John Nash and his wife Alicia died in an automobile accident on May 23rd, 2015. Nash was associated with Princeton University since the late 1940s, where he received his doctorate in 1950. He was 22 years old and had written a dissertation that contained what came to be called the Nash equilibrium. This work eventually led to him receiving the Nobel Prize in Economics in 1994. One of the most brilliant mathematicians of the twentieth century, his theories are used in economics, computing, evolutionary biology, artificial intelligence, accounting, computer science, politics, and military theory. And he struggled with schizophrenia.
I was introduced to the life and struggles of John Nash, the Princeton mathematician, when I saw the 2001 movie “A Beautiful Mind.” Soon afterwards I taught a Sociology course that had a section on mental illness where I showed the documentary, “A Brilliant Madness,” which was about his contributions to mathematics and decent into insanity. It struck me that the radical changes in my thinking about psychiatric medication and treatment occurred over the fourteen years since I learned about John Nash. I can’t say his life story instigated that change, but it has been part of my journey. So to hear of his death came as a shock.
So I’ve re-watched “A Brilliant Madness” (available here on YouTube), and decided to use a reflection on his life to frame an article I intended to write. The article is about sudden unexplained death and other health problems related to a drastically shortened lifespan for people with mental disorders. The fact of a shortened lifespan is widely acknowledged, but whether or not it is due to the long-term use of psychiatric medications is in dispute. What follows is a series of brief reports and reflections on some of the existing research.
According to a recent meta-analysis reported in Jama Psychiatry, “Mortality in Mental Disorders and Global Disease Burden Implications,” people diagnosed with mental disorders are twice as likely to die ten years younger than the general population. Mad in America reported that over two-thirds of the deaths were due to natural causes. Psychiatric drug use was not studied as a possible contributing factor to early mortality. However, they did find that people who spent longer times in psychiatric hospitals were even more likely to die younger. At least one individual said the findings were vastly overestimated. Yet another person commented it was by far the lowest estimate of the shortened life of individuals diagnosed with mental disorders in decades. She also pointed to a 2006 report by the National Association of State Mental Health Program Directors that supported this claim, “Morbidity and Mortality in People with Serious Mental Illness.”
The report found that people with serious mental illness (SMI) died, on average, 25 years earlier than the general population. Suicide and injury accounted for 30-40% of the excess mortality, but “60% of premature deaths in persons with schizophrenia are due to medical conditions such as cardiovascular, pulmonary and infectious diseases.” Mortality rates for cardiovascular disease, diabetes, respiratory disease and infectious disease were said to be several times those of the general population. The association of the mortality rates for the SMI and atypical (second generation) antipsychotics is hard to miss. Looking at the introduction of the atypical antipsychotics since 1991, they said:
The second generation antipsychotic medications have become more highly associated with weight gain, diabetes, dyslipidemia, insulin resistance and the metabolic syndrome.
Appleby et al. reported there has been controversy over the possibility of sudden death in people using antipsychotic medication since 1970. Reinert and Hermann speculated as far back as 1960 that the sudden unexplained deaths of five individuals receiving chlorpromazine (Thorazine) could have been due to the drug. Subramaniam et al. reported that there was an overwhelming body of evidence that patients with serious mental illness are at a significantly higher risk for cardiovascular illness and death than the general population. A 2011 review by Foley and Morley found that the risk of cardiovascular disease increased after the exposure to any antipsychotic drug.
Psychotropic medications can have a variety of effects on the heart, ranging from hypotension and tachycardia [a heart that beats faster than normal] to more severe problems such as arrythmias [irregular heartbeat], bradycardia [a heart that beats slower than normal] and sudden death.
CNS Drugs did a comprehensive literature review of atypical antipsychotics and their metabolic effects. The review found that atypical antidepressants differed in their effects on weight and obesity and on blood glucose and lipid levels. Clozaril and Zyprexa were associated with a substantial risk of weight gain and an increased risk of developing diabetes.
Risperdal and Seroquel are associated with a mild or moderate weight gain. Although they do not have any direct evidence of an increased risk of diabetes, there is an increased risk factor due to the possibility of weight gain or obesity from the drugs. Geodon and Abilify were associated with minimal weight gain. Data on the risks of diabetes or high cholesterol was limited.
Joukamaa et al did a long term, 17-year follow-up study of 99 individuals with schizophrenia. They demonstrated a greater risk of dying if the individual was taking more than one neuroleptic (antipsychotic) drug. This was said to be a replication of a study done by Waddington et al. in 1998. They concluded: “Future research needs to determine whether the high mortality among those with schizophrenia is mainly attributable to the disorder per se or to the antipsychotic medication.”
On the other hand, a study by Manu et al did not find that unexplained death was associated with higher utilization of first generation or atypical antipsychotics. They did suggest that the role of diabetes and high cholesterol as risk factors for sudden death in psychiatric patients needed careful longitudinal studies.
John Nash was hospitalized several times and took medication sporadically between 1961 and 1970. He was reunited with his then estranged wife, Alicia, and never used another psychiatric medication. He also was never hospitalized again. Nash said he never went to a hospital voluntarily. “I didn’t feel that I belonged locked up.” The film, “A Beautiful Mind,” wrongly implied he was using newer antipsychotic medication when he remitted from his illness. When Nash died, he was 86 years old and hadn’t used medication for forty-five years.
Nash saw madness as a kind of escape. He said: “To some extent, sanity is a form of conformity; and to some extent people who are insane are nonconformists.” The DVD for “A Brilliant Madness” contained an interview with John Nash where he reflected on various aspects of his life. Once when discussing with a friend how such a brilliant mathematician could believe he was hearing aliens speak to him, Nash said those thoughts came to him the same way his thoughts on mathematics came. So he took them seriously. Reflecting on that earlier time during the interview, he said: “Jumping to an incorrect conclusion about causality when you see a correlation is the most often made logical mistake.”
The evidence connecting sudden death to psychiatric drugs is not conclusively causative at this point in time. From my reading of the above and other material such as Anatomy of an Epidemic by Robert Whitaker, I’d say it is strongly correlationa; and I wait for the day when it is conclusively causative. You can read a short bio of John Nash on the Princeton University website here. I’ll close with one final quote from John Nash that spoke to me, taken from his biographical essay on the Nobel Prize website:
At the present time I seem to be thinking rationally again in the style that is characteristic of scientists. However this is not entirely a matter of joy as if someone returned from physical disability to good physical health. One aspect of this is that rationality of thought imposes a limit on a person’s concept of his relation to the cosmos.