,000 mg) of secobarbital in capsules or 10 grams (10,000 mg) of pentobarbital liquid, to be consumed at one time [Okie, 2005]. Note that the usual therapeutic dosage of both secobarbital and pentobarbital, when prescribed for insomnia, is 100 mg at bedtime. 

Since the Oregon DWDA took effect in 1997, 460 patients have died by self-administration of a lethal dose of a prescription medication [Oregon Dept of Human Services, 2010]. In 2009, 95 prescriptions were written for lethal medications, resulting in 59 deaths (in the remaining cases, the medication was not ingested). About 80% of the patients had malignant cancer, and the most commonly ingested lethal medication was secobarbital (85% of cases). About 78% of the patients were 55–84 years of age. The time from ingestion to death ranged from 2 minutes to 4.5 days [Oregon Dept of Human Services, 2010].

According to the AFSP, if you suspect someone may be at risk for suicide:
1. Do not leave the person alone.
2. Remove any firearms, alcohol, drugs or sharp objects that could be used in a suicide attempt.
3. Call the US National Suicide Prevention Lifeline at 1-800-273-TALK (8255).
4. Take the person to an emergency room or seek help from a medical or mental health professional.

Ron Gasbarro, PharmD is a registered pharmacist, medical writer, and principal at Rx-Press.com. Read more at www.rx-press.com   

References
Centers for Disease Control and Prevention (CDC). Web-based Injury Statistics Query and Reporting System (WISQARS); 2018. Available at: http://www.cdc.gov/injury/wisqars/index.html  

Cheng AT, Hawton K, Lee CT, Chen TH. The influence of media reporting of the suicide of a celebrity on suicide rates: a population-based study. Int J Epidemiol. 2007;36:1229–34. 

Fink DS, Santaella-Tenorio J, Keyes KM. Increase in suicides the months after the death of Robin Williams in the US. PLoS ONE. 2018;13: e0191405. 

Mesoudi A. The cultural dynamics of copycat suicide. PLoS ONE. 2009;4:e7252. 

Niederkrotenthaler T, Fu KW, Yip PS, et al. Changes in suicide rates following media reports on celebrity suicide: a meta-analysis. J Epidemiol Community Health. 2012;66:1037–42. 

Okie S. Physician-assisted suicide— Oregon and beyond. N Engl J Med. 2005; 352:1627-30.

Oregon Department of Human Services. 2009 summary of Oregon's Death with Dignity Act; 2010. 

Oregon Department of Human Services. Table 1. Characteristics and end-of-life care of 460 DWDA patients who died after ingesting a lethal dose of medication, by year, Oregon, 1998–2009. www.oregon.gov/DHS/ph/pas/docs/yr12-tbl-1.pdf  

Oregon Health Authority, Public Health Division, Oregon Death with Dignity Act Data Summary; 2017.

Phillips DP. Overview of evidence linking copycat suicide and the media. Panel discussion at the American Association of Suicidology; St. Louis, MO; April 1996..

Stack S. Suicide in the media: A quantitative review of suicide based on non-fictional stories. Suicide Life Threat Behav. 2005;35:121–33. 

Substance Abuse and Mental Health Services Administration (SAMHSA). Results from the 2013 National Survey on Drug Use and Health: Mental Health Findings, NSDUH Series H-49, HHS Publication No. (SMA) 14-4887. Rockville, MD: Substance Abuse and Mental Health Services; 2014. Available at: http://www.samhsa.gov/data/sites/default/files/NSDUHmhfr2013/NSDUHmhfr2013.pdf 

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