Schizophrenia Research 159 (2014) 249–250

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Letter to the Editor Harmine for catatonic schizophrenia. A forgotten experiment

Dear Editors, The purpose of this letter is to present a lesser-known experiment suggesting a positive response of catatonic schizophrenia to Harmine, a monoamine oxidase A inhibitor(MAO-A), a study conducted by Petre Tomescu, in the late 1920's. Petre Tomescu (1890–1972) was a professor of Psychiatry, Dean of the Faculty of Medicine Bucharest, and Minister of Health in Romania, between 1941 and 1944, in the legionnaire government lead by Gen. I. Antonescu. He was arrested by the Communist Regime in 1945, and sentenced to 15 years of forced labor. He was imprisoned at Jilava and Aiud, two of the most severe imprisonments camps for political detainees in Romania (Muraru, 2013, May 9–15). All his contributions, together with those of the other two preeminent psychiatrists from the interwar period (Al. Obregia and C. Urechia) were denied by the early communist psychiatry, their ideas being considered idealistic and reactionary (Tudose and Tudose, 2012). Harmine, was found in the 1920's to have a possible use in the treatment of Parkinsonism (Beringer, 1929). As in schizophrenic catatonia muscle rigidity was one of the most important symptoms, Tomescu designed an experiment to test whether Harmine could be used as a potential therapeutic agent for catatonic schizophrenia with it, by using three patients with this disease. A dosage of 0.03–0.04 cg was found to be optimal. In the first patient injecting 0.03 cg Harmine caused a complete disappearance of the rigidity after an hour, with free passive movements in the upper limbs and only a slight residual rigidity in the lower limbs. Moreover, this dosage had positive effects on negativity, as the patient started saying a few words, and asked for his favorite foods. The patient was able to reveal various information from his past but also information from the time he was admitted (from the time he has been in a catatonic state). The symptoms reemerged gradually a few hours after the treatment; however the patient remained in an ameliorated state for a few days. After this initial success, Tomescu treated the patient for 25 days with Harmine, obtaining the same effects as those from the initial experiment. The patient was cooperative, with an almost complete remission of negativity, no muscle rigidity, and a significant increase in weight. The effects of the drug completely disappeared at 5–6 days after discontinuing it. On the second patient he obtained a complete remission of the muscle rigidity and negativity with a dosage of 0.04 cg. Moreover, the use of the drug on a longer period of time (20 days) had effects on his affectivity as he showed signs of falling in love with a nurse. The effect diminished significantly after 2–3 days. On the third patient similar results were obtained at a dosage of 0.04 cg; the use of the drug on a longer period of time (20 days) caused him to want to leave the hospital and stay with his family. The study concluded that, even if Harmine had a purely symptomatic effect, it

http://dx.doi.org/10.1016/j.schres.2014.08.006 0920-9964/© 2014 Elsevier B.V. All rights reserved.

did cause significant improvement of the symptoms and of the quality of life. The experiments were not continued due to the prohibitive costs of Harmine (Tomescu and Russu, 1930). The effect disappeared in about five days. Starting with the 1970's were published a series of studies suggesting a possible role of MAO in schizophrenia. For example in 1972, Murphy and Wyatt showed that patients with schizophrenia have a lower MAO activity compared to healthy controls (Wyatt and Murphy, 1976). Lewine and Meltzer found a positive correlation between platelet MAO activity and negative symptoms in male schizophrenic patients (Lewine and Meltzer, 1984). Sharma et al. found a significantly lower value for platelet MAO in patients with paranoid, catatonic, and disorganized schizophrenia (Sharma et al., 1990). Interestingly, the study of Tomescu showed a remarkable improvement of negative symptoms, usually less responsive to conventional (nowadays) monoamine antagonists (Conn et al., 2008). It did not show a response of positive symptoms however. The study was written in Romanian, and the circulation of his experiment outside Romania was close to none, as we could not identify any citation of this work in the main scientific flow. It is however one of the first studies able to identify a positive response of schizophrenia to a pharmacological agent. Role of funding source This work was possible with the financial support of the Sectoral Operational Programme for Human Resources Development 2007–2013 (137390), cofinanced by the European Social Fund, under the project number POSDRU/159/1.5/S/137390 for author 1 and by a grant of the Romanian National Authority for Scientific Research, CNCS-UEFISCDI, project number PN-II-RUTE-2012-3-44 for author 2. Individual contributions HS analyzed the initial text, wrote the first draft and approved the manuscript, BO analyzed the historical context, corrected the first draft and approved the manuscript, and DAI reviewed the physiopathology of MAO I, corrected the first draft and approved the final version. Conflicts of interests None. Acknowledgments None.

References Beringer, K., 1929. Zur Banisterin-und Harminfrage. Nervenarzt 2, 548–549. Conn, P.J., Tamminga, C., Schoepp, D.D., Lindsley, C., 2008. Schizophrenia: moving beyond monoamine antagonists. Mol. Interv. 8 (2), 99–107. Lewine, R.J., Meltzer, H.Y., 1984. Negative symptoms and platelet monoamine oxidase activity in male schizophrenic patients. Psychiatry Res. 12 (2), 99–109. Muraru, A., 2013. Digging out the crimes of the communism (Dezgropând crimele comunismului). Observator Cult. 414 (672), 2–3 (May 9–15). Sharma, I., Kumar, A., Chansouria, J.P.N., 1990. Platelet MAO activity in subgroups of schizophrenia. Indian J. Psychiatry 32 (4), 324. Tomescu, P., Russu, E., 1930. Experimental researches regarding the therapeutic action of Harmine on the catatonic syndrome (Cercetări experimentale referitoare la ac iunea terapeutică a Harminei asupra sindromului catatonic). Rev. Spitalul 6.

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Letter to the Editor

Tudose, C., Tudose, F., 2012. The history of psychotherapy in Rumania during the socialist dictatorship of Nicolae Ceauşescu. Eur. J. Ment. Health 7 (1). Wyatt, R.J., Murphy, D.L., 1976. Low platelet monoamine oxidase activity and schizophrenia. Schizophr. Bull. 2 (1), 77–89.

Sorin Hostiuc National Institute of Legal Medicine Bucharest, Bucharest, Romania Carol Davila University of Medicine and Pharmacy, Bucharest, Romania E-mail addresses: [email protected], [email protected] Corresponding author at: National Institute of Legal Medicine, Sos. Vitan Barzesti 9, 042122 Bucharest, Romania. Tel.: +40 723791072.

Octavian Buda National Institute of Legal Medicine Bucharest, Bucharest, Romania Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Daniela Adriana Ion Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

30 June 2014

Harmine for catatonic schizophrenia. A forgotten experiment.

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