Other factors may have contributed to the patient’s improvement, including her medical treatment (eg, antibiotics), as well as a change of setting from a psychiatric to a medical unit, the authors noted. They suggested further research into the role of fever in treatment of psychiatric illness, acknowledging that this cannot be done through the deliberate introduction of an infectious agent into a patient. Potential avenues for investigation include using sulforaphane or a similar noninfectious pyrogenic agent as adjunctive treatment for refractory psychosis, as well as examining whether there are specific febrile illnesses that are associated with improvement in psychosis.

An accompanying commentary by David A. Kahn, MD, noted that when pyrotherapy was used for treating psychosis, it was generally ineffective in cases not caused by syphilis.8 Additionally, the patient might have been suffering from an underlying central nervous system infection, such as Lyme disease, which might have improved as a result of the intravenous antibiotics.

Another explanation he suggested is that the antibiotics themselves, rather than the fever, were responsible for the improvement in the patient’s psychosis. He noted that certain antibiotics can cause adverse central nervous system reactions.9 If antibiotics may cause psychosis in a small subset of patients, it is conversely true that they may alter neurotransmitters and cause improvements in psychotic symptoms. “By time course, this cannot be excluded as a possible source of brain alteration in the current case,” he stated.

He added that it “behooves us to watch closely how medical comorbidities affect psychiatric illness.”


1.      Zuschlag ZD, Lalich CJ, Short EB, Hamner M, Kahn DA. Pyrotherapy for the treatment of psychosis in the 21st century: a case report and literature review.  J Psychiatr Pract. 2016 Sep;22(5):410-5.

2.      Whitrow M. Wagner-Jauregg and fever therapy. Med Hist. 1990 Jul;34(3):294-310.

3.      Moreira MB. [Mechanism of action of pyretotherapy of neurosyphilis & of its eventual use in leprosy; preliminary note]. Rev Bras Med. 1958 Sep;15(9):624-8.

4.      Sager O, Badenski R, Roth RR, et al. The role of the central nervous system in pyretotherapy for syphilitic meningo-encephalitis; the action of malaric fever and of fever produced by typho-paratyphic vaccine.  Rum Med Rev. 1957 Apr-Jun;1(2):47-9.

5.      Keck PE Jr, Caroff SN, McElroy SL. Neuroleptic malignant syndrome and malignant hyperthermia: end of a controversy? J Neuropsychiatry Clin Neurosci. 1995 Spring;7(2):135-44.

6.      Ford DM, Klugman KP. Contrasting roles of 5-hydroxytryptamine and noradrenaline in fever in rats. J Physiol. 1980 Jul;304:51-7.

7.      Singh K, Connors SL, Macklin EA, Smith KD, Fahey JW, Talalay P, Zimmerman AW. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15550-5.

8.      Lieberman J. Shrinks: The Untold Story. New York, NY: Little, Brown and Company, 2015.

9.      Bhattacharyya S, Darby RR, Raibagkar P, Gonzalez Castro LN, Berkowitz AL. Antibiotic-associated encephalopathy. Neurology. 2016 Mar 8;86(10):963-71.