Nicolas Roberto Robles 
Badajoz, Spain

 

Figure 1. Jean-Baptiste Denys (1643–1704). Via Wikimedia Public Domain.

“You seek for knowledge and wisdom, as I once did, and I ardently hope that the gratification of your wishes may not be a serpent to sting you, as mine has been.”

Mary W. Shelley, Frankenstein (The Modern Prometheus)

 

Jean-Baptiste Denys (1643–3 October 1704), a French physician who was the personal doctor to King Louis XIV, is credited with performing the first fully documented blood transfusion on June 15, 1667. He transfused about twelve ounces of sheep’s blood into a fifteen-year-old boy, who required blood after having been bled with leeches twenty times. The boy survived the transfusion, likely because of the small amount of blood that was actually transfused, as did Denys’ next subject, an adult laborer.

That winter, Denys transfused calf’s blood to Antoine Mauroy, a madman, in the first documented attempt to use exchange transfusion to treat psychosis. Mauroy’s symptoms initially improved, but he died during the third transfusion. Much controversy surrounded his death: Mauroy’s wife asserted that Denys was responsible and he was charged with murder. After he was acquitted, Mauroy’s wife was then accused and Denys quit the practice of medicine. It was later determined that Mauroy had died from arsenic poisoning.¹

In 1938, Reiter performed exchange transfusion to treat three patients with acute catatonic schizophrenia and reported abatement of the disease in all three. However, no change was observed in a patient who suffered from chronic schizophrenia. Reiter proposed that acute schizophrenia was caused by endogenous intoxication.²

Hemodialysis for the treatment of schizophrenia was first tried in 1960 by Thoelen and co-workers, who used it in four patients suffering from the catatonic form of schizophrenia. Three patients showed a good response.³ In 1964 Kolff and coworkers dialyzed a series of schizophrenic patients at the Cleveland Clinic and reported favorable results but did not pursue the project. Then in 1977 Wagemaker and Cade published a further report on the treatment of schizophrenia by hemodialysis. The patients were dialyzed once a week until improvement in their symptoms was observed; they were then dialyzed less frequently (from every two weeks to once every three months) for at least one year. They observed a remission in five out of six schizophrenics.⁴ Even more, Hippius et al in a joint effort with thirty-six psychiatrists and nephrologists authored “Recommendations for the Evaluation of Possible Therapeutic Effects of Blood Purification Methods in Chronic Schizophrenic Patients” in 1978.⁵

Figure 2. Cutting the Stone by Hieronymus Bosch. Museo del Prado, Madrid. A man wearing a funnel hat extracts the stone of madness. Public Domain.

Nedopil and co-workers, with the support of the Registry of the European Dialysis and Transplant Association (EDTA), systematically evaluated detoxication treatment for schizophrenia. Of 1,090 European renal units replying to the Registry in 1978, eighty-two indicated that they had treated schizophrenics by blood purification methods including hemodialysis, hemoperfusion, hemofiltration, and peritoneal dialysis. Of the ninety-five centers that originally treated schizophrenic patients with detoxification and were asked to send data to the Registry of the EDTA, thirty-nine centers replied (thirty-five from Europe and four from the United States). Of 100 patients in Europe, seventeen were reported to be very much improved and twenty-two to be improved. On the other hand, 61% of patients received no benefits from treatment.⁶ Palmour and Ervin reported in 1979 that the plasma and dialysate of some patients contained large amounts of p-Ieucine5-endorphin, a variant of naturally occurring p-methionine5-endorphin, which is not detectable in the plasma of healthy subjects.⁷

Recently Cox and coworkers reviewed the use of hemodialysis as a treatment for schizophrenia. They found fifty evaluable articles but only nine with adequate experimental design (performed between 1978 and 1985). They concluded that the early positive findings of benefit from hemodialysis in the treatment of schizophrenia were most likely driven by a placebo effect, potentially magnified by the invasive nature of extra-corporeal circulation and the intensive nursing and medical input required. There may also have been a publication bias in favor of positive results. In all, the initial uncontrolled studies included hardly more than 100 patients.⁸

Schizophrenia remains an important and life-altering condition, but the attempt to treat it with hemodialysis appears to have been a well-intentioned illusion.

 

 

References

1. Hurland HJ et al. Dialysis and haemofiltration for non-renal conditions. In: Drukker W, Parsons FM and Maher JF (Eds). Replacement of renal function by dialysis A textbook of dialysis. 2nd Ed. 1986. Martinus Nijhoff Publishers. Pp. 884-896.
2. Philipp M: Hamodialyse und die Idee der Blutreinigung in der Schizophreniebehandlung Haemodialsysis and the idea of purification of the blood in the therapy of schizophrenia) Fortschr Neurol Psychiatr 1979; 47: 36-46
3. Tholen H, Stricker E, Feer H, Massine MA, Staub H: Uber die Anwendung der kunstlichen Niere bei Schizophrenie und Myasthenia gravis. Dtsch Med Wochenschr, 1960; 85: 1012-1015
4. Wagemaker H, Cade R: The use of hemodialysis in chronic schizophrenia. Am J Psychiatry, 1977; 134: 684-685
5. Hippius H, Matussek N, Nedopil N, Strauss A, v. Zerssen GD, Emrich H, Kolff WJ, Gurland HJ: Recommendations for the evaluation of possible therapeutic effects of blood purification methods in chronic schizophrenic patients. Artif Organs , 1979; 3: 104-107
6. Nedopil N, Dieterle D, Gurland HJ, Koepcke W, Wing AJ, Selwood NA: Detoxication treatment in chronic schizophrenia. Results from a survey. Artificial Organs (1983;7:304-309Palmour RM, Ervin FR: Biochemical and physiological characterization of a peptide from the hemodialysate of psychotic patients. Psychopharmacol Bull 1979;15:21-14.
7. Cox ER, Marwick KFM, Hunter RW, Priller J, Lawrie SM. Dialysis and plasmapheresis for schizophrenia: a systematic review. Psychol Med. 2020;50(8):1233-1240.

 

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NICOLAS ROBERTO ROBLES is professor of Nephrology at the University of Extremadura.

 

Winter 2021 |  Sections  |  Psychiatry & Psychology